An Experimental Investigation of Silicone-to-Metal Bond Strength in Composite Space Docking System Seals

NASA Technical Reports Server (NTRS)

Gaier, James R.; Siamidis, John; Larkin, Elizabeth M. G.

2010-01-01

The National Aeronautics and Space Administration (NASA) is currently developing a new universal docking mechanism for future space exploration missions called the Low Impact Docking System (LIDS). A candidate LIDS main interface seal design is a composite assembly of silicone elastomer seals vacuum molded into grooves in an electroless nickel plated aluminum retainer. The strength of the silicone-tometal bond is a critical consideration for the new system, especially due to the presence of small areas of disbond created during the molding process. In the work presented herein, seal-to-retainer bonds of subscale seal specimens with different sizes of intentional disbond were destructively tensile tested. Nominal specimens without intentional disbonds were also tested. Tension was applied either uniformly on the entire seal circumference or locally in one short circumferential length. Bond failure due to uniform tension produced a wide scatter of observable failure modes and measured load-displacement behaviors. Although the preferable failure mode for the seal-to-retainer bond is cohesive failure of the elastomer material, the dominant observed failure mode under the uniform loading condition was found to be the less desirable adhesive failure of the bond in question. The uniform tension case results did not show a correlation between disbond size and bond strength. Localized tension was found to produce failure either as immediate tearing of the elastomer material outside the bond region or as complete peel-out of the seal in one piece. The obtained results represent a valuable benchmark for comparison in the future between adhesion loads under various separation conditions and composite seal bond strength.

Sterility Testing of Prototype Plastic Aseptic Docking Tubes

DTIC Science & Technology

1982-09-01

Bacillus stearothermophilus CL21. AmerRACT (Coat~e- aeids uIf 8" niev teIi by block n"Unbee) Fifty-nine pairs of sterile docking tabs, manufactured...of Bacillus stearothermophilus , _J sealed, and flushed with sterile culture medium. Twenty five percent of the LA_.. seals failed because of...were similarly attached to sterile tubes of Becton Dickenson supplemented peptone broth. A 25 ul aliquot of Bacillus stearothermophilus spores (Ix]O

Effects of Atomic Oxygen and Grease on Outgassing and Adhesion of Silicone Elastomers for Space Applications

NASA Astrophysics Data System (ADS)

de Groh, Henry C.; Puleo, Bernadette J.; Steinetz, Bruce M.

An investigation of silicone elastomers for seals used in docking and habitat systems for future space exploration vehicles is being conducted at NASA. For certain missions, NASA is considering androgynous docking systems where two vehicles each having a seal would be required to: dock for a period of time, seal effectively, and then separate with minimum push-off forces for undocking. Silicone materials are generally chosen for their wide operating temperatures and low leakage rates. However silicone materials are often sticky and usually exhibit considerable adhesion when mated against metals and silicone surfaces. This paper investigates the adhesion unit pressure for a space rated silicone material (S0383-70) for either seal-on-seal (SoS) or seal-on-aluminum (SoAl) operation modes in the following conditions: as-received, after ground-based atomic-oxygen (AO) pre-treatment, after application of a thin coating of a space-qualified grease (Braycote 601EF), and after a combination of AO pre-treatment and grease coating. In order of descending adhesion reduction, the AO treatment reduced seal adhesion the most, followed by the AO plus grease pre-treatment, followed by the grease treatment. The effects of various treatments on silicone (S0383-70 and ELA-SA-401) outgassing properties were also investigated. The leading adhesion AO pre-treatment reduction led to a slight decrease in outgassing for the S0383-70 material and virtually no change in ELA-SA-401 outgassing.

Effects of Atomic Oxygen and Grease on Outgassing and Adhesion of Silicone Elastomers for Space Applications

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Puleo, Bernadette J.; Steinetz, Bruce M.

2011-01-01

An investigation of silicone elastomers for seals used in docking and habitat systems for future space exploration vehicles is being conducted at NASA. For certain missions, NASA is considering androgynous docking systems where two vehicles each having a seal would be required to: dock for a period of time, seal effectively, and then separate with minimum push-off forces for undocking. Sili-cone materials are generally chosen for their wide operating temperatures and low leakage rates. However silicone materials are often sticky and usually exhibit considerable adhesion when mated against metals and silicone surfaces. This paper investigates the adhesion unit pressure for a space rated silicone material (S0383-70) for either seal-on-seal (SoS) or seal-on-aluminum (SoAl) operation modes in the following conditions: as-received, after ground-based atomic-oxygen (AO) pre-treatment, after application of a thin coating of a space-qualified grease (Bray-cote 601EF), and after a combination of AO pre-treatment and grease coating. In order of descending adhesion reduction, the AO treatment reduced seal adhesion the most, followed by the AO plus grease pre-treatment, followed by the grease treatment. The effects of various treatments on silicone (S0383-70 and ELA-SA-401) outgassing properties were also investigated. The leading adhesion AO pre-treatment reduction led to a slight decrease in outgassing for the S0383-70 material and virtually no change in ELA-SA-401 outgassing.

Effects of Atomic Oxygen and Grease on Outgassing and Adhesion of Silicone Elastomers for Space Applications

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Puleo, Bernadette J.; Steinetz, Bruce M.

2012-01-01

An investigation of silicone elastomers for seals used in docking and habitat systems for future space exploration vehicles is being conducted at NASA. For certain missions, NASA is considering androgynous docking systems where two vehicles each having a seal would be required to: dock for a period of time, seal effectively, and then separate with minimum push-off forces for undocking. Silicone materials are generally chosen for their wide operating temperatures and low leakage rates. However silicone materials are often sticky and usually exhibit considerable adhesion when mated against metals and silicone surfaces. This paper investigates the adhesion unit pressure for a space rated silicone material (S0383-70) for either seal-on-seal (SoS) or seal-on-aluminum (SoAl) operation modes in the following conditions: as-received, after ground-based atomic-oxygen (AO) pre-treatment, after application of a thin coating of a space-qualified grease (Braycote 601EF), and after a combination of AO pre-treatment and grease coating. In order of descending adhesion reduction, the AO treatment reduced seal adhesion the most, followed by the AO plus grease pre-treatment, followed by the grease treatment. The effects of various treatments on silicone (S0383-70 and ELA-SA-401) outgassing properties were also investigated. The leading adhesion AO pretreatment reduction led to a slight decrease in outgassing for the S0383-70 material and virtually no change in ELA-SA-401 outgassing.

Effects of Hypervelocity Impacts on Silicone Elastomer Seals and Mating Aluminum Surfaces

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Steinetz, Bruce M.

2009-01-01

While in space silicone based elastomer seals planned for use on NASA's Crew Exploration Vehicle (CEV) are exposed to threats from micrometeoroids and orbital debris (MMOD). An understanding of these threats is required to assess risks to the crew, the CEV orbiter, and missions. An Earth based campaign of hypervelocity impacts on small scale seal rings has been done to help estimate MMOD threats to the primary docking seal being developed for the Low Impact Docking System (LIDS). LIDS is being developed to enable the CEV to dock to the ISS (International Space Station) or to Altair (NASA's next lunar lander). The silicone seal on LIDS seals against aluminum alloy flanges on ISS or Altair. Since the integrity of a seal depends on both sealing surfaces, aluminum targets were also impacted. The variables considered in this study included projectile mass, density, speed, incidence angle, seal materials, and target surface treatments and coatings. Most of the impacts used a velocity near 8 km/s and spherical aluminum projectiles (density = 2.7 g/cubic cm), however, a few tests were done near 5.6 km/s. Tests were also performed using projectile densities of 7.7, 2.79, 2.5 or 1.14 g/cubic cm. Projectile incidence angles examined included 0 deg, 45 deg, and 60 deg from normal to the plane of the target. Elastomer compounds impacted include Parker's S0383-70 and Esterline's ELA-SA-401 in the as received condition, or after an atomic oxygen treatment. Bare, anodized and nickel coated aluminum targets were tested simulating the candidate mating seal surface materials. After impact, seals and aluminum plates were leak tested: damaged seals were tested against an undamaged aluminum plate; and undamaged seals were placed at various locations over craters in aluminum plates. It has been shown that silicone elastomer seals can withstand an impressive level of damage before leaking beyond allowable limits. In general on the tests performed to date, the diameter of the crater in either the elastomer, or the aluminum, must be at least as big as 80% to 90% of width of the bulb of the seal before significant leakage occurs.

Effects of Hypervelocity Impacts on Silicone Elastomer Seals and Mating Aluminum Surfaces

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Steinetz, Bruce M.

2009-01-01

While in space silicone based elastomer seals planned for use on NASA's Crew Exploration Vehicle (CEV) are exposed to threats from micrometeoroids and orbital debris (MMOD). An understanding of these threats is required to assess risks to the crew, the CEV orbiter, and missions. An Earth based campaign of hypervelocity impacts on small scale seal rings has been done to help estimate MMOD threats to the primary docking seal being developed for the Low Impact Docking System (LIDS). LIDS is being developed to enable the CEV to dock to the ISS (International Space Station) or to Altair (NASA's next lunar lander). The silicone seal on LIDS seals against aluminum alloy flanges on ISS or Altair. Since the integrity of a seal depends on both sealing surfaces, aluminum targets were also impacted. The variables considered in this study included projectile mass, density, speed, incidence angle, seal materials, and target surface treatments and coatings. Most of the impacts used a velocity near 8 km/s and spherical aluminum projectiles (density = 2.7 g/cubic centimeter), however, a few tests were done near 5.6 km/s. Tests were also performed using projectile densities of 7.7, 2.79, 2.5 or 1.14 g/cubic centimeter. Projectile incidence angles examined included 0 degrees, 45 degrees , and 60 degrees from normal to the plane of the target. Elastomer compounds impacted include Parker's S0383-70 and Esterline's ELA-SA-401 in the as received condition, or after an atomic oxygen treatment. Bare, anodized and nickel coated aluminum targets were tested simulating the candidate mating seal surface materials. After impact, seals and aluminum plates were leak tested: damaged seals were tested against an undamaged aluminum plate; and undamaged seals were placed at various locations over craters in aluminum plates. It has been shown that silicone elastomer seals can withstand an impressive level of damage before leaking beyond allowable limits. In general on the tests performed to date, the diameter of the crater in either the elastomer, or the aluminum, must be at least as big as 80% to 90% of width of the bulb of the seal before significant leakage occurs.

Assessing MMOD Impacts on Seal Performance

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Daniels, C.; Dunlap, P.; Steinetz, B.

2007-01-01

The elastomer seal needed to seal in cabin air when NASA s Crew Exploration Vehicle is docked is exposed to space prior to docking. While open to space, the seal might be hit by orbital debris or meteoroids. The likelihood of damage of this type depends on the size of the particle. Our campaign is designed to find the smallest particle that will cause seal failure resulting in loss of mission. We will then be able to estimate environmental risks to the seal. Preliminary tests indicate seals can withstand a surprising amount of damage and still function. Collaborations with internal and external partners are in place and include seal leak testing, modeling of the space environment using a computer code known as BUMPER, and hypervelocity impact (HVI) studies at Caltech. Preliminary work at White Sands Test Facility showed a 0.5 mm diameter HVI damaged areas about 7 times that diameter, boring deep (5 mm) into elastomer specimens. BUMPER simulations indicate there is a 1 in 1440 chance of getting hit by a particle of diameter 0.08 cm for current Lunar missions; and 0.27 cm for a 10 year ISS LIDS seal area exposure.

Seal with integrated shroud for androgenous docking and berthing in contaminated environments

NASA Technical Reports Server (NTRS)

Daniels, Christopher C. (Inventor)

2012-01-01

The present invention is directed to a specially configured seal system which provides a barrier to gas leakage flow between a pressurized module and its external environment. The seal includes a shroud covering which protects the sealing interface from its environment when not in use, and retracts to expose the sealing interface when mated. The seal system is constructed and arranged to mate with a seal of identical construction and arrangement or to mate with a flat surface.

GRC-2009-C-01749

NASA Image and Video Library

2005-07-01

Photographs of the Low Impact Docking System (LIDS); this hardware is a test for the ORION docking birthing system to connect the Crew Exploration Vehicle (CEV) to the International Space Station (ISS); atomic oxygen 12 inch seals testing

Material Properties of Three Candidate Elastomers for Space Seals Applications

NASA Technical Reports Server (NTRS)

Bastrzyk, Marta B.; Daniels, Christopher C.; Oswald, Jay J.; Dunlap, Patrick H., Jr.; Steinetz, Bruce M.

2010-01-01

A next-generation docking system is being developed by the National Aeronautics and Space Administration (NASA) to support Constellation Space Exploration Missions to low Earth orbit (LEO), to the Moon, and to Mars. A number of investigations were carried out to quantify the properties of candidate elastomer materials for use in the main interface seal of the Low Impact Docking System (LIDS). This seal forms the gas pressure seal between two mating spacecraft. Three candidate silicone elastomer compounds were examined: Esterline ELA-SA-401, Parker Hannifin S0383-70, and Parker Hannifin S0899-50. All three materials were characterized as low-outgassing compounds, per ASTM E595, so as to minimize the contamination of optical and solar array systems. Important seal properties such as outgas levels, durometer, tensile strength, elongation to failure, glass transition temperature, permeability, compression set, Yeoh strain energy coefficients, coefficients of friction, coefficients of thermal expansion, thermal conductivity and diffusivity were measured and are reported herein.

Evolution of the IBDM Structural Latch Development into a Generic Simplified Design

NASA Technical Reports Server (NTRS)

DeVriendt, K.; Dittmer, H.; Vrancken, D.; Urmston, P.; Gracia, O.

2010-01-01

This paper presents the evolution in the development of the structural latch for the International Berthing Docking Mechanism (IBDM, see Figure 1). It reports on the lessons learned since completion of the test program on the engineering development unit of the first generation latching system in 2007. The initial latch design has been through a second generation concept in 2008, and now evolved into a third generation of this mechanism. Functional and structural testing on the latest latch hardware has recently been completed with good results. The IBDM latching system will provide the structural connection between two mated space vehicles after berthing or docking. The mechanism guarantees that the interface seals become compressed to form a leak-tight pressure system that creates a passageway for the astronauts.

Space Environment's Effects on Seal Materials

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Daniels, Christopher C.; Dunlap, Patrick; Miller, Sharon; Dever, Joyce; Waters, Deborah; Steinetz, Bruce M.

2007-01-01

A Low Impact Docking System (LIDS) is being developed by the NASA Johnson Space Center to support future missions of the Crew Exploration Vehicle (CEV). The LIDS is androgynous, such that each system half is identical, thus any two vehicles or modules with LIDS can be coupled. Since each system half is a replica, the main interface seals must seal against each other instead of a conventional flat metal surface. These sealing surfaces are also expected to be exposed to the space environment when vehicles are not docked. The NASA Glenn Research Center (NASA GRC) is supporting this project by developing the main interface seals for the LIDS and determining the durability of candidate seal materials in the space environment. In space, the seals will be exposed to temperatures of between 50 to 50 C, vacuum, atomic oxygen, particle and ultraviolet radiation, and micrometeoroid and orbital debris (MMOD). NASA GRC is presently engaged in determining the effects of these environments on our candidate elastomers. Since silicone rubber is the only class of seal elastomer that functions across the expected temperature range, NASA GRC is focusing on three silicone elastomers: two provided by Parker Hannifin (S0-899-50 and S0-383-70) and one from Esterline Kirkhill (ELA-SA-401). Our results from compression set, elastomer to elastomer adhesion, and seal leakage tests before and after various simulated space exposures will be presented.

Explosion Welding for Hermetic Containerization

NASA Technical Reports Server (NTRS)

Dolgin, Benjamin; Sanok, Joseph

2003-01-01

A container designed for storing samples of hazardous material features a double wall, part of which is sacrificed during an explosion-welding process in which the container is sealed and transferred to a clean environment. The major advantage of this container sealing process is that once the samples have been sealed inside, the outer wall of what remains of the container is a clean surface that has not come into contact with the environment from which the samples were taken. Thus, there is no need to devise a decontamination process capable of mitigating all hazards that might be posed by unanticipated radioactive, chemical, and/or biological contamination of the outside of the container. The container sealing method was originally intended to be used to return samples from Mars to Earth, but it could also be used to store samples of hazardous materials, without the need to decontaminate its outer surface. The process stages are shown. In its initial double-wall form, the volume between the walls is isolated from the environment; in other words, the outer wall (which is later sacrificed) initially serves to protect the inner container from contamination. The sample is placed inside the container through an opening at one end, then the container is placed into a transfer dock/lid. The surfaces that will be welded together under the explosive have been coated with a soft metallic sacrificial layer. During the explosion, the sacrificial layer is ejected, and the container walls are welded together, creating a strong metallic seal. The inner container is released during the same event and enters the clean environment.

Suitlock Docking Mechanism

NASA Technical Reports Server (NTRS)

Culbertson, Philip, Jr. (Inventor)

1997-01-01

An environmental protective suit used for hazardous clean-up or space applications includes a suitlock docking mechanism that allows for easy egress and ingress of a crew member between a sealed vessel and a possibly contaminated environment. The suitlock docking mechanism comprises a single actuator that controls latches which, in turn, respectfully control rack and pinion assemblies that allow for easy removal and attachment of a life support equipment enclosure shell to the environmental protective suit or to the vehicle from which the operator performs his/her duties.

Overview of NASA Glenn Seal Project

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Dunlap, Patrick H., Jr.; Proctor, Margaret; Delgado, Irebert; Finkbeiner,Joshua; deGroh, Henry; Ritzert, Frank; Daniels, Christopher; DeMange, Jeff; Taylor, Shawn;

Metallic Seal Development for Advanced Docking/Berthing System

NASA Technical Reports Server (NTRS)

Oswald, Jay; Daniels, Christopher; Dunlap, Patrick, Jr.; Steinetz, Bruce

2006-01-01

Feasibility of metal-to-metal androgenous seals has been demonstrated. Techniques to minimize surface irregularities must be examined. Two concepts investigated: 1) Flexible metal interface with elastomeric preloader; 2) Flexibility will accommodate any surface irregularities from the mating surface. Rigid metal interface with elastomeric preloader. Rigidity of the metal surface will prevent irregularities (waves) from occurring.

iLIDS Simulations and Videos for Docking TIM

NASA Technical Reports Server (NTRS)

Lewis, James L.

2010-01-01

The video shows various aspects of the International Low Impact Docking System, including team members, some production, configuration, mated androgynous iLIDS, SCS Lockdown system, thermal analysis, electrical engineering aspects, the iLIDS control box and emulator, radiation testing at BNL, component environmental testing, component vibration testing, 3G processor board delivery system, GTA vibe test, EMA testbed, hook and hook disassembly, flex shaftdrive assembly, GSE cradle MISSE-6 Columbus, MISSE 6 and 7 seal experiments, actuated full scale seal test rig, LIDS on Hubble, dynamics test prep, EDU 54 mass emulation and SCS, load ring characterization, 6DOF proof test, SCS at 6DOF, machining EEMS and inner ring assembly, APAS assembly, inner ring fitting, rotation stand assembly, EEMS mating, and EEMS proof of concept demonstration.

Structures and mechanisms - Streamlining for fuel economy

NASA Technical Reports Server (NTRS)

Card, M. F.

1983-01-01

The design of prospective NASA space station components which inherently possess the means for structural growth without compromising initial system characteristics is considered. In structural design terms, space station growth can be achieved by increasing design safety factors, introducing dynamic isolators to prevent loads from reaching the initial components, or preplanning the refurbishment of the original structure with stronger elements. Design tradeoffs will be based on the definition of on-orbit loads, including docking and maneuvering, whose derived load spectra will allow the estimation of fatigue life. Improvements must be made in structural materials selection in order to reduce contamination, slow degradation, and extend the life of coatings. To minimize on-orbit maintenance, long service life lubrication systems with advanced sealing devices must be developed.

Apollo Seals: A Basis for the Crew Exploration Vehicle Seals

NASA Technical Reports Server (NTRS)

Finkbeiner, Joshua R.; Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Daniels, Christopher C.

2006-01-01

The National Aeronautics and Space Administration is currently designing the Crew Exploration Vehicle (CEV) as a replacement for the Space Shuttle for manned missions to the International Space Station, as a command module for returning astronauts to the moon, and as an earth reentry vehicle for the final leg of manned missions to the moon and Mars. The CEV resembles a scaled-up version of the heritage Apollo vehicle; however, the CEV seal requirements are different than those from Apollo because of its different mission requirements. A review is presented of some of the seals used on the Apollo spacecraft for the gap between the heat shield and backshell and for penetrations through the heat shield, docking hatches, windows, and the capsule pressure hull.

Apollo Seals: A Basis for the Crew Exploration Vehicle Seals

NASA Technical Reports Server (NTRS)

Finkbeiner, Joshua R.; Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Daniels, Christopher C.

2007-01-01

The National Aeronautics and Space Administration is currently designing the Crew Exploration Vehicle (CEV) as a replacement for the Space Shuttle for manned missions to the International Space Station, as a command module for returning astronauts to the moon, and as an earth reentry vehicle for the final leg of manned missions to the moon and Mars. The CEV resembles a scaled-up version of the heritage Apollo vehicle; however, the CEV seal requirements are different than those from Apollo because of its different mission requirements. A review is presented of some of the seals used on the Apollo spacecraft for the gap between the heat shield and backshell and for penetrations through the heat shield, docking hatches, windows, and the capsule pressure hull.

Effects of Low Earth Orbit on Docking Seal Materials

NASA Technical Reports Server (NTRS)

Imka, Emily C.; Asmar, Olivia C.; deGroh, Henry C., III; Banks, Bruce A.

2014-01-01

Spacecraft docking seals are typically made of silicone elastomers. When such seals are exposed to low Earth orbit (LEO) conditions, they can suffer damage from ultraviolet (UV) radiation and atomic oxygen (AO, or monoatomic oxygen, the predominant oxygen species in LEO). An experiment flew on the International Space Station (ISS) to measure the effects of LEO on seal materials S0383-70 and ELA-SA-401 and various mating counterface materials which included anodized aluminum. Samples flown in different orientations received different amounts of UV and AO. The hypotheses were that most of the damage would be from UV, and 10 days or more of exposure in LEO would badly damage the seals. Eighteen seals were exposed for 543 days in ram (windward), zenith (away from Earth), or wake (leeward) orientations, and 15 control samples (not flown) provided undamaged baseline leakage. To determine post-flight leak rates, each of the 33 seals were placed in an O-ring groove of a leak test fixture and pressure tested over time. Resistance temperature detectors (RTDs), pressure transducers, and LabVIEW (National Instruments) programs were used to measure and analyze the temperature and pressure and calculate leakage. Average leakage of control samples was 2.6 x 10(exp -7) lbs/day. LEO exposure did not considerably damage ELA-SA-401. The S0383-70 flight samples leaked at least 10 times more than ELA-SA-401 in all cases except one, demonstrating that ELA-SA-401 may be a more suitable sealing material in LEO. AO caused greater damage than UV; samples in ram orientation (receiving an AO fluence of 4.3 x 10(exp 21) atoms/(sq cm) and in wake (2.9x 10(exp 20) atoms/(sq cm)) leaked more than those in zenith orientation (1.58 x 10(exp 20) atoms/(sq cm)), whereas variations in UV exposure did not seem to affect the samples. Exposure to LEO did less damage to the seals than hypothesized, and the data did not support the conjecture that UV causes more damage than AO.

Full-Scale System for Quantifying Loads and Leak Rates of Seals for Space Applications

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; Daniels, Christopher C.; Wasowski, Janice L.; Robbie, Malcolm G.; Erker, Arthur H.; Drlik, Gary J.; Mayer, John J.

2010-01-01

NASA is developing advanced space-rated vacuum seals in support of future space exploration missions to low-Earth orbit and other destinations. These seals may be 50 to 60 in. (127 to 152 cm) in diameter and must exhibit extremely low leak rates to ensure that astronauts have sufficient breathable air for extended missions to the International Space Station or the Moon. Seal compression loads must be below prescribed limits so as not to overload the mechanisms that compress them during docking or mating, and seal adhesion forces must be low to allow two mated systems to separate when required. NASA Glenn Research Center has developed a new test apparatus to measure leak rates and compression and adhesion loads of candidate full-scale seals under simulated thermal, vacuum, and engagement conditions. Tests can be performed in seal-on-seal or seal-on-flange configurations at temperatures from -76 to 140 F (-60 to 60 C) under operational pressure gradients. Nominal and off-nominal mating conditions (e.g., incomplete seal compression) can also be simulated. This paper describes the main design features of the test apparatus as well as techniques used to overcome some of the design challenges.

An Overview of Advanced Elastomeric Seal Development and Testing Capabilities at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.

2014-01-01

NASA is developing advanced space-rated elastomeric seals to support future space exploration missions to low Earth orbit, the Moon, near Earth asteroids, and other destinations. This includes seals for a new docking system and vehicle hatches. These seals must exhibit extremely low leak rates to ensure that astronauts have sufficient breathable air for extended missions. Seal compression loads must be below prescribed limits so as not to overload the mechanisms that compress them, and seal adhesion forces must be low to allow the sealed interface to be separated when required (e.g., during undocking or hatch opening). NASA Glenn Research Center has developed a number of unique test fixtures to measure the leak rates and compression and adhesion loads of candidate seal designs under simulated thermal, vacuum, and engagement conditions. Tests can be performed on fullscale seals with diameters on the order of 50 in., subscale seals that are about 12 in. in diameter, and smaller specimens such as O-rings. Test conditions include temperatures ranging from -238 to 662degF (-150 to 350degC), operational pressure gradients, and seal-on-seal or seal-on-flange mating configurations. Nominal and off-nominal conditions (e.g., incomplete seal compression) can also be simulated. This paper describes the main design features and capabilities of each type of test apparatus and provides an overview of advanced seal development activities at NASA Glenn.

An Overview of Advanced Elastomeric Seal Development and Testing Capabilities at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H.

2014-01-01

NASA is developing advanced space-rated elastomeric seals to support future space exploration missions to low Earth orbit, the Moon, near Earth asteroids, and other destinations. This includes seals for a new docking system and vehicle hatches. These seals must exhibit extremely low leak rates to ensure that astronauts have sufficient breathable air for extended missions. Seal compression loads must be below prescribed limits so as not to overload the mechanisms that compress them, and seal adhesion forces must be low to allow the sealed interface to be separated when required (e.g., during undocking or hatch opening). NASA Glenn Research Center has developed a number of unique test fixtures to measure the leak rates and compression and adhesion loads of candidate seal designs under simulated thermal, vacuum, and engagement conditions. Tests can be performed on full-scale seals with diameters on the order of 50 in., subscale seals that are about 12 in. in diameter, and smaller specimens such as O-rings. Test conditions include temperatures ranging from -238 to 662 F (-150 to 350 C), operational pressure gradients, and seal-on-seal or seal-on-flange mating configurations. Nominal and off-nominal conditions (e.g., incomplete seal compression) can also be simulated. This paper describes the main design features and capabilities of each type of test apparatus and provides an overview of advanced seal development activities at NASA Glenn.

Characteristics of Elastomer Seals Exposed to Space Environments

NASA Technical Reports Server (NTRS)

Daniels, Christopher C.; deGroh, Henry, III; Dunlap, Patrick H., Jr.; Finkbeiner, Joshua R.; Steinetz, Bruce M.; Bastrzyk, Marta B.; Oswald, Jay J.; Banks, Bruce A.; Dever, Joyce A.; Miller, Sharon K.;

Autonomous docking system for space structures and satellites

NASA Astrophysics Data System (ADS)

Prasad, Guru; Tajudeen, Eddie; Spenser, James

2005-05-01

Aximetric proposes Distributed Command and Control (C2) architecture for autonomous on-orbit assembly in space with our unique vision and sensor driven docking mechanism. Aximetric is currently working on ip based distributed control strategies, docking/mating plate, alignment and latching mechanism, umbilical structure/cord designs, and hardware/software in a closed loop architecture for smart autonomous demonstration utilizing proven developments in sensor and docking technology. These technologies can be effectively applied to many transferring/conveying and on-orbit servicing applications to include the capturing and coupling of space bound vehicles and components. The autonomous system will be a "smart" system that will incorporate a vision system used for identifying, tracking, locating and mating the transferring device to the receiving device. A robustly designed coupler for the transfer of the fuel will be integrated. Advanced sealing technology will be utilized for isolation and purging of resulting cavities from the mating process and/or from the incorporation of other electrical and data acquisition devices used as part of the overall smart system.

Use of VUV Radiation to Control Elastomer Seal Adhesion

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Puleo, Bernadette J.; Waters, Deborah L.

2013-01-01

Due to their wide operating temperatures and low leakage rates, silicone elastomers are the only class of flight qualified elastomer materials that currently meet NASA's needs for various seal applications, which include docking and hatch seals for future space exploration vehicles. However, silicone elastomers are naturally sticky and exhibit sizeable adhesion when mated against metals and other silicone surfaces. This undesirable adhesion can make undocking spacecraft or opening a hatch problematic. Two approaches that can be used to reduce seal adhesion include use of grease or, application of low doses of atomic oxygen (AO). This paper investigates a third approach: the application of light doses of vacuum ultraviolet (VUV) radiation. Presented are the adhesion and leakage characteristics of S0383-70 silicone elastomer exposed to various VUV doses in the 115 to 200 nm wavelength range. The data indicate that adhesion is expected to be less than the target threshold maximum of 2 lb/in(exp2) after about 1 J/cm(exp2) of VUV exposure for seal-to-metal configurations and after 2 J/cm(exp2) for seal-to-seal configurations with no significant damage, or increase in seal leakage. This paper shows that VUV, without AO or grease, can be an effective means to reduce adhesion to the desired levels necessary for space seals with minimal change in seal leak rates.

Comparison of Adhesion and Retention Forces for Two Candidate Docking Seal Elastomers

NASA Technical Reports Server (NTRS)

Hartzler, Brad D.; Panickar, Marta B.; Wasowski, Janice L.; Daniels, Christopher C.

2011-01-01

To successfully mate two pressurized vehicles or structures in space, advanced seals are required at the interface to prevent the loss of breathable air to the vacuum of space. A critical part of the development testing of candidate seal designs was a verification of the integrity of the retaining mechanism that holds the silicone seal component to the structure. Failure to retain the elastomer seal during flight could liberate seal material in the event of high adhesive loads during undocking. This work presents an investigation of the force required to separate the elastomer from its metal counter-face surface during simulated undocking as well as a comparison to that force which was necessary to destructively remove the elastomer from its retaining device. Two silicone elastomers, Wacker 007-49524 and Esterline ELASA-401, were evaluated. During the course of the investigation, modifications were made to the retaining devices to determine if the modifications improved the force needed to destructively remove the seal. The tests were completed at the expected operating temperatures of -50, +23, and +75 C. Under the conditions investigated, the comparison indicated that the adhesion between the elastomer and the metal counter-face was significantly less than the force needed to forcibly remove the elastomer seal from its retainer, and no failure would be expected.

IFACEwat: the interfacial water-implemented re-ranking algorithm to improve the discrimination of near native structures for protein rigid docking.

PubMed

Su, Chinh; Nguyen, Thuy-Diem; Zheng, Jie; Kwoh, Chee-Keong

2014-01-01

Protein-protein docking is an in silico method to predict the formation of protein complexes. Due to limited computational resources, the protein-protein docking approach has been developed under the assumption of rigid docking, in which one of the two protein partners remains rigid during the protein associations and water contribution is ignored or implicitly presented. Despite obtaining a number of acceptable complex predictions, it seems to-date that most initial rigid docking algorithms still find it difficult or even fail to discriminate successfully the correct predictions from the other incorrect or false positive ones. To improve the rigid docking results, re-ranking is one of the effective methods that help re-locate the correct predictions in top high ranks, discriminating them from the other incorrect ones. Our results showed that the IFACEwat increased both the numbers of the near-native structures and improved their ranks as compared to the initial rigid docking ZDOCK3.0.2. In fact, the IFACEwat achieved a success rate of 83.8% for Antigen/Antibody complexes, which is 10% better than ZDOCK3.0.2. As compared to another re-ranking technique ZRANK, the IFACEwat obtains success rates of 92.3% (8% better) and 90% (5% better) respectively for medium and difficult cases. When comparing with the latest published re-ranking method F2Dock, the IFACEwat performed equivalently well or even better for several Antigen/Antibody complexes. With the inclusion of interfacial water, the IFACEwat improves mostly results of the initial rigid docking, especially for Antigen/Antibody complexes. The improvement is achieved by explicitly taking into account the contribution of water during the protein interactions, which was ignored or not fully presented by the initial rigid docking and other re-ranking techniques. In addition, the IFACEwat maintains sufficient computational efficiency of the initial docking algorithm, yet improves the ranks as well as the number of the near native structures found. As our implementation so far targeted to improve the results of ZDOCK3.0.2, and particularly for the Antigen/Antibody complexes, it is expected in the near future that more implementations will be conducted to be applicable for other initial rigid docking algorithms.

Treatment to Control Adhesion of Silicone-Based Elastomers

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Puleo, Bernadette J.; Waters, Deborah L.

2013-01-01

Seals are used to facilitate the joining of two items, usually temporarily. At some point in the future, it is expected that the items will need to be separated. This innovation enables control of the adhesive properties of silicone-based elastomers. The innovation may also be effective on elastomers other than the silicone-based ones. A technique has been discovered that decreases the level of adhesion of silicone- based elastomers to negligible levels. The new technique causes less damage to the material compared to alternative adhesion mitigation techniques. Silicone-based elastomers are the only class of rubber-like materials that currently meet NASA s needs for various seal applications. However, silicone-based elastomers have natural inherent adhesive properties. This stickiness can be helpful, but it can frequently cause problems as well, such as when trying to get items apart. In the past, seal adhesion was not always adequately addressed, and has caused in-flight failures where seals were actually pulled from their grooves, preventing subsequent spacecraft docking until the seal was physically removed from the flange via an extravehicular activity (EVA). The primary method used in the past to lower elastomer seal adhesion has been the application of some type of lubricant or grease to the surface of the seal. A newer method uses ultraviolet (UV) radiation a mixture of UV wavelengths in the range of near ultraviolet (NUV) and vacuum ultraviolet (VUV) wavelengths.

IFACEwat: the interfacial water-implemented re-ranking algorithm to improve the discrimination of near native structures for protein rigid docking

PubMed Central

2014-01-01

Background Protein-protein docking is an in silico method to predict the formation of protein complexes. Due to limited computational resources, the protein-protein docking approach has been developed under the assumption of rigid docking, in which one of the two protein partners remains rigid during the protein associations and water contribution is ignored or implicitly presented. Despite obtaining a number of acceptable complex predictions, it seems to-date that most initial rigid docking algorithms still find it difficult or even fail to discriminate successfully the correct predictions from the other incorrect or false positive ones. To improve the rigid docking results, re-ranking is one of the effective methods that help re-locate the correct predictions in top high ranks, discriminating them from the other incorrect ones. In this paper, we propose a new re-ranking technique using a new energy-based scoring function, namely IFACEwat - a combined Interface Atomic Contact Energy (IFACE) and water effect. The IFACEwat aims to further improve the discrimination of the near-native structures of the initial rigid docking algorithm ZDOCK3.0.2. Unlike other re-ranking techniques, the IFACEwat explicitly implements interfacial water into the protein interfaces to account for the water-mediated contacts during the protein interactions. Results Our results showed that the IFACEwat increased both the numbers of the near-native structures and improved their ranks as compared to the initial rigid docking ZDOCK3.0.2. In fact, the IFACEwat achieved a success rate of 83.8% for Antigen/Antibody complexes, which is 10% better than ZDOCK3.0.2. As compared to another re-ranking technique ZRANK, the IFACEwat obtains success rates of 92.3% (8% better) and 90% (5% better) respectively for medium and difficult cases. When comparing with the latest published re-ranking method F2Dock, the IFACEwat performed equivalently well or even better for several Antigen/Antibody complexes. Conclusions With the inclusion of interfacial water, the IFACEwat improves mostly results of the initial rigid docking, especially for Antigen/Antibody complexes. The improvement is achieved by explicitly taking into account the contribution of water during the protein interactions, which was ignored or not fully presented by the initial rigid docking and other re-ranking techniques. In addition, the IFACEwat maintains sufficient computational efficiency of the initial docking algorithm, yet improves the ranks as well as the number of the near native structures found. As our implementation so far targeted to improve the results of ZDOCK3.0.2, and particularly for the Antigen/Antibody complexes, it is expected in the near future that more implementations will be conducted to be applicable for other initial rigid docking algorithms. PMID:25521441

Orion Handling Qualities During ISS Rendezvous and Docking

NASA Technical Reports Server (NTRS)

Hart, Jeremy J.; Stephens, J. P.; Spehar, P.; Bilimoria, K.; Foster, C.; Gonzalex, R.; Sullivan, K.; Jackson, B.; Brazzel, J.; Hart, J.

2011-01-01

The Orion spacecraft was designed to rendezvous with multiple vehicles in low earth orbit (LEO) and beyond. To perform the required rendezvous and docking task, Orion must provide enough control authority to perform coarse translational maneuvers while maintaining precision to perform the delicate docking corrections. While Orion has autonomous docking capabilities, it is expected that final approach and docking operations with the International Space Station (ISS) will initially be performed in a manual mode. A series of evaluations was conducted by NASA and Lockheed Martin at the Johnson Space Center to determine the handling qualities (HQ) of the Orion spacecraft during different docking and rendezvous conditions using the Cooper-Harper scale. This paper will address the specifics of the handling qualities methodology, vehicle configuration, scenarios flown, data collection tools, and subject ratings and comments. The initial Orion HQ assessment examined Orion docking to the ISS. This scenario demonstrates the Translational Hand Controller (THC) handling qualities of Orion. During this initial assessment, two different scenarios were evaluated. The first was a nominal docking approach to a stable ISS, with Orion initializing with relative position dispersions and a closing rate of approximately 0.1 ft/sec. The second docking scenario was identical to the first, except the attitude motion of the ISS was modeled to simulate a stress case ( 1 degree deadband per axis and 0.01 deg/sec rate deadband per axis). For both scenarios, subjects started each run on final approach at a docking port-to-port range of 20 ft. Subjects used the THC in pulse mode with cues from the docking camera image, window views, and range and range rate data displayed on the Orion display units. As in the actual design, the attitude of the Orion vehicle was held by the automated flight control system at 0.5 degree deadband per axis. Several error sources were modeled including Reaction Control System (RCS) jet angular and position misalignment, RCS thrust magnitude uncertainty, RCS jet force direction uncertainty due to self plume impingement, and Orion center of mass uncertainty.

General engineering specifications for 6000 tpd SRC-I Demonstration Plant

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

Not Available

This volume contains specifications for architectural features of buildings for the SRC-1 Demonstration Plant: skylights, ventilators, sealants, doors, mirrors, furring and lathing, gypsum plaster, lightweight plaster, wallboard, ceramic tile, acoustic ceiling systems, resilient flooring, carpeting, brick flooring, architectural painting, vinyl wall covering, chalkboards, tackboards, toilets, access flooring, lockers, partitions, washroom accessories, unit kitchens, dock levels, seals, shelters, custom casework, auditorium seats, drapery tacks, prefabricated buildings, stairs, elevators, shelves, etc. (LTN).

Experimental validation of docking and capture using space robotics testbeds

NASA Technical Reports Server (NTRS)

Spofford, John

1991-01-01

Docking concepts include capture, berthing, and docking. The definitions of these terms, consistent with AIAA, are as follows: (1) capture (grasping)--the use of a manipulator to make initial contact and attachment between transfer vehicle and a platform; (2) berthing--positioning of a transfer vehicle or payload into platform restraints using a manipulator; and (3) docking--propulsive mechanical connection between vehicle and platform. The combination of the capture and berthing operations is effectively the same as docking; i.e., capture (grasping) + berthing = docking. These concepts are discussed in terms of Martin Marietta's ability to develop validation methods using robotics testbeds.

New Standard Weir Design for Dredged Material Management Area, Jacksonville District

DTIC Science & Technology

2014-08-01

dock access, Bartram Island Cell B2, Jacksonville, Florida. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 ERDC/TN DOTS-14-01 August 2014 2 US Army Corps of Engineers • Engineer Research...and through the riser stack of weir boards. This requires secondary sealing measures in the form of plastic sheeting, geotextiles, and/or burlap

Investigation of MM-PBSA rescoring of docking poses.

PubMed

Thompson, David C; Humblet, Christine; Joseph-McCarthy, Diane

2008-05-01

Target-based virtual screening is increasingly used to generate leads for targets for which high quality three-dimensional (3D) structures are available. To allow large molecular databases to be screened rapidly, a tiered scoring scheme is often employed whereby a simple scoring function is used as a fast filter of the entire database and a more rigorous and time-consuming scoring function is used to rescore the top hits to produce the final list of ranked compounds. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches are currently thought to be quite effective at incorporating implicit solvation into the estimation of ligand binding free energies. In this paper, the ability of a high-throughput MM-PBSA rescoring function to discriminate between correct and incorrect docking poses is investigated in detail. Various initial scoring functions are used to generate docked poses for a subset of the CCDC/Astex test set and to dock one set of actives/inactives from the DUD data set. The effectiveness of each of these initial scoring functions is discussed. Overall, the ability of the MM-PBSA rescoring function to (i) regenerate the set of X-ray complexes when docking the bound conformation of the ligand, (ii) regenerate the X-ray complexes when docking conformationally expanded databases for each ligand which include "conformation decoys" of the ligand, and (iii) enrich known actives in a virtual screen for the mineralocorticoid receptor in the presence of "ligand decoys" is assessed. While a pharmacophore-based molecular docking approach, PhDock, is used to carry out the docking, the results are expected to be general to use with any docking method.

Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand

PubMed Central

DeLuca, Samuel; Khar, Karen; Meiler, Jens

2015-01-01

RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand) making it unfeasible for use in virtual High Throughput Screening (vHTS). To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial ‘low-resolution’ docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10–15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the ‘high-resolution’ full atom refinement step. PMID:26207742

Optimization of protein-protein docking for predicting Fc-protein interactions.

PubMed

Agostino, Mark; Mancera, Ricardo L; Ramsland, Paul A; Fernández-Recio, Juan

2016-11-01

The antibody crystallizable fragment (Fc) is recognized by effector proteins as part of the immune system. Pathogens produce proteins that bind Fc in order to subvert or evade the immune response. The structural characterization of the determinants of Fc-protein association is essential to improve our understanding of the immune system at the molecular level and to develop new therapeutic agents. Furthermore, Fc-binding peptides and proteins are frequently used to purify therapeutic antibodies. Although several structures of Fc-protein complexes are available, numerous others have not yet been determined. Protein-protein docking could be used to investigate Fc-protein complexes; however, improved approaches are necessary to efficiently model such cases. In this study, a docking-based structural bioinformatics approach is developed for predicting the structures of Fc-protein complexes. Based on the available set of X-ray structures of Fc-protein complexes, three regions of the Fc, loosely corresponding to three turns within the structure, were defined as containing the essential features for protein recognition and used as restraints to filter the initial docking search. Rescoring the filtered poses with an optimal scoring strategy provided a success rate of approximately 80% of the test cases examined within the top ranked 20 poses, compared to approximately 20% by the initial unrestrained docking. The developed docking protocol provides a significant improvement over the initial unrestrained docking and will be valuable for predicting the structures of currently undetermined Fc-protein complexes, as well as in the design of peptides and proteins that target Fc. Copyright © 2016 John Wiley & Sons, Ltd.

Docking simulation analysis of range data requirements for the orbital maneuvering vehicle

NASA Technical Reports Server (NTRS)

Micheal, J. D.; Vinz, F. L.

1985-01-01

The results of an initial study are reported assess the controllability of the Orbital Maneuvering Vehicle (OMV) for terminal closure and docking are reported. The vehicle characteristics used in this study are those of the Marshall Space Flight Center (MSFC) baseline OMV which were published with the request for proposals for preliminary design of this vehicle. This simulation was conducted at MSFC using the Target Motion Simulator. The study focused on the OMV manual mode capability to accommodate both stabilized and tumbling target engagements with varying complements of range and range rate data displayed to the OMV operator. Four trained test subjects performed over 400 simulated orbital dockings during this study. A firm requirement for radar during the terminal closure and dock phase of the OMV mission was not established by these simulations. Fifteen pound thrusters recommended in the MSFC baseline design were found to be advantageous for initial rate matching maneuvers with unstabilized targets; however, lower thrust levels were desirable for making the final docking maneuvers.

Twist seal for high-pressure vessels such as space shuttle rocket motors

NASA Technical Reports Server (NTRS)

von Pragenau, George L. (Inventor)

1989-01-01

Seals for sealing clevis and flange joints (14) of a solid rocket booster motor, and more particularly to a seal (30) which is twisted upon application of expansion forces to an edge seal (36). This twisting motion initially causes a leading edge seal (44) to be urged into sealing engagement with a surface (48) of an adjacent member (20) and thereafter, increasing fluid pressure on a pressurized side (64) of a seal (30) drives a broad sealing region (46) into sealing engagement with a surface (48).

Air Force seal activities

NASA Astrophysics Data System (ADS)

Mayhew, Ellen R.

1994-07-01

Seal technology development is an important part of the Air Force's participation in the Integrated High Performance Turbine Engine Technology (IHPTET) initiative, the joint DOD, NASA, ARPA, and industry endeavor to double turbine engine capabilities by the turn of the century. Significant performance and efficiency improvements can be obtained through reducing internal flow system leakage, but seal environment requirements continue to become more extreme as the engine thermodynamic cycles advance towards these IHPTET goals. Brush seal technology continues to be pursued by the Air Force to reduce leakage at the required conditions. Likewise, challenges in engine mainshaft air/oil seals are also being addressed. Counter-rotating intershaft applications within the IHPTET initiative involve very high rubbing velocities. This viewgraph presentation briefly describes past and current seal research and development programs and gives a summary of seal applications in demonstrator and developmental engine testing.

A open loop guidance architecture for navigationally robust on-orbit docking

NASA Technical Reports Server (NTRS)

Chern, Hung-Sheng

1995-01-01

The development of an open-hop guidance architecture is outlined for autonomous rendezvous and docking (AR&D) missions to determine whether the Global Positioning System (GPS) can be used in place of optical sensors for relative initial position determination of the chase vehicle. Feasible command trajectories for one, two, and three impulse AR&D maneuvers are determined using constrained trajectory optimization. Early AR&D command trajectory results suggest that docking accuracies are most sensitive to vertical position errors at the initial conduction of the chase vehicle. Thus, a feasible command trajectory is based on maximizing the size of the locus of initial vertical positions for which a fixed sequence of impulses will translate the chase vehicle into the target while satisfying docking accuracy requirements. Documented accuracies are used to determine whether relative GPS can achieve the vertical position error requirements of the impulsive command trajectories. Preliminary development of a thruster management system for the Cargo Transfer Vehicle (CTV) based on optimal throttle settings is presented to complete the guidance architecture. Results show that a guidance architecture based on a two impulse maneuvers generated the best performance in terms of initial position error and total velocity change for the chase vehicle.

Investigations of Shuttle Main Landing Gear Door Environmental Seals

NASA Technical Reports Server (NTRS)

Finkbeiner, Joshua; DeMange, Jeff; Dunlap, Pat; Steinetz, Bruce; Newswander, Daniel

2006-01-01

The Columbia Accident investigation Board (CAIB) requested an investigation into the MLG door seals. Initially, the MLG door seals were thought to have been a potential contributor to the loss of Columbia. These suspicions were later found to be untrue, but the seals remained as a cause for concern in future flights. MLG door seals comprised of thermal barrier and environmental seal. This study focuses on the environmental seal for the MLG door.

PRELIMINARY REPORT: EFFECTS OF IRRADIATION AND THERMAL EXPOSURE ON ELASTOMERIC SEALS FOR CASK TRANSPORTATION AND STORAGE

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

Verst, C.; Skidmore, E.; Daugherty, W.

2014-05-30

A testing and analysis approach to predict the sealing behavior of elastomeric seal materials in dry storage casks and evaluate their ability to maintain a seal under thermal and radiation exposure conditions of extended storage and beyond was developed, and initial tests have been conducted. The initial tests evaluate the aging response of EPDM elastomer O-ring seals. The thermal and radiation exposure conditions of the CASTOR® V/21 casks were selected for testing as this cask design is of interest due to its widespread use, and close proximity of the seals to the fuel compared to other cask designs leading tomore » a relatively high temperature and dose under storage conditions. A novel test fixture was developed to enable compression stress relaxation measurements for the seal material at the thermal and radiation exposure conditions. A loss of compression stress of 90% is suggested as the threshold at which sealing ability of an elastomeric seal would be lost. Previous studies have shown this value to be conservative to actual leakage failure for most aging conditions. These initial results indicate that the seal would be expected to retain sealing ability throughout extended storage at the cask design conditions, though longer exposure times are needed to validate this assumption. The high constant dose rate used in the testing is not prototypic of the decreasingly low dose rate that would occur under extended storage. The primary degradation mechanism of oxidation of polymeric compounds is highly dependent on temperature and time of exposure, and with radiation expected to exacerbate the oxidation.« less

Pressure Seal For Frequently Opened Hatch

NASA Technical Reports Server (NTRS)

Kennedy, Steven E.; Kramer, Joel M.

1994-01-01

Pressure-assisted seal for frequently opened hatch includes two sealing rings retained positively so not pulled out during opening. Seal makes contact with hatch well before hatch starts to squeeze rings extending distance over which seal becomes engaged. Improvements include more-secure mounting, redundancy, and better initial sealing action. Also minimizes loss of gas during closure by deflecting inward and closing gap. This action helps differential pressure to force hatch closed.

DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina.

PubMed

Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

2017-02-01

Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

NASA Astrophysics Data System (ADS)

Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

2017-02-01

Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

A multipurpose model of Hermes-Columbus docking mechanism

NASA Technical Reports Server (NTRS)

Gonzalez-Vallejo, J. J.; Fehse, W.; Tobias, A.

1992-01-01

One of the foreseen missions of the HERMES spacevehicle is the servicing to the Columbus Free Flying Laboratory (MTFF). Docking between the two spacecraft is a critical operation in which the Docking Mechanism (DM) has a major role. In order to analyze and assess robustness of initially selected concepts and to identify suitable implementation solutions, through the investigation of main parameters involved in the docking functions, a multipurpose model of DM was developed and tested. This paper describes the main design features as well as the process of calibrating and testing.

Evaluation of a conventional chip seal under an overlay to mitigate reflective cracking (informal).

DOT National Transportation Integrated Search

2015-03-01

The Billings District initiated an experimental project in placing a conventional : chip seal (as an interlayer) on an existing pavement prior to an overlay : (composed of a 0.25 PMS thickness). The intent of the chip seal (CS) was to : seal exist...

CPdock: the complementarity plot for docking of proteins: implementing multi-dielectric continuum electrostatics.

PubMed

Basu, Sankar

2017-12-07

The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S m , E m ) for amino acid side-chains buried within the protein interior or interface and plots them in a two-dimensional plot having knowledge-based probabilistic quality estimates for the residues as well as for the whole structure. The current report essentially presents an upgraded version of the plot with the implementation of the advanced multi-dielectric functionality (as in Delphi version 6.2 or higher) in the computation of electrostatic complementarity to make the validation tool physico-chemically more realistic. The two methods (single- and multi-dielectric) agree decently in their resultant E m values, and hence, provisions for both methods have been kept in the software suite. So to speak, the global electrostatic balance within a well-folded protein and/or a well-packed interface seems only marginally perturbed by the choice of different internal dielectric values. However, both from theoretical as well as practical grounds, the more advanced multi-dielectric version of the plot is certainly recommended for potentially producing more reliable results. The report also presents a new methodology and a variant plot, namely CP dock , based on the same principles of complementarity specifically designed to be used in the docking of proteins. The efficacy of the method to discriminate between good and bad docked protein complexes has been tested on a recent state-of-the-art docking benchmark. The results unambiguously indicate that CP dock can indeed be effective in the initial screening phase of a docking scoring pipeline before going into more sophisticated and computationally expensive scoring functions. CP dock has been made available at https://github.com/nemo8130/CPdock . Graphical Abstract An example showing the efficacy of CP dock to be used in the initial screening phase of a protein-protein docking scoring pipeline.

Evaluation of new plastic compression (Ziegler) type of seals for long life planetary batteries

NASA Technical Reports Server (NTRS)

Frank, H. A.

1973-01-01

A program was initiated to develop improved types of terminal seals for aerospace Ni-Cd batteries. The approach used has not involved attempts, such as employed elsewhere, to improve the ceramic-to-metal seal that is now extensively employed for this application. Rather the approach has been directed toward the development and evaluation of new types of seals. Of prime interest in this initial investigation has been the Ziegler type of compression seal and in particular the injection molded version developed by the Bell Telephone Laboratories (BTL). A number of these units were designed, fabricated, and evaluated on an accelerated life test under a simulated battery environment. Results have shown that there are no major problems involved in scaling up the BTL small-size (5-amp) seal to a larger size (up to 50-amp) seal suitable for most JPL flight batteries. Five out of five such seals successfully completed over 10 months of continuous thermal cycling without developing any leaks greater than 1.8 x to 10 to the minus 9th power atm-cc-He/s.

Improved Ball-and-Socket Docking Mechanism

NASA Technical Reports Server (NTRS)

Cloyd, Richard; Bryan, Tom

2004-01-01

A proposed docking mechanism would form a ball-and-socket joint in the docked condition. The mechanism could tolerate significant initial misalignment because it would include an alignment cone that would guide the ball into the socket. Like other ball-and-socket joints, the joint would have three rotational degrees of freedom. This docking mechanism would be a successor to the one described in Passive Capture Joint With Three Degrees of Freedom (MFS-31146), NASA Tech Briefs, Vol. 22, No. 7 (July 1998), page 65. It would contain most of the components of the prior mechanism, plus some additional components that would expand its capabilities.

Inhibition of osteoclast bone resorption activity through osteoprotegerin-induced damage of the sealing zone.

PubMed

Song, Ruilong; Gu, Jianhong; Liu, Xuezhong; Zhu, Jiaqiao; Wang, Qichao; Gao, Qian; Zhang, Jiaming; Cheng, Laiyang; Tong, Xishuai; Qi, Xinyi; Yuan, Yan; Liu, Zongping

2014-09-01

Bone remodeling is dependent on the dynamic equilibrium between osteoclast-mediated bone resorption and osteoblast-mediated osteogenesis. The sealing zone is an osteoclast-specific cytoskeletal structure, the integrity of which is critical for osteoclast-mediated bone resorption. To date, studies have focused mainly on the osteoprotegerin (OPG)‑induced inhibition of osteoclast differentiation through the OPG/receptor activator of the nuclear factor kappa-B ligand (RANKL)/RANK system, which affects the bone resorption of osteoclasts. However, the effects of OPG on the sealing zone have not been reported to date. In this study, the formation of the sealing zone was observed by Hoffman modulation contrast (HMC) microscopy and confocal laser scanning microscopy. The effects of OPG on the existing sealing zone and osteoclast-mediated bone resorption activity, as well as the regulatory role of genes involved in the formation of the sealing zone were examined by immunofluorescence staining, HMC microscopy, quantitative reverse transcription polymerase chain reaction (RT-qPCR), western blot analysis and scanning electron microscopy. The sealing zone was formed on day 5, with belt-like protuberances at the cell edge and scattered distribution of cell nuclei, but no filopodia. The sealing zone was intact in the untreated control group. However, defects in the sealing zone were observed in the OPG-treated group (20 ng/ml) and the structure was absent in the groups treated with 40 and 80 ng/ml OPG. The podosomes showed a scattered or clustered distribution between the basal surface of the osteoclasts and the well surface. Furthermore, resorption lacunae were not detected in the 20 ng/ml OPG-treated group, indicating the loss of osteoclast-mediated bone resorption activity. Treatment with OPG resulted in a significant decrease in the expression of Arhgef8/Net1 and DOCK5 Rho guanine nucleotide exchange factors (RhoGEFs), 10 of 18 RhoGTPases (RhoA, RhoB, cdc42v1, cdc42v2, RhoU/Wrch1, RhoF/Rif, Rac2, RhoG, Rnd1 and RhoBTB1), ROCK1 and ROCK2. In conclusion, podosome distribution was affected by the OPG-induced inhibition of the expression of genes in the RhoGTPase signaling pathway. This resulted in damage to or destruction of the sealing zone, thus inhibiting osteoclast-mediated bone resorption activity.

Destabilization of the metal site as a hub for the pathogenic mechanism of five ALS-linked mutants of copper, zinc superoxide dismutase.

PubMed

Mera-Adasme, Raúl; Erdmann, Hannes; Bereźniak, Tomasz; Ochsenfeld, Christian

2016-10-01

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, with no effective pharmacological treatment. Its pathogenesis is unknown, although a subset of the cases is linked to genetic mutations. A significant fraction of the mutations occur in one protein, copper, zinc superoxide dismutase (SOD1). The toxic function of mutant SOD1 has not been elucidated, but damage to the metal site of the protein is believed to play a major role. In this work, we study the electrostatic loop of SOD1, which we had previously proposed to work as a "solvent seal" isolating the metal site from water molecules. Out of the five contact points identified between the electrostatic loop and its dock in the rest of the protein, three points were found to be affected by ALS-linked mutations, with a total of five mutations identified. The effect of the five mutations was studied using methods of computational chemistry. We found that four of the mutations destabilize the proposed solvent seal, while the fifth mutation directly affects the metal-site stability. In the two contact points unaffected by ALS-linked mutations, the side chains of the residues were not found to play a stabilizing role. Our results show that the docking of the electrostatic loop to the rest of SOD1 plays a role in ALS pathogenesis, in support of that structure acting as a solvent barrier for the metal site. The results provide a unified pathogenic mechanism for five different ALS-linked mutations of SOD1.

Performance oriented guidance for Mississippi chip seals - volume II.

DOT National Transportation Integrated Search

2013-12-01

A laboratory and field study was conducted related to long term chip seal performance. This reports primary : objective was to initiate development of a long term performance (LTP) test protocol for chip seals focused on : aggregate retention. Key...

Enabling Exploration Through Docking Standards

NASA Technical Reports Server (NTRS)

Hatfield, Caris A.

2012-01-01

Human exploration missions beyond low earth orbit will likely require international cooperation in order to leverage limited resources. International standards can help enable cooperative missions by providing well understood, predefined interfaces allowing compatibility between unique spacecraft and systems. The International Space Station (ISS) partnership has developed a publicly available International Docking System Standard (IDSS) that provides a solution to one of these key interfaces by defining a common docking interface. The docking interface provides a way for even dissimilar spacecraft to dock for exchange of crew and cargo, as well as enabling the assembly of large space systems. This paper provides an overview of the key attributes of the IDSS, an overview of the NASA Docking System (NDS), and the plans for updating the ISS with IDSS compatible interfaces. The NDS provides a state of the art, low impact docking system that will initially be made available to commercial crew and cargo providers. The ISS will be used to demonstrate the operational utility of the IDSS interface as a foundational technology for cooperative exploration.

Remote operation of an orbital maneuvering vehicle in simulated docking maneuvers

NASA Technical Reports Server (NTRS)

Brody, Adam R.

1990-01-01

Simulated docking maneuvers were performed to assess the effect of initial velocity on docking failure rate, mission duration, and delta v (fuel consumption). Subjects performed simulated docking maneuvers of an orbital maneuvering vehicle (OMV) to a space station. The effect of the removal of the range and rate displays (simulating a ranging instrumentation failure) was also examined. Naive subjects were capable of achieving a high success rate in performing simulated docking maneuvers without extensive training. Failure rate was a function of individual differences; there was no treatment effect on failure rate. The amount of time subjects reserved for final approach increased with starting velocity. Piloting of docking maneuvers was not significantly affected in any way by the removal of range and rate displays. Radial impulse was significant both by subject and by treatment. NASA's 0.1 percent rule, dictating an approach rate no greater than 0.1 percent of the range, is seen to be overly conservative for nominal docking missions.

Seals/Secondary Fluid Flows Workshop 1997; Volume II: HSR Engine Special Session

NASA Technical Reports Server (NTRS)

Hendricks, Robert C. (Editor)

2006-01-01

The High Speed Civil Transport (HSCT) will be the largest engine ever built and operated at maximum conditions for long periods of time. It is being developed collaboratively with NASA, FAA, Boeing-McDonnell Douglas, Pratt & Whitney, and General Electric. This document provides an initial step toward defining high speed research (HSR) sealing needs. The overview for HSR seals includes defining objectives, summarizing sealing and material requirements, presenting relevant seal cross-sections, and identifying technology needs. Overview presentations are given for the inlet, turbomachinery, combustor and nozzle. The HSCT and HSR seal issues center on durability and efficiency of rotating equipment seals, structural seals and high speed bearing and sump seals. Tighter clearances, propulsion system size and thermal requirements challenge component designers.

Brucella Antibodies in Alaskan True Seals and Eared Seals-Two Different Stories.

PubMed

Nymo, Ingebjørg H; Rødven, Rolf; Beckmen, Kimberlee; Larsen, Anett K; Tryland, Morten; Quakenbush, Lori; Godfroid, Jacques

2018-01-01

Brucella pinnipedialis was first isolated from true seals in 1994 and from eared seals in 2008. Although few pathological findings have been associated with infection in true seals, reproductive pathology including abortions, and the isolation of the zoonotic strain type 27 have been documented in eared seals. In this study, a Brucella enzyme-linked immunosorbent assay (ELISA) and the Rose Bengal test (RBT) were initially compared for 206 serum samples and a discrepancy between the tests was found. Following removal of lipids from the serum samples, ELISA results were unaltered while the agreement between the tests was improved, indicating that serum lipids affected the initial RBT outcome. For the remaining screening, we used ELISA to investigate the presence of Brucella antibodies in sera of 231 eared and 1,412 true seals from Alaskan waters sampled between 1975 and 2011. In eared seals, Brucella antibodies were found in two Steller sea lions ( Eumetopias jubatus ) (2%) and none of the 107 Northern fur seals ( Callorhinus ursinus ). The low seroprevalence in eared seals indicate a low level of exposure or lack of susceptibility to infection. Alternatively, mortality due to the Brucella infection may remove seropositive animals from the population. Brucella antibodies were detected in all true seal species investigated; harbor seals ( Phoca vitulina ) (25%), spotted seals ( Phoca largha ) (19%), ribbon seals ( Histriophoca fasciata ) (16%), and ringed seals ( Pusa hispida hispida ) (14%). There was a low seroprevalence among pups, a higher seroprevalence among juveniles, and a subsequent decreasing probability of seropositivity with age in harbor seals. Similar patterns were present for the other true seal species; however, solid conclusions could not be made due to sample size. This pattern is in accordance with previous reports on B. pinnipedialis infections in true seals and may suggest environmental exposure to B. pinnipedialis at the juvenile stage, with a following clearance of infection. Furthermore, analyses by region showed minor differences in the probability of being seropositive for harbor seals from different regions regardless of the local seal population trend, signifying that the Brucella infection may not cause significant mortality in these populations. In conclusion, the Brucella infection pattern is very different for eared and true seals.

Dynamically Movable Exhausting Emc Sealing System

DOEpatents

Barringer, Dennis R.; Seminaro, Edward J.; Toffler, Harold M.

2003-12-09

A docking apparatus for printed circuit boards including a cassette housing, having a housing base, a housing cover and a housing wall, wherein the housing base and the housing wall are disposed relative to each other so as to define a housing cavity for containing a printed circuit card and wherein the housing wall includes a cable opening disposed so as to be communicated with the housing cavity, a housing bezel, disposed relative to the cassette housing so as to be associated with the cable opening, the housing bezel includes an outer bezel having a first plurality of openings and an inner bezel having a second plurality of apertures, the inner bezel in electrical communication with the printed circuit card, wherein said housing bezel is removable, and an EMC gasket disposed between the outer and inner bezels of said housing bezel, the EMC gasket configured to provide a removable EMC seal proximate the cable opening while still allowing airflow through the first and second plurality of apertures having the EMC gasket therebetween. A docking apparatus for printed circuit boards including a cassette housing, having a housing base, a housing cover and a housing wall, wherein the housing base and the housing wall are disposed relative to each other so as to define a housing cavity for containing a printed circuit card and wherein the housing wall includes a cable opening disposed so as to be communicated with the housing cavity, a housing bezel, disposed relative to the cassette housing so as to be associated with the cable opening, the housing bezel includes an outer bezel having a first plurality of openings and an inner bezel having a second plurality of apertures, the inner bezel in electrical communication with the printed circuit card, wherein said housing bezel is removable, and an EMC gasket disposed between the outer and inner bezels of said housing bezel, the EMC gasket configured to provide a removable EMC seal proximate the cable opening while still allowing airflow through the first and second plurality of apertures having the EMC gasket therebetween.

A comparison of experimental and theoretical results for rotordynamic coefficients of four annular gas seals

NASA Technical Reports Server (NTRS)

Childs, D. W.; Nelson, C. C.; Elrod, D.; Nicks, C.

1985-01-01

The test facility and initial test program developed to experimentally measure the fluid forces induced by annular gas seals is described. A comparison of theoretically predicted and experimentally obtained data for smooth and honeycomb seals is provided. And a comparison of experimental data from the tests of three smooth-rotor/smooth-stator seals is provided. The leakage of the working fluid through the seal, the pressure gradient along the seal length, entrance pressure-loss data, and rotordynamic coefficients provide a basis for comparison. A short discussion on seal theory is included, and various rotordynamic coefficient identification schemes are described.

Ligand- and receptor-based docking with LiBELa

NASA Astrophysics Data System (ADS)

dos Santos Muniz, Heloisa; Nascimento, Alessandro S.

2015-08-01

Methodologies on molecular docking are constantly improving. The problem consists on finding an optimal interplay between the computational cost and a satisfactory physical description of ligand-receptor interaction. In pursuit of an advance in current methods we developed a mixed docking approach combining ligand- and receptor-based strategies in a docking engine, where tridimensional descriptors for shape and charge distribution of a reference ligand guide the initial placement of the docking molecule and an interaction energy-based global minimization follows. This hybrid docking was evaluated with soft-core and force field potentials taking into account ligand pose and scoring. Our approach was found to be competitive to a purely receptor-based dock resulting in improved logAUC values when evaluated with DUD and DUD-E. Furthermore, the smoothed potential as evaluated here, was not advantageous when ligand binding poses were compared to experimentally determined conformations. In conclusion we show that a combination of ligand- and receptor-based strategy docking with a force field energy model results in good reproduction of binding poses and enrichment of active molecules against decoys. This strategy is implemented in our tool, LiBELa, available to the scientific community.

A dynamic analysis of rotary combustion engine seals

NASA Technical Reports Server (NTRS)

Knoll, J.; Vilmann, C. R.; Schock, H. J.; Stumpf, R. P.

1984-01-01

Real time work cell pressures are incorporated into a dynamic analysis of the gas sealing grid in Rotary Combustion Engines. The analysis which utilizes only first principal concepts accounts for apex seal separation from the crochoidal bore, apex seal shifting between the sides of its restraining channel, and apex seal rotation within the restraining channel. The results predict that apex seals do separate from the trochoidal bore and shift between the sides of their channels. The results also show that these two motions are regularly initiated by a seal rotation. The predicted motion of the apex seals compares favorably with experimental results. Frictional losses associated with the sealing grid are also calculated and compare well with measurements obtained in a similar engine. A comparison of frictional losses when using steel and carbon apex seals has also been made as well as friction losses for single and dual side sealing.

An Elmo–Dock complex locally controls Rho GTPases and actin remodeling during cadherin-mediated adhesion

PubMed Central

Collins, Caitlin

2014-01-01

Cell–cell contact formation is a dynamic process requiring the coordination of cadherin-based cell–cell adhesion and integrin-based cell migration. A genome-wide RNA interference screen for proteins required specifically for cadherin-dependent cell–cell adhesion identified an Elmo–Dock complex. This was unexpected as Elmo–Dock complexes act downstream of integrin signaling as Rac guanine-nucleotide exchange factors. In this paper, we show that Elmo2 recruits Dock1 to initial cell–cell contacts in Madin–Darby canine kidney cells. At cell–cell contacts, both Elmo2 and Dock1 are essential for the rapid recruitment and spreading of E-cadherin, actin reorganization, localized Rac and Rho GTPase activities, and the development of strong cell–cell adhesion. Upon completion of cell–cell adhesion, Elmo2 and Dock1 no longer localize to cell–cell contacts and are not required subsequently for the maintenance of cell–cell adhesion. These studies show that Elmo–Dock complexes are involved in both integrin- and cadherin-based adhesions, which may help to coordinate the transition of cells from migration to strong cell–cell adhesion. PMID:25452388

Molecular Docking Studies of Flavonoids Derivatives on the Flavonoid 3- O-Glucosyltransferase.

PubMed

Harsa, Alexandra M; Harsa, Teodora E; Diudea, Mircea V; Janezic, Dusanka

2015-01-01

A study of 30 flavonoid derivatives, taken from PubChem database and docked on flavonoid 3-O-glucosyltransferase 3HBF, next submitted to a QSAR study, performed within a hypermolecule frame, to model their LD50 values, is reported. The initial set of molecules was split into a training set and the test set (taken from the best scored molecules in the docking test); the predicted LD50 values, computed on similarity clusters, built up for each of the molecules of the test set, surpassed in accuracy the best model. The binding energies to 3HBF protein, provided by the docking step, are not related to the LD50 of these flavonoids, more protein targets are to be investigated in this respect. However, the docking step was useful in choosing the test set of molecules.

Knowing when to give up: early-rejection stratagems in ligand docking

NASA Astrophysics Data System (ADS)

Skone, Gwyn; Voiculescu, Irina; Cameron, Stephen

2009-10-01

Virtual screening is an important resource in the drug discovery community, of which protein-ligand docking is a significant part. Much software has been developed for this purpose, largely by biochemists and those in related disciplines, who pursue ever more accurate representations of molecular interactions. The resulting tools, however, are very processor-intensive. This paper describes some initial results from a project to review computational chemistry techniques for docking from a non-chemistry standpoint. An abstract blueprint for protein-ligand docking using empirical scoring functions is suggested, and this is used to discuss potential improvements. By introducing computer science tactics such as lazy function evaluation, dramatic increases to throughput can and have been realized using a real-world docking program. Naturally, they can be extended to any system that approximately corresponds to the architecture outlined.

49 CFR 174.114 - Record to be made of change of seals on “Cars loaded with Division 1.1 or 1.2 (explosive...

Code of Federal Regulations, 2010 CFR

2010-10-01

... car to its destination: RailroadPlaceDate Car InitialsCar NumberNumber or description of seal broken Number or description of seal used to reseal car Reasons for opening car Condition of load Name and...

Aspirating Seal Development: Analytical Modeling and Seal Test Rig

NASA Technical Reports Server (NTRS)

Bagepalli, Bharat

1996-01-01

This effort is to develop large diameter (22 - 36 inch) Aspirating Seals for application in aircraft engines. Stein Seal Co. will be fabricating the 36-inch seal(s) for testing. GE's task is to establish a thorough understanding of the operation of Aspirating Seals through analytical modeling and full-scale testing. The two primary objectives of this project are to develop the analytical models of the aspirating seal system, to upgrade using GE's funds, GE's 50-inch seal test rig for testing the Aspirating Seal (back-to-back with a corresponding brush seal), test the aspirating seal(s) for seal closure, tracking and maneuver transients (tilt) at operating pressures and temperatures, and validate the analytical model. The objective of the analytical model development is to evaluate the transient and steady-state dynamic performance characteristics of the seal designed by Stein. The transient dynamic model uses a multi-body system approach: the Stator, Seal face and the rotor are treated as individual bodies with relative degrees of freedom. Initially, the thirty-six springs are represented as a single one trying to keep open the aspirating face. Stops (Contact elements) are provided between the stator and the seal (to compensate the preload in the fully-open position) and between the rotor face and Seal face (to detect rub). The secondary seal is considered as part of the stator. The film's load, damping and stiffness characteristics as functions of pressure and clearance are evaluated using a separate (NASA) code GFACE. Initially, a laminar flow theory is used. Special two-dimensional interpolation routines are written to establish exact film load and damping values at each integration time step. Additionally, other user-routines are written to read-in actual pressure, rpm, stator-growth and rotor growth data and, later, to transfer these as appropriate loads/motions in the system-dynamic model. The transient dynamic model evaluates the various motions, clearances and forces as the seals are subjected to different aircraft maneuvers: Windmilling restart; start-ground idle; ground idle-takeoff; takeoff-burst chop, etc. Results of this model show that the seal closes appropriately and does not ram into the rotor for all of the conditions analyzed. The rig upgrade design for testing Aspirating Seals has been completed. Long lead-time items (forgings, etc.) have been ordered.

Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm.

PubMed

Wu, Guosheng; Robertson, Daniel H; Brooks, Charles L; Vieth, Michal

2003-10-01

The influence of various factors on the accuracy of protein-ligand docking is examined. The factors investigated include the role of a grid representation of protein-ligand interactions, the initial ligand conformation and orientation, the sampling rate of the energy hyper-surface, and the final minimization. A representative docking method is used to study these factors, namely, CDOCKER, a molecular dynamics (MD) simulated-annealing-based algorithm. A major emphasis in these studies is to compare the relative performance and accuracy of various grid-based approximations to explicit all-atom force field calculations. In these docking studies, the protein is kept rigid while the ligands are treated as fully flexible and a final minimization step is used to refine the docked poses. A docking success rate of 74% is observed when an explicit all-atom representation of the protein (full force field) is used, while a lower accuracy of 66-76% is observed for grid-based methods. All docking experiments considered a 41-member protein-ligand validation set. A significant improvement in accuracy (76 vs. 66%) for the grid-based docking is achieved if the explicit all-atom force field is used in a final minimization step to refine the docking poses. Statistical analysis shows that even lower-accuracy grid-based energy representations can be effectively used when followed with full force field minimization. The results of these grid-based protocols are statistically indistinguishable from the detailed atomic dockings and provide up to a sixfold reduction in computation time. For the test case examined here, improving the docking accuracy did not necessarily enhance the ability to estimate binding affinities using the docked structures. Copyright 2003 Wiley Periodicals, Inc.

High Misalignment Carbon Seals for the Fan Drive Gear System Technologies

NASA Technical Reports Server (NTRS)

Shaughnessy, Dennis; Dobek, Lou

2006-01-01

Aircraft engines of the future will require capability bearing compartment seals than found in current engines. Geared systems driving the fan will be subjected to inertia and gyroscopic forces resulting in extremely high angular and radial misalignments. Because of the high misalignment levels, compartment seals capable of accommodating angularities and eccentricities are required. Pratt & Whitney and Stein Seal Company selected the segmented circumferential carbon seal as the best candidate to operate at highly misaligned conditions. Initial seal tests established the misalignment limits of the current technology circumferential seal. From these results a more compliant seal configuration was conceived, designed, fabricated, and tested. Further improvements to the design are underway and plans are to conduct a durability test of the next phase configuration. A technical approach is presented, including design modification to a "baseline"seal, carbon grade selection, test rig configuration, test plan and results of analysis of seal testing.

iATTRACT: simultaneous global and local interface optimization for protein-protein docking refinement.

PubMed

Schindler, Christina E M; de Vries, Sjoerd J; Zacharias, Martin

2015-02-01

Protein-protein interactions are abundant in the cell but to date structural data for a large number of complexes is lacking. Computational docking methods can complement experiments by providing structural models of complexes based on structures of the individual partners. A major caveat for docking success is accounting for protein flexibility. Especially, interface residues undergo significant conformational changes upon binding. This limits the performance of docking methods that keep partner structures rigid or allow limited flexibility. A new docking refinement approach, iATTRACT, has been developed which combines simultaneous full interface flexibility and rigid body optimizations during docking energy minimization. It employs an atomistic molecular mechanics force field for intermolecular interface interactions and a structure-based force field for intramolecular contributions. The approach was systematically evaluated on a large protein-protein docking benchmark, starting from an enriched decoy set of rigidly docked protein-protein complexes deviating by up to 15 Å from the native structure at the interface. Large improvements in sampling and slight but significant improvements in scoring/discrimination of near native docking solutions were observed. Complexes with initial deviations at the interface of up to 5.5 Å were refined to significantly better agreement with the native structure. Improvements in the fraction of native contacts were especially favorable, yielding increases of up to 70%. © 2014 Wiley Periodicals, Inc.

Predicting the Accuracy of Protein–Ligand Docking on Homology Models

PubMed Central

BORDOGNA, ANNALISA; PANDINI, ALESSANDRO; BONATI, LAURA

2011-01-01

Ligand–protein docking is increasingly used in Drug Discovery. The initial limitations imposed by a reduced availability of target protein structures have been overcome by the use of theoretical models, especially those derived by homology modeling techniques. While this greatly extended the use of docking simulations, it also introduced the need for general and robust criteria to estimate the reliability of docking results given the model quality. To this end, a large-scale experiment was performed on a diverse set including experimental structures and homology models for a group of representative ligand–protein complexes. A wide spectrum of model quality was sampled using templates at different evolutionary distances and different strategies for target–template alignment and modeling. The obtained models were scored by a selection of the most used model quality indices. The binding geometries were generated using AutoDock, one of the most common docking programs. An important result of this study is that indeed quantitative and robust correlations exist between the accuracy of docking results and the model quality, especially in the binding site. Moreover, state-of-the-art indices for model quality assessment are already an effective tool for an a priori prediction of the accuracy of docking experiments in the context of groups of proteins with conserved structural characteristics. PMID:20607693

Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations

NASA Astrophysics Data System (ADS)

Selwa, Edithe; Elisée, Eddy; Zavala, Agustin; Iorga, Bogdan I.

2018-01-01

Our participation to the D3R Grand Challenge 2 involved a protocol in two steps, with an initial analysis of the available structural data from the PDB allowing the selection of the most appropriate combination of docking software and scoring function. Subsequent docking calculations showed that the pose prediction can be carried out with a certain precision, but this is dependent on the specific nature of the ligands. The correct ranking of docking poses is still a problem and cannot be successful in the absence of good pose predictions. Our free energy calculations on two different subsets provided contrasted results, which might have the origin in non-optimal force field parameters associated with the sulfonamide chemical moiety.

Protein-Protein Docking with F2Dock 2.0 and GB-Rerank

PubMed Central

Chowdhury, Rezaul; Rasheed, Muhibur; Keidel, Donald; Moussalem, Maysam; Olson, Arthur; Sanner, Michel; Bajaj, Chandrajit

2013-01-01

Motivation Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA) based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. Results The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. Availability The docking protocol has been implemented as a server with a graphical client (TexMol) which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dock.shtml. Client: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dockclient.shtml. PMID:23483883

Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2.

PubMed

Ritchie, David W

2003-07-01

This article describes and reviews our efforts using Hex 3.1 to predict the docking modes of the seven target protein-protein complexes presented in the CAPRI (Critical Assessment of Predicted Interactions) blind docking trial. For each target, the structure of at least one of the docking partners was given in its unbound form, and several of the targets involved large multimeric structures (e.g., Lactobacillus HPr kinase, hemagglutinin, bovine rotavirus VP6). Here we describe several enhancements to our original spherical polar Fourier docking correlation algorithm. For example, a novel surface sphere smothering algorithm is introduced to generate multiple local coordinate systems around the surface of a large receptor molecule, which may be used to define a small number of initial ligand-docking orientations distributed over the receptor surface. High-resolution spherical polar docking correlations are performed over the resulting receptor surface patches, and candidate docking solutions are refined by using a novel soft molecular mechanics energy minimization procedure. Overall, this approach identified two good solutions at rank 5 or less for two of the seven CAPRI complexes. Subsequent analysis of our results shows that Hex 3.1 is able to place good solutions within a list of

48 CFR 52.214-25 - Step Two of Two-Step Sealed Bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Step Two of Two-Step... Clauses 52.214-25 Step Two of Two-Step Sealed Bidding. As prescribed in 14.201-6(t), insert the following provision: Step Two of Two-Step Sealed Bidding (APR 1985) (a) This invitation for bids is issued to initiate...

Development of a CFD Code for Analysis of Fluid Dynamic Forces in Seals

NASA Technical Reports Server (NTRS)

Athavale, Mahesh M.; Przekwas, Andrzej J.; Singhal, Ashok K.

1991-01-01

The aim is to develop a 3-D computational fluid dynamics (CFD) code for the analysis of fluid flow in cylindrical seals and evaluation of the dynamic forces on the seals. This code is expected to serve as a scientific tool for detailed flow analysis as well as a check for the accuracy of the 2D industrial codes. The features necessary in the CFD code are outlined. The initial focus was to develop or modify and implement new techniques and physical models. These include collocated grid formulation, rotating coordinate frames and moving grid formulation. Other advanced numerical techniques include higher order spatial and temporal differencing and an efficient linear equation solver. These techniques were implemented in a 2D flow solver for initial testing. Several benchmark test cases were computed using the 2D code, and the results of these were compared to analytical solutions or experimental data to check the accuracy. Tests presented here include planar wedge flow, flow due to an enclosed rotor, and flow in a 2D seal with a whirling rotor. Comparisons between numerical and experimental results for an annular seal and a 7-cavity labyrinth seal are also included.

Hydrodynamically Lubricated Rotary Shaft Having Twist Resistant Geometry

DOEpatents

Dietle, Lannie; Gobeli, Jeffrey D.

1993-07-27

A hydrodynamically lubricated squeeze packing type rotary shaft with a cross-sectional geometry suitable for pressurized lubricant retention is provided which, in the preferred embodiment, incorporates a protuberant static sealing interface that, compared to prior art, dramatically improves the exclusionary action of the dynamic sealing interface in low pressure and unpressurized applications by achieving symmetrical deformation of the seal at the static and dynamic sealing interfaces. In abrasive environments, the improved exclusionary action results in a dramatic reduction of seal and shaft wear, compared to prior art, and provides a significant increase in seal life. The invention also increases seal life by making higher levels of initial compression possible, compared to prior art, without compromising hydrodynamic lubrication; this added compression makes the seal more tolerant of compression set, abrasive wear, mechanical misalignment, dynamic runout, and manufacturing tolerances, and also makes hydrodynamic seals with smaller cross-sections more practical. In alternate embodiments, the benefits enumerated above are achieved by cooperative configurations of the seal and the gland which achieve symmetrical deformation of the seal at the static and dynamic sealing interfaces. The seal may also be configured such that predetermined radial compression deforms it to a desired operative configuration, even through symmetrical deformation is lacking.

Collaboration and Commitment to Sealed Source Safety, Security, and Disposition - 13627

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

Jennison, Meaghan; Martin, David W.

2013-07-01

EnergySolutions, the Division of Radiation Control at the Utah Department of Environmental Quality (UDEQ), the Conference of Radiation Control Program Directors (CRCPD), and the Department of Energy's Global Threat Reduction Initiative (GTRI) are collaborating on a truly innovative effort to expand opportunities for cost-effective sealed source disposal. These entities have developed a first-of-its-kind initiative to dispose of certain sealed sources at the EnergySolutions disposal facility near Clive, Utah, which normally cannot accept sealed sources of any type. This creative and collaborative effort to improve radiation health, safety, and security exemplifies the spirit and commitment represented by the Richard S. Hodes,more » M.D. Honor Lecture Award, which is presented annually at the Waste Management Symposia by the Southeast Compact Commission to encourage environmental professionals and political leaders to develop innovative approaches to waste management in the United States. The participants in the collaborative initiative are honored to receive special recognition for their efforts thus far. They also recognize that the hard work remains to be done. (authors)« less

Preliminary GN&C Design for the On-Orbit Autonomous Assembly of Nanosatellite Demonstration Mission

NASA Technical Reports Server (NTRS)

Pei, Jing; Walsh, Matt; Roithmayr, Carlos; Karlgaard, Chris; Peck, Mason; Murchison, Luke

2017-01-01

Small spacecraft autonomous rendezvous and docking (ARD) is an essential technology for future space structure assembly missions. The On-orbit Autonomous Assembly of Nanosatellites (OAAN) team at NASA Langley Research Center (LaRC) intends to demonstrate the technology to autonomously dock two nanosatellites to form an integrated system. The team has developed a novel magnetic capture and latching mechanism that allows for docking of two CubeSats without precise sensors and actuators. The proposed magnetic docking hardware not only provides the means to latch the CubeSats, but it also significantly increases the likelihood of successful docking in the presence of relative attitude and position errors. The simplicity of the design allows it to be implemented on many CubeSat rendezvous missions. Prior to demonstrating the docking subsystem capabilities on orbit, the GN&C subsystem should have a robust design such that it is capable of bringing the CubeSats from an arbitrary initial separation distance of as many as a few thousand kilometers down to a few meters. The main OAAN Mission can be separated into the following phases: 1) Launch, checkout, and drift, 2) Far-Field Rendezvous or Drift Recovery, 3) Proximity Operations, 4) Docking. This paper discusses the preliminary GN&C design and simulation results for each phase of the mission.

Method of assembling and sealing an alkali metal battery

DOEpatents

Elkins, Perry E.; Bell, Jerry E.; Harlow, Richard A.; Chase, Gordon G.

1983-01-01

A method of initially assembling and then subsequently hermetically sealing a container portion of an alkali metal battery to a ceramic portion of such a battery is disclosed. Sealing surfaces are formed respectively on a container portion and a ceramic portion of an alkali metal battery. These sealing surfaces are brought into juxtaposition and a material is interposed therebetween. This interposed material is one which will diffuse into sealing relationship with both the container portion and the ceramic portion of the alkali metal battery at operational temperatures of such a battery. A pressure is applied between these sealing surfaces to cause the interposed material to be brought into intimate physical contact with such juxtaposed surfaces. A temporary sealing material which will provide a seal against a flow of alkali metal battery reactants therethrough at room temperatures and is applied over the juxtaposed sealing surfaces and material interposed therebetween. The entire assembly is heated to an operational temperature so that the interposed material diffuses into the container portion and the ceramic portion to form a hermetic seal therebetween. The pressure applied to the juxtaposed sealing surfaces is maintained in order to ensure the continuation of the hermetic seal.

Method of assembling and sealing an alkali metal battery

DOEpatents

Elkins, P.E.; Bell, J.E.; Harlow, R.A.; Chase, G.G.

1983-03-01

A method of initially assembling and then subsequently hermetically sealing a container portion of an alkali metal battery to a ceramic portion of such a battery is disclosed. Sealing surfaces are formed respectively on a container portion and a ceramic portion of an alkali metal battery. These sealing surfaces are brought into juxtaposition and a material is interposed there between. This interposed material is one which will diffuse into sealing relationship with both the container portion and the ceramic portion of the alkali metal battery at operational temperatures of such a battery. A pressure is applied between these sealing surfaces to cause the interposed material to be brought into intimate physical contact with such juxtaposed surfaces. A temporary sealing material which will provide a seal against a flow of alkali metal battery reactants there through at room temperatures and is applied over the juxtaposed sealing surfaces and material interposed there between. The entire assembly is heated to an operational temperature so that the interposed material diffuses into the container portion and the ceramic portion to form a hermetic seal there between. The pressure applied to the juxtaposed sealing surfaces is maintained in order to ensure the continuation of the hermetic seal. 4 figs.

Sealing Penetrating Eye Injuries Using Photoactivated Bonding

DTIC Science & Technology

2014-10-01

treatment parameters that produce strong, immediate water- tight sealing of penetrating cornea and scleral wounds using rabbit eye models. The seal...conventional, bare fiber system using ex vivo rabbit eyes and the standard treatment protocol (Appendix 1). The bonding strength produced by two...wounds in rabbit eyes . Initial studies demonstrated that thermal damage to the iris are not a concern during the 7 treatment . A prototype light delivery

Advanced Docking System With Magnetic Initial Capture

NASA Technical Reports Server (NTRS)

Lewis, James L.; Carroll, Monty B.; Morales, Ray; Le, Thang

2004-01-01

An advanced docking system is undergoing development to enable softer, safer docking than was possible when using prior docking systems. This system is intended for original use in docking of visiting spacecraft and berthing the Crew Return Vehicle at the International Space Station (ISS). The system could also be adapted to a variety of other uses in outer space and on Earth, including mating submersible vehicles, assembling structures, and robotic berthing/handling of payloads and cargo. Heretofore, two large spacecraft have been docked by causing the spacecraft to approach each other at a speed sufficient to activate capture latches - a procedure that results in large docking loads and is made more difficult because of the speed. The basic design and mode of operation of the present advanced docking system would eliminate the need to rely on speed of approach to activate capture latches, thereby making it possible to reduce approach speed and thus docking loads substantially. The system would comprise an active subsystem on one spacecraft and a passive subsystem on another spacecraft with which the active subsystem will be docked. The passive subsystem would include an extensible ring containing magnetic striker plates and guide petals. The active subsystem would include mating guide petals and electromagnets containing limit switches and would be arranged to mate with the magnetic striker plates and guide petals of the passive assembly. The electromagnets would be carried on (but not rigidly attached to) a structural ring that would be instrumented with load sensors. The outputs of the sensors would be sent, along with position information, as feedback to an electronic control subsystem. The system would also include electromechanical actuators that would extend or retract the ring upon command by the control subsystem.

Corrosion sealing of amalgam restorations in vitro.

PubMed

Mahler, David B; Pham, Bao V; Adey, Jerry D

2009-01-01

Amalgam restorations, when first placed, have been shown to exhibit a gap at the amalgam/tooth interface. With time in service, this gap fills with corrosion products that have the potential to "seal" the restoration. With the advent of high-copper, more corrosion-resistant amalgams, there has been concern that the time required to create this seal would be increased significantly when compared with low-copper traditional amalgams. The current study was designed to address this concern. Amalgam was condensed into a MACOR mold, simulating a Class I cavity form and then immersed into a 1.0% NaCl solution to simulate oral conditions. Using an air pressure test, the sealing was monitored over time. The results showed that the sealing was influenced by the size of the initial gap prior to immersion as well as corrosion resistance of the amalgam and that a corrosion-resistant amalgam with a small initial gap size can seal as quickly as a corrosion-prone amalgam. Therefore, it is not possible to predict sealing behavior based on corrosion resistance, alone. Furthermore, the presence of zinc in the amalgam alloy has been shown to result in the formation of zinc corrosion products in the amalgam/mold margin, which contributes to more rapid sealing. Analysis of a tooth extracted after 16 years of clinical service that had been restored with an amalgam-containing zinc was also shown to contain zinc corrosion products in the occlusal marginal area. This could explain the reported reduction in marginal fracture of clinically placed amalgam restorations made from zinc-containing alloys.

Actively controlled shaft seals for aerospace applications

NASA Astrophysics Data System (ADS)

Salant, Richard F.

The objective of years 4 and 5 of this project (1992 and 1993) is to determine experimentally the behavior and operating characteristics of a controllable mechanical seal, and to identify potential problem areas. A controllable mechanical seal is one in which the thickness of the lubricating film separating the sealing surfaces is adjustable, and can be controlled by an electronic control system, based on information supplied by sensors that monitor the condition of the film. This work builds upon work done during years 1-3, in which a controllable mechanical seal was designed, analyzed, and fabricated. At the beginning of year 4, the mechanical seal and test rig was assembled, and preliminary testing begun. The five major tasks of years 4 and 5 encompass instrumentation, configuration changes of the mechanical seal to optimize its performance, systematic steady state tests, systematic transient tests, and a final report. During this reporting period, significant progress was made on instrumenting the test rig and modifying the design to optimize the seal's performance. Initial steady state tests were also performed.

Docking and molecular dynamics simulation of quinone compounds with trypanocidal activity.

PubMed

de Molfetta, Fábio Alberto; de Freitas, Renato Ferreira; da Silva, Albérico Borges Ferreira; Montanari, Carlos Alberto

2009-10-01

In this work, two different docking programs were used, AutoDock and FlexX, which use different types of scoring functions and searching methods. The docking poses of all quinone compounds studied stayed in the same region in the trypanothione reductase. This region is a hydrophobic pocket near to Phe396, Pro398 and Leu399 amino acid residues. The compounds studied displays a higher affinity in trypanothione reductase (TR) than glutathione reductase (GR), since only two out of 28 quinone compounds presented more favorable docking energy in the site of human enzyme. The interaction of quinone compounds with the TR enzyme is in agreement with other studies, which showed different binding sites from the ones formed by cysteines 52 and 58. To verify the results obtained by docking, we carried out a molecular dynamics simulation with the compounds that presented the highest and lowest docking energies. The results showed that the root mean square deviation (RMSD) between the initial and final pose were very small. In addition, the hydrogen bond pattern was conserved along the simulation. In the parasite enzyme, the amino acid residues Leu399, Met400 and Lys402 are replaced in the human enzyme by Met406, Tyr407 and Ala409, respectively. In view of the fact that Leu399 is an amino acid of the Z site, this difference could be explored to design selective inhibitors of TR.

Autonomous docking ground demonstration

NASA Technical Reports Server (NTRS)

Lamkin, Steve L.; Le, Thomas Quan; Othon, L. T.; Prather, Joseph L.; Eick, Richard E.; Baxter, Jim M.; Boyd, M. G.; Clark, Fred D.; Spehar, Peter T.; Teters, Rebecca T.

1991-01-01

The Autonomous Docking Ground Demonstration is an evaluation of the laser sensor system to support the docking phase (12 ft to contact) when operated in conjunction with the guidance, navigation, and control (GN&C) software. The docking mechanism being used was developed for the Apollo/Soyuz Test Program. This demonstration will be conducted using the 6-DOF Dynamic Test System (DTS). The DTS simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration, the laser sensor will be mounted on the target vehicle and the retroflectors will be on the chase vehicle. This arrangement was chosen to prevent potential damage to the laser. The laser sensor system, GN&C, and 6-DOF DTS will be operated closed-loop. Initial conditions to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved.

Multi-Axis Independent Electromechanical Load Control for Docking System Actuation Development and Verification Using dSPACE

NASA Technical Reports Server (NTRS)

Oesch, Christopher; Dick, Brandon; Rupp, Timothy

2015-01-01

The development of highly complex and advanced actuation systems to meet customer demands has accelerated as the use of real-time testing technology expands into multiple markets at Moog. Systems developed for the autonomous docking of human rated spacecraft to the International Space Station (ISS), envelope multi-operational characteristics which place unique constraints on an actuation system. Real-time testing hardware has been used as a platform for incremental testing and development for the linear actuation system which controls initial capture and docking for vehicles visiting the ISS. This presentation will outline the role of dSPACE hardware as a platform for rapid control-algorithm prototyping as well as an Electromechanical Actuator (EMA) system dynamic loading simulator, both conducted at Moog to develop the safety critical Linear Actuator System (LAS) of the NASA Docking System (NDS).

Vision Based Navigation for Autonomous Cooperative Docking of CubeSats

NASA Astrophysics Data System (ADS)

Pirat, Camille; Ankersen, Finn; Walker, Roger; Gass, Volker

2018-05-01

A realistic rendezvous and docking navigation solution applicable to CubeSats is investigated. The scalability analysis of the ESA Autonomous Transfer Vehicle Guidance, Navigation & Control (GNC) performances and the Russian docking system, shows that the docking of two CubeSats would require a lateral control performance of the order of 1 cm. Line of sight constraints and multipath effects affecting Global Navigation Satellite System (GNSS) measurements in close proximity prevent the use of this sensor for the final approach. This consideration and the high control accuracy requirement led to the use of vision sensors for the final 10 m of the rendezvous and docking sequence. A single monocular camera on the chaser satellite and various sets of Light-Emitting Diodes (LEDs) on the target vehicle ensure the observability of the system throughout the approach trajectory. The simple and novel formulation of the measurement equations allows differentiating unambiguously rotations from translations between the target and chaser docking port and allows a navigation performance better than 1 mm at docking. Furthermore, the non-linear measurement equations can be solved in order to provide an analytic navigation solution. This solution can be used to monitor the navigation filter solution and ensure its stability, adding an extra layer of robustness for autonomous rendezvous and docking. The navigation filter initialization is addressed in detail. The proposed method is able to differentiate LEDs signals from Sun reflections as demonstrated by experimental data. The navigation filter uses a comprehensive linearised coupled rotation/translation dynamics, describing the chaser to target docking port motion. The handover, between GNSS and vision sensor measurements, is assessed. The performances of the navigation function along the approach trajectory is discussed.

The status and management of the harp seal in the north-west Atlantic: a review and evaluation. Final report Jan-Sep 79

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

Beddington, J.R.; Williams, H.A.

1980-07-01

This study initially reviews the history of exploitation and management of the harp seal in the north-west Atlantic up to the present time. A consideration of the life history and biology of this species indicates a need for investigation of the implication of current harvesting which involves both the harp seal and several of its prey species.

Brush Seal Performance and Durability Issues Based on T-700 Engine Test Results

NASA Technical Reports Server (NTRS)

Hendricks, R. C.

1994-01-01

The integrity and performance of brush seals have been established. Severe bench and engine tests have shown high initial wear or run-in rates, material smearing at the interface, and bristle and rub-runner wear, but the brush seals did not fail. Short-duration (46 hr) experimental T-700 engine testing of the compressor discharge seal established over 1-percent engine performance gain (brush versus labyrinth). Long-term gains were established only as leakage comparisons, with the brush at least 20 percent better at controlling leakage. Long-term materials issues, such as wear and ultimately seal life, remain to be resolved. Future needs are cited for materials and analysis tools that account for heat generation, thermomechanical behavior, and tribological pairing to enable original equipment manufacturers to design high-temperature, high-surface-speed seals with confidence.

Computational Exploration of a Protein Receptor Binding Space with Student Proposed Peptide Ligands

PubMed Central

King, Matthew D.; Phillips, Paul; Turner, Matthew W.; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; Mcdougal, Owen M.

2017-01-01

Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results. PMID:26537635

North Carolina "sealed corridor" phase I : U.S. DOT assessment report : report to Congress

DOT National Transportation Integrated Search

2001-09-01

In response to a request in the Senate Report 107-38 accompanying the Department of Transportation and Related Agencies Appropriations Act, 2001, this report documents the benefits of the State of North Carolina 's Sealed Corridor " initiative and th...

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan

NASA Astrophysics Data System (ADS)

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan.

PubMed

Tsai, Tsung-Ying; Chang, Kai-Wei; Chen, Calvin Yu-Chian

2011-06-01

The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at http://iScreen.cmu.edu.tw/.

Berthing simulator for space station and orbiter

NASA Technical Reports Server (NTRS)

Veerasamy, Sam

1991-01-01

The development of a real-time man-in-the-loop berthing simulator is in progress at NASA Lyndon B. Johnson Space Center (JSC) to conduct a parametric study and to measure forces during contact conditions of the actual docking mechanisms for the Space Station Freedom and the orbiter. In berthing, the docking ports of the Space Station and the orbiter are brought together using the orbiter robotic arm to control the relative motion of the vehicles. The berthing simulator consists of a dynamics docking test system (DDTS), computer system, simulator software, and workstations. In the DDTS, the Space Station, and the orbiter docking mechanisms are mounted on a six-degree-of-freedom (6 DOF) table and a fixed platform above the table. Six load cells are used on the fixed platform to measure forces during contact conditions of the docking mechanisms. Two Encore Concept 32/9780 computers are used to simulate the orbiter robotic arm and to operate the berthing simulator. A systematic procedure for a real-time dynamic initialization is being developed to synchronize the Space Station docking port trajectory with the 6 DOF table movement. The berthing test can be conducted manually or automatically and can be extended for any two orbiting vehicles using a simulated robotic arm. The real-time operation of the berthing simulator is briefly described.

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

Smartt, Heidi A.; Romero, Juan A.; Custer, Joyce Olsen

Containment/Surveillance (C/S) measures are critical to any verification regime in order to maintain Continuity of Knowledge (CoK). The Ceramic Seal project is research into the next generation technologies to advance C/S, in particular improving security and efficiency. The Ceramic Seal is a small form factor loop seal with improved tamper-indication including a frangible seal body, tamper planes, external coatings, and electronic monitoring of the seal body integrity. It improves efficiency through a self-securing wire and in-situ verification with a handheld reader. Sandia National Laboratories (SNL) and Savannah River National Laboratory (SRNL), under sponsorship from the U.S. National Nuclear Security Administrationmore » (NNSA) Office of Defense Nuclear Nonproliferation Research and Development (DNN R&D), have previously designed and have now fabricated and tested Ceramic Seals. Tests have occurred at both SNL and SRNL, with different types of tests occurring at each facility. This interim report will describe the Ceramic Seal prototype, the design and development of a handheld standalone reader and an interface to a data acquisition system, fabrication of the seals, and results of initial testing.« less

High-Pressure Hot-Gas Self-Acting Floating Ring Shaft Seal for Liquid Rocket Turbopumps. [tapered bore seals

NASA Technical Reports Server (NTRS)

Burcham, R. E.; Diamond, W. A.

1980-01-01

Design analysis, detail design, fabrication, and experimental evaluation was performed on two self acting floating ring shaft seals for a rocket engine turbopump high pressure 24132500 n/sq m (3500 psig) hot gas 533 K 9500 F) high speed 3142 rad/sec (30000 rmp) turbine. The initial design used Rayleigh step hydrodynamic lift pads to assist in centering the seal ring with minimum rubbing contact. The final design used a convergent tapered bore to provide hydrostatic centering force. The Rayleigh step design was tested for 107 starts and 4.52 hours total. The leakage was satisfactory; however, the design was not acceptable due to excessive wear caused by inadequate centering force and failure of the sealing dam caused by erosion damage. The tapered bore design was tested for 370 starts and 15.93 hours total. Satisfactory performance for the required life of 7.5 hours per seal was successfully demonstrated.

Development of seals for a geothermal downhole intensifier. Progress report

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

Captain, K.M.; Harvey, A.C.; Caskey, B.C.

1985-08-01

A system using high-velocity fluid jets in conjunction with a rotary diamond bit is currently considered as the best candidate for reducing the cost of drilling geothermal wells. Technical, safety and cost considerations indicate that the required jet supply pressure can best be established by a downhole pressure intensifier. Key intensifier components are the check valve and plunger seals, which must prevent leakage of the high-pressure, high-temperature abrasive fluid (drilling mud). To achieve the required performance, novel ceramic seals are currently being developed. The check valve seal includes a tapered polymeric plug and ceramic stop acting against a ceramic seat.more » The ceramic plunger seal is a variant of the ''stepped-joint'' piston ring and is designed to minimize contact pressure and abrasive wear. Initial testing of these seals in the laboratory shows encouraging results; design refinement and further testing is in progress. 2 refs., 6 figs., 3 tabs.« less

A New Tribological Test for Candidate Brush Seal Materials Evaluation

NASA Technical Reports Server (NTRS)

Fellenstein, James A.; Dellacorte, Christopher

1994-01-01

A new tribological test for candidate brush seal materials evaluation has been developed. The sliding contact between the brush seal wires and their mating counterface journal is simulated by testing a small tuft of wire against the outside diameter of a high speed rotating shaft. The test configuration is similar to a standard block on ring geometry. The new tester provides the capability to measure both the friction and wear of candidate wire and counterface materials under controlled loading conditions in the gram to kilogram range. A wide test condition latitude of speeds (1 to 27 m/s), temperatures (25 to 700 C), and loads (0.5 to 10 N) enables the simulation of many of the important tribological parameters found in turbine engine brush seals. This paper describes the new test rig and specimen configuration and presents initial data for candidate seal materials comparing tuft test results and wear surface morphology to field tested seal components.

Peel/seal properties of poly(ethylene methyl acrylate)/polybutene-1 blend films

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

Mohammdi, Seyedeh Raziyeh; Ajji, Abdellah; Tabatabaei, Seyed H.

Nowadays, the possibility to easy open a food package is of great interest both from the consumer and food producers’ perspective. In this study, the peel/seal properties of poly (ethylene methyl acrylate) (EMA)/polybutene-1 (PB-1) blend films were investigated. Three blends of EMA/PB-1 with different methyl acrylate (MA) content were prepared using cast extrusion process. Differential Scanning Calorimetry (DSC) was used to investigate the thermal behavior as well as the crystalinity of the blends. The effect of polymer matrix on the crystalline structure of PB-1 was studied using Wide Angle X-ray Diffraction (WAXD) and DSC. T-peel tests were carried out onmore » the heat sealed films at various seal temperatures. The effect of MA content and heat seal temperature on peel/seal properties (i.e. peel initiation temperature, temperature window of sealability and peel strength) of the films were studied.« less

Spacecraft flight simulation: A human factors investigation into the man-machine interface between an astronaut and a spacecraft performing docking maneuvers and other proximity operations

NASA Technical Reports Server (NTRS)

Brody, Adam R.

1988-01-01

The anticipated increase in rendezvous and docking activities in the various space programs in the Space Station era necessitates a renewed interest in manual docking procedures. Ten test subjects participated in computer simulated docking missions in which the influence of initial velocity was examined. All missions started from a resting position of 304.8 meters (1000 feet) along the space station's +V-bar axis. Test subjects controlled their vehicle with a translational hand controller and digital auto pilot which are both virtually identical to their space shuttle counterparts. While the 0.1 percent rule (range rate is equal to 0.1 percent of the range) used by space shuttle pilots is comfortably safe, it is revealed to be extremely inefficient in terms of time and not justifiable in terms of marginal safety. Time is worth money, not only because of training and launch costs, but because the sooner a pilot and spacecraft return from a mission, the sooner they can begin the next one. Inexperienced test subjects reduced the costs of simulated docking by close to a factor of 2 and achieved safe dockings in less than 4 percent of the time the baseline approach would entail. This reduction in time can be used to save lives in the event of an accident on orbit, and can tremendously reduce docking costs if fuel is produced from waste water on orbit.

Computational Design of Apolipoprotein E4 Inhibitors for Alzheimer's Disease Therapy from Traditional Chinese Medicine

PubMed Central

Huang, Hung-Jin; Chen, Hsin-Yi; Lee, Cheng-Chun

2014-01-01

Apolipoprotein E4 (Apo E4) is the major genetic risk factor in the causation of Alzheimer's disease (AD). In this study we utilize virtual screening of the world's largest traditional Chinese medicine (TCM) database and investigate potential compounds for the inhibition of ApoE4. We present the top three TCM candidates: Solapalmitine, Isodesacetyluvaricin, and Budmunchiamine L5 for further investigation. Dynamics analysis and molecular dynamics (MD) simulation were used to simulate protein-ligand complexes for observing the interactions and protein variations. Budmunchiamine L5 did not have the highest score from virtual screening; however, the dynamics pose is similar to the initial docking pose after MD simulation. Trajectory analysis reveals that Budmunchiamine L5 was stable over all simulation times. The migration distance of Budmunchiamine L5 illustrates that docked ligands are not variable from the initial docked site. Interestingly, Arg158 was observed to form H-bonds with Budmunchiamine L5 in the docking pose and MD snapshot, which indicates that the TCM compounds could stably bind to ApoE4. Our results show that Budmunchiamine L5 has good absorption, blood brain barrier (BBB) penetration, and less toxicity according to absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and could, therefore, be safely used for developing novel ApoE4 inhibitors. PMID:24967370

Actively controlled shaft seals for aerospace applications

NASA Technical Reports Server (NTRS)

Salant, Richard F.

1994-01-01

This study experimentally investigates an actively controlled mechanical seal for aerospace applications. The seal of interest is a gas seal, which is considerably more compact than previous actively controlled mechanical seals that were developed for industrial use. In a mechanical seal, the radial convergence of the seal interface has a primary effect on the film thickness. Active control of the film thickness is established by controlling the radial convergence of the seal interface with piezoelectric actuator. An actively controlled mechanical seal was initially designed and evaluated using a mathematical model. Based on these results, a seal was fabricated and tested under laboratory conditions. The seal was tested with both helium and air, at rotational speeds up to 3770 rad/sec, and at sealed pressures as high as 1.48 x 10(exp 6) Pa. The seal was operated with both manual control and with a closed-loop control system that used either the leakage rate or face temperature as the feedback. The output of the controller was the voltage applied to the piezoelectric actuator. The seal operated successfully for both short term tests (less than one hour) and for longer term tests (four hours) with a closed-loop control system. The leakage rates were typically 5-15 slm (standard liters per minute), and the face temperatures were generally maintained below 100 C. When leakage rate was used as the feedback signal, the setpoint leakage rate was typically maintained within 1 slm. However, larger deviations occurred during sudden changes in sealed pressure. When face temperature was used as the feedback signal, the setpoint face temperature was generally maintained within 3 C, with larger deviations occurring when the sealed pressure changed suddenly.

Sealed-cell nickel-cadmium battery applications manual

NASA Technical Reports Server (NTRS)

Scott, W. R.; Rusta, D. W.

1979-01-01

The design, procurement, testing, and application of aerospace quality, hermetically sealed nickel-cadmium cells and batteries are presented. Cell technology, cell and battery development, and spacecraft applications are emphasized. Long term performance is discussed in terms of the effect of initial design, process, and application variables. Design guidelines and practices are given.

Dynamic Inversion based Control of a Docking Mechanism

NASA Technical Reports Server (NTRS)

Kulkarni, Nilesh V.; Ippolito, Corey; Krishnakumar, Kalmanje

2006-01-01

The problem of position and attitude control of the Stewart platform based docking mechanism is considered motivated by its future application in space missions requiring the autonomous docking capability. The control design is initiated based on the framework of the intelligent flight control architecture being developed at NASA Ames Research Center. In this paper, the baseline position and attitude control system is designed using dynamic inversion with proportional-integral augmentation. The inverse dynamics uses a Newton-Euler formulation that includes the platform dynamics, the dynamics of the individual legs along with viscous friction in the joints. Simulation results are presented using forward dynamics simulated by a commercial physics engine that builds the system as individual elements with appropriate joints and uses constrained numerical integration,

Analysis of Apex Seal Friction Power Loss in Rotary Engines

NASA Technical Reports Server (NTRS)

Handschuh, Robert F.; Owen, A. Karl

2010-01-01

An analysis of the frictional losses from the apex seals in a rotary engine was developed. The modeling was initiated with a kinematic analysis of the rotary engine. Next a modern internal combustion engine analysis code was altered for use in a rotary engine to allow the calculation of the internal combustion pressure as a function of rotor rotation. Finally the forces from the spring, inertial, and combustion pressure on the seal were combined to provide the frictional horsepower assessment.

Modulation of interaction of mutant TP53 and wild type BRCA1 by alkaloids: a computational approach towards targeting protein-protein interaction as a futuristic therapeutic intervention strategy for breast cancer impediment.

PubMed

Tiwari, Sameeksha; Awasthi, Manika; Singh, Swati; Pandey, Veda P; Dwivedi, Upendra N

2017-10-23

Protein-protein interactions (PPI) are a new emerging class of novel therapeutic targets. In order to probe these interactions, computational tools provide a convenient and quick method towards the development of therapeutics. Keeping this in view the present study was initiated to analyse interaction of tumour suppressor protein p53 (TP53) and breast cancer associated protein (BRCA1) as promising target against breast cancer. Using computational approaches such as protein-protein docking, hot spot analyses, molecular docking and molecular dynamics simulation (MDS), stepwise analyses of the interactions of the wild type and mutant TP53 with that of wild type BRCA1 and their modulation by alkaloids were done. Protein-protein docking method was used to generate both wild type and mutant complexes of TP53-BRCA1. Subsequently, the complexes were docked using sixteen different alkaloids, fulfilling ADMET and Lipinski's rule of five criteria, and were compared with that of a well-known inhibitor of PPI, namely nutlin. The alkaloid dicentrine was found to be the best docked alkaloid among all the docked alklaloids as well as that of nutlin. Furthermore, MDS analyses of both wild type and mutant complexes with the best docked alkaloid i.e. dicentrine, revealed higher stability of mutant complex than that of the wild one, in terms of average RMSD, RMSF and binding free energy, corroborating the results of docking. Results suggested more pronounced interaction of BRCA1 with mutant TP53 leading to increased expression of mutated TP53 thus showing a dominant negative gain of function and hampering wild type TP53 function leading to tumour progression.

Computational exploration of a protein receptor binding space with student proposed peptide ligands.

PubMed

King, Matthew D; Phillips, Paul; Turner, Matthew W; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; McDougal, Owen M

2016-01-01

Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results. © 2015 The International Union of Biochemistry and Molecular Biology.

Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.

PubMed

Antony, Priya; Vijayan, Ranjit

2015-01-01

Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.

Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study

PubMed Central

Antony, Priya; Vijayan, Ranjit

2015-01-01

Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors. PMID:26384019

Knowledge-Guided Docking of WW Domain Proteins and Flexible Ligands

NASA Astrophysics Data System (ADS)

Lu, Haiyun; Li, Hao; Banu Bte Sm Rashid, Shamima; Leow, Wee Kheng; Liou, Yih-Cherng

Studies of interactions between protein domains and ligands are important in many aspects such as cellular signaling. We present a knowledge-guided approach for docking protein domains and flexible ligands. The approach is applied to the WW domain, a small protein module mediating signaling complexes which have been implicated in diseases such as muscular dystrophy and Liddle’s syndrome. The first stage of the approach employs a substring search for two binding grooves of WW domains and possible binding motifs of peptide ligands based on known features. The second stage aligns the ligand’s peptide backbone to the two binding grooves using a quasi-Newton constrained optimization algorithm. The backbone-aligned ligands produced serve as good starting points to the third stage which uses any flexible docking algorithm to perform the docking. The experimental results demonstrate that the backbone alignment method in the second stage performs better than conventional rigid superposition given two binding constraints. It is also shown that using the backbone-aligned ligands as initial configurations improves the flexible docking in the third stage. The presented approach can also be applied to other protein domains that involve binding of flexible ligand to two or more binding sites.

Resident CAPS on dense-core vesicles docks and primes vesicles for fusion

PubMed Central

Kabachinski, Greg; Kielar-Grevstad, D. Michelle; Zhang, Xingmin; James, Declan J.; Martin, Thomas F. J.

2016-01-01

The Ca2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro­scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2–dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly. PMID:26700319

Engineering Evaluation of International Low Impact Docking System Latch Hooks

NASA Technical Reports Server (NTRS)

Martinez, J.; Patin, R.; Figert, J.

2013-01-01

The international Low Impact Docking System (iLIDS) provides a structural arrangement that allows for visiting vehicles to dock with the International Space Station (ISS) (Fig 1). The iLIDS docking units are mechanically joined together by a series of active and passive latch hooks. In order to preserve docking capability at the existing Russian docking interfaces, the iLIDS latch hooks are required to conform to the existing Russian design. The latch hooks are classified as being fail-safe. Since the latch hooks are fail-safe, the hooks are not fracture critical and a fatigue based service life assessment will satisfy the structural integrity requirements. Constant amplitude fatigue testing to failure on four sets of active/passive iLIDS latch hooks was performed at load magnitudes of 10, 11, and 12 kips. Failure analysis of the hook fatigue failures identified multi-site fatigue initiation that was effectively centered about the hook mid-plane (consistent with the 3D model results). The fatigue crack initiation distribution implies that the fatigue damage accumulation effectively results in a very low aspect ratio surface crack (which can be simulated as thru-thickness crack). Fatigue damage progression resulted in numerous close proximity fatigue crack initiation sites. It was not possible to determine if fatigue crack coalescence occurs during cyclic loading or as result of the fast fracture response. The presence of multiple fatigue crack initiation sites on different planes will result in the formation of ratchet marks as the cracks coalesce. Once the stable fatigue crack becomes unstable and the fast fracture advances across the remaining ligament and the plane stress condition at a free-surface will result in failure along a 45 deg. shear plane (slant fracture) and the resulting inclined edge is called a shear lip. The hook thickness on the plane of fatigue crack initiation is 0.787". The distance between the shear lips on this plane was on the order of 0.48" and it was effectively centered about the mid-plane of the section. The numerous ratchet marks between the shear lips on the fracture initiation plane are indicative of multiple fatigue initiation sites within this region. The distribution of the fatigue damage about the centerline of the hook is consistent with the analytical results that demonstrate peak stress/strain response at the mid-plane that decreases in the direction of the hook outer surfaces. Scanning electron microscope images of the failed sections detected fatigue crack striations in close proximity to the free surface of the hook radius. These findings were documented at three locations on the fracture surface : 1) adjacent to the left shear lip, 2) adjacent to the right shear lip, and 3) near the centerline of the section. The features of the titanium fracture surface did not allow for a determination of a critical crack size via identification of the region where the fatigue crack propagation became unstable. The fracture based service life projections where benchmarked with strain-life analyses. The strainrange response in the hook radius was defined via the correlated finite element models and the modified method of universal slopes was incorporated to define the strain-life equation for the titanium alloy. The strain-life assessment confirmed that the fracture based projections were reasonable for the loading range of interest. Based upon the analysis and component level fatigue test data a preliminary service life capability for the iLIDS active and passive hooks of 2 lifetimes is projected (includes a scatter factor of 4).

A model for the space shuttle main engine high pressure oxidizer turbopump shaft seal system

NASA Technical Reports Server (NTRS)

Paxson, Daniel E.

1990-01-01

A simple static model is presented which solves for the flow properties of pressure, temperature, and mass flow in the Space Shuttle Main Engine pressure Oxidizer Turbopump Shaft Seal Systems. This system includes the primary and secondary turbine seals, the primary and secondary turbine drains, the helium purge seals and feed line, the primary oxygen drain, and the slinger/labyrinth oxygen seal pair. The model predicts the changes in flow variables that occur during and after failures of the various seals. Such information would be particularly useful in a post flight situation where processing of sensor information using this model could identify a particular seal that had experienced excessive wear. Most of the seals in the system are modeled using simple one dimensional equations which can be applied to almost any seal provided that the fluid is gaseous. A failure is modeled as an increase in the clearance between the shaft and the seal. Thus, the model does not attempt to predict how the failure process actually occurs (e.g., wear, seal crack initiation). The results presented were obtained using a FORTRAN implementation of the model running on a VAX computer. Solution for the seal system properties is obtained iteratively; however, a further simplified implementation (which does not include the slinger/labyrinth combination) was also developed which provides fast and reasonable results for most engine operating conditions. Results from the model compare favorably with the limited redline data available.

Insight into the da Vinci® Xi - technical notes for single-docking left-sided colorectal procedures.

PubMed

Ngu, James Chi-Yong; Sim, Sarah; Yusof, Sulaiman; Ng, Chee-Yung; Wong, Andrew Siang-Yih

2017-12-01

The adoption of robot-assisted laparoscopic colorectal surgery has been hampered by issues with docking, operative duration, technical difficulties in multi-quadrant access, and cost. The da Vinci® Xi has been designed to overcome some of these limitations. We describe our experience with the system and offer technical insights to its application in left-sided colorectal procedures. Our initial series of left-sided robotic colorectal procedures was evaluated. Patient demographics and operative outcomes were recorded prospectively using a predefined database. Between March 2015 and April 2016, 54 cases of robot-assisted laparoscopic left-sided colorectal procedures were successfully completed with no cases of conversion. The majority were low anterior resections for colorectal malignancies. Using the da Vinci® Xi Surgical System, multi-quadrant surgery involving dissection from the splenic flexure to the pelvis was possible without redocking. The da Vinci® Xi simplifies the docking procedure and makes single-docking feasible for multi-quadrant left-sided colorectal procedures. Copyright © 2016 John Wiley & Sons, Ltd.

A conservation and biophysics guided stochastic approach to refining docked multimeric proteins.

PubMed

Akbal-Delibas, Bahar; Haspel, Nurit

2013-01-01

We introduce a protein docking refinement method that accepts complexes consisting of any number of monomeric units. The method uses a scoring function based on a tight coupling between evolutionary conservation, geometry and physico-chemical interactions. Understanding the role of protein complexes in the basic biology of organisms heavily relies on the detection of protein complexes and their structures. Different computational docking methods are developed for this purpose, however, these methods are often not accurate and their results need to be further refined to improve the geometry and the energy of the resulting complexes. Also, despite the fact that complexes in nature often have more than two monomers, most docking methods focus on dimers since the computational complexity increases exponentially due to the addition of monomeric units. Our results show that the refinement scheme can efficiently handle complexes with more than two monomers by biasing the results towards complexes with native interactions, filtering out false positive results. Our refined complexes have better IRMSDs with respect to the known complexes and lower energies than those initial docked structures. Evolutionary conservation information allows us to bias our results towards possible functional interfaces, and the probabilistic selection scheme helps us to escape local energy minima. We aim to incorporate our refinement method in a larger framework which also enables docking of multimeric complexes given only monomeric structures.

New generation of docking programs: Supercomputer validation of force fields and quantum-chemical methods for docking.

PubMed

Sulimov, Alexey V; Kutov, Danil C; Katkova, Ekaterina V; Ilin, Ivan S; Sulimov, Vladimir B

2017-11-01

Discovery of new inhibitors of the protein associated with a given disease is the initial and most important stage of the whole process of the rational development of new pharmaceutical substances. New inhibitors block the active site of the target protein and the disease is cured. Computer-aided molecular modeling can considerably increase effectiveness of new inhibitors development. Reliable predictions of the target protein inhibition by a small molecule, ligand, is defined by the accuracy of docking programs. Such programs position a ligand in the target protein and estimate the protein-ligand binding energy. Positioning accuracy of modern docking programs is satisfactory. However, the accuracy of binding energy calculations is too low to predict good inhibitors. For effective application of docking programs to new inhibitors development the accuracy of binding energy calculations should be higher than 1kcal/mol. Reasons of limited accuracy of modern docking programs are discussed. One of the most important aspects limiting this accuracy is imperfection of protein-ligand energy calculations. Results of supercomputer validation of several force fields and quantum-chemical methods for docking are presented. The validation was performed by quasi-docking as follows. First, the low energy minima spectra of 16 protein-ligand complexes were found by exhaustive minima search in the MMFF94 force field. Second, energies of the lowest 8192 minima are recalculated with CHARMM force field and PM6-D3H4X and PM7 quantum-chemical methods for each complex. The analysis of minima energies reveals the docking positioning accuracies of the PM7 and PM6-D3H4X quantum-chemical methods and the CHARMM force field are close to one another and they are better than the positioning accuracy of the MMFF94 force field. Copyright © 2017 Elsevier Inc. All rights reserved.

Bypass control valve seal and bearing life cycle test report

NASA Technical Reports Server (NTRS)

Lundback, A. V.

1972-01-01

The operating characteristics of a bypass control valve seal and bearing life cycle tests are reported. Data from the initial assembly, leak, torque, and deflection tests are included along with the cycle life test results and conclusions. The equipment involved was to be used in the nuclear engine for the rocket vehicles program.

International Docking Standard (IDSS) Interface Definition Document (IDD) . E; Revision

NASA Technical Reports Server (NTRS)

Kelly, Sean M.; Cryan, Scott P.

2016-01-01

This International Docking System Standard (IDSS) Interface Definition Document (IDD) is the result of a collaboration by the International Space Station membership to establish a standard docking interface to enable on-orbit crew rescue operations and joint collaborative endeavors utilizing different spacecraft. This IDSS IDD details the physical geometric mating interface and design loads requirements. The physical geometric interface requirements must be strictly followed to ensure physical spacecraft mating compatibility. This includes both defined components and areas that are void of components. The IDD also identifies common design parameters as identified in section 3.0, e.g., docking initial conditions and vehicle mass properties. This information represents a recommended set of design values enveloping a broad set of design reference missions and conditions, which if accommodated in the docking system design, increases the probability of successful docking between different spacecraft. This IDD does not address operational procedures or off-nominal situations, nor does it dictate implementation or design features behind the mating interface. It is the responsibility of the spacecraft developer to perform all hardware verification and validation, and to perform final docking analyses to ensure the needed docking performance and to develop the final certification loads for their application. While there are many other critical requirements needed in the development of a docking system such as fault tolerance, reliability, and environments (e.g. vibration, etc.), it is not the intent of the IDSS IDD to mandate all of these requirements; these requirements must be addressed as part of the specific developer's unique program, spacecraft and mission needs. This approach allows designers the flexibility to design and build docking mechanisms to their unique program needs and requirements. The purpose of the IDSS IDD is to provide basic common design parameters to allow developers to independently design compatible docking systems. The IDSS is intended for uses ranging from crewed to autonomous space vehicles, and from Low Earth Orbit (LEO) to deep-space exploration missions.The purpose of the IDSS IDD is to provide basic common design parameters to allow developers to independently design compatible docking systems. The IDSS is intended for uses ranging from crewed to autonomous space vehicles, and from Low Earth Orbit (LEO) to deep-space exploration missions. The purpose of the IDSS IDD is to provide basic common design parameters to allow developers to independently design compatible docking systems. The IDSS is intended for uses ranging from crewed to autonomous space vehicles, and from Low Earth Orbit (LEO) to deep-space exploration missions.

Machine Vision for Relative Spacecraft Navigation During Approach to Docking

NASA Technical Reports Server (NTRS)

Chien, Chiun-Hong; Baker, Kenneth

2011-01-01

This paper describes a machine vision system for relative spacecraft navigation during the terminal phase of approach to docking that: 1) matches high contrast image features of the target vehicle, as seen by a camera that is bore-sighted to the docking adapter on the chase vehicle, to the corresponding features in a 3d model of the docking adapter on the target vehicle and 2) is robust to on-orbit lighting. An implementation is provided for the case of the Space Shuttle Orbiter docking to the International Space Station (ISS) with quantitative test results using a full scale, medium fidelity mock-up of the ISS docking adapter mounted on a 6-DOF motion platform at the NASA Marshall Spaceflight Center Flight Robotics Laboratory and qualitative test results using recorded video from the Orbiter Docking System Camera (ODSC) during multiple orbiter to ISS docking missions. The Natural Feature Image Registration (NFIR) system consists of two modules: 1) Tracking which tracks the target object from image to image and estimates the position and orientation (pose) of the docking camera relative to the target object and 2) Acquisition which recognizes the target object if it is in the docking camera Field-of-View and provides an approximate pose that is used to initialize tracking. Detected image edges are matched to the 3d model edges whose predicted location, based on the pose estimate and its first time derivative from the previous frame, is closest to the detected edge1 . Mismatches are eliminated using a rigid motion constraint. The remaining 2d image to 3d model matches are used to make a least squares estimate of the change in relative pose from the previous image to the current image. The changes in position and in attitude are used as data for two Kalman filters whose outputs are smoothed estimate of position and velocity plus attitude and attitude rate that are then used to predict the location of the 3d model features in the next image.

Brush Seals for Cryogenic Applications: Performance, Stage Effects, and Preliminary Wear Results in LN2 and LH2

NASA Technical Reports Server (NTRS)

Proctor, Margaret P.; Walker, James F.; Perkins, H. Douglas; Hoopes, Joan F.; Williamson, G. Scott

1996-01-01

Brush seals are compliant contacting seals and have significantly lower leakage than labyrinth seals in gas turbine applications. Their long life and low leakage make them candidates for use in rocket engine turbopumps. Brush seals, 50.8 mm (2 in.) in diameter with a nominal 127-micron (0.005-in.) radial interference, were tested in liquid nitrogen (LN2) and liquid hydrogen (LH2) at shaft speeds up to 35,000 and 65,000 rpm, respectively, and at pressure drops up to 1.21 MPa (175 psid) per brush. A labyrinth seal was also tested in liquid nitrogen to provide a baseline. The LN2 leakage rate of a single brush seal with an initial radial shaft interference of 127 micron (0.005 in.) measured one-half to one-third the leakage rate of a 12-tooth labyrinth seal with a radial clearance of 127 micron (0.005 in.). Two brushes spaced 7.21 micron (0.248 in.) apart leaked about one-half as much as a single brush, and two brushes tightly packed together leaked about three-fourths as much as a single brush. The maximum measured groove depth on the Inconel 718 rotor with a surface finish of 0.81 micron (32 microinch) was 25 micron (0.0010 in.) after 4.3 hr of shaft rotation in liquid nitrogen. The Haynes-25 bristles wore approximately 25 to 76 micron (0.001 to 0.003 in.) under the same conditions. Wear results in liquid hydrogen were significantly different. In liquid hydrogen the rotor did not wear, but the bristle material transferred onto the rotor and the initial 127 micron (0.005 in.) radial interference was consumed. Relatively high leakage rates were measured in liquid hydrogen. More testing is required to verify the leakage performance, to validate and calibrate analysis techniques, and to determine the wear mechanisms. Performance, staging effects, and preliminary wear results are presented.

Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking.

PubMed

Martínez, José Mario; Martínez, Leandro

2003-05-01

Molecular Dynamics is a powerful methodology for the comprehension at molecular level of many chemical and biochemical systems. The theories and techniques developed for structural and thermodynamic analyses are well established, and many software packages are available. However, designing starting configurations for dynamics can be cumbersome. Easily generated regular lattices can be used when simple liquids or mixtures are studied. However, for complex mixtures, polymer solutions or solid adsorbed liquids (for example) this approach is inefficient, and it turns out to be very hard to obtain an adequate coordinate file. In this article, the problem of obtaining an adequate initial configuration is treated as a "packing" problem and solved by an optimization procedure. The initial configuration is chosen in such a way that the minimum distance between atoms of different molecules is greater than a fixed tolerance. The optimization uses a well-known algorithm for box-constrained minimization. Applications are given for biomolecule solvation, many-component mixtures, and interfaces. This approach can reduce the work of designing starting configurations from days or weeks to few minutes or hours, in an automated fashion. Packing optimization is also shown to be a powerful methodology for space search in docking of small ligands to proteins. This is demonstrated by docking of the thyroid hormone to its nuclear receptor. Copyright 2003 Wiley Periodicals, Inc. J Comput Chem 24: 819-825, 2003

76 FR 77467 - Endangered and Threatened Species; Initiation of Status Review for Ribbon Seal

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

... management on ribbon seals; (2) Information on the effects of climate change and sea ice change on the...) Information on the effects of other potential threat factors, including oil and gas exploration and... concern about threats to this species' habitat from climate warming and loss of sea ice. The Petitioner...

Continued development of abradable gas path seals. [for gas turbine engines

NASA Technical Reports Server (NTRS)

Shiembob, L. T.

1975-01-01

Major program objectives were the continued development of NiCrAlY feltmetal and honeycomb systems for knife edge seal applications in the 1144 to 1366 K temperature range, and to initiate abradable seal material evaluation for blade tip seal applications in the 1366 to 1589 K temperature range. Larger fiber size, higher density feltmetal showed greatly improved erosion resistance with a slight reduction in abradability compared to the baseline feltmetal. Pack aluminide coating of the honeycomb extended the oxidation resistance and slightly improved the abradability of this material. Evaluation through selected abradability, erosion and oxidation testing, and pertinent metallography led to selection of a plasma sprayed yttria stabilized zirconia (ZrO2)/CoCrAlY layered system as the system with the most potential to meet the 1589 K requirement for blade tip seals. This system demonstrated structural integrity, erosion resistance, and some degree of abradability.

Thermoconvective flow velocity in a high-speed magnetofluid seal after it has stopped

NASA Astrophysics Data System (ADS)

Krakov, M. S.; Nikiforov, I. V.

2012-09-01

Convective flow is investigated in the high-speed (linear velocity of the shaft seal is more than 1 m/s) magnetofluid shaft seal after it has been stopped. Magnetic fluid is preliminarily heated due to viscous friction in the moving seal. After the shaft has been stopped, nonuniform heated fluid remains under the action of a high-gradient magnetic field. Numerical analysis has revealed that in this situation, intense thermomagnetic convection is initiated. The velocity of magnetic fluid depends on its viscosity. For the fluid with viscosity of 2 × 10-4 m2/s the maximum flow velocity within the volume of magnetic fluid with a characteristic size of 1 mm can attain a value of 10 m/s.

Preliminary Test Results of a Non-Contacting Finger Seal on a Herringbone-Grooved Rotor

NASA Technical Reports Server (NTRS)

Proctor, Margaret P.; Degado, Irebert R.

2008-01-01

Low leakage, non-contacting finger seals have potential to reduce gas turbine engine specific fuel consumption by 2 to 3 percent and to reduce direct operating costs by increasing the time between engine overhauls. A non-contacting finger seal with concentric lift-pads operating adjacent to a test rotor with herringbone grooves was statically tested at 300, 533, and 700 K inlet air temperatures at pressure differentials up to 576 kPa. Leakage flow factors were approximately 70 percent less than state-of-the-art labyrinth seals. Leakage rates are compared to first order predictions. Initial spin tests at 5000 rpm, 300 K inlet air temperature and pressure differentials to 241 kPa produced no measurable wear.

Peptide docking of HIV-1 p24 with single chain fragment variable (scFv) by CDOCKER algorithm

NASA Astrophysics Data System (ADS)

Karim, Hana Atiqah Abdul; Tayapiwatana, Chatchai; Nimmanpipug, Piyarat; Zain, Sharifuddin M.; Rahman, Noorsaadah Abdul; Lee, Vannajan Sanghiran

2014-10-01

In search for the important residues that might have involve in the binding interaction between the p24 caspid protein of HIV-1 fragment (MET68 - PRO90) with the single chain fragment variable (scFv) of FAB23.5, modern computational chemistry approach has been conducted and applied. The p24 fragment was initially taken out from the 1AFV protein molecule consisting of both light (VL) and heavy (VH) chains of FAB23.5 as well as the HIV-1 caspid protein. From there, the p24 (antigen) fragment was made to dock back into the protein pocket receptor (antibody) by using the CDOCKER algorithm to conduct the molecular docking process. The score calculated from the CDOCKER gave 15 possible docked poses with various docked ligand's positions, the interaction energy as well as the binding energy. The best docked pose that imitates the original antigen's position was determined and further processed to the In Situ minimization to obtain the residues interaction energy as well as to observe the hydrogen bonds interaction in the protein-peptide complex. Based on the results demonstrated, the specific residues in the complex that have shown immense lower interaction energies in the 5Å vicinity region from the peptide are from the heavy chain (VH:TYR105) and light chain (VL: ASN31, TYR32, and GLU97). Those residues play vital roles in the binding mechanism of Antibody-Antigen (Ab-Ag) complex of p24 with FAB23.5.

Platelet factor 4 (CXCL4) seals blood clots by altering the structure of fibrin.

PubMed

Amelot, Aymeric A; Tagzirt, Madjid; Ducouret, Guylaine; Kuen, René Lai; Le Bonniec, Bernard F

2007-01-05

Platelet factor-4 (PF4/CXCL4) is an orphan chemokine released in large quantities in the vicinity of growing blood clots. Coagulation of plasma supplemented with a matching amount of PF4 results in a translucent jelly-like clot. Saturating amounts of PF4 reduce the porosity of the fibrin network 4.4-fold and decrease the values of the elastic and loss moduli by 31- and 59-fold, respectively. PF4 alters neither the cleavage of fibrinogen by thrombin nor the cross-linking of protofibrils by activated factor XIII but binds to fibrin and dramatically transforms the structure of the ensuing network. Scanning electron microscopy showed that PF4 gives rise to a previously unreported pattern of polymerization where fibrin assembles to form a sealed network. The subunits constituting PF4 form a tetrahedron having at its corners a RPRH motif that mimics (in reverse orientation) the Gly-His-Arg-Pro-amide peptides that co-crystallize with fibrin. Molecular modeling showed that PF4 could be docked to fibrin with remarkable complementarities and absence of steric clashes, allowing the assembly of irregular polymers. Consistent with this hypothesis, as little as 50 microm the QVRPRHIT peptide derived from PF4 affects the polymerization of fibrin.

Actively Controlled Shaft Seals for Aerospace Applications

NASA Technical Reports Server (NTRS)

Salant, Richard F.; Wolff, Paul

1995-01-01

This study experimentally investigates an actively controlled mechanical seal for aerospace applications. The seal of interest is a gas seal, which is considerably more compact than previous actively controlled mechanical seals that were developed for industrial use. In a mechanical seal, the radial convergence of the seal interface has a primary effect on the film thickness. Active control of the film thickness is established by controlling the radial convergence of the seal interface with a piezoelectric actuator. An actively controlled mechanical seal was initially designed and evaluated using a mathematical model. Based on these results, a seal was fabricated and tested under laboratory conditions. The seal was tested with both helium and air, at rotational speeds up to 3770 rad/sec, and at sealed pressures as high as 1.48 x 10(exp 6) Pa. The seal was operated with both manual control and with a closed-loop control system that used either the leakage rate or face temperature as the feedback. The output of the controller was the voltage applied to the piezoelectric actuator. The seal operated successfully for both short term tests (less than one hour) and for longer term tests (four hours) with a closed-loop control system. The leakage rates were typically 5-15 slm (standard liters per minute), and the face temperatures were generally maintained below 100C. When leakage rate was used as the feedback signal, the setpoint leakage rate was typically maintained within 1 slm. However, larger deviations occurred during sudden changes in sealed pressure. When face temperature was used as the feedback signal, the setpoint face temperature was generally maintained within 3 C, with larger deviations occurring when the sealed pressure changes suddenly. the experimental results were compared to the predictions from the mathematical model. The model was successful in predicting the trends in leakage rate that occurred as the balance ratio and sealed pressure changed, although the leakage rates were not quantitatively predicted with a high degree of accuracy. This model could be useful in providing valuable design information for future actively controlled mechanical seals.

Adherence evaluation of vented chest seals in a swine skin model.

PubMed

Arnaud, Françoise; Maudlin-Jeronimo, Eric; Higgins, Adam; Kheirabadi, Bijan; McCarron, Richard; Kennedy, Daniel; Housler, Greggory

2016-10-01

Perforation of the chest (open pneumothorax) with and without lung injury can cause air accumulation in the chest, positive intrapleural pressure and lead to tension pneumothorax if untreated. The performance of chest seals to prevent tension physiology depends partially on their ability to adhere to the skin and seal the chest wound. Novel non-occlusive vented chest seals were assessed for their adhesiveness on skin of live swine under normal and extreme environmental conditions to simulate austere battlefield conditions. Chest seals were applied on the back of the swine on skin that was soiled by various environmental contaminants to represent battlefield situations. A peeling (horizontal rim peeling) and detachment and breaching (vertical pulling) techniques were used to quantify the adhesive performance of vented chest seals. Among eight initially selected vented seals, five (Bolin, Russell, Fast breathe, Hyfin and SAM) were further down-selected based on their superior adherence scores at ambient temperatures. The adherence of these seals was then assessed after approximately 17h storage at extreme cold (-19.5°C) and hot (71.5°C) temperatures. Adherence scores for peeling (above 90%) and detachment scores (less than 25%) were comparable for four vented chest seals when tested at ambient temperature, except for the Bolin seal which had higher breaching. Under extreme storage temperatures, adherence peeling scores were comparable to those at ambient temperatures for four chest seals. Scores were significantly lower for the Bolin seal at extreme temperatures. This seal also had the highest detachment and breaching scores. In contrast, the Russell, Fast breathe, Hyfin and SAM seals showed similar ability to stay air tight without breaching after hot storage. No significant difference was found in skin adherence of the five vented chest seals at ambient temperature and the four seals (Russell, Fast breathe, Hyfin and SAM) maintained superior adherence even after exposure to extreme temperatures compared to the Bolin. To select the most effective product from the 5 selected vented chest seals, further functional evaluation of the valve of these chest seals on a chest wound with the potential for tension in the pneumothorax or hemopneumothorax is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamic analysis of Apollo-Salyut/Soyuz docking

NASA Technical Reports Server (NTRS)

Schliesing, J. A.

1972-01-01

The use of a docking-system computer program in analyzing the dynamic environment produced by two impacting spacecraft and the attitude control systems is discussed. Performance studies were conducted to determine the mechanism load and capture sensitivity to parametric changes in the initial impact conditions. As indicated by the studies, capture latching is most sensitive to vehicle angular-alinement errors and is least sensitive to lateral-miss error. As proved by load-sensitivity studies, peak loads acting on the Apollo spacecraft are considerably lower than the Apollo design-limit loads.

A modified proportional navigation scheme for rendezvous and docking with tumbling targets: The Planar case

NASA Technical Reports Server (NTRS)

Fitz-Coy, Norman; Liu, Ming-Cheng

1995-01-01

A two-phase proportional navigation scheme is developed for the case of two rigid bodies engaged in a rendezvous/docking maneuver. The target vehicle is nonmaneuvering, but does have constant nonzero angular and linear velocities. Under these conditions, it is shown that previously obtained solutions are not applicable. Analytical solutions are obtained leading to relationships between the transverse and LOS navigation constants. It is shown that the transverse navigation constant for the second phase of the maneuver must be 2. Also, initial conditions necessary for rendezvous are presented.

Automated Rendezvous and Capture System Development and Simulation for NASA

NASA Technical Reports Server (NTRS)

Roe, Fred D.; Howard, Richard T.; Murphy, Leslie

2004-01-01

The United States does not have an Automated Rendezvous and Capture/Docking (AR and C) capability and is reliant on manned control for rendezvous and docking of orbiting spacecraft. This reliance on the labor intensive manned interface for control of rendezvous and docking vehicles has a significant impact on the cost of the operation of the International Space Station (ISS) and precludes the use of any U.S. expendable launch capabilities for Space Station resupply. The Soviets have the capability to autonomously dock in space, but their system produces a hard docking with excessive force and contact velocity. Automated Rendezvous and Capture/Docking has been identified as a key enabling technology for the Space Launch Initiative (SLI) Program, DARPA Orbital Express and other DOD Programs. The development and implementation of an AR&C capability can significantly enhance system flexibility, improve safety, and lower the cost of maintaining, supplying, and operating the International Space Station. The Marshall Space Flight Center (MSFC) has conducted pioneering research in the development of an automated rendezvous and capture (or docking) (AR and C) system for U.S. space vehicles. This AR&C system was tested extensively using hardware-in-the-loop simulations in the Flight Robotics Laboratory, and a rendezvous sensor, the Video Guidance Sensor was developed and successfully flown on the Space Shuttle on flights STS-87 and STS-95, proving the concept of a video- based sensor. Further developments in sensor technology and vehicle and target configuration have lead to continued improvements and changes in AR&C system development and simulation. A new Advanced Video Guidance Sensor (AVGS) with target will be utilized on the Demonstration of Autonomous Rendezvous Technologies (DART) flight experiment in 2004.

Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses.

PubMed

Miki, Takafumi; Kaufmann, Walter A; Malagon, Gerardo; Gomez, Laura; Tabuchi, Katsuhiko; Watanabe, Masahiko; Shigemoto, Ryuichi; Marty, Alain

2017-06-27

Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such "simple synapses" indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Ca v 2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Ca v 2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1-10) and 2.03 at 4 wk (range: 1-4), whereas the mean numbers of Ca v 2.1 clusters were 2.84 at 2 wk (range: 1-8) and 2.37 at 4 wk (range: 1-5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm 2 to 0.0234 μm 2 ), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels.

Applying Pose Clustering and MD Simulations To Eliminate False Positives in Molecular Docking.

PubMed

Makeneni, Spandana; Thieker, David F; Woods, Robert J

2018-03-26

In this work, we developed a computational protocol that employs multiple molecular docking experiments, followed by pose clustering, molecular dynamic simulations (10 ns), and energy rescoring to produce reliable 3D models of antibody-carbohydrate complexes. The protocol was applied to 10 antibody-carbohydrate co-complexes and three unliganded (apo) antibodies. Pose clustering significantly reduced the number of potential poses. For each system, 15 or fewer clusters out of 100 initial poses were generated and chosen for further analysis. Molecular dynamics (MD) simulations allowed the docked poses to either converge or disperse, and rescoring increased the likelihood that the best-ranked pose was an acceptable pose. This approach is amenable to automation and can be a valuable aid in determining the structure of antibody-carbohydrate complexes provided there is no major side chain rearrangement or backbone conformational change in the H3 loop of the CDR regions. Further, the basic protocol of docking a small ligand to a known binding site, clustering the results, and performing MD with a suitable force field is applicable to any protein ligand system.

High pressure rotary piston coal feeder

NASA Technical Reports Server (NTRS)

Gardner, J. F.; Gencsoy, H. T.; Strimbeck, D. C.

1977-01-01

This feeder concept uniquely combines the functions of solids feeding, metering, and pressurization into one compact system. Success with the rotary-piston concept would provide a lower-cost alternative to lock-hopper systems. The design of the feeder is presented, with special emphasis on the difficult problem of seal design. Initial tests will be to check seal performance. Subsequent tests will evaluate solids-feeding ability.

Dynamics of face and annular seals with two-phase flow

NASA Technical Reports Server (NTRS)

Hughes, William F.; Basu, Prithwish; Beatty, Paul A.; Beeler, Richard M.; Lau, Stephen

1989-01-01

A detailed study was made of face and annular seals under conditions where boiling, i.e., phase change of the leaking fluid, occurs within the seal. Many seals operate in this mode because of flashing due to pressure drop and/or heat input from frictional heating. High pressure, water pumps, industrial chemical pumps, and cryogenic pumps are mentioned as a few of many applications. The initial motivation was the LOX-GOX seals for the space shuttle main engine, but the study was expanded to include any face or annular seal where boiling occurs. Some of the distinctive behavior characteristics of two-phase seals were discussed, particularly their axial stability. While two-phase seals probably exhibit instability to disturbances of other degrees of freedom such as wobble, etc., under certain conditions, such analyses are too complex to be treated at present. Since an all liquid seal (with parallel faces) has a neutral axial stiffness curve, and is stabilized axially by convergent coning, other degrees of freedom stability analyses are necessary. However, the axial stability behavior of the two-phase seal is always a consideration no matter how well the seal is aligned and regardless of the speed. Hence, axial stability is thought of as the primary design consideration for two-phase seals and indeed the stability behavior under sub-cooling variations probably overshadows other concerns. The main thrust was the dynamic analysis of axial motion of two-phase face seals, principally the determination of axial stiffness, and the steady behavior of two-phase annular seals. The main conclusions are that seals with two-phase flow may be unstable if improperly balanced. Detailed theoretical analyses of low (laminar) and high (turbulent) leakage seals are presented along with computer codes, parametric studies, and in particular a simplified PC based code that allows for rapid performance prediction. A simplified combined computer code for the performance prediction over the laminar and turbulent ranges of a two-phase seal is described and documented. The analyses, results, and computer codes are summarized.

Creep analysis of solid oxide fuel cell with bonded compliant seal design

NASA Astrophysics Data System (ADS)

Jiang, Wenchun; Zhang, Yucai; Luo, Yun; Gong, J. M.; Tu, S. T.

2013-12-01

Solid oxide fuel cell (SOFC) requires good sealant because it works in harsh conditions (high temperature, thermal cycle, oxidative and reducing gas environments). Bonded compliant seal (BCS) is a new sealing method for planar SOFC. It uses a thin foil metal to bond the window frame and cell, achieving the seal between window frame and cell. At high temperature, a comprehensive evaluation of its creep strength is essential for the adoption of BCS design. In order to characterize the creep behavior, the creep induced by thermal stresses in SOFC with BCS design is simulated by finite element method. The results show that the foil is compressed and large thermal stresses are generated. The initial peak thermal stress is located in the thin foil because the foil acts as a spring stores the thermal stresses by elastic and plastic deformation in itself. Serving at high temperature, initial thermal displacement is partially recovered because of the creep relaxation, which becomes a new discovered advantage for BCS design. It predicts that the failures are likely to happen in the middle of the cell edge and BNi-2 filler metal, because the maximum residual displacement and creep strain are located.

Steam Turbine Flow Path Seals (a Review)

NASA Astrophysics Data System (ADS)

Neuimin, V. M.

2018-03-01

Various types of shroud, diaphragm, and end seals preventing idle leak of working steam are installed in the flow paths of steam turbine cylinders for improving their efficiency. Widely known labyrinth seals are most extensively used in the Russian turbine construction industry. The category of labyrinth seals also includes seals with honeycomb inserts. The developers of seals with honeycomb inserts state that the use of such seals makes it possible to achieve certain gain due to smaller leaks of working fluid and more reliable operation of the system under the conditions in which the rotor rotating parts may rub against the stator elements. However, a positive effect can only be achieved if the optimal design parameters of the honeycomb structure are fulfilled with due regard to the specific features of its manufacturing technology and provided that this structure is applied in a goal-seeking manner in the seals of steam and gas turbines and compressors without degrading their vibration stability. Calculated and preliminary assessments made by experts testify that the replacement of conventional labyrinth seals by seals with honeycomb inserts alone, due to which the radial gaps in the shroud seal can be decreased from 1.5 to 0.5 mm, allows the turbine cylinder efficiency to be increased at the initial stage by approximately 1% with the corresponding gain in the turbine set power output. The use of rectangular-cellular seals may result, according to estimates made by their developers, in a further improvement of turbine efficiency by 0.5-1.0%. The labor input required to fabricate such seals is six to eight times smaller than that to fabricate labyrinth seals with honeycomb inserts. Recent years have seen the turbine construction companies of the United States and Germany advertising the use of abradable (sealing) coatings (borrowed from the gas turbine construction technology) in the turbine designs instead of labyrinth seals. The most efficient performance of such seals in the turbine flow path is achieved with the sealing material-to-blade linear wear ratio equal to 10 : 1. According to estimates of the developers, application of abradable (sealing) coatings to all problem surfaces (resulting in the power output increased by 0.5-1.0%) is economically profitable even if this procedure is carried out under field conditions at a thermal power plant.

Unique Tuft Test Facility Dramatically Reduces Brush Seal Development Costs

NASA Technical Reports Server (NTRS)

Fellenstein, James A.

1997-01-01

Brush seals have been incorporated in the latest turbine engines to reduce leakage and improve efficiency. However, the life of these seals is limited by wear. Studies have shown that optimal sealing characteristics for a brush seal occur before the interference fit between the brush and shaft is excessively worn. Research to develop improved tribopairs (brush and coating) with reduced wear and lower friction has been hindered by the lack of an accurate, low-cost, efficient test methodology. Estimated costs for evaluating a new material combination in an engine company seal test program are on the order of $100,000. To address this need, the NASA Lewis Research Center designed, built, and validated a unique, innovative brush seal tuft tester that slides a single tuft of brush seal wire against a rotating shaft under controlled loads, speeds, and temperatures comparable to those in turbine engines. As an initial screening tool, the brush seal tuft tester can tribologicaly evaluate candidate seal materials for 1/10th the cost of full-scale seal tests. Previous to the development of the brush seal tuft tester facility, most relevant tribological data had been obtained from full-scale seal tests conducted primarily to determine seal leakage characteristics. However, from a tribological point of view, these tests included the confounding effects of varying contact pressures, bristle flaring, high-temperature oxidation, and varying bristle contact angles. These confounding effects are overcome in tuft testing. The interface contact pressures can be either constant or varying depending on the tuft mounting device, and bristle wear can be measured optically with inscribed witness marks. In a recent cooperative program with a U.S. turbine engine manufacturer, five metallic wire candidates were tested against a plasma-sprayed Nichrome-bonded chrome carbide. The wire materials used during this collaboration were either nickel-chrome- or cobaltchrome-based superalloys. These tests corroborated full-scale seal test results and provided insight into previously untested combinations. As the cycle temperature for improved efficiency turbine engines increases, new brush seal materials combinations must be considered. Future brush seal tuft testing will include both metallic and ceramic bristles versus commercial and NASA-developed shaft coatings. The ultimate goal of this work is to expand the current data base so that seal designers can tailor brush seal materials to specific applications.

HSR Overview

NASA Technical Reports Server (NTRS)

Hendricks, R. C.; Steinetz, B. M.

2006-01-01

The leading Aeronautics program within NASA is the High Speed Research Program (HSR). The HSR program's highest priorities are high pay-off technologies for airframe and propulsion systems required for a high speed civil transport (HSCT). These priorities have been developed collaboratively with NASA, FAA and the US Industry (Boeing-McDonnell Douglas, Pratt & Whitney and General Electric). Phase one of the HSR program started on 1990, and concentrated on the environmental challenges of minimizing NOx and noise. The first program goal is to reduce the NOx emission index to less than 5 (Concord NOx index is 20 and is unacceptable), in order to have little impact on the earth's ozone layer. The second goal is to reduce noise levels to FAR Stage 3 (or better), comparable to those of subsonic aircraft (far below the Concorde noise levels that require exemptions form less stringent standards). This requirement greatly impacts the nozzle design increasing its length and complexity and poses unique sealing challenges. Phase two started in 1993 and initiated work on the technologies required for an economical HSCT. Materials technologies under development include a ceramic-matrix-composite combustion liner, lightweight materials for the nozzle, as well long-life turbomachinery disk and blade alloys. Other required materials are being developed under the DOD-IHPTET program, where there is close cooperation. Economic goals translate into the development of technologies for tri-class service, 5000 nautical mile range aircraft with a ticket price no more than 20% over the subsonic ticket price. The potential market could be as large as 1500 aircraft, according to a Boeing study. Technology alone will not enable this airplane, yet without enabling technologies "on the shelf", it will not occur. The HSCT engine will be the largest engine ever built and operate at maximum conditions for long periods of time posing a number of challenges. The HSR engine mission requires that rotating equipment stay at take-off condition temperatures for hours not minutes per flight. Hence rotating equipment and seals must operate for many thousands of hours at extreme temperatures. It is anticipated that the nozzle will be 12 feet long and roughly 4 ft. by 5 ft. in cross-section with a nominal airflow of 800 lbs/sec. The complex function of the nozzle (including an ejector for noise attenuation) combined with long life place new demands on nozzle seal design. Three inlet configurations are under consideration with attendant sealing challenges, as will be illustrated herein. Four of these engines are required to propel a 5000 nautical mile class vehicle which demand that component reliability be at the highest possible level. In response, an HSR seals session was implemented as a part of the 1997-Seals and Secondary Flow Workshop. Overview presentations were given for each of the following areas: inlet, turbomachinery, combustor and nozzle. The HSCT seal issues center on durability and efficiency of rotating equipment seals (including brush seals), structural seals (including rope seals and other advanced concepts), and high-speed bearing and sump seals. Tighter clearances, propulsion system size and thermal requirements represent extremes that challenge the component designers. This document provides an initial step toward defining HSR seal needs. The overview for HSR seal designs includes, defining seal objectives, summarizing sealing and materials requirements, presenting relevant seal cross-sections, and identifying technology needs for the HSR office.

Large-Vessel Sealing in Laparoscopic Colectomy with an Ultrasonic Device

PubMed Central

Plasencia, Gustavo; Van der Speeten, Kurt; Hinoul, Piet; Batiller, Jonathan; Severin, Kimberley S.; Schwiers, Michael L.; Rockall, Tim

2016-01-01

Background and Objective: The Harmonic ACE+7 Shears with Advanced Hemostasis Mode (Ethicon, Somerville, NJ, USA) is an ultrasonic device designed to transect and seal vessels up to 7 mm in diameter. The device applies an algorithm that optimizes ultrasonic energy delivery combined with a longer sealing cycle. The purpose of this study was to assess the initial clinical experience with the Harmonic device by evaluating large-vessel sealing during laparoscopic colectomy in consecutive cases. Methods: This prospective, multicenter, observational series involved 40 adult patients who were to undergo elective laparoscopic colectomy where dissection and transection of the inferior mesenteric artery was indicated. The primary study endpoint was first-pass hemostasis, defined as a single activation of the Advanced Hemostasis Mode to transect and seal the inferior mesenteric artery. The use of any additional energy device or hemostatic product to establish or maintain hemostasis was noted. Patients were observed after surgery for ∼4 weeks for adverse events that were considered to be related to the study procedure or study device. Descriptive statistical analyses were performed for study endpoints. Results: Forty patients underwent the laparoscopic colectomy procedure. First-pass hemostasis of the inferior mesenteric artery was achieved and maintained in all 40 patients, with no required additional hemostatic measures. Exposure of the vessel was reported as skeletonized in 22 of 40 (55%) patients. Mean transection time was 21.9 ± 7.4 s. One adverse event (postoperative anemia) was considered possibly related to the study device. Conclusion: In this initial clinical consecutive series, the device demonstrated successful transection and sealing of the large mesenteric vessels during laparoscopic colorectal surgery. PMID:27186065

Crack - seal veins - what we learnt since the seminal work of John Ramsay

NASA Astrophysics Data System (ADS)

Urai, Janos L.; Bons, Paul D.

2017-04-01

In the nineteen-eighties, John Ramsay and co-workers have laid the basis for much of our current understanding of tectonic veins, by proposing that tectonic veins accrete in many small increments of cracking and sealing, making the link to cyclic stress and fluid pressure cycles and the earthquake cycle, and by proposing that fibrous veins track the opening trajectory, which has created a toolbox to analyse progressive deformation in rocks. They recognised syntaxial and antitaxial veins, which grow depending on the composition of the wall rock and the vein. Following on these seminal contributions, advances in analysing the microstructure and chemical signature in crack-seal veins made a lot of progress, facilitated by the rapid increase in micro analytical tools like cathodeluminescence and EBSD. Initial modelling of crystal growth in crack- seal veins provided an explanation of how crystals become fibrous without being deformed and explained how fibres sometimes do and sometimes don't follow the opening trajectory. This was followed by numerical models of crystal growth to study the development of crystal facets after larger crack increments, and experimental study of the sealing dynamics of syntaxial veins. These models were initially kinematic, using the ELLE microdynamic simulation package, and more recently incorporating the physics of the growing interface using the Phase Field method, which now allows 3D simulation of both syntaxial and antitaxial veins and can simultaneously compute the evolving permeability of the crack using Lattice Boltzmann techniques. Parallel to these developments we developed an understanding of the strength of the vein cement, and, using Discrete Element Techniques, explored the effects of differences of the strength of the vein and its adhesion to the wall rock on fracture patterns in crack-seal systems in changing stress fields. This presentation will review these developments, showing how the ideas of John Ramsay inspired follow up work leading to a much better understanding of the complex feedback systems between fracture growth, crystal growth and fluid flow in crack-seal systems.

Carbon dioxide sequestration induced mineral precipitation healing of fractured reservoir seals

NASA Astrophysics Data System (ADS)

Welch, N.; Crawshaw, J.

2017-12-01

Initial experiments and the thermodynaic basis for carbon dioxide sequestration induced mineral precipitation healing of fractures through reservoir seals will be presented. The basis of this work is the potential exists for the dissolution of reservoir host rock formation carbonate minerals in the acidified injection front of CO2 during sequestration or EOR. This enriched brine and the bulk CO2 phase will then flow through the reservoir until contact with the reservoir seal. At this point any fractures present in the reservoir seal will be the preferential flow path for the bulk CO2 phase as well as the acidified brine front. These fractures would currently be filled with non-acidified brine saturated in seal formation brine. When the acidifeid brine from the host formation and the cap rock brine mix there is the potential for minerals to fall out of solution, and for these precipitated minerals to decrease or entirely cut off the fluid flow through the fractures present in a reservoir seal. Initial equilibrium simulations performed using the PHREEQC1 database drived from the PHREEQE2 database are used to show the favorable conditions under which this mineral precipitation can occurs. Bench scale fluid mixing experiments were then performed to determine the kinetics of the mineral precipitation process, and determine the progress of future experiemnts involving fluid flow within fractured anhydrite reservoir seal samples. 1Parkhurst, D.L., and Appelo, C.A.J., 2013, Description of input and examples for PHREEQC version 3—A computer program for speciation, batch-reaction, one-dimensional transport, and inverse geochemical calculations: U.S. Geological Survey Techniques and Methods, book 6, chap. A43, 497 p., available only at https://pubs.usgs.gov/tm/06/a43/. 2Parkhurst, David L., Donald C. Thorstenson, and L. Niel Plummer. PHREEQE: a computer program for geochemical calculations. No. 80-96. US Geological Survey, Water Resources Division,, 1980.

Gemini Simulator and Neil Armstrong

NASA Image and Video Library

1963-11-06

Astronaut Neil Armstrong (left) was one of 14 astronauts, 8 NASA test pilots, and 2 McDonnell test pilots who took part in simulator studies. Armstrong was the first astronaut to participate (November 6, 1963). A.W. Vogeley described the simulator in his paper "Discussion of Existing and Planned Simulators For Space Research," "Many of the astronauts have flown this simulator in support of the Gemini studies and they, without exception, appreciated the realism of the visual scene. The simulator has also been used in the development of pilot techniques to handle certain jet malfunctions in order that aborts could be avoided. In these situations large attitude changes are sometimes necessary and the false motion cues that were generated due to earth gravity were somewhat objectionable; however, the pilots were readily able to overlook these false motion cues in favor of the visual realism." Roy F. Brissenden, noted in his paper "Initial Operations with Langley's Rendezvous Docking Facility," "The basic Gemini control studies developed the necessary techniques and demonstrated the ability of human pilots to perform final space docking with the specified Gemini-Agena systems using only visual references. ... Results... showed that trained astronauts can effect the docking with direct acceleration control and even with jet malfunctions as long as good visual conditions exist.... Probably more important than data results was the early confidence that the astronauts themselves gained in their ability to perform the maneuver in the ultimate flight mission." Francis B. Smith, noted in his paper "Simulators for Manned Space Research," "Some major areas of interest in these flights were fuel requirements, docking accuracies, the development of visual aids to assist alignment of the vehicles, and investigation of alternate control techniques with partial failure modes. However, the familiarization and confidence developed by the astronaut through flying and safely docking the simulator during these tests was one of the major contributions. For example, it was found that fuel used in docking from 200 feet typically dropped from about 20 pounds to 7 pounds after an astronaut had made a few training flights." -- Published in Barton C. Hacker and James M. Grimwood, On the Shoulders of Titans: A History of Project Gemini, NASA SP-4203; A.W. Vogeley, "Discussion of Existing and Planned Simulators For Space Research," Paper presented at the Conference on the Role of Simulation in Space Technology, August 17-21, 1964; Roy F. Brissenden, "Initial Operations with Langley's Rendezvous Docking Facility," Langley Working Paper, LWP-21, 1964; Francis B. Smith, "Simulators for Manned Space Research," Paper presented at the 1966 IEEE International convention, March 21-25, 1966.

A flexible docking scheme to explore the binding selectivity of PDZ domains.

PubMed

Gerek, Z Nevin; Ozkan, S Banu

2010-05-01

Modeling of protein binding site flexibility in molecular docking is still a challenging problem due to the large conformational space that needs sampling. Here, we propose a flexible receptor docking scheme: A dihedral restrained replica exchange molecular dynamics (REMD), where we incorporate the normal modes obtained by the Elastic Network Model (ENM) as dihedral restraints to speed up the search towards correct binding site conformations. To our knowledge, this is the first approach that uses ENM modes to bias REMD simulations towards binding induced fluctuations in docking studies. In our docking scheme, we first obtain the deformed structures of the unbound protein as initial conformations by moving along the binding fluctuation mode, and perform REMD using the ENM modes as dihedral restraints. Then, we generate an ensemble of multiple receptor conformations (MRCs) by clustering the lowest replica trajectory. Using ROSETTALIGAND, we dock ligands to the clustered conformations to predict the binding pose and affinity. We apply this method to postsynaptic density-95/Dlg/ZO-1 (PDZ) domains; whose dynamics govern their binding specificity. Our approach produces the lowest energy bound complexes with an average ligand root mean square deviation of 0.36 A. We further test our method on (i) homologs and (ii) mutant structures of PDZ where mutations alter the binding selectivity. In both cases, our approach succeeds to predict the correct pose and the affinity of binding peptides. Overall, with this approach, we generate an ensemble of MRCs that leads to predict the binding poses and specificities of a protein complex accurately.

A flexible docking scheme to explore the binding selectivity of PDZ domains

PubMed Central

Gerek, Z Nevin; Ozkan, S Banu

2010-01-01

Modeling of protein binding site flexibility in molecular docking is still a challenging problem due to the large conformational space that needs sampling. Here, we propose a flexible receptor docking scheme: A dihedral restrained replica exchange molecular dynamics (REMD), where we incorporate the normal modes obtained by the Elastic Network Model (ENM) as dihedral restraints to speed up the search towards correct binding site conformations. To our knowledge, this is the first approach that uses ENM modes to bias REMD simulations towards binding induced fluctuations in docking studies. In our docking scheme, we first obtain the deformed structures of the unbound protein as initial conformations by moving along the binding fluctuation mode, and perform REMD using the ENM modes as dihedral restraints. Then, we generate an ensemble of multiple receptor conformations (MRCs) by clustering the lowest replica trajectory. Using RosettaLigand, we dock ligands to the clustered conformations to predict the binding pose and affinity. We apply this method to postsynaptic density-95/Dlg/ZO-1 (PDZ) domains; whose dynamics govern their binding specificity. Our approach produces the lowest energy bound complexes with an average ligand root mean square deviation of 0.36 Å. We further test our method on (i) homologs and (ii) mutant structures of PDZ where mutations alter the binding selectivity. In both cases, our approach succeeds to predict the correct pose and the affinity of binding peptides. Overall, with this approach, we generate an ensemble of MRCs that leads to predict the binding poses and specificities of a protein complex accurately. PMID:20196074

[Study on anti-hyperlipidemia mechanism of high frequency herb pairs by molecular docking method].

PubMed

Jiang, Lu-di; He, Yu-su; Chen, Xi; Tao, Ou; Li, Gong-Yu; Zhang, Yan-ling

2015-06-01

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.

Enhancing the Effects of Teacher Attunement to Student Peer Group Affiliations on the School Social-Affective Context: Promotive Effects of the SEALS Intervention

ERIC Educational Resources Information Center

Hamm, Jill V.

2011-01-01

The purpose of this study was to examine teachers' attunement to student peer group affiliations as a factor in students' experiences of the school social-affect context. First, the author and her colleagues hypothesize that teacher attunement will be greater in intervention versus control schools following initial SEALS training. Second, they…

Sealing vessels up to 7 mm in diameter solely with ultrasonic technology.

PubMed

Timm, Richard W; Asher, Ryan M; Tellio, Karalyn R; Welling, Alissa L; Clymer, Jeffrey W; Amaral, Joseph F

2014-01-01

Ultrasonic energy is a mainstay in the armamentarium of surgeons, providing multifunctionality, precision, and control when dissecting and sealing vessels up to 5 mm in diameter. Historically, the inability to seal vessels in the 5-7 mm range has been perceived as an inherent limitation of ultrasonic technology. The purpose of this study was to evaluate sealing of vessels up to 7 mm in diameter with an ultrasonic device that modulates energy delivery during the sealing period. In ex vivo benchtop and in vivo acute and survival preclinical models, a new ultrasonic device, Harmonic ACE(®)+7 Shears (Harmonic 7), was compared with advanced bipolar devices in sealing vessels 1-7 mm in diameter with respect of burst pressure, seal reliability, and seal durability. Lateral thermal damage and transection time were also evaluated. Ex vivo tests of Harmonic 7 demonstrated significantly greater median burst pressures than an advanced bipolar device both for vessels <5 mm in diameter (1,078 mmHg and 836 mmHg, respectively, P=0.046) and for those in the range of 5-7 mm (1,419 mmHg and 591 mmHg, P<0.001). In vivo tests in porcine and caprine models demonstrated similar rates of hemostasis between Harmonic 7 and advanced bipolar devices, with high success rates at initial transection and seal durability of 100% after a 30-day survival period. Sealing 5-7 mm vessels is not a limitation of the type of energy used but of how energy is delivered to tissue. These studies document the ability of ultrasonic energy alone to reliably seal large vessels 5-7 mm in diameter, with significantly greater burst pressure observed in in vitro studies than those observed with an advanced bipolar technology when energy delivery is modulated during the sealing cycle. Furthermore, the seals created in 5-7 mm vessels are shown to be reliable and durable in in vivo preclinical studies.

Development of a plasma sprayed ceramic gas path seal for high pressure turbine applications

NASA Technical Reports Server (NTRS)

Shiembob, L. T.

1977-01-01

The plasma sprayed graded layered yittria stabilized zirconia (ZrO2)/metal(CoCrAlY) seal system for gas turbine blade tip applications up to 1589 K (2400 F) seal temperatures was studied. Abradability, erosion, and thermal fatigue characteristics of the graded layered system were evaluated by rig tests. Satisfactory abradability and erosion resistance was demonstrated. Encouraging thermal fatigue tolerance was shown. Initial properties for the plasma sprayed materials in the graded, layered seal system was obtained, and thermal stress analyses were performed. Sprayed residual stresses were determined. Thermal stability of the sprayed layer materials was evaluated at estimated maximum operating temperatures in each layer. Anisotropic behavior in the layer thickness direction was demonstrated by all layers. Residual stresses and thermal stability effects were not included in the analyses. Analytical results correlated reasonably well with results of the thermal fatigue tests. Analytical application of the seal system to a typical gas turbine engine application predicted performance similar to rig specimen thermal fatigue performance. A model for predicting crack propagation in the sprayed ZrO2/CoCrAlY seal system was proposed, and recommendations for improving thermal fatigue resistance were made. Seal system layer thicknesses were analytically optimized to minimize thermal stresses in the abradability specimen during thermal fatigue testing. Rig tests on the optimized seal configuration demonstrated some improvement in thermal fatigue characteristics.

Solubility and bacterial sealing ability of MTA and root-end filling materials.

PubMed

Espir, Camila Galletti; Guerreiro-Tanomaru, Juliane Maria; Spin-Neto, Rubens; Chávez-Andrade, Gisselle Moraima; Berbert, Fabio Luiz Camargo Villela; Tanomaru-Filho, Mario

2016-04-01

Objective To evaluate solubility and sealing ability of Mineral Trioxide Aggregate (MTA) and root-end filling materials. Material and Methods The materials evaluated were: MTA, Calcium Silicate Cement with zirconium oxide (CSC/ZrO2), and zinc oxide/eugenol (ZOE). Solubility test was performed according to ANSI/ADA. The difference between initial and final mass of the materials was analyzed after immersion in distilled water for 7 and 30 days. Retrograde cavities in human teeth with single straight root canal were performed by using ultrasonic tip CVD 9.5107-8. The cavities were filled with the evaluated materials to evaluate sealing ability using the bacterial leakage test with Enterococcus faecalis. Bacterial leakage was evaluated every 24 hours for six weeks observing the turbidity of Brain Heart infusion (BHI) medium in contact with root apex. Data were submitted to ANOVA followed by Tukey tests (solubility), and Kruskal-Wallis and Dunn tests (sealing ability) at a 5% significance level. Results For the 7-day period, ZOE presented highest solubility when compared with the other groups (p<0.05). For the 30-day period, no difference was observed among the materials. Lower bacterial leakage was observed for MTA and CSC/ZrO2, and both presented better results than ZOE (p<0.05). Conclusion MTA and CSC/ZrO2 presented better bacterial sealing capacity, which may be related to lower initial solubility observed for these materials in relation to ZOE.

MSFC Three Point Docking Mechanism design review

NASA Technical Reports Server (NTRS)

Schaefer, Otto; Ambrosio, Anthony

1992-01-01

In the next few decades, we will be launching expensive satellites and space platforms that will require recovery for economic reasons, because of initial malfunction, servicing, repairs, or out of a concern for post lifetime debris removal. The planned availability of a Three Point Docking Mechanism (TPDM) is a positive step towards an operational satellite retrieval infrastructure. This study effort supports NASA/MSFC engineering work in developing an automated docking capability. The work was performed by the Grumman Space & Electronics Group as a concept evaluation/test for the Tumbling Satellite Retrieval Kit. Simulation of a TPDM capture was performed in Grumman's Large Amplitude Space Simulator (LASS) using mockups of both parts (the mechanism and payload). Similar TPDM simulation activities and more extensive hardware testing was performed at NASA/MSFC in the Flight Robotics Laboratory and Space Station/Space Operations Mechanism Test Bed (6-DOF Facility).

Autonomous rendezvous and docking: A commercial approach to on-orbit technology validation

NASA Technical Reports Server (NTRS)

Tchoryk, Peter, Jr.; Whitten, Raymond P.

1991-01-01

SpARC, in conjunction with its corporate affiliates, is planning an on-orbit validation of autonomous rendezvous and docking (ARD) technology. The emphasis in this program is to utilize existing technology and commercially available components wherever possible. The primary subsystems to be validated by this demonstration include GPS receivers for navigation, a video-based sensor for proximity operations, a fluid connector mechanism to demonstrate fluid resupply capability, and a compliant, single-point docking mechanism. The focus for this initial experiment will be ELV based and will make use of two residual Commercial Experiment Transporter (COMET) service modules. The first COMET spacecraft will be launched in late 1992 and will serve as the target vehicle. After the second COMET spacecraft has been launched in late 1994, the ARD demonstration will take place. The service module from the second COMET will serve as the chase vehicle.

Molecular docking and 3D-QSAR studies on triazolinone and pyridazinone, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

PubMed

Sivan, Sree Kanth; Manga, Vijjulatha

2010-06-01

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of the HIV-1 reverse transcriptase. Recently a series of Triazolinone and Pyridazinone were reported as potent inhibitors of HIV-1 wild type reverse transcriptase. In the present study, docking and 3D quantitative structure activity relationship (3D QSAR) studies involving comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on 31 molecules. Ligands were built and minimized using Tripos force field and applying Gasteiger-Hückel charges. These ligands were docked into protein active site using GLIDE 4.0. The docked poses were analyzed; the best docked poses were selected and aligned. CoMFA and CoMSIA fields were calculated using SYBYL6.9. The molecules were divided into training set and test set, a PLS analysis was performed and QSAR models were generated. The model showed good statistical reliability which is evident from the r2 nv, q2 loo and r2 pred values. The CoMFA model provides the most significant correlation of steric and electrostatic fields with biological activities. The CoMSIA model provides a correlation of steric, electrostatic, acceptor and hydrophobic fields with biological activities. The information rendered by 3D QSAR model initiated us to optimize the lead and design new potential inhibitors.

Seal Formation Mechanism Beneath Animal Waste Holding Ponds

NASA Astrophysics Data System (ADS)

Cihan, A.; Tyner, J. S.; Wright, W. C.

2005-12-01

Infiltration of animal waste from holding ponds can cause contamination of groundwater. Typically, the initial flux from a pond decreases rapidly as a seal of animal waste particulates is deposited at the base of the pond. The purpose of this study was to investigate the mechanism of the seal formation. Twenty-four soil columns (10-cm diameter by 43-cm long) were hand-packed with sand, silty loam or clay soils. A 2.3 m column of dairy or swine waste was applied to the top of the each column. The leakage rate from each column was measured with respect to time to analyze the effect of seal formation on different soil textures and animal waste types. We tested our hypothesis that seal growth and the subsequent decrease of leachate production adheres to a filter cake growth model. Said model predicts that the cumulative leakage rate is proportional to the square root of time and to the square root of the height of the waste.

Spectrophotometric studies on the interaction between (-)-epigallocatechin gallate and lysozyme

NASA Astrophysics Data System (ADS)

Ghosh, Kalyan Sundar; Sahoo, Bijaya Ketan; Dasgupta, Swagata

2008-02-01

Various reported antibacterial activities of (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea prompted us to study its binding with lysozyme. This has been investigated by fluorescence, circular dichroism (CD) and protein-ligand docking. The binding parameters were determined using a modified Stern-Volmer equation. The thermodynamic parameters are indicative of an initial hydrophobic association. The complex is, however, held together predominantly by van der Waals interactions and hydrogen bonding. CD studies do not indicate any significant changes in the secondary structure of lysozyme. Docking studies revealed that specific interactions are observed with residues Trp 62 and Trp 63.

Efficiency of a borehole seal by means of pre-compacted bentonite blocks

NASA Astrophysics Data System (ADS)

Van Geet, M.; Volckaert, G.; Bastiaens, W.; Maes, N.; Weetjens, E.; Sillen, X.; Vallejan, B.; Gens, A.

The backfilling and sealing of shafts and galleries is an essential part of the design of underground repositories for high-level radioactive waste. Part of the EC funded project RESEAL studied the feasibility of sealing off a borehole in plastic Boom Clay by means of pre-compacted bentonite blocks. Two bentonites, namely the FoCa and Serrata clay, have been used. Based on laboratory tests, the bentonite blocks had an initial dry density of about 1.8 g/cm 3 to obtain a swelling pressure of about 4.4 MPa, corresponding to the in situ lithostatic stress, at full saturation. The set-up was equipped with several sensors to follow-up the behaviour of the seal and the surrounding host rock during hydration. Full saturation was reached after five months and was mainly reached by natural hydration. Swelling pressure was lower than originally foreseen due to the slow reconsolidation of the host rock. Later on, the efficiency of the seal with respect to water, gas and radionuclide migration was tested. The in situ measured permeability of the seals was about 5 × 10 -13 m/s. A gas breakthrough experiment did not show any preferential gas migration through the seal. No evidences of a preferential pathway could be detected from 125I tracer test results.

A Ground Testbed to Advance US Capability in Autonomous Rendezvous and Docking Project

NASA Technical Reports Server (NTRS)

D'Souza, Chris

2014-01-01

This project will advance the Autonomous Rendezvous and Docking (AR&D) GNC system by testing it on hardware, particularly in a flight processor, with a goal of testing it in IPAS with the Waypoint L2 AR&D scenario. The entire Agency supports development of a Commodity for Autonomous Rendezvous and Docking (CARD) as outlined in the Agency-wide Community of Practice whitepaper entitled: "A Strategy for the U.S. to Develop and Maintain a Mainstream Capability for Automated/Autonomous Rendezvous and Docking in Low Earth Orbit and Beyond". The whitepaper establishes that 1) the US is in a continual state of AR&D point-designs and therefore there is no US "off-the-shelf" AR&D capability in existence today, 2) the US has fallen behind our foreign counterparts particularly in the autonomy of AR&D systems, 3) development of an AR&D commodity is a national need that would benefit NASA, our commercial partners, and DoD, and 4) an initial estimate indicates that the development of a standardized AR&D capability could save the US approximately $60M for each AR&D project and cut each project's AR&D flight system implementation time in half.

Molecular docking, 3D QSAR and dynamics simulation studies of imidazo-pyrrolopyridines as janus kinase 1 (JAK 1) inhibitors.

PubMed

Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

2016-10-01

Janus kinase 1 (JAK 1) plays a critical role in initiating responses to cytokines by the JAK-signal transducer and activator of transcription (JAK-STAT). This controls survival, proliferation and differentiation of a variety of cells. Docking, 3D quantitative structure activity relationship (3D-QSAR) and molecular dynamics (MD) studies were performed on a series of Imidazo-pyrrolopyridine derivatives reported as JAK 1 inhibitors. QSAR model was generated using 30 molecules in the training set; developed model showed good statistical reliability, which is evident from r 2 ncv and r 2 loo values. The predictive ability of this model was determined using a test set of 13 molecules that gave acceptable predictive correlation (r 2 Pred ) values. Finally, molecular dynamics simulation was performed to validate docking results and MM/GBSA calculations. This facilitated us to compare binding free energies of cocrystal ligand and newly designed molecule R1. The good concordance between the docking results and CoMFA/CoMSIA contour maps afforded obliging clues for the rational modification of molecules to design more potent JAK 1 inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

An investigation of the impact of Melbourne Zoo's "Seal-the-Loop" donate call-to-action on visitor satisfaction and behavior.

PubMed

Mellish, Sarah; Sanders, Ben; Litchfield, Carla A; Pearson, Elissa L

2017-05-01

Modern zoos are uniquely positioned to educate the public about environmental issues and promote conservation action. This report investigates the introduction of a donation request during an interactive fur seal presentation (as part of Melbourne Zoo's "Seal-the-Loop" initiative) on visitor satisfaction, perceptions of donation as a way to help wild fur seals, and donation behaviors. Comparisons are made between three groups surveyed upon exit: (1) viewed the interactive fur seal presentation prior to the donation request implementation (pledge-presentation: N = 86; see Mellish, Pearson, Sanders, and Litchfield []; International Zoo Yearbook 129:129-154); (2) viewed the interactive fur seal presentation including the donation request (donate-presentation: N = 82); and (3) viewed the fur seal exhibit and donation point but not the presentation and were not directly asked to make a donation (donate-exhibit: N = 82). Findings demonstrate visitor satisfaction with the interactive fur seal presentation was not negatively impacted following the implementation of the donate request (with >92% of pledge-presentation and donate-presentation visitors providing a "satisfied" or "very satisfied" rating). Only the donate-presentation visitors reported donation as a conservation action to help wild fur seals (19.18%; 0% for pledge-presentation visitors). While both donate-exhibit (39.51%) and donate-presentation visitors (60.75%) self-reported making donations or intending to do so, donation behavior was significantly increased for visitors who had viewed the fur seal presentation. Findings provide preliminary support that zoos may utilize interactive educational presentations to effectively ask visitors for donations to support specific conservation projects, without negatively impacting on satisfaction and with a relatively high level of visitor engagement. © 2017 Wiley Periodicals, Inc.

The Eco-Hydrological Role of Physical Surface Sealing in Dry Environments

NASA Astrophysics Data System (ADS)

Sela, Shai; Svoray, Tal; Assouline, Shmuel

2016-04-01

Soil surface sealing is a widespread natural process in dry environments occurring frequently in bare soil areas between vegetation patches. The low hydraulic conductivity that characterizes the seal layer reduces both infiltration and evaporation fluxes from the soil, and thus has the potential to affect local vegetation water availability and consequently transpiration rates. This effect is investigated here using two separate physically based models - a runoff model, and a root water uptake model. High resolution rainfall data is used to demonstrate the seal layer effect on runoff generation and vegetation water availability, while the seal layer effect on vegetation water uptake is studied using a long-term climatic dataset (44 years) from three dry sites presenting a climatic gradient in the Negev Desert, Israel. The Feddes water uptake parameters for the dominant shrub at the study site (Sarcopoterium spinosum) were acquired using an inverse calibration procedure using data from a lysimeter experiment. The results indicate that the presence of surface sealing increases significantly vegetation water availability through runoff generation. Following water infiltration, the shrub transpiration generally increases if the shrub is surrounded by a seal layer, but this effect can switch from positive to negative depending on initial soil water content, rainfall intensity, and the duration of the subsequent drying intervals. These factors have a marked effect on inter-annual variability of the seal layer effect on the shrub transpiration, which on average was found to be 26% higher under sealed conditions than in the case of unsealed soil surfaces. These results shed light on the importance of surface sealing on the eco-hydrology of dry environments and its contribution to the resilience of woody vegetation.

1999 NASA Seal/Secondary Air System Workshop

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Hendricks, Robert C.

2000-01-01

NASA Glenn hosted the Seals/Secondary Air System Workshop on October 2829, 1999. Each year NASA and our industry and university partners share their respective seal technology development. We use these workshops as a technical forum to exchange recent advancements and "lessons-learned" in advancing seal technology and solving problems of common interest. As in the past we are publishing two volumes. Volume 1 will be publicly available and will be made available on-line through the web page address listed at the end of this chapter. Volume 2 will be restricted under International Traffic and Arms Regulations (I.T.A.R.) In this conference participants gained an appreciation of NASA's new Ultra Efficient Engine Technology (UEET) program and how this program will be partnering with ongoing DOE -industrial power production and DOD- military aircraft engine programs. In addition to gaining a deeper understanding into sealing advancements and challenges that lie ahead, participants gained new working and personal relationships with the attendees. When the seals and secondary fluid management program was initiated, the emphasis was on rocket engines with spinoffs to gas turbines. Today, the opposite is true and we are, again building our involvement in the rocket engine and space vehicle demonstration programs.

Performance of MDockPP in CAPRI rounds 28-29 and 31-35 including the prediction of water-mediated interactions.

PubMed

Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Ma, Zhiwei; Grinter, Sam Z; Zou, Xiaoqin

2017-03-01

Protein-protein interactions are either through direct contacts between two binding partners or mediated by structural waters. Both direct contacts and water-mediated interactions are crucial to the formation of a protein-protein complex. During the recent CAPRI rounds, a novel parallel searching strategy for predicting water-mediated interactions is introduced into our protein-protein docking method, MDockPP. Briefly, a FFT-based docking algorithm is employed in generating putative binding modes, and an iteratively derived statistical potential-based scoring function, ITScorePP, in conjunction with biological information is used to assess and rank the binding modes. Up to 10 binding modes are selected as the initial protein-protein complex structures for MD simulations in explicit solvent. Water molecules near the interface are clustered based on the snapshots extracted from independent equilibrated trajectories. Then, protein-ligand docking is employed for a parallel search for water molecules near the protein-protein interface. The water molecules generated by ligand docking and the clustered water molecules generated by MD simulations are merged, referred to as the predicted structural water molecules. Here, we report the performance of this protocol for CAPRI rounds 28-29 and 31-35 containing 20 valid docking targets and 11 scoring targets. In the docking experiments, we predicted correct binding modes for nine targets, including one high-accuracy, two medium-accuracy, and six acceptable predictions. Regarding the two targets for the prediction of water-mediated interactions, we achieved models ranked as "excellent" in accordance with the CAPRI evaluation criteria; one of these two targets is considered as a difficult target for structural water prediction. Proteins 2017; 85:424-434. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Autonomous Vision-Based Tethered-Assisted Rover Docking

NASA Technical Reports Server (NTRS)

Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

2013-01-01

Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

Underwater and surface behavior of homing juvenile northern elephant seals.

PubMed

Matsumura, Moe; Watanabe, Yuuki Y; Robinson, Patrick W; Miller, Patrick J O; Costa, Daniel P; Miyazaki, Nobuyuki

2011-02-15

Northern elephant seals, Mirounga angustirostris, travel between colonies along the west coast of North America and foraging areas in the North Pacific. They also have the ability to return to their home colony after being experimentally translocated. However, the mechanisms of this navigation are not known. Visual information could serve an important role in navigation, either primary or supplementary. We examined the role of visual cues in elephant seal navigation by translocating three seals and recording their heading direction continuously using GPS, and acceleration and geomagnetic data loggers while they returned to the colony. The seals first reached the coast and then proceeded to the colony by swimming along the coast. While underwater the animals exhibited a horizontally straight course (mean net-to-gross displacement ratio=0.94±0.02). In contrast, while at the surface they changed their headings up to 360 deg. These results are consistent with the use of visual cues for navigation to the colony. The seals may visually orient by using landmarks as they swim along the coast. We further assessed whether the seals could maintain a consistent heading while underwater during drift dives where one might expect that passive spiraling during drift dives could cause disorientation. However, seals were able to maintain the initial course heading even while underwater during drift dives where there was spiral motion (to within 20 deg). This behavior may imply the use of non-visual cues such as acoustic signals or magnetic fields for underwater orientation.

C2 Domain of Protein Kinase Cα: Elucidation of the Membrane Docking Surface by Site-Directed Fluorescence and Spin Labeling†

PubMed Central

Kohout, Susy C.; Corbalán-García, Senena; Gómez-Fernández, Juan C.; Falke, Joseph J.

2013-01-01

The C2 domain is a conserved signaling motif that triggers membrane docking in a Ca2+-dependent manner, but the membrane docking surfaces of many C2 domains have not yet been identified. Two extreme models can be proposed for the docking of the protein kinase Cα (PKCα) C2 domain to membranes. In the parallel model, the membrane-docking surface includes the Ca2+ binding loops and an anion binding site on β-strands 3–4, such that the β-strands are oriented parallel to the membrane. In the perpendicular model, the docking surface is localized to the Ca2+ binding loops and the β-strands are oriented perpendicular to the membrane surface. The present study utilizes site-directed fluorescence and spin-labeling to map out the membrane docking surface of the PKCα C2 domain. Single cysteine residues were engineered into 18 locations scattered over all regions of the protein surface, and were used as attachment sites for spectroscopic probes. The environmentally sensitive fluorescein probe identified positions where Ca2+ activation or membrane docking trigger measurable fluorescence changes. Ca2+ binding was found to initiate a global conformational change, while membrane docking triggered the largest fluorescein environmental changes at labeling positions on the three Ca2+ binding loops (CBL), thereby localizing these loops to the membrane docking surface. Complementary EPR power saturation measurements were carried out using a nitroxide spin probe to determine a membrane depth parameter, Φ, for each spin-labeled mutant. Positive membrane depth parameters indicative of membrane insertion were found for three positions, all located on the Ca2+ binding loops: N189 on CBL 1, and both R249 and R252 on CBL 3. In addition, EPR power saturation revealed that five positions near the anion binding site are partially protected from collisions with an aqueous paramagnetic probe, indicating that the anion binding site lies at or near the surface of the headgroup layer. Together, the fluorescence and EPR results indicate that the Ca2+ first and third Ca2+ binding loops insert directly into the lipid headgroup region of the membrane, and that the anion binding site on β-strands 3–4 lies near the headgroups. The data support a model in which the β-strands are tilted toward the parallel orientation relative to the membrane surface. PMID:12564928

Abradable compressor and turbine seals, volume 1. [for turbofan engines

NASA Technical Reports Server (NTRS)

Sundberg, D. V.; Dennis, R. E.; Hurst, L. G.

1979-01-01

The application and advantages of abradable coatings as gas-path seals in a general aviation turbine engine were evaluated for use on the high-pressure compressor, the high-pressure turbine, and the low-pressure turbine shrouds. Topics covered include: (1) the initial selection of candidate materials for interim full-scale engine testing; (2) interim engine testing of the initially selected materials and additional candidate materials; (3) the design of the component required to adapt the hardware to permit full-scale engine testing of the most promising materials; (4) finalization of the fabrication methods used in the manufacture of engine test hardware; and (5) the manufacture of the hardware necessary to support the final full-scale engine tests.

Sealed operation, and circulation and purification of gas in the HARPO TPC

NASA Astrophysics Data System (ADS)

Frotin, M.; Gros, P.; Attié, D.; Bernard, D.; Dauvois, V.; Delbart, A.; Durand, D.; Geerebaert, Y.; Legand, S.; Magnier, P.; Poilleux, P.; Semeniouk, I.

2018-02-01

HARPO is a time projection chamber (TPC) demonstrator of a gamma-ray telescope and polarimeter in the MeV-GeV range, for a future space mission. We present the evolution of the TPC performance over a five month sealed-mode operation, by the analysis of cosmic-ray data, followed by the fast and complete recovery of the initial gas properties using a lightweight gas circulation and purification system.

Autonomous docking ground demonstration (category 3)

NASA Technical Reports Server (NTRS)

Lamkin, Steve L.; Eick, Richard E.; Baxter, James M.; Boyd, M. G.; Clark, Fred D.; Lee, Thomas Q.; Othon, L. T.; Prather, Joseph L.; Spehar, Peter T.; Teders, Rebecca J.

1991-01-01

The NASA Johnson Space Center (JSC) is involved in the development of an autonomous docking ground demonstration. The demonstration combines the technologies, expertise and facilities of the JSC Tracking and Communications Division (EE), Structures and Mechanics Division (ES), and the Navigation, Guidance and Control Division (EG) and their supporting contractors. The autonomous docking ground demonstration is an evaluation of the capabilities of the laser sensor system to support the docking phase (12ft to contact) when operated in conjunction with the Guidance, Navigation and Control Software. The docking mechanism being used was developed for the Apollo Soyuz Test Program. This demonstration will be conducted using the Six-Degrees of Freedom (6-DOF) Dynamic Test System (DTS). The DTS environment simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration the laser sensor will be mounted on the target vehicle and the retroreflectors on the chase vehicle. This arrangement was used to prevent potential damage to the laser. The sensor system. GN&C and 6-DOF DTS will be operated closed-loop. Initial condition to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved. Detailed description of each of the demonstration components (e.g., Sensor System, GN&C, 6-DOF DTS and supporting computer configuration) including their capabilities and limitations will be discussed. A demonstration architecture drawing and photographs of the test configuration will be presented.

Autonomous docking ground demonstration (category 3)

NASA Astrophysics Data System (ADS)

Lamkin, Steve L.; Eick, Richard E.; Baxter, James M.; Boyd, M. G.; Clark, Fred D.; Lee, Thomas Q.; Othon, L. T.; Prather, Joseph L.; Spehar, Peter T.; Teders, Rebecca J.

The NASA Johnson Space Center (JSC) is involved in the development of an autonomous docking ground demonstration. The demonstration combines the technologies, expertise and facilities of the JSC Tracking and Communications Division (EE), Structures and Mechanics Division (ES), and the Navigation, Guidance and Control Division (EG) and their supporting contractors. The autonomous docking ground demonstration is an evaluation of the capabilities of the laser sensor system to support the docking phase (12ft to contact) when operated in conjunction with the Guidance, Navigation and Control Software. The docking mechanism being used was developed for the Apollo Soyuz Test Program. This demonstration will be conducted using the Six-Degrees of Freedom (6-DOF) Dynamic Test System (DTS). The DTS environment simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration the laser sensor will be mounted on the target vehicle and the retroreflectors on the chase vehicle. This arrangement was used to prevent potential damage to the laser. The sensor system. GN&C and 6-DOF DTS will be operated closed-loop. Initial condition to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved. Detailed description of each of the demonstration components (e.g., Sensor System, GN&C, 6-DOF DTS and supporting computer configuration) including their capabilities and limitations will be discussed. A demonstration architecture drawing and photographs of the test configuration will be presented.

An atomistic model for cross-linked HNBR elastomers used in seals

NASA Astrophysics Data System (ADS)

Molinari, Nicola; Sutton, Adrian; Stevens, John; Mostofi, Arash

2015-03-01

Hydrogenated nitrile butadiene rubber (HNBR) is one of the most common elastomeric materials used for seals in the oil and gas industry. These seals sometimes suffer ``explosive decompression,'' a costly problem in which gases permeate a seal at the elevated temperatures and pressures pertaining in oil and gas wells, leading to rupture when the seal is brought back to the surface. The experimental evidence that HNBR and its unsaturated parent NBR have markedly different swelling properties suggests that cross-linking may occur during hydrogenation of NBR to produce HNBR. We have developed a code compatible with the LAMMPS molecular dynamics package to generate fully atomistic HNBR configurations by hydrogenating initial NBR structures. This can be done with any desired degree of cross-linking. The code uses a model of atomic interactions based on the OPLS-AA force-field. We present calculations of the dependence of a number of bulk properties on the degree of cross-linking. Using our atomistic representations of HNBR and NBR, we hope to develop a better molecular understanding of the mechanisms that result in explosive decompression.

Self-Rupturing Hermetic Valve

NASA Technical Reports Server (NTRS)

Tucker, Curtis E., Jr.; Sherrit, Stewart

2011-01-01

For commercial, military, and aerospace applications, low-cost, small, reliable, and lightweight gas and liquid hermetically sealed valves with post initiation on/off capability are highly desirable for pressurized systems. Applications include remote fire suppression, single-use system-pressurization systems, spacecraft propellant systems, and in situ instruments. Current pyrotechnic- activated rupture disk hermetic valves were designed for physically larger systems and are heavy and integrate poorly with portable equipment, aircraft, and small spacecraft and instrument systems. Additionally, current pyrotechnically activated systems impart high g-force shock loads to surrounding components and structures, which increase the risk of damage and can require additional mitigation. The disclosed mechanism addresses the need for producing a hermetically sealed micro-isolation valve for low and high pressure for commercial, aerospace, and spacecraft applications. High-precision electrical discharge machining (EDM) parts allow for the machining of mated parts with gaps less than a thousandth of an inch. These high-precision parts are used to support against pressure and extrusion, a thin hermetically welded diaphragm. This diaphragm ruptures from a pressure differential when the support is removed and/or when the plunger is forced against the diaphragm. With the addition of conventional seals to the plunger and a two-way actuator, a derivative of this design would allow nonhermetic use as an on/off or metering valve after the initial rupturing of the hermetic sealing disk. In addition, in a single-use hermetically sealed isolation valve, the valve can be activated without the use of potential leak-inducing valve body penetrations. One implementation of this technology is a high-pressure, high-flow-rate rupture valve that is self-rupturing, which is advantageous for high-pressure applications such as gas isolation valves. Once initiated, this technology is self-energizing and requires low force compared to current pyrotechnic-based burst disk hermetic valves. This is a novel design for producing a single-use, self-rupturing, hermetically sealed valve for isolation of pressurized gas and/or liquids. This design can also be applied for single-use disposable valves for chemical instruments. A welded foil diaphragm is fully supported by two mated surfaces that are machined to micron accuracies using EDM. To open the valve, one of the surfaces is moved relative to the other to (a) remove the support creating an unsupported diaphragm that ruptures due to over pressure, and/or (b) produce tension in the diaphragm and rupture it.

Assessment of two-phase flow on the chemical alteration and sealing of leakage pathways in cemented wellbores

DOE PAGES

Iyer, Jaisree; Walsh, Stuart D. C.; Hao, Yue; ...

2018-01-08

Wellbore leakage tops the list of perceived risks to the long-term geologic storage of CO 2, because wells provide a direct path between the CO 2 storage reservoir and the atmosphere. In this paper, we have coupled a two-phase flow model with our original framework that combined models for reactive transport of carbonated brine, geochemistry of reacting cement, and geomechanics to predict the permeability evolution of cement fractures. Additionally, this makes the framework suitable for field conditions in geological storage sites, permitting simulation of contact between cement and mixtures of brine and supercritical CO 2. Due to lack of conclusivemore » experimental data, we tried both linear and Corey relative permeability models to simulate flow of the two phases in cement fractures. The model also includes two options to account for the inconsistent experimental observations regarding cement reactivity with two-phase CO 2-brine mixtures. One option assumes that the reactive surface area is independent of the brine saturation and the second option assumes that the reactive surface area is proportional to the brine saturation. We have applied the model to predict the extent of cement alteration, the conditions under which fractures seal, the time it takes to seal a fracture, and the leakage rates of CO 2 and brine when damage zones in the wellbore are exposed to two-phase CO 2-brine mixtures. Initial brine residence time and the initial fracture aperture are critical parameters that affect the fracture sealing behavior. We also evaluated the importance of the model assumptions regarding relative permeability and cement reactivity. These results illustrate the need to understand how mixtures of carbon dioxide and brine flow through fractures and react with cement to make reasonable predictions regarding well integrity. For example, a reduction in the cement reactivity with two-phase CO 2-brine mixture can not only significantly increase the sealing time for fractures but may also prevent fracture sealing.« less

Assessment of two-phase flow on the chemical alteration and sealing of leakage pathways in cemented wellbores

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

Iyer, Jaisree; Walsh, Stuart D. C.; Hao, Yue

Wellbore leakage tops the list of perceived risks to the long-term geologic storage of CO 2, because wells provide a direct path between the CO 2 storage reservoir and the atmosphere. In this paper, we have coupled a two-phase flow model with our original framework that combined models for reactive transport of carbonated brine, geochemistry of reacting cement, and geomechanics to predict the permeability evolution of cement fractures. Additionally, this makes the framework suitable for field conditions in geological storage sites, permitting simulation of contact between cement and mixtures of brine and supercritical CO 2. Due to lack of conclusivemore » experimental data, we tried both linear and Corey relative permeability models to simulate flow of the two phases in cement fractures. The model also includes two options to account for the inconsistent experimental observations regarding cement reactivity with two-phase CO 2-brine mixtures. One option assumes that the reactive surface area is independent of the brine saturation and the second option assumes that the reactive surface area is proportional to the brine saturation. We have applied the model to predict the extent of cement alteration, the conditions under which fractures seal, the time it takes to seal a fracture, and the leakage rates of CO 2 and brine when damage zones in the wellbore are exposed to two-phase CO 2-brine mixtures. Initial brine residence time and the initial fracture aperture are critical parameters that affect the fracture sealing behavior. We also evaluated the importance of the model assumptions regarding relative permeability and cement reactivity. These results illustrate the need to understand how mixtures of carbon dioxide and brine flow through fractures and react with cement to make reasonable predictions regarding well integrity. For example, a reduction in the cement reactivity with two-phase CO 2-brine mixture can not only significantly increase the sealing time for fractures but may also prevent fracture sealing.« less

Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

DOE PAGES

Helgren, Travis R.; Chen, Congling; Wangtrakuldee, Phumvadee; ...

2016-11-10

Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. In this study, we tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii. We first identified potent RpMetAP inhibitory species by employing an in vitro enzymatic activity assay. The molecular docking program AutoDock wasmore » then utilized to compare published crystal structures of inhibited MetAP species to docked poses of RpMetAP. Based on these in silico and in vitro screens, a subset of 17 compounds was tested for inhibition of R. prowazekii growth in a pulmonary vascular endothelial cell (EC) culture infection model system. All compounds were tested over concentration ranges that were determined to be non-toxic to the ECs and 8 of the 17 compounds displayed substantial inhibition of R. prowazekii growth. Lastly, these data highlight the therapeutic potential for inhibiting RpMetAP as a novel antimicrobial strategy and set the stage for future studies in pre-clinical animal models of infection.« less

Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

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

Helgren, Travis R.; Chen, Congling; Wangtrakuldee, Phumvadee

Methionine aminopeptidase (MetAP) is a class of ubiquitous enzymes essential for the survival of numerous bacterial species. These enzymes are responsible for the cleavage of N-terminal formyl-methionine initiators from nascent proteins to initiate post-translational modifications that are often essential to proper protein function. Thus, inhibition of MetAP activity has been implicated as a novel antibacterial target. In this study, we tested this idea in the present study by targeting the MetAP enzyme in the obligate intracellular pathogen Rickettsia prowazekii. We first identified potent RpMetAP inhibitory species by employing an in vitro enzymatic activity assay. The molecular docking program AutoDock wasmore » then utilized to compare published crystal structures of inhibited MetAP species to docked poses of RpMetAP. Based on these in silico and in vitro screens, a subset of 17 compounds was tested for inhibition of R. prowazekii growth in a pulmonary vascular endothelial cell (EC) culture infection model system. All compounds were tested over concentration ranges that were determined to be non-toxic to the ECs and 8 of the 17 compounds displayed substantial inhibition of R. prowazekii growth. Lastly, these data highlight the therapeutic potential for inhibiting RpMetAP as a novel antimicrobial strategy and set the stage for future studies in pre-clinical animal models of infection.« less

Evaluation of GPS position and attitude determination for automated rendezvous and docking missions. M.S. Thesis

NASA Technical Reports Server (NTRS)

Diprinzio, Marc D.; Tolson, Robert H.

1994-01-01

The use of the Global Positioning System for position and attitude determination is evaluated for an automated rendezvous and docking mission. The typical mission scenario involves the chaser docking with the target for resupply or repair purposes, and is divided into three sections. During the homing phase, the chaser utilizes coarse acquisition pseudorange data to approach the target; guidance laws for this stage are investigated. In the second phase, differential carrier phase positioning is utilized. The chaser must maintain a quasiconstant distance from the target, in order to resolve the initial integer ambiguities. Once the ambiguities are determined, the terminal phase is entered, and the rendezvous is completed with continuous carrier phase tracking. Attitude knowledge is maintained in all phases through the use of the carrier phase observable. A Kalman filter is utilized to estimate all states from the noisy measurement data. The effects of selective availability and cycle slips are also investigated.

Autonomous rendezvous and docking: A commercial approach to on-orbit technology validation

NASA Technical Reports Server (NTRS)

Tchoryk, Peter, Jr.; Dobbs, Michael E.; Conrad, David J.; Apley, Dale J.; Whitten, Raymond P.

1991-01-01

The Space Automation and Robotics Center (SpARC), a NASA-sponsored Center for the Commercial Development of Space (CCDS), in conjunction with its corporate affiliates, is planning an on-orbit validation of autonomous rendezvous and docking (ARD) technology. The emphasis in this program is to utilize existing technology and commercially available components whenever possible. The primary subsystems that will be validated by this demonstration include GPS receivers for navigation, a video-based sensor for proximity operations, a fluid connector mechanism to demonstrate fluid resupply capability, and a compliant, single-point docking mechanism. The focus for this initial experiment will be expendable launch vehicle (ELV) based and will make use of two residual Commercial Experiment Transporter (COMET) service modules. The first COMET spacecraft will be launched in late 1992 and will serve as the target vehicle. The ARD demonstration will take place in late 1994, after the second COMET spacecraft has been launched. The service module from the second COMET will serve as the chase vehicle.

Imidazole-containing farnesyltransferase inhibitors: 3D quantitative structure-activity relationships and molecular docking

NASA Astrophysics Data System (ADS)

Xie, Aihua; Odde, Srinivas; Prasanna, Sivaprakasam; Doerksen, Robert J.

2009-07-01

One of the most promising anticancer and recent antimalarial targets is the heterodimeric zinc-containing protein farnesyltransferase (FT). In this work, we studied a highly diverse series of 192 Abbott-initiated imidazole-containing compounds and their FT inhibitory activities using 3D-QSAR and docking, in order to gain understanding of the interaction of these inhibitors with FT to aid development of a rational strategy for further lead optimization. We report several highly significant and predictive CoMFA and CoMSIA models. The best model, composed of CoMFA steric and electrostatic fields combined with CoMSIA hydrophobic and H-bond acceptor fields, had r 2 = 0.878, q 2 = 0.630, and r pred 2 = 0.614. Docking studies on the statistical outliers revealed that some of them had a different binding mode in the FT active site based on steric bulk and available active site space, explaining why the predicted activities differed from the experimental activities.

Impact of closed-system drug transfer device on exposure of environment and healthcare provider to cyclophosphamide in Japanese hospital.

PubMed

Miyake, Tomohiro; Iwamoto, Takuya; Tanimura, Manabu; Okuda, Masahiro

2013-12-01

In spite of current recommended safe handling procedures, the potential for the exposure of healthcare providers to hazardous drugs exists in the workplace. A reliance on biological safety cabinets to provide total protection against the exposure to hazardous drugs is insufficient. Preventing workplace contamination is the best strategy to minimize cytotoxic drug exposure in healthcare providers. This study was conducted to compare surface contamination and personnel exposure to cyclophosphamide before and after the implementation of a closed-system drug transfer device, PhaSeal, under the influence of cleaning according to the Japanese guidelines. Personnel exposure was evaluated by collecting 24 h urine samples from 4 pharmacists. Surface contamination was assessed by the wiping test. Four of 6 wipe samples collected before PhaSeal indicated a detectable level of cyclophosphamide. About 7 months after the initiation of PhaSeal, only one of 6 wipe samples indicated a detectable level of cyclophosphamide. Although all 4 employees who provided urine samples had positive results for the urinary excretion of cyclophosphamide before PhaSeal, these levels returned to minimal levels in 2 pharmacists after PhaSeal. In combination with the biological safety cabinet and cleaning according to the Japanese guidelines, PhaSeal further reduces surface contamination and healthcare providers exposure to cyclophosphamide to almost undetectable levels.

Study of Geometric Stability and Structural Integrity of Self-Healing Glass Seal System Used in Solid Oxide Fuel Cells

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

Liu, Wenning N.; Sun, Xin; Khaleel, Mohammad A.

A self-healing glass seal has the potential of restoring its mechanical properties upon being reheated to SOFC stack operating temperature, even when it has experienced some cooling induced damage/cracking at room temperature. Such a self-healing feature is desirable for achieving high seal reliability during thermal cycling. On the other hand, self-healing glass is also characterized by its low mechanical stiffness and high creep rate at the typical operating temperature of SOFCs. Therefore, geometry stability and structural integrity of the glass seal system becomes critical to its successful application in SOFCs. In this paper, the geometry stability of the self-healing glassmore » and the influence of various interfacial conditions of ceramic stoppers with the PEN, IC, and glass seal on the structural integrity of the glass seal during the operating and cooling down processes are studied using finite element analyses. For this purpose, the test cell used in the leakage tests for compliant glass seals conducted at PNNL is taken as the initial modeling geometry. The effect of the ceramic stopper on the geometry stability of the self-healing glass sealants is studied first. Two interfacial conditions of the ceramic stopper and glass seals, i.e., bonded (strong) or un-bonded (weak), are considered. Then the influences of interfacial strengths at various interfaces, i.e., stopper/glass, stopper/PEN, as well as stopper/IC plate, on the geometry stability and reliability of glass during the operating and cooling processes are examined.« less

Development and Control of the Naval Postgraduate School Planar Autonomous Docking Simulator (NPADS)

NASA Astrophysics Data System (ADS)

Porter, Robert D.

2002-09-01

The objective of this thesis was to design, construct and develop the initial autonomous control algorithm for the NPS Planar Autonomous Docking Simulator (NPADS) The effort included hardware design, fabrication, installation and integration; mass property determination; and the development and testing of control laws utilizing MATLAB and Simulink for modeling and LabView for NPADS control, The NPADS vehicle uses air pads and a granite table to simulate a 2-D, drag-free, zero-g space environment, It is a completely self-contained vehicle equipped with eight cold-gas, bang-bang type thrusters and a reaction wheel for motion control, A 'star sensor' CCD camera locates the vehicle on the table while a color CCD docking camera and two robotic arms will locate and dock with a target vehicle, The on-board computer system leverages PXI technology and a single source, simplifying systems integration, The vehicle is powered by two lead-acid batteries for completely autonomous operation, A graphical user interface and wireless Ethernet enable the user to command and monitor the vehicle from a remote command and data acquisition computer. Two control algorithms were developed and allow the user to either control the thrusters and reaction wheel manually or simply specify a desired location and rotation angle,

Molecular docking to Toxoplasma gondii thymidylate synthase-dihydrofolate reductase and efficacy of raltitrexed in infected mice.

PubMed

de Paula Reis, Michelle; de Lima, Daniely Alves; Pauli, Karoline Bach; Andreotti, Carlos Eduardo Linhares; de Moraes, André Luiz Soares; Gonçalves, Daniela Dib; Navarro, Italmar Teodorico; Bueno, Paulo Sérgio Alves; Seixas, Flavio Augusto Vicente; Gasparotto Junior, Arquimedes; Lourenço, Emerson Luiz Botelho

2018-05-01

Toxoplasmosis is a zoonosis of worldwide distribution. Currently, two drugs, pyrimethamine and sulfadiazine, are used as a reference in the treatment of toxoplasmosis, but the resistance of Toxoplasma gondii appears as a relevant public health problem. In order to identify new drugs to toxoplasmosis treatment, we performed a molecular docking of raltitrexed to T. gondii thymidylate synthase-dihydrofolate reductase (TS-DHFR) and also evaluated its efficacy in infected mice. Initially, raltitrexed was docked on the crystallographic structures of TS-DHFR from T. gondii and Mus musculus. Then, 48 h after infection with the T. gondii RH strain, different groups of mice received an oral dose of raltitrexed (0.15, 0.75, and 1.5 mg kg -1 ). Two days after treatments, raltitrexed was able to prevent mortality and reduce the number of tachyzoites in the peritoneal fluid and liver imprints from infected mice. The results showed that raltitrexed has important protective activities against the T. gondii RH strain. Molecular docking still suggests that the effects against the parasite may be dependent on the inhibition of T. gondii thymidylate synthase. This study opens new perspectives for the use of raltitrexed in patients infected with T. gondii, especially when conventional treatments do not exhibit the expected efficacy.

Volatilization of polycyclic aromatic hydrocarbons from coal-tar-sealed pavement

USGS Publications Warehouse

Van Metre, Peter C.; Majewski, Michael S.; Mahler, Barbara J.; Foreman, William T.; Braun, Christopher L.; Wilson, Jennifer T.; Burbank, Teresa L.

2012-01-01

Coal-tar-based pavement sealants, a major source of PAHs to urban water bodies, are a potential source of volatile PAHs to the atmosphere. An initial assessment of volatilization of PAHs from coal-tar-sealed pavement is presented here in which we measured summertime gas-phase PAH concentrations 0.03 m and 1.28 m above the pavement surface of seven sealed (six with coal-tar-based sealant and one with asphalt-based sealant) and three unsealed (two asphalt and one concrete) parking lots in central Texas. PAHs also were measured in parking lot dust. The geometric mean concentration of the sum of eight frequently detected PAHs (ΣPAH8) in the 0.03-m samples above sealed lots (1320 ng m-3) during the hottest part of the day was 20 times greater than that above unsealed lots (66.5 ng m-3). The geometric mean concentration in the 1.28-m samples above sealed lots (138 ng m-3) was five times greater than above unsealed lots (26.0 ng m-3). Estimated PAH flux from the sealed lots was 60 times greater than that from unsealed lots (geometric means of 88 and 1.4 μg m-2 h-1, respectively). Although the data set presented here is small, the much higher estimated fluxes from sealed pavement than from unsealed pavement indicate that coal-tar-based sealants are emitting PAHs to urban air at high rates compared to other paved surfaces.

Efficacy of Sealing Agents on Preload Maintenance of Screw-Retained Implant-Supported Prostheses.

PubMed

Seloto, Camila Berbel; Strazzi Sahyon, Henrico Badaoui; Dos Santos, Paulo Henrique; Delben, Juliana Aparecida; Assunção, Wirley Gonçalves

The aim of this study was to evaluate the effect of sealing agents on preload maintenance of screw joints. A total of four groups (n = 10 in each group) of abutment/implant systems, including external hexagon implants and antirotational UCLA abutments with a metallic collar in cobalt-chromium alloy, were assessed. In the control group (CG), no sealing agent was used at the abutment screw/implant interface. In the other groups, three different sealing agents were used at the abutment screw/implant interface: anaerobic sealing agent for medium torque (ASMT), anaerobic sealing agent for high torque (ASHT), and cyanoacrylate-based bonding agent (CYAB). All abutments were attached to the implants at 32 ± 1 N.cm. After 48 ± 2 hours of initial tightening, loosing torque (detorque) was measured using a digital torque wrench. Data were analyzed using Shapiro-Wilk, Wilcoxon, and Kruskal-Wallis tests, at 5% level of significance. In the CG and ASMT groups, detorque was lower than the insertion torque (24.6 ± 1.5 N.cm and 24.3 ± 1.1 N.cm, respectively). In the ASHT and CYAB groups, mean detorque increased in comparison to the insertion torque (51.0 ± 7.4 N.cm and 47.7 ± 15.1 N.cm, respectively). The ASHT was more efficient than the other sealing agents, increasing the remaining preload (detorque value) 58.88%. Although the cyanoacrylate-based bonding agent also generated high detorque values, the high standard deviation suggested its lower reliability.

Volatilization of polycyclic aromatic hydrocarbons from coal-tar-sealed pavement.

PubMed

Van Metre, Peter C; Majewski, Michael S; Mahler, Barbara J; Foreman, William T; Braun, Christopher L; Wilson, Jennifer T; Burbank, Teresa L

2012-06-01

Coal-tar-based pavement sealants, a major source of PAHs to urban water bodies, are a potential source of volatile PAHs to the atmosphere. An initial assessment of volatilization of PAHs from coal-tar-sealed pavement is presented here in which we measured summertime gas-phase PAH concentrations 0.03 m and 1.28 m above the pavement surface of seven sealed (six with coal-tar-based sealant and one with asphalt-based sealant) and three unsealed (two asphalt and one concrete) parking lots in central Texas. PAHs also were measured in parking lot dust. The geometric mean concentration of the sum of eight frequently detected PAHs (ΣPAH(8)) in the 0.03-m samples above sealed lots (1320 ng m(-3)) during the hottest part of the day was 20 times greater than that above unsealed lots (66.5 ng m(-3)). The geometric mean concentration in the 1.28-m samples above sealed lots (138 ng m(-3)) was five times greater than above unsealed lots (26.0 ng m(-3)). Estimated PAH flux from the sealed lots was 60 times greater than that from unsealed lots (geometric means of 88 and 1.4 μg m(-2) h(-1), respectively). Although the data set presented here is small, the much higher estimated fluxes from sealed pavement than from unsealed pavement indicate that coal-tar-based sealants are emitting PAHs to urban air at high rates compared to other paved surfaces. Published by Elsevier Ltd.

Resident CAPS on dense-core vesicles docks and primes vesicles for fusion.

PubMed

Kabachinski, Greg; Kielar-Grevstad, D Michelle; Zhang, Xingmin; James, Declan J; Martin, Thomas F J

2016-02-15

The Ca(2+)-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro-scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2-dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly. © 2016 Kabachinski, Kielar-Grevstad, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Exploring the conformational and binding properties of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 through docking and molecular dynamics simulations.

PubMed

Zacarías-Lara, Oscar J; Correa-Basurto, José; Bello, Martiniano

2016-07-01

B-cell lymphoma (Bcl-2) is commonly associated with the progression and preservation of cancer and certain lymphomas; therefore, it is considered as a biological target against cancer. Nevertheless, evidence of all its structural binding sites has been hidden because of the lack of a complete Bcl-2 model, given the presence of a flexible loop domain (FLD), which is responsible for its complex behavior. FLD region has been implicated in phosphorylation, homotrimerization, and heterodimerization associated with Bcl-2 antiapoptotic function. In this contribution, homology modeling, molecular dynamics (MD) simulations in the microsecond (µs) time-scale and docking calculations were combined to explore the conformational complexity of unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 systems. Conformational ensembles generated through MD simulations allowed for identifying the most populated unphosphorylated/phosphorylated monomeric conformations, which were used as starting models to obtain trimeric complexes through protein-protein docking calculations, also submitted to µs MD simulations. Principal component analysis showed that FLD represents the main contributor to total Bcl-2 mobility, and is affected by phosphorylation and oligomerization. Subsequently, based on the most representative unphosphorylated/phosphorylated monomeric and trimeric Bcl-2 conformations, docking studies were initiated to identify the ligand binding site of several known Bcl-2 inhibitors to explain their influence in homo-complex formation and phosphorylation. Docking studies showed that the different conformational states experienced by FLD, such as phosphorylation and oligomerization, play an essential role in the ability to make homo and hetero-complexes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 393-413, 2016. © 2016 Wiley Periodicals, Inc.

Study of process variables associated with manufacturing hermetically-sealed nickel-cadmium cells

NASA Technical Reports Server (NTRS)

Miller, L.

1972-01-01

The effort and results of a program to determine and study the critical process variables associated with the manufacture of aerospace, hermetically-sealed, nickel-cadmium cells are reported. During the period, the impregnation/polarization process variable study was brought to a close with the completion of a series of related experiments. The results of the experiments are summarized. During this period, a general characterization of cell separator materials was initiated. The major conclusions resulting from the characterization of materials are included.

Development and Evaluation of Integrity Assessment Tests for Polymeric Hermetic Seals

DTIC Science & Technology

2006-02-19

Knoxville, the wires were pulled from the seals and then the packages were dipped in the microorganism Enterobacter aerogene . The polytrays were exposed for...inoculated) 5 samples Total Polytrays 80 Microorganism Washes 1. Prepare Cultures of Enterobacter aerogenes a. 5 tubes (10 mL each) in...initial number – 6 log CFU/mL a. Add two tubes (20 mL) of Enterobacter aerogenes culture to 5 gallons of water with sodium thiosulfate b. Ca. 9 log CFU

Pneumatic Control Device for the Pershing 2 Adaption Kit

DTIC Science & Technology

1979-03-14

forward force to main- tain a pressure seal (this, versus an-I6-to 25 pound maximum reverse .force component due to pressure). In all probability, initial...stem forward force to main- tain a pressure seal (this, versus an 48-to-25-pound maximum " reverse.force, component due-topressue). In-all probability...PII Li L! Ramn Eniern Inc Contrato . 2960635 GAS GENERATOR COMPATIBILITY U TEST REPORT 1.j Requirement s The requirements for the Pershing II, Phase I

Pathfinder autonomous rendezvous and docking project

NASA Technical Reports Server (NTRS)

Lamkin, Stephen (Editor); Mccandless, Wayne (Editor)

1990-01-01

Capabilities are being developed and demonstrated to support manned and unmanned vehicle operations in lunar and planetary orbits. In this initial phase, primary emphasis is placed on definition of the system requirements for candidate Pathfinder mission applications and correlation of these system-level requirements with specific requirements. The FY-89 activities detailed are best characterized as foundation building. The majority of the efforts were dedicated to assessing the current state of the art, identifying desired elaborations and expansions to this level of development and charting a course that will realize the desired objectives in the future. Efforts are detailed across all work packages in developing those requirements and tools needed to test, refine, and validate basic autonomous rendezvous and docking elements.

Engine Seal Technology Requirements to Meet NASA's Advanced Subsonic Technology Program Goals

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Hendricks, Robert C.

1994-01-01

Cycle studies have shown the benefits of increasing engine pressure ratios and cycle temperatures to decrease engine weight and improve performance of commercial turbine engines. NASA is working with industry to define technology requirements of advanced engines and engine technology to meet the goals of NASA's Advanced Subsonic Technology Initiative. As engine operating conditions become more severe and customers demand lower operating costs, NASA and engine manufacturers are investigating methods of improving engine efficiency and reducing operating costs. A number of new technologies are being examined that will allow next generation engines to operate at higher pressures and temperatures. Improving seal performance - reducing leakage and increasing service life while operating under more demanding conditions - will play an important role in meeting overall program goals of reducing specific fuel consumption and ultimately reducing direct operating costs. This paper provides an overview of the Advanced Subsonic Technology program goals, discusses the motivation for advanced seal development, and highlights seal technology requirements to meet future engine performance goals.

Performance Evaluation of an Actuator Dust Seal for Lunar Operation

NASA Technical Reports Server (NTRS)

Delgado, Irebert R.; Gaier, James R.; Handschuh, Michael; Panko, Scott; Sechkar, Ed

2013-01-01

Exploration of extraterrestrial surfaces (e.g. moon, Mars, asteroid) will require durable space mechanisms that will survive potentially dusty surface conditions in addition to the hard vacuum and extreme temperatures of space. Baseline tests with lunar simulant were recently completed at NASA GRC on a new Low-Temperature Mechanism (LTM) dust seal for space actuator application. Following are top-level findings of the tests completed to date in vacuum using NU-LHT-2M lunar-highlands simulant. A complete set of findings are found in the conclusions section.Tests were run at approximately 10-7 torr with unidirectional rotational speed of 39 RPM.Initial break-in runs were performed at atmospheric conditions with no simulant. During the break-in runs, the maximum torque observed was 16.7 lbf-in. while the maximum seal outer diameter temperature was 103F. Only 0.4 milligrams of NU-LHT-2M simulant passed through the sealshaft interface in the first 511,000 cycles while under vacuum despite a chip on the secondary sealing surface.Approximately 650,000 of a planned 1,000,000 cycles were completed in vacuum with NU-LHT-2M simulant.Upon test disassembly NU-LHT-2M was found on the secondary sealing surface.

Dry-running gas seals save $200,000/yr in retrofit hydrogen recycle compressor

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

Pennacchi, R.P.; Germain, A.

1987-10-01

Texaco Chemical Company was using three drums of oil per day in the seal oil system of a hydrogen recycle compressor, resulting in maintenance and operational expenses of more than $160,000 per year. Running 24 hours/day, 365 days/yr, the 26-yr-old compressor is the heart of the benzene manufacturing process unit at the Port Arthur, Texas plant. In the event of an unscheduled shutdown, the important aromatics unit process would halt and cause production losses of thousands of dollars per day. In addition, the close monitoring and minimization of leakage are essential since the gas consists of over 75% hydrogen, withmore » methane, ethane, propane, isobutane, N-butane and pentanes. Texaco Chemical Company decided that retrofit of the hydrogen recycle compressor should be undertaken if the system could be developed to sharply reduce operations and maintenance costs, and increase efficiencies. Texaco engineers selected a dry running-type gas sealing system developed for pipeline compressors in the United States, Canada, and overseas. A tandem-type sealing system was designed to meet specific needs of a hydrogen recycle compressor. The retrofit was scheduled for August 1986 to coincide with the plant's preventative maintenance program. The seal system installation required five days. The retrofit progressed according to schedule, with no problems experienced at the first and several startups since the initial installation. Oil consumption has been eliminated, along with seal support and parasitic energy requirements. With the savings in seal oil, energy, operations and maintenance, payback period for the retrofit sealing system was just over six months. Savings are expected to continue at an annual rate of over $200,000.« less

Laparoscopic prototype for optical sealing of renal blood vessels

NASA Astrophysics Data System (ADS)

Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

2017-02-01

Energy-based, radiofrequency and ultrasonic devices provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternative for vessel sealing with less collateral thermal damage. Previous studies demonstrated vessel sealing in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices in surgical use was developed, and tests were conducted on porcine renal blood vessels. The 5-mm-OD prototype featured a traditional Maryland jaw configuration. Laser energy was delivered through a 550-μm-core fiber and side-delivery from the lower jaw, with beam dimensions of 18-mm-length x 1.2-mm-width. The 1470-nm diode laser delivered 68 W with 3 s activation time. A total of 69 porcine renal vessels with mean diameter of 3.3 +/- 1.7 mm were tested, ex vivo. Vessels smaller than 5 mm were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038 +/- 474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174 +/- 221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7 +/- 0.8, 3.4 +/- 0.7, and 1.0 +/- 0.4 mm. A novel optical laparoscopic prototype with 5-mm- OD shaft integrated within a standard Maryland jaw design consistently sealed vessels less than 5 mm with minimal thermal spread. Further in vivo studies are planned to test performance across a variety of vessels and tissues.

Concurrent-scene/alternate-pattern analysis for robust video-based docking systems

NASA Technical Reports Server (NTRS)

Udomkesmalee, Suraphol

1991-01-01

A typical docking target employs a three-point design of retroreflective tape, one at each endpoint of the center-line, and one on the tip of the central post. Scenes, sensed via laser diode illumination, produce pictures with spots corresponding to desired reflection from the retroreflectors and other reflections. Control corrections for each axis of the vehicle can then be properly applied if the desired spots are accurately tracked. However, initial acquisition of these three spots (detection and identification problem) are non-trivial under a severe noise environment. Signal-to-noise enhancement, accomplished by subtracting the non-illuminated scene from the target scene illuminated by laser diodes, can not eliminate every false spot. Hence, minimization of docking failures due to target mistracking would suggest needed inclusion of added processing features pertaining to target locations. In this paper, we present a concurrent processing scheme for a modified docking target scene which could lead to a perfect docking system. Since the non-illuminated target scene is already available, adding another feature to the three-point design by marking two non-reflective lines, one between the two end-points and one from the tip of the central post to the center-line, would allow this line feature to be picked-up only when capturing the background scene (sensor data without laser illumination). Therefore, instead of performing the image subtraction to generate a picture with a high signal-to-noise ratio, a processed line-image based on the robust line detection technique (Hough transform) can be used to fuse with the actively sensed three-point target image to deduce the true locations of the docking target. This dual-channel confirmation scheme is necessary if a fail-safe system is to be realized from both the sensing and processing point-of-views. Detailed algorithms and preliminary results are presented.

Numerical simulation for the coupled thermo-mechanical performance of a lined rock cavern for underground compressed air energy storage

NASA Astrophysics Data System (ADS)

Zhou, Shu-Wei; Xia, Cai-Chu; Zhao, Hai-Bin; Mei, Song-Hua; Zhou, Yu

2017-12-01

Compressed air energy storage (CAES) is a technology that uses compressed air to store surplus electricity generated from low power consumption time for use at peak times. This paper presents a thermo-mechanical modeling for the thermodynamic and mechanical responses of a lined rock cavern used for CAES. The simulation was accomplished in COMSOL Multiphysics and comparisons of the numerical simulation and some analytical solutions validated the thermo-mechanical modeling. Air pressure and temperatures in the sealing layer and concrete lining exhibited a similar trend of ‘up-down-down-up’ in one cycle. Significant temperature fluctuation occurred only in the concrete lining and sealing layer, and no strong fluctuation was observed in the host rock. In the case of steel sealing, principal stresses in the sealing layer were larger than those in the concrete and host rock. The maximum compressive stresses of the three layers and the displacement on the cavern surface increased with the increase of cycle number. However, the maximum tensile stresses exhibited the opposite trend. Polymer sealing achieved a relatively larger air temperature and pressure compared with steel and air-tight concrete sealing. For concrete layer thicknesses of 0 and 0.1 m and an initial air pressure of 4.5 MPa, the maximum rock temperature could reach 135 °C and 123 °C respectively in a 30 day simulation.

Archeological Data Recovery at Algiers Point. Volume 1.

DTIC Science & Technology

1984-10-15

the Mississippi River directly across from the Vieux Carre, the Historic French Quarter of New Orleans. Algiers initially was settled in 1718 by early... French colonists, and today it is home to the large scale ship repair and dry dock facilities that support the Port of New Orleans. The Algiers Point...fourth period, from 1977 to the present, simply represents current occupation and land use. The initial, or Colonial period, began with French

Isothermal Dendritic Growth Experiment - Science, engineering, and hardware development for USMP space flights

NASA Technical Reports Server (NTRS)

Glicksman, M. E.; Hahn, R. C.; Koss, M. B.; Tirmizi, S. H.; Selleck, M. E.; Velosa, A.; Winsa, E.

1991-01-01

The Isothermal Dendritic Growth Experiment (IDGE) has been designed to provide microgravity data on dendritic growth for a critical test of theory. This paper updates progress on constructing a crystal growth chamber suitable for space flight. The IDGE chamber is constructed from glass and stainless steel and is hermetically sealed by electron beam welds and glass-metal seals. Initial tests of the chambers sample's melting point plateau show that the new chamber design is capable of preserving the 99.9995 percent purity of succinonitrile. Dendrite growth can be initiated in the center of the IDGE chamber by means of thermo-electric coolers and a capillary injector tube (stinger). The new IDGE chamber is ready for fully integrated tests with the prototype IDGE engineering hardware at NASA's Lewis Research Center.

Portable Hyperbaric Chamber

NASA Technical Reports Server (NTRS)

Schneider, William C. (Inventor); Locke, James P. (Inventor); DeLaFuente, Horacio (Inventor)

2001-01-01

A portable, collapsible hyperbaric chamber was developed. A toroidal inflatable skeleton provides initial structural support for the chamber, allowing the attendant and/or patient to enter the chamber. Oval hatches mate against bulkhead rings, and the hyperbaric chamber is pressurized. The hatches seal against an o-ring, and the internal pressure of the chamber provides the required pressure against the hatch to maintain an airtight seal. In the preferred embodiment, the hyperbaric chamber has an airlock to allow the attendant to enter and exit the patient chamber during treatment. Visual communication is provided through portholes in the patient and/or airlock chamber. Life monitoring and support systems are in communication with the interior of the hyperbaric chamber and/or airlock chamber through conduits and/or sealed feed-through connectors into the hyperbaric chamber.

Relevance of Trust Marks and CE Labels in German-Language Store Descriptions of Health Apps: Analysis

PubMed Central

Hillebrand, Uta; von Jan, Ute

2018-01-01

Background In addition to mandatory CE marking (“CE” representing Conformité Européenne, with the CE marking being a symbol of free marketability in the European Economic Area) for medical devices, there are various seals, initiatives, action groups, etc, in the health app context. However, whether manufacturers use them to distinguish their apps and attach relevance to them is unclear. Objective The objective was to take a snapshot of quality seals, regulatory marks, and other orientation aids available on the German app market and to determine whether manufacturers deem such labels relevant enough to apply them to their apps, namely as reflected by mentions in app description texts in a typical app store (ie, Apple’s App Store). Methods A full survey of the metadata of 103,046 apps from Apple’s German App Store in the Medicine and Health & Fitness categories was carried out. For apps with German-language store descriptions (N=8767), these were automatically searched for the occurrence of relevant keywords and validated manually (N=41). In addition, the websites of various app seal providers were checked for assigned seals. Results Few manufacturers referenced seals in the descriptions (5/41), although this would have been expected more often based on the seals we were able to identify from the seal providers’ Web pages, and there were 34 of 41 that mentioned CE status in the descriptions. Two apps referenced an app directory curated by experts; however, this is not an alternative to CE marks and seals of approval. Conclusions Currently, quality seals seem to be irrelevant for manufacturers. In line with regulatory requirements, mentions of medical device status are more frequent; however, neither characteristic is effective for identifying high-quality apps. To improve this situation, a possibly legally obligatory, standardized reporting system should be implemented. PMID:29695374

Innovative Self-Healing Seals for Solid Oxide Fuel Cells (SOFC)

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

Raj Singh

Solid oxide fuel cell (SOFC) technology is critical to several national initiatives. Solid State Energy Conversion Alliance (SECA) addresses the technology needs through its comprehensive programs on SOFC. A reliable and cost-effective seal that works at high temperatures is essential to the long-term performance of the SOFC for 40,000 hours at 800°C. Consequently, seals remain an area of highest priority for the SECA program and its industry teams. An innovative concept based on self-healing glasses was advanced and successfully demonstrated through seal tests for 3000 hours and 300 thermal cycles to minimize internal stresses under both steady state and thermalmore » transients for making reliable seals for the SECA program. The self-healing concept requires glasses with low viscosity at the SOFC operating temperature of 800°C but this requirement may lead to excessive flow of the glass in areas forming the seal. To address this challenge, a modification to glass properties by addition of particulate fillers is pursued in the project. The underlying idea is that a non-reactive ceramic particulate filler is expected to form glass-ceramic composite and increase the seal viscosity thereby increasing the creep resistance of the glass-composite seals under load. The objectives of the program are to select appropriate filler materials for making glass-composite, fabricate glass-composites, measure thermal expansion behaviors, and determine stability of the glass-composites in air and fuel environments of a SOFC. Self-healing glass-YSZ composites are further developed and tested over a longer time periods under conditions typical of the SOFCs to validate the long-term stability up to 2000 hours. The new concepts of glass-composite seals, developed and nurtured in this program, are expected to be cost-effective as these are based on conventional processing approaches and use of the inexpensive materials.« less

Relevance of Trust Marks and CE Labels in German-Language Store Descriptions of Health Apps: Analysis.

PubMed

Albrecht, Urs-Vito; Hillebrand, Uta; von Jan, Ute

2018-04-25

In addition to mandatory CE marking ("CE" representing Conformité Européenne, with the CE marking being a symbol of free marketability in the European Economic Area) for medical devices, there are various seals, initiatives, action groups, etc, in the health app context. However, whether manufacturers use them to distinguish their apps and attach relevance to them is unclear. The objective was to take a snapshot of quality seals, regulatory marks, and other orientation aids available on the German app market and to determine whether manufacturers deem such labels relevant enough to apply them to their apps, namely as reflected by mentions in app description texts in a typical app store (ie, Apple's App Store). A full survey of the metadata of 103,046 apps from Apple's German App Store in the Medicine and Health & Fitness categories was carried out. For apps with German-language store descriptions (N=8767), these were automatically searched for the occurrence of relevant keywords and validated manually (N=41). In addition, the websites of various app seal providers were checked for assigned seals. Few manufacturers referenced seals in the descriptions (5/41), although this would have been expected more often based on the seals we were able to identify from the seal providers' Web pages, and there were 34 of 41 that mentioned CE status in the descriptions. Two apps referenced an app directory curated by experts; however, this is not an alternative to CE marks and seals of approval. Currently, quality seals seem to be irrelevant for manufacturers. In line with regulatory requirements, mentions of medical device status are more frequent; however, neither characteristic is effective for identifying high-quality apps. To improve this situation, a possibly legally obligatory, standardized reporting system should be implemented. ©Urs-Vito Albrecht, Uta Hillebrand, Ute von Jan. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 25.04.2018.

Rapid sealing of porcine renal blood vessels, ex vivo, using a high power, 1470-nm laser, and laparoscopic prototype

NASA Astrophysics Data System (ADS)

Hardy, Luke A.; Hutchens, Thomas C.; Larson, Eric R.; Gonzalez, David A.; Chang, Chun-Hung; Nau, William H.; Fried, Nathaniel M.

2017-05-01

Energy-based, radiofrequency (RF) and ultrasonic (US) devices currently provide rapid sealing of blood vessels during laparoscopic procedures. We are exploring infrared lasers as an alternate energy modality for vessel sealing, capable of generating less collateral thermal damage. Previous studies demonstrated feasibility of sealing vessels in an in vivo porcine model using a 1470-nm laser. However, the initial prototype was designed for testing in open surgery and featured tissue clasping and light delivery mechanisms incompatible with laparoscopic surgery. In this study, a laparoscopic prototype similar to devices currently in surgical use was developed, and performance tests were conducted on porcine renal blood vessels, ex vivo. The 5-mm outer-diameter laparoscopic prototype featured a traditional Maryland jaw configuration that enables tissue manipulation and blunt dissection. Laser energy was delivered through a 550-μm-core-diameter optical fiber with side-delivery from the lower jaw and beam dimensions of 18-mm length×1.2-mm width. The 1470-nm diode laser delivered 68 W with 3-s activation time, consistent with vessel seal times associated with RF and US-based devices. A total of 69 fresh porcine renal vessels with mean diameter of 3.3±1.7 mm were tested, ex vivo. Vessels smaller than 5-mm diameter were consistently sealed (48/51) with burst pressures greater than malignant hypertension blood pressure (180 mmHg), averaging 1038±474 mmHg. Vessels larger than 5 mm were not consistently sealed (6/18), yielding burst pressures of only 174±221 mmHg. Seal width, thermal damage zone, and thermal spread averaged 1.7±0.8, 3.4±0.7, and 1.0±0.4 mm, respectively. Results demonstrated that the 5-mm optical laparoscopic prototype consistently sealed vessels less than 5-mm diameter with low thermal spread. Further in vivo studies are planned to test the performance across a variety of vessels and tissues.

CLINICAL AND EPIDEMIOLOGIC CONSIDERATIONS OF CLOSTRIDIUM DIFFICILE IN HARBOR SEALS (PHOCA VITULINA) AT A MARINE MAMMAL REHABILITATION CENTER.

PubMed

Anderson, Chelsea E; Haulena, Martin; Zabek, Erin; Habing, Gregory; Raverty, Stephen

2015-06-01

Between 1998 and 2008, 15 cases of segmental to diffuse hemorrhagic to necrohemorrhagic enterocolitis were diagnosed in neonatal and weaned juvenile harbor seals (Phoca vitulina) presented from the Vancouver Aquarium Marine Mammal Rescue Centre for rehabilitation. Based on a combination of gross pathology, histopathology, bacterial isolation, and toxin testing, Clostridium difficile enterocolitis was diagnosed. Most pups were anorexic or inappetant and died acutely with few other premonitory signs. Due to ongoing clinical concerns and possible emergence of this pathogen at the facility, efforts to better characterize the disease and understand the epidemiology of C. difficile was initiated in 95 harbor seal pups presented for rehabilitation in a single stranding season. Fecal samples were collected on admission, following completion of antibiotic treatment, and also prerelease or postmortem. All samples were collected fresh and submitted either directly or stored frozen. Fecal samples were inoculated into selective media for culture and screened by enzyme-linked immunosorbant assay (ELISA) for C. difficile toxins A, B, or both. Results of the 95 seals in the study were as follows: on hospital admit 72 seals were sampled, 10 were culture positive, 12 were ELISA positive; following antibiotic therapy 46 seals were sampled noting three culture positive and nine ELISA positive; prior to release 58 seals were sampled noting zero culture positive and one ELISA positive; and on postmortem exam seven seals were sampled noting zero culture positive and two ELISA positive. Clostridium difficile was not deemed to be the cause of death in any of the animals. Although the exact mechanism of disease is unknown, this study suggests that C. difficile infection is not a significant cause of mortality and may be part of the normal flora in harbor seals undergoing rehabilitation. Morbidity and mortality from this bacterium can likely be minimized by judicious use of antibiotics, effective biosecurity-biocontainment protocols, and clean husbandry practices.

Computerized X-ray Microtomography Observations and Fluid Flow Measurements of the Effect of Effective Stress on Fractured Reservoir Seal Shale

NASA Astrophysics Data System (ADS)

Welch, N.; Crawshaw, J.; Boek, E.

2014-12-01

The successful storage of carbon dioxide in geologic formations requires an in-depth understanding of all reservoir characteristics and morphologies. An intact and substantial seal formation above a storage reservoir is required for a significant portion of the initial sealing mechanisms believed to occur during carbon dioxide storage operations. Shales are a common seal formation rock types found above numerous hydrocarbon reservoirs, as well as potential saline aquifer storage locations. Shales commonly have very low permeability, however they also have the tendency to be quite fissile, and the formation of fractures within these seals can have a significant detrimental effect on the sealing potential of a reservoir and amount to large areas of high permeability and low capillary pressures compared to the surrounding intact rock. Fractured shales also have an increased current interest due to the increasing development of shale gas reservoirs using hydraulic fracturing techniques. This work shows the observed changes that occur within fractured pieces of reservoir seal shale samples, along with quarry analogues, using an in-situ micro-CT fluid flow imaging apparatus with a Hassler type core holder. Changes within the preferential flow path under different stress regimes as well as physical changes to the fracture geometry are reported. Lattice Boltzmann flow simulations were then performed on the extracted flow paths and compared to experiment permeability measurements. The preferential flow path of carbon dioxide through the fracture network is also observed and compared to the results two-phase Lattice Boltzmann fluid flow simulations.

A python-based docking program utilizing a receptor bound ligand shape: PythDock.

PubMed

Chung, Jae Yoon; Cho, Seung Joo; Hah, Jung-Mi

2011-09-01

PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design.

Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking.

PubMed

Chen, Meimei; Yang, Fafu; Kang, Jie; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

2016-11-29

In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

Insights into the structural basis of N2 and O6 substituted guanine derivatives as cyclin-dependent kinase 2 (CDK2) inhibitors: prediction of the binding modes and potency of the inhibitors by docking and ONIOM calculations.

PubMed

Alzate-Morales, Jans H; Caballero, Julio; Vergara Jague, Ariela; González Nilo, Fernando D

2009-04-01

N2 and O6 substituted guanine derivatives are well-known as potent and selective CDK2 inhibitors. The ability of molecular docking using the program AutoDock3 and the hybrid method ONIOM, to obtain some quantum chemical descriptors with the aim to successfully rank these inhibitors, was assessed. The quantum chemical descriptors were used to explain the affinity, of the series studied, by a model of the CDK2 binding site. The initial structures were obtained from docking studies and the ONIOM method was applied with only a single point energy calculation on the protein-ligand structure. We obtained a good correlation model between the ONIOM derived quantum chemical descriptor "H-bond interaction energy" and the experimental biological activity, with a correlation coefficient value of R = 0.80 for 75 compounds. To the best of our knowledge, this is the first time that both methodologies are used in conjunction in order to obtain a correlation model. The model suggests that electrostatic interactions are the principal driving force in this protein-ligand interaction. Overall, the approach was successful for the cases considered, and it suggests that could be useful for the design of inhibitors in the lead optimization phase of drug discovery.

Application of binding free energy calculations to prediction of binding modes and affinities of MDM2 and MDMX inhibitors.

PubMed

Lee, Hui Sun; Jo, Sunhwan; Lim, Hyun-Suk; Im, Wonpil

2012-07-23

Molecular docking is widely used to obtain binding modes and binding affinities of a molecule to a given target protein. Despite considerable efforts, however, prediction of both properties by docking remains challenging mainly due to protein's structural flexibility and inaccuracy of scoring functions. Here, an integrated approach has been developed to improve the accuracy of binding mode and affinity prediction and tested for small molecule MDM2 and MDMX antagonists. In this approach, initial candidate models selected from docking are subjected to equilibration MD simulations to further filter the models. Free energy perturbation molecular dynamics (FEP/MD) simulations are then applied to the filtered ligand models to enhance the ability in predicting the near-native ligand conformation. The calculated binding free energies for MDM2 complexes are overestimated compared to experimental measurements mainly due to the difficulties in sampling highly flexible apo-MDM2. Nonetheless, the FEP/MD binding free energy calculations are more promising for discriminating binders from nonbinders than docking scores. In particular, the comparison between the MDM2 and MDMX results suggests that apo-MDMX has lower flexibility than apo-MDM2. In addition, the FEP/MD calculations provide detailed information on the different energetic contributions to ligand binding, leading to a better understanding of the sensitivity and specificity of protein-ligand interactions.

Initial Investigation of Reaction Control System Design on Spacecraft Handling Qualities for Earth Orbit Docking

NASA Technical Reports Server (NTRS)

Bailey, Randall E.; Jackson, E. Bruce; Goodrich, Kenneth H.; Ragsdale, W. Al; Neuhaus, Jason; Barnes, Jim

2008-01-01

A program of research, development, test, and evaluation is planned for the development of Spacecraft Handling Qualities guidelines. In this first experiment, the effects of Reaction Control System design characteristics and rotational control laws were evaluated during simulated proximity operations and docking. Also, the influence of piloting demands resulting from varying closure rates was assessed. The pilot-in-the-loop simulation results showed that significantly different spacecraft handling qualities result from the design of the Reaction Control System. In particular, cross-coupling between translational and rotational motions significantly affected handling qualities as reflected by Cooper-Harper pilot ratings and pilot workload, as reflected by Task-Load Index ratings. This influence is masked but only slightly by the rotational control system mode. While rotational control augmentation using Rate Command Attitude Hold can reduce the workload (principally, physical workload) created by cross-coupling, the handling qualities are not significantly improved. The attitude and rate deadbands of the RCAH introduced significant mental workload and control compensation to evaluate when deadband firings would occur, assess their impact on docking performance, and apply control inputs to mitigate that impact.

Distinct Involvement of the Gab1 and Grb2 Adaptor Proteins in Signal Transduction by the Related Receptor Tyrosine Kinases RON and MET

PubMed Central

Chaudhuri, Amitabha; Xie, Ming-Hong; Yang, Becky; Mahapatra, Kaushiki; Liu, Jinfeng; Marsters, Scot; Bodepudi, Sweta; Ashkenazi, Avi

2011-01-01

Although the signal transduction mechanisms of the receptor tyrosine kinase MET are well defined, less is known about its close relative RON. MET initiates intracellular signaling by autophosphorylation on specific cytoplasmic tyrosines that form docking sites for the adaptor proteins Grb2 and Gab1. Grb2 binds directly and is essential for all of the biological activities of MET. Gab1 docks either directly or indirectly via Grb2 and controls only a subset of MET functions. Because MET and RON possess similar adaptor binding sites, it was anticipated that their adaptor interactions would be conserved. Here we show that in contrast to MET, RON relies primarily on Gab1 for signal transmission. Surprisingly, disruption of the Grb2 docking site of RON or Grb2 depletion augments activity, whereas enhancement of Grb2 binding attenuates Gab1 recruitment and signaling. Hence, RON and MET differ in their adaptor interactions; furthermore, Grb2 performs a novel antagonistic role in the context of RON signaling. PMID:21784853

Comprehensive Mechanistic Analysis of Hits from High-Throughput and Docking Screens against β-Lactamase

PubMed Central

Babaoglu, Kerim; Simeonov, Anton; Irwin, John J.; Nelson, Michael E.; Feng, Brian; Thomas, Craig J.; Cancian, Laura; Costi, M. Paola; Maltby, David A.; Jadhav, Ajit; Inglese, James; Austin, Christopher P.; Shoichet, Brian K.

2009-01-01

High-throughput screening (HTS) is widely used in drug discovery. Especially for screens of unbiased libraries, false positives can dominate “hit lists”; their origins are much debated. Here we determine the mechanism of every active hit from a screen of 70,563 unbiased molecules against β-lactamase using quantitative HTS (qHTS). Of the 1274 initial inhibitors, 95% were detergent-sensitive and were classified as aggregators. Among the 70 remaining were 25 potent, covalent-acting β-lactams. Mass spectra, counter-screens, and crystallography identified 12 as promiscuous covalent inhibitors. The remaining 33 were either aggregators or irreproducible. No specific reversible inhibitors were found. We turned to molecular docking to prioritize molecules from the same library for testing at higher concentrations. Of 16 tested, 2 were modest inhibitors. Subsequent X-ray structures corresponded to the docking prediction. Analog synthesis improved affinity to 8 µM. These results suggest that it may be the physical behavior of organic molecules, not their reactivity, that accounts for most screening artifacts. Structure-based methods may prioritize weak-but-novel chemotypes in unbiased library screens. PMID:18333608

Initiation Mechanism of Kinesin’s Neck Linker Docking Process

NASA Astrophysics Data System (ADS)

Geng, Yi-Zhao; Zhang, Hui; Lyu, Gang; Ji, Qing

2017-02-01

Not Available Supported by the National Natural Science Foundation of China under Grant Nos 11545014 and 11605038, and the Open Project Program of State Key Laboratory of Theoretical Physics of Institute of Theoretical Physics of Chinese Academy of Science under Grant No Y5KF211CJ1.

Molecular mechanism of membrane binding of the GRP1 PH domain.

PubMed

Lai, Chun-Liang; Srivastava, Anand; Pilling, Carissa; Chase, Anna R; Falke, Joseph J; Voth, Gregory A

2013-09-09

The pleckstrin homology (PH) domain of the general receptor of phosphoinositides 1 (GRP1) protein selectively binds to a rare signaling phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), in the membrane. The specific PIP3 lipid docking of GRP1 PH domain is essential to protein cellular function and is believed to occur in a stepwise process, electrostatic-driven membrane association followed by the specific PIP3 binding. By a combination of all-atom molecular dynamics (MD) simulations, coarse-grained analysis, electron paramagnetic resonance (EPR) membrane docking geometry, and fluorescence resonance energy transfer (FRET) kinetic studies, we have investigated the search and bind process in the GRP1 PH domain at the molecular scale. We simulated the two membrane binding states of the GRP1 PH domain in the PIP3 search process, before and after the GRP1 PH domain docks with the PIP3 lipid. Our results suggest that the background anionic phosphatidylserine lipids, which constitute around one-fifth of the membrane by composition, play a critical role in the initial stages of recruiting protein to the membrane surface through non-specific electrostatic interactions. Our data also reveal a previously unseen transient membrane association mechanism that is proposed to enable a two-dimensional "hopping" search of the membrane surface for the rare PIP3 target lipid. We further modeled the PIP3-bound membrane-protein system using the EPR membrane docking structure for the MD simulations, quantitatively validating the EPR membrane docking structure and augmenting our understanding of the binding interface with atomic-level detail. Several observations and hypotheses reached from our MD simulations are also supported by experimental kinetic studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique.

PubMed

Tamhankar, Anup Sunil; Jatal, Sudhir; Saklani, Avanish

2016-12-01

This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Interaction between clay-based sealing components and crystalline host rock

NASA Astrophysics Data System (ADS)

Priyanto, D. G.; Dixon, D. A.; Man, A. G.

The results of hydraulic-mechanical (H-M) numerical simulation of a shaft seal installed at a fracture zone (FZ) in a crystalline host rock using the finite element method are presented. The primary function of a shaft seal is to limit short-circuiting of the groundwater flow regime via the shaft in a deep geological repository. Two different stages of system evolution were considered in this numerical modelling. Stage 1 simulates the groundwater flow into an open shaft, prior to seal installation. Stage 2 simulates the groundwater flow into the shaft seal after seal installation. Four different cases were completed to: (i) evaluate H-M response due to the interaction between clay-based sealing material and crystalline host rock in the shaft seal structure; (ii) quantify the effect of the different times between the completion of the shaft excavation and the completion of shaft seal installation on the H-M response; and (iii) define the potential effects of different sealing material configurations. Shaft sealing materials include the bentonite-sand mixture (BSM), dense backfill (DBF), and concrete plug (CP). The BSM has greater swelling capacity and lower hydraulic conductivity ( K) than the DBF. The results of these analyses show that the decrease of the pore water pressure is concentrated along the fracture zone (FZ), which has the greatest K. As the time increases, the greatest decrease in pore water pressure is found around the FZ. Following FZ isolation and the subsequent filling of the shaft with water as it floods, the pore water pressure profile tends to recover back to the initial conditions prior to shaft excavation. The majority of the fluids that ultimately saturate the centre of the shaft seal flow radially inwards from the FZ. The time between the completion of the shaft excavation and the completion of shaft seal installation has a significant effect on the saturation time. A shorter time can reduce the saturation time. Since most of the inflow comes from the FZ, application of the BSM for extended distances above and below the FZ does not significantly affect the saturation time of the volume adjacent to the FZ. The application of BSM near the FZ rather than a low swelling capacity, more permeable filling material is very significant. This study assumed a perfect contact between seal materials and host rock. Limited to the assumptions used in this study, use of BSM near the FZ was found to increase the time before the centre of the shaft seal became fully saturated from between 4 and 30 years (when the DBF is used) to between 90 and 100 years (when the BSM is used).

Shifts in Ross Sea food web structure as indicated by δ15N and δ13C values of fossil Antarctic seals

NASA Astrophysics Data System (ADS)

Leopold, A.; Brault, E.; McMahon, K.

2013-12-01

As climate change continues to mount, there is a growing need for understanding its effects on biological-physical interactions of marine ecosystems. Assessing the effects of anthropogenic activities on the coastal marine ecosystem involves understanding the underlying mechanisms driving these changes as well as establishing baselines of the natural system. Preliminary findings have indicated shifts in bulk carbon (C) and nitrogen (N) isotopic values of southern elephant seal (Mirounga leonina) samples, collected in the Dry Valleys of Antarctica in the Ross Sea region, over approximately the last 7,000 years. These shifts could result from 1) seals changing their foraging location and/or diet over this time, 2) climate change-induced shifts in the biogeochemistry at the base of the food web, or 3) some combination of both processes. We explored the patterns of long-term change in Ross Sea food web structure by examining the stable isotope values of three top predators in this system, Weddell seals (Leptonychotes weddellii), leopard seals (Hydrurga leptonyx), and crabeater seals (Lobodon carcinophagus). Fossil seal samples were collected in the Dry Valleys during the austral summer of 2012/13 and then analyzed for bulk C and N isotopes via an elemental analyzer/isotope-ratio mass spectrometer (EA/IRMS). Our initial findings indicate that C isotopic values of fossil seal samples from Weddell, leopard, and crabeater seals were more enriched than isotopic values of modern seals of the same species (e.g., δ13C = -22.79 × 0.92 ‰ and -26.71 × 0.50 ‰ for fossil and modern crabeater seals, respectively). Given the relatively consistent diet of crabeater seals, these findings suggest a shift in baseline food web structure occurred over the last 10,000 years, either through changes in foraging location or local shifts in biogeochemistry. For all species, N isotopic values are widely variable (e.g., 7.28 to 16.0 δ15N ‰ for the Weddell seal), which may be a result of greatly changing diets in the last ~10,000 years, or a changing baseline N value for the Ross Sea. Seal bones will be radiocarbon-dated to isolate the key shifts in C and N isotopic values. Once those major shifts are temporally constrained, compound-specific isotopic analysis of the bone samples will be used to tease apart the diet vs. baseline effects on the bulk isotopic signatures of the seals. Our results suggests that during the last ~10,000 years, there was a fundamental shift in Ross Sea food web structure likely related to long term climatic variability.

Escherichia coli Ribosomal Protein S1 Unfolds Structured mRNAs Onto the Ribosome for Active Translation Initiation

PubMed Central

Duval, Mélodie; Korepanov, Alexey; Fuchsbauer, Olivier; Fechter, Pierre; Haller, Andrea; Fabbretti, Attilio; Choulier, Laurence; Micura, Ronald; Klaholz, Bruno P.; Romby, Pascale; Springer, Mathias; Marzi, Stefano

2013-01-01

Regulation of translation initiation is well appropriate to adapt cell growth in response to stress and environmental changes. Many bacterial mRNAs adopt structures in their 5′ untranslated regions that modulate the accessibility of the 30S ribosomal subunit. Structured mRNAs interact with the 30S in a two-step process where the docking of a folded mRNA precedes an accommodation step. Here, we used a combination of experimental approaches in vitro (kinetic of mRNA unfolding and binding experiments to analyze mRNA–protein or mRNA–ribosome complexes, toeprinting assays to follow the formation of ribosomal initiation complexes) and in vivo (genetic) to monitor the action of ribosomal protein S1 on the initiation of structured and regulated mRNAs. We demonstrate that r-protein S1 endows the 30S with an RNA chaperone activity that is essential for the docking and the unfolding of structured mRNAs, and for the correct positioning of the initiation codon inside the decoding channel. The first three OB-fold domains of S1 retain all its activities (mRNA and 30S binding, RNA melting activity) on the 30S subunit. S1 is not required for all mRNAs and acts differently on mRNAs according to the signals present at their 5′ ends. This work shows that S1 confers to the ribosome dynamic properties to initiate translation of a large set of mRNAs with diverse structural features. PMID:24339747

Hydra Rendezvous and Docking Sensor

NASA Technical Reports Server (NTRS)

Roe, Fred; Carrington, Connie

2007-01-01

The U.S. technology to support a CEV AR&D activity is mature and was developed by NASA and supporting industry during an extensive research and development program conducted during the 1990's and early 2000 time frame at the Marshall Space Flight Center. Development and demonstration of a rendezvous/docking sensor was identified early in the AR&D Program as the critical enabling technology that allows automated proxinity operations and docking. A first generation rendezvous/docking sensor, the Video Guidance Sensor (VGS) was developed and successfully flown on STS 87 and again on STS 95, proving the concept of a video-based sensor. Advances in both video and signal processing technologies and the lessons learned from the two successful flight experiments provided a baseline for the development of a new generation of video based rendezvous/docking sensor. The Advanced Video Guidance Sensor (AVGS) has greatly increased performance and additional capability for longer-range operation. A Demonstration Automatic Rendezvous Technology (DART) flight experiment was flown in April 2005 using AVGS as the primary proximity operations sensor. Because of the absence of a docking mechanism on the target satellite, this mission did not demonstrate the ability of the sensor to coltrold ocking. Mission results indicate that the rendezvous sensor operated successfully in "spot mode" (2 km acquisition of the target, bearing data only) but was never commanded to "acquire and track" the docking target. Parts obsolescence issues prevent the construction of current design AVGS units to support the NASA Exploration initiative. This flight proven AR&D technology is being modularized and upgraded with additional capabilities through the Hydra project at the Marshall Space Flight Center. Hydra brings a unique engineering approach and sensor architecture to the table, to solve the continuing issues of parts obsolescence and multiple sensor integration. This paper presents an approach to sensor hardware trades, to address the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS). It will also discuss approaches for upgrading AVGS to address parts obsolescence, and concepts for modularizing the sensor to provide configuration flexibility for multiple vehicle applications. Options for complementary sensors to be integrated into the multi-head Hydra system will also be presented. Complementary sensor options include ULTOR, a digital image correlator system that could provide relative six-degree-of-freedom information independently from AVGS, and time-of-flight sensors, which determine the range between vehicles by timing pulses that travel from the sensor to the target and back. Common targets and integrated targets, suitable for use with the multi-sensor options in Hydra, will also be addressed.

Centaur Standard Shroud (CSS) cryogenic unlatch tests

NASA Technical Reports Server (NTRS)

1973-01-01

Cryogenic tanking and partial jettison (unlatch) tests were performed on a full scale Centaur vehicle and Centaur Standard Shroud (CSS) to develop and qualify the CSS insulation system, the CSS and Centaur ground-hold purge systems, and the Centaur hydrogen tank flight vent system. Operation of the shroud/Centaur pyrotechnic systems, seals, and the shroud jettison springs, hinges, and other separation systems was demonstrated by a partial jettison of the shroud into catch nets. The Centaur tanks were filled with liquid hydrogen and liquid nitrogen. Prelaunch operations were performed, and data taken to establish system performances. Results from the initial tests showed a higher than expected heat transfer rate to the Centaur hydrogen tank. In addition, the release mechanism for the forward seal between the Centaur and the CSS did not function properly, and the seal was torn during jettison of the shroud.

Implementation as a Focus of Consultation to Evaluate Academic Tutoring Services in an Urban School District: A Case Study Example

ERIC Educational Resources Information Center

Morrison, Julie Q.; English, Sarah Baker

2012-01-01

This article describes a multiagency initiative to evaluate academic tutoring services by focusing on the processes that contribute to effective program implementation. Community-based tutoring service providers serving students in the Cincinnati Public Schools (OH) partnered to initiate a "Seal of Approval" process for promoting…

Isothermal dendritic growth experiment: Science, engineering, and hardware development for USMP space flights

NASA Astrophysics Data System (ADS)

Glicksman, M. E.; Hahn, R. C.; Koss, M. B.; Tirmizi, S. H.; Selleck, M. E.; Velosa, A.; Winsa, E.

The Isothermal Dendritic Growth Experiment (IDGE) has been designed to provide microgravity data on dendritic growth for a critical test of theory. This paper updates our progress on constructing a crystal growth chamber suitable for space flight. The IDGE chamber is constructed from glass and stainless steel and is hermetically sealed by electron beam welds and glass-metal seals. Initial tests of the chambers sample's melting point plateau show that the new chamber design is capable of preserving the 99.9995 pct purity of succinonitrile (SCN). One can initiate dendrite growth in the center of the IDGE chamber by means of thermo-electric coolers and a capillary injector tube (stinger). The new IDGE chamber is ready for fully integrated tests with the prototype IDGE engineering hardware at NASA's Lewis Research Center.

Sliding durability of candidate seal fiber materials in hydrogen from 25 to 900 C

NASA Technical Reports Server (NTRS)

Dellacorte, Christopher; Steinetz, Bruce M.

1992-01-01

Sliding durability studies of candidate ceramic fibers were conducted in hydrogen to support the high temperature seal development program at NASA LeRC. Pin-on-disk tests were used to measure the friction and durability of a tow or bundle of ceramic fibers in sliding against a superalloy disk. This procedure was used previously to test candidate fibers in an air environment. The fibers based upon mullite (Al2O3-SiO2) chemistry (Nextel 550, 440, and 312) exhibited better durability in hydrogen than in air. HPZ, a complex silicon carboxynitride fiber which showed good durabilty in air, however, showed a significant loss of durability in hot hydrogen. These results are consistent with recent thermodynamic and experimental studies of ceramic compatibility with hydrogen at elevated temperatures. These research results indicate that only oxide fibers display good durability in both air and hydrogen environments. Also, simple, low cost testing in air can provide an adequate data base for initial seal material screening and selection, especially for oxide fiber candidates. The findings of this research provide critical input to the seal design team.

Lifespan estimation of seal welded super stainless steels for water condenser of nuclear power plants

NASA Astrophysics Data System (ADS)

Kim, Young Sik; Park, Sujin; Chang, Hyun Young

2014-01-01

When sea water was used as cooling water for water condenser of nuclear power plants, commercial stainless steels can not be applied because chloride concentration exceeds 20,000 ppm. There are many opinions for the materials selection of tube and tube sheets of a condenser. This work reviewed the application guide line of stainless steels for sea-water facilities and the estimation equations of lifespan were proposed from the analyses of both field data for sea water condenser and experimental results of corrosion. Empirical equations for lifespan estimation were derived from the pit initiation time and re-tubing time of stainless steel tubing in sea water condenser of nuclear power plants. The lifespan of seal-welded super austenitic stainless steel tube/tube sheet was calculated from these equations. Critical pitting temperature of seal-welded PRE 50 grade super stainless steel was evaluated as 60 °C. Using the proposed equation in engineering aspect, tube pitting corrosion time of seal-welded tube/tube sheet was calculated as 69.8 years and re-tubing time was estimated as 82.0 years.

AMTEC recirculating test cell component testing and operation

NASA Technical Reports Server (NTRS)

Underwood, M. L.; Sievers, R. K.; O'Connor, D.; Williams, R. M.; Jeffries-Nakamura, B.; Bankston, C. P.

1989-01-01

Alkali metal thermoelectric converter operation in a recirculating test cell (RTC), which requires a small electromagnetic pump (EM) and a high-temperature beta-double-prime alumina-solid-electrolyte (BASE)-to-metal seal, is discussed. The design of a pump and an active metal braze seal and the initial operation of a cell using these components are described. The pump delivered 0.25 cu cm/min against a 28-psia head. A braze seal system was selected after shear strength tests of Ta or Nb brazed to BASE by a variety of fillers including TiCuNi, TiNi, and TiNiCr. The TiCuNi filler was chosen for environment cell testing and showed no failure or observable degradation after short-term tests up to 1055 K. The pump and the Nb/TiCuNi/BASE seal were used in a test that demonstrated all the operational functions of the RTC for the first time. An increase in the radiation reduction factor at constant input power was observed, indicating that the condenser was being wet by sodium resulting in an increased reflectivity.

Protein docking prediction using predicted protein-protein interface.

PubMed

Li, Bin; Kihara, Daisuke

2012-01-10

Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm), is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

Lessons in molecular recognition. 2. Assessing and improving cross-docking accuracy.

PubMed

Sutherland, Jeffrey J; Nandigam, Ravi K; Erickson, Jon A; Vieth, Michal

2007-01-01

Docking methods are used to predict the manner in which a ligand binds to a protein receptor. Many studies have assessed the success rate of programs in self-docking tests, whereby a ligand is docked into the protein structure from which it was extracted. Cross-docking, or using a protein structure from a complex containing a different ligand, provides a more realistic assessment of a docking program's ability to reproduce X-ray results. In this work, cross-docking was performed with CDocker, Fred, and Rocs using multiple X-ray structures for eight proteins (two kinases, one nuclear hormone receptor, one serine protease, two metalloproteases, and two phosphodiesterases). While average cross-docking accuracy is not encouraging, it is shown that using the protein structure from the complex that contains the bound ligand most similar to the docked ligand increases docking accuracy for all methods ("similarity selection"). Identifying the most successful protein conformer ("best selection") and similarity selection substantially reduce the difference between self-docking and average cross-docking accuracy. We identify universal predictors of docking accuracy (i.e., showing consistent behavior across most protein-method combinations), and show that models for predicting docking accuracy built using these parameters can be used to select the most appropriate docking method.

Conceptual design of a moving belt radiator shuttle-attached experiments: Technical requirement Document

NASA Technical Reports Server (NTRS)

Aguilar, Jerry L.

1989-01-01

The technical requirements for a shuttle-attached Moving Belt Radiator (MBR) experiment are defined. The MBR is an advanced radiator concept in which a rotating belt radiates thermal energy to space. The requirements for integrating the MBR experiment in the shuttle bay are discussed. Requirements for the belt material and working fluid are outlined along with some possible options. The proposed size and relationship to a full scale Moving Belt Radiator are defined. The experiment is defined with the primary goal of dynamic testing and a secondary goal of demonstrating the sealing and heat transfer characteristics. A perturbation system which will simulate a docking maneuver or other type of short term acceleration is proposed for inclusion in the experimental apparatus. A deployment and retraction capability which will aid in evaluating the dynamics of a belt during such a maneuver is also described. The proposed test sequence for the experiment is presented. Details of the conceptual design are not presented herein, but rather in a separate Final Report.

Easy-To-Use Connector

NASA Technical Reports Server (NTRS)

Wightman, William D.; Gernhardt, Michael

1993-01-01

Quick-connect/disconnect mechanism consists of two mating assemblies put together easily, even when initially misaligned by fairly large amounts. Used as electrical- or fluid-connection interface. Operated by humans or robots when fast connections must be made without precise positioning, -- for example, on offshore oil rigs, ship-to-dock links, nuclear facilities, and aircraft at loading gates.

Distribution and survival of Pseudomonas sp. on Italian ryegrass and Curly dock in Georgia

USDA-ARS?s Scientific Manuscript database

Yellow bud, caused by Pseudomonas sp. is an emerging bacterial disease of onion. Polymerase chain reaction (PCR) assay based on the coronafacate ligase (cfl) and HrpZ genes were used to detect initial suspected bacteria on weeds. Growth on an agar medium, ability to cause a hypersensitive response i...

PharmDock: a pharmacophore-based docking program

PubMed Central

2014-01-01

Background Protein-based pharmacophore models are enriched with the information of potential interactions between ligands and the protein target. We have shown in a previous study that protein-based pharmacophore models can be applied for ligand pose prediction and pose ranking. In this publication, we present a new pharmacophore-based docking program PharmDock that combines pose sampling and ranking based on optimized protein-based pharmacophore models with local optimization using an empirical scoring function. Results Tests of PharmDock on ligand pose prediction, binding affinity estimation, compound ranking and virtual screening yielded comparable or better performance to existing and widely used docking programs. The docking program comes with an easy-to-use GUI within PyMOL. Two features have been incorporated in the program suite that allow for user-defined guidance of the docking process based on previous experimental data. Docking with those features demonstrated superior performance compared to unbiased docking. Conclusion A protein pharmacophore-based docking program, PharmDock, has been made available with a PyMOL plugin. PharmDock and the PyMOL plugin are freely available from http://people.pharmacy.purdue.edu/~mlill/software/pharmdock. PMID:24739488

An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design.

PubMed

Ballante, Flavio; Marshall, Garland R

2016-01-25

Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated.

Characterizing SHP2 as a Novel Therapeutic Target in Breast Cancer

DTIC Science & Technology

2012-02-01

50(12), 2339-56. doi:10.1021/bi1014453 Zhang, X., He, Y., Liu, S., Yu, Z., Jiang, Z. X., Yang, Z., Dong, Y., et al. (2010). Salicylic Acid Based...Overall, what we have found so far has been surprising, with the data suggesting that the presence of a -2 acidic residue in the substrate peptide...helped to refine the initial docking poses, with the initial hypothesis being that the pY -1 and -4 position acidic amino acids will bind a pair of

Long-term animal experiments with an intraventricular axial flow blood pump.

PubMed

Yamazaki, K; Kormos, R L; Litwak, P; Tagusari, O; Mori, T; Antaki, J F; Kameneva, M; Watach, M; Gordon, L; Mukuo, H; Umezu, M; Tomioka, J; Outa, E; Griffith, B P; Koyanagai, H

1997-01-01

A miniature intraventricular axial flow blood pump (IVAP) is undergoing in vivo evaluation in calves. The IVAP system consists of a miniature (phi 13.9 mm) axial flow pump that resides within the left ventricular (LV) chamber and a brushless DC motor. The pump is fabricated from titanium alloy, and the pump weight is 170 g. It produces a flow rate of over 5 L/min against 100 mmHg pressure at 9,000 rpm with an 8 W total power consumption. The maximum total efficiency exceeds 17%. A purged lip seal system is used in prototype no. 8, and a newly developed "Cool-Seal" (a low temperature mechanical seal) is used in prototype no. 9. In the Cool-Seal system, a large amount of purge flow is introduced behind the seal faces to augment convective heat transfer, keeping the seal face temperature at a low level for prevention of heat denaturation of blood proteins. The Cool-Seal system consumes < 10 cc purge fluid per day and has greatly extended seal life. The pumps were implanted in three calves (26, 30, and 168 days of support). The pump was inserted through a left thoracotomy at the fifth intercostal space. Two pursestring sutures were placed on the LV apex, and the apex was cored with a myocardial punch. The pump was inserted into the LV with the outlet cannula smoothly passing through the aortic valve without any difficulty. Only 5 min elapsed between the time of chest opening and initiation of pumping. Pump function remained stable throughout in all experiments. No cardiac arrhythmias were detected, even at treadmill exercise tests. The plasma free hemoglobin level remained in the acceptable range. Post mortem examination did not reveal any interference between the pump and the mitral apparatus. No major thromboembolism was detected in the vital organs in Cases 1 or 2, but a few small renal infarcts were detected in Case 3.

InterEvDock2: an expanded server for protein docking using evolutionary and biological information from homology models and multimeric inputs.

PubMed

Quignot, Chloé; Rey, Julien; Yu, Jinchao; Tufféry, Pierre; Guerois, Raphaël; Andreani, Jessica

2018-05-08

Computational protein docking is a powerful strategy to predict structures of protein-protein interactions and provides crucial insights for the functional characterization of macromolecular cross-talks. We previously developed InterEvDock, a server for ab initio protein docking based on rigid-body sampling followed by consensus scoring using physics-based and statistical potentials, including the InterEvScore function specifically developed to incorporate co-evolutionary information in docking. InterEvDock2 is a major evolution of InterEvDock which allows users to submit input sequences - not only structures - and multimeric inputs and to specify constraints for the pairwise docking process based on previous knowledge about the interaction. For this purpose, we added modules in InterEvDock2 for automatic template search and comparative modeling of the input proteins. The InterEvDock2 pipeline was benchmarked on 812 complexes for which unbound homology models of the two partners and co-evolutionary information are available in the PPI4DOCK database. InterEvDock2 identified a correct model among the top 10 consensus in 29% of these cases (compared to 15-24% for individual scoring functions) and at least one correct interface residue among 10 predicted in 91% of these cases. InterEvDock2 is thus a unique protein docking server, designed to be useful for the experimental biology community. The InterEvDock2 web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock2/.

Binding Mode Analyses and Pharmacophore Model Development for Stilbene Derivatives as a Novel and Competitive Class of α-Glucosidase Inhibitors

PubMed Central

Kim, Jun Young; Arooj, Mahreen; Kim, Siu; Hwang, Swan; Kim, Byeong-Woo; Park, Ki Hun; Lee, Keun Woo

2014-01-01

Stilbene urea derivatives as a novel and competitive class of non-glycosidic α-glucosidase inhibitors are effective for the treatment of type II diabetes and obesity. The main purposes of our molecular modeling study are to explore the most suitable binding poses of stilbene derivatives with analyzing the binding affinity differences and finally to develop a pharmacophore model which would represents critical features responsible for α-glucosidase inhibitory activity. Three-dimensional structure of S. cerevisiae α-glucosidase was built by homology modeling method and the structure was used for the molecular docking study to find out the initial binding mode of compound 12, which is the most highly active one. The initial structure was subjected to molecular dynamics (MD) simulations for protein structure adjustment at compound 12-bound state. Based on the adjusted conformation, the more reasonable binding modes of the stilbene urea derivatives were obtained from molecular docking and MD simulations. The binding mode of the derivatives was validated by correlation analysis between experimental Ki value and interaction energy. Our results revealed that the binding modes of the potent inhibitors were engaged with important hydrogen bond, hydrophobic, and π-interactions. With the validated compound 12-bound structure obtained from combining approach of docking and MD simulation, a proper four featured pharmacophore model was generated. It was also validated by comparison of fit values with the Ki values. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from stilbene derivatives. PMID:24465730

76 FR 10335 - Ball Bearings and Parts Thereof From Germany: Initiation of Antidumping Duty Changed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-24

... classified under the following categories: Antifriction balls, ball bearings with integral shafts, ball..., outer race, cage, rollers, balls, seals, shields, etc.) outlined above with certain limitations. With...

49 CFR 178.813 - Leakproofness test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... vent must be sealed. For metal IBC design types, the initial test must be carried out before the... the seams and joints with a heavy oil, a soap solution and water, or other methods suitable for the...

Neural networks for self-learning control systems

NASA Technical Reports Server (NTRS)

Nguyen, Derrick H.; Widrow, Bernard

1990-01-01

It is shown how a neural network can learn of its own accord to control a nonlinear dynamic system. An emulator, a multilayered neural network, learns to identify the system's dynamic characteristics. The controller, another multilayered neural network, next learns to control the emulator. The self-trained controller is then used to control the actual dynamic system. The learning process continues as the emulator and controller improve and track the physical process. An example is given to illustrate these ideas. The 'truck backer-upper,' a neural network controller that steers a trailer truck while the truck is backing up to a loading dock, is demonstrated. The controller is able to guide the truck to the dock from almost any initial position. The technique explored should be applicable to a wide variety of nonlinear control problems.

40 CFR 60.5411 - What additional requirements must I meet to determine initial compliance for my covers and closed...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 7 2014-07-01 2014-07-01 false What additional requirements must I meet to determine initial compliance for my covers and closed vent systems routing materials from storage vessels and centrifugal compressor wet seal degassing systems? 60.5411 Section 60.5411 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY ...

40 CFR 60.5411 - What additional requirements must I meet to determine initial compliance for my closed vent...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 7 2013-07-01 2013-07-01 false What additional requirements must I meet to determine initial compliance for my closed vent systems routing materials from storage vessels and centrifugal compressor wet seal degassing systems? 60.5411 Section 60.5411 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic insights into the anti-herpetic mode of action of herbal drug withaferin A.

PubMed

Grover, Abhinav; Agrawal, Vibhuti; Shandilya, Ashutosh; Bisaria, Virendra S; Sundar, Durai

2011-01-01

Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug. Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured. We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex virus. Results of these studies will also guide the design of selective inhibitors of DNA POL with high specificity and potent activity in order to strengthen the therapeutic arsenal available today against the dangerous biological warfare agent represented by Herpes Simplex Virus.

Non-nucleosidic inhibition of Herpes simplex virus DNA polymerase: mechanistic insights into the anti-herpetic mode of action of herbal drug withaferin A

PubMed Central

2011-01-01

Background Herpes Simplex Virus 1 and 2 causes several infections in humans including cold sores and encephalitis. Previous antiviral studies on herpes viruses have focussed on developing nucleoside analogues that can inhibit viral polymerase and terminate the replicating viral DNA. However, these drugs bear an intrinsic non-specificity as they can also inhibit cellular polymerase apart from the viral one. The present study is an attempt to elucidate the action mechanism of naturally occurring withaferin A in inhibiting viral DNA polymerase, thus providing an evidence for its development as a novel anti-herpetic drug. Results Withaferin A was found to bind very similarly to that of the previously reported 4-oxo-DHQ inhibitor. Withaferin A was observed binding to the residues Gln 617, Gln 618, Asn 815 and Tyr 818, all of which are crucial to the proper functioning of the polymerase. A comparison of the conformation obtained from docking and the molecular dynamics simulations shows that substantial changes in the binding conformations have occurred. These results indicate that the initial receptor-ligand interaction observed after docking can be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favoured. Conclusions We have performed docking and molecular dynamics simulation studies to elucidate the binding mechanism of prospective herbal drug withaferin A onto the structure of DNA polymerase of Herpes simplex virus. Our docking simulations results give high binding affinity of the ligand to the receptor. Long de novo MD simulations for 10 ns performed allowed us to evaluate the dynamic behaviour of the system studied and corroborate the docking results, as well as identify key residues in the enzyme-inhibitor interactions. The present MD simulations support the hypothesis that withaferin A is a potential ligand to target/inhibit DNA polymerase of the Herpes simplex virus. Results of these studies will also guide the design of selective inhibitors of DNA POL with high specificity and potent activity in order to strengthen the therapeutic arsenal available today against the dangerous biological warfare agent represented by Herpes Simplex Virus. PMID:22373101

The 100 ampere-hour nickel cadmium battery development program, volume 1

NASA Technical Reports Server (NTRS)

Gaston, S.

1974-01-01

A program to develop a long-life, reliable and safe 100 ampere-hour sealed nickel-cadmium cell and battery module with ancillary charge control and automated test equipment to fulfill the requirements of a large Manned Orbital Space Station which uses Solar Arrays as its prime source for 25 kW of electrical power was conducted. A sealed 100 ampere-hour cell with long life potential and a replaceable, space maintainable battery module has been developed for Manned Space Station applications. The 100 ampere-hour cell has been characterized for initial (early life) anticipated conditions.

Pitting and Repair of the Space Shuttle's Inconel(Registered TradeMark) Honeycomb Conical Seal Panel

NASA Technical Reports Server (NTRS)

Zimmerman, Frank R.; Gentz, Steven J.; Miller, James B.; MacKay, Rebecca A.; Bright, Mark L.

2006-01-01

During return to flight servicing of the rudder speed brake (RSB) for each Space Shuttle Orbiter, inspectors discovered numerous small pits on the surface of the #4 right hand side honeycomb panel that covers the rudder speed brake actuators. Shortly after detection of the problem, concurrent investigations were initiated to determine the extent of damage, the root cause, and to develop a repair plan, since fabrication of a replacement panel is impractical for cost, schedule, and sourcing considerations. This paper describes the approach, findings, conclusions and recommendations associated with the investigation of the conical seal pitting. It documents the cause and contributing factors of the pitting, the means used to isolate each contributor, and the supporting evidence for the primary cause of the pitting. Finally, the selection, development and verification of the repair procedure used to restore the conical seal panel is described with supporting process and metallurgical rationale for selection.

F2Dock: Fast Fourier Protein-Protein Docking

PubMed Central

Bajaj, Chandrajit; Chowdhury, Rezaul; Siddavanahalli, Vinay

2009-01-01

The functions of proteins is often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination and understanding function and structure relationships. In this paper we extend our non-uniform fast Fourier transform docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic potential based scores only, F2Dock is structured to incorporate Lennard-Jones potential and re-ranking docking solutions based on desolvation energy. PMID:21071796

Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach

NASA Astrophysics Data System (ADS)

Lam, Polo C.-H.; Abagyan, Ruben; Totrov, Maxim

2018-01-01

Ligand docking to flexible protein molecules can be efficiently carried out through ensemble docking to multiple protein conformations, either from experimental X-ray structures or from in silico simulations. The success of ensemble docking often requires the careful selection of complementary protein conformations, through docking and scoring of known co-crystallized ligands. False positives, in which a ligand in a wrong pose achieves a better docking score than that of native pose, arise as additional protein conformations are added. In the current study, we developed a new ligand-biased ensemble receptor docking method and composite scoring function which combine the use of ligand-based atomic property field (APF) method with receptor structure-based docking. This method helps us to correctly dock 30 out of 36 ligands presented by the D3R docking challenge. For the six mis-docked ligands, the cognate receptor structures prove to be too different from the 40 available experimental Pocketome conformations used for docking and could be identified only by receptor sampling beyond experimentally explored conformational subspace.

Molecular docking.

PubMed

Morris, Garrett M; Lim-Wilby, Marguerita

2008-01-01

Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?

PubMed

Ramírez, David; Caballero, Julio

2018-04-28

Molecular docking is the most frequently used computational method for studying the interactions between organic molecules and biological macromolecules. In this context, docking allows predicting the preferred pose of a ligand inside a receptor binding site. However, the selection of the “best” solution is not a trivial task, despite the widely accepted selection criterion that the best pose corresponds to the best energy score. Here, several rigid-target docking methods were evaluated on the same dataset with respect to their ability to reproduce crystallographic binding orientations, to test if the best energy score is a reliable criterion for selecting the best solution. For this, two experiments were performed: (A) to reconstruct the ligand-receptor complex by performing docking of the ligand in its own crystal structure receptor (defined as self-docking), and (B) to reconstruct the ligand-receptor complex by performing docking of the ligand in a crystal structure receptor that contains other ligand (defined as cross-docking). Root-mean square deviation (RMSD) was used to evaluate how different the obtained docking orientation is from the corresponding co-crystallized pose of the same ligand molecule. We found that docking score function is capable of predicting crystallographic binding orientations, but the best ranked solution according to the docking energy is not always the pose that reproduces the experimental binding orientation. This happened when self-docking was achieved, but it was critical in cross-docking. Taking into account that docking is typically used with predictive purposes, during cross-docking experiments, our results indicate that the best energy score is not a reliable criterion to select the best solution in common docking applications. It is strongly recommended to choose the best docking solution according to the scoring function along with additional structural criteria described for analogue ligands to assure the selection of a correct docking solution.

Computation-based virtual screening for designing novel antimalarial drugs by targeting falcipain-III: a structure-based drug designing approach.

PubMed

Kesharwani, Rajesh Kumar; Singh, Durg Vijay; Misra, Krishna

2013-01-01

Cysteine proteases (falcipains), a papain-family of enzymes of Plasmodium falciparum, are responsible for haemoglobin degradation and thus necessary for its survival during asexual life cycle phase inside the human red blood cells while remaining non-functional for the human body. Therefore, these can act as potential targets for designing antimalarial drugs. The P. falciparum cysteine proteases, falcipain-II and falcipain- III are the enzymes which initiate the haemoglobin degradation, therefore, have been selected as targets. In the present study, we have designed new leupeptin analogues and subjected to virtual screening using Glide at the active site cavity of falcipain-II and falcipain-III to select the best docked analogues on the basis of Glide score and also compare with the result of AutoDock. The proposed analogues can be synthesized and tested in vivo as future potent antimalarial drugs. Protein falcipain-II and falcipain-III together with bounds inhibitors epoxysuccinate E64 (E64) and leupeptin respectively were retrieved from protein data bank (PDB) and latter leupeptin was used as lead molecule to design new analogues by using Ligbuilder software and refined the molecules on the basis of Lipinski rule of five and fitness score parameters. All the designed leupeptin analogues were screened via docking simulation at the active site cavity of falcipain-II and falcipain-III by using Glide software and AutoDock. The 104 new leupeptin-based antimalarial ligands were designed using structure-based drug designing approach with the help of Ligbuilder and subjected for virtual screening via docking simulation method against falcipain-II and falcipain-III receptor proteins. The Glide docking results suggest that the ligands namely result_037 shows good binding and other two, result_044 and result_042 show nearly similar binding than naturally occurring PDB bound ligand E64 against falcipain-II and in case of falcipain-III, 15 designed leupeptin analogues having better binding affinity compared to the PDB bound inhibitor of falcipain-III. The docking simulation results of falcipain-III with designed leupeptin analogues using Glide compared with AutoDock and find 80% similarity as better binder than leupeptin. These results further highlight new leupeptin analogues as promising future inhibitors for chemotherapeutic prevention of malaria. The result of Glide for falcipain-III has been compared with the result of AutoDock and finds very less differences in their order of binding affinity. Although there are no extra hydrogen bonds, however, equal number of hydrogen bonds with variable strength as compared to leupeptin along with the enhanced hydrophobic and electrostatic interactions in case of analogues supports our study that it holds the ligand molecules strongly within the receptor. The comparative e-pharmacophoric study also suggests and supports our predictions regarding the minimum features required in ligand molecule to behave as falcipain- III inhibitors and is also helpful in screening the large database as future antimalarial inhibitors.

Fourth Report of the Task Force on the Shuttle-Mir Rendezvous and Docking Missions

NASA Technical Reports Server (NTRS)

1995-01-01

On December 6, 1994, the NASA Administrator, Mr. Daniel Goldin, requested that Lt. Gen. Thomas P. Stafford, in his role as the Chairman of the NASA Advisory Council Task Force on the Shuttle-Mir Rendezvous and Docking Missions, lead a team composed of several Task Force members and technical advisors' to Russia with the goal of reviewing preparations and readiness for the upcoming international Space Station Phase 1 missions. In his directions to Gen. Stafford, Mr. Goldin requested that the review team focus its initial efforts on safety of flight issues for the following Phase 1A missions: the Soyuz TM-21 mission which will carry U.S. astronaut Dr. Norman Thagard and cosmonauts Lt. Col. Vladimir Dezhurov and Mr. Gennady Strekalov aboard a Soyuz spacecraft to the Mir Station; the Mir 18 Main Expedition during which Thagard and his fellow cosmonauts, Dezhurov and Strokalov, will spend approximately three months aboard the Mir Station; the STS-71 Space Shuttle mission which will perform the first Shuttle-Mir docking, carry cosmonauts Col. Anatoly SoloViev and Mr. Nikolai Budarin to the Mir Station, and return Thagard, Dezhurov, and Strekalov to Earth.

SRMS Assisted Docking and Undocking for the Orbiter Repair Maneuver

NASA Technical Reports Server (NTRS)

Quiocho, Leslie J.; Briscoe, Timothy J.; Schliesing, John A.; Braman, Julia M.

2005-01-01

As part of the Orbiter Repair Maneuver (ORM) planned for Return to Flight (RTF) operations, the Shuttle Remote Manipulator System (SRMS) must undock the Orbiter, maneuver it through a complex trajectory at extremely low rates, present it to an EVA crewman at the end of the Space Station Remote Manipulator System to perform the Thermal Protection System (TPS) repair, and then retrace back through the trajectory to dock the Orbiter with the Orbiter Docking System (ODs). The initial and final segments of this operation involve the interaction between the SRMS, ISS, Orbiter and ODs. This paper first provides an overview of the Monte-Carlo screening analysis for the installation (both nominal and contingency), including the variation of separation distance, misalignment conditions, SRMS joint/brake parameter characteristics, and PRCS jet combinations and corresponding thrust durations. The resulting 'optimum' solution is presented based on trade studies between predicted capture success and integrated system loads. This paper then discusses the upgrades to the APAS math model associated with the new SRMS assisted undocking technique and reviews simulation results for various options investigated for either the active and passive separation of the ISS from the Orbiter.

Six degree of freedom FORTRAN program, ASTP docking dynamics, users guide

NASA Technical Reports Server (NTRS)

Mount, G. O., Jr.; Mikhalkin, B.

1974-01-01

The digital program ASTP Docking Dynamics as outlined is intended to aid the engineer using the program to determine the docking system loads and attendant vehicular motion resulting from docking two vehicles that have an androgynous, six-hydraulic-attenuator, guide ring, docking interface similar to that designed for the Apollo/Soyuz Test Project (ASTP). This program is set up to analyze two different vehicle combinations: the Apollo CSM docking to Soyuz and the shuttle orbiter docking to another orbiter. The subroutine modifies the vehicle control systems to describe one or the other vehicle combinations; the rest of the vehicle characteristics are changed by input data. To date, the program has been used to predict and correlate ASTP docking loads and performance with docking test program results from dynamic testing. The program modified for use on IBM 360 computers. Parts of the original docking system equations in the areas of hydraulic damping and capture latches are modified to better describe the detail design of the ASTP docking system.

Replica Exchange Improves Sampling in Low-Resolution Docking Stage of RosettaDock

PubMed Central

Zhang, Zhe; Lange, Oliver F.

2013-01-01

Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sampling as low-resolution stage of RosettaDock with RosettaDock's original shotgun sampling as well as with ZDOCK. A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense. ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling. Accordingly, they both improve typical metrics of prediction quality of complex structures after refinement. Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied. PMID:24009670

Packaging Considerations for Biopreservation

PubMed Central

Woods, Erik J.; Thirumala, Sreedhar

2011-01-01

Summary The packaging system chosen for biopreservation is critical for many reasons. An ideal biopreservation container system must provide for closure integrity, sample stability and ready access to the preserved material. This means the system needs to be hermetically sealed to ensure integrity of the specimen is maintained throughout processing, storage and distribution; the system must remain stable over long periods of time as many biobanked samples may be stored indefinitely; and functionally closed access systems must be used to avoid contamination upon sample withdraw. This study reviews the suitability of a new commercially available vial configuration container utilizing blood bag style closure and access systems that can be hermetically sealed and remain stable through cryopreservation and biobanking procedures. This vial based systems allow for current good manufacturing/tissue practice (cGTP) requirements during processing of samples and may provide the benefit of ease of delivery by a care giver. In this study, the CellSeal® closed system cryovial was evaluated and compared to standard screw cap vials. The CellSeal system was evaluated for durability, closure integrity through transportation and maintenance of functional viability of a cryopreserved mesenchymal stem cell model. The results of this initial proof-of-concept study indicated that the CellSeal vials are highly suitable for biopreservation and biobanking, and provide a suitable container system for clinical and commercial cell therapy products frozen in small volumes. PMID:21566715

Sealing rice field boundaries in Bangladesh: a pilot study demonstrating reductions in water use, arsenic loading to field soils, and methane emissions from irrigation water.

PubMed

Neumann, Rebecca B; Pracht, Lara E; Polizzotto, Matthew L; Badruzzaman, A Borhan M; Ali, M Ashraf

2014-08-19

Irrigation of rice fields in Bangladesh with arsenic-contaminated and methane-rich groundwater loads arsenic into field soils and releases methane into the atmosphere. We tested the water-savings potential of sealing field bunds (raised boundaries around field edges) as a way to mitigate these negative outcomes. We found that, on average, bund sealing reduced seasonal water use by 52 ± 17% and decreased arsenic loading to field soils by 15 ± 4%; greater savings in both water use and arsenic loading were achieved in fields with larger perimeter-to-area ratios (i.e., smaller fields). Our study is the first to quantify emission of methane from irrigation water in Bangladesh, a currently unaccounted-for methane source. Irrigation water applied to unsealed fields at our site emits 18 to 31 g of methane per square-meter of field area per season, potentially doubling the atmospheric input of methane from rice cultivation. Bund sealing reduced the emission of methane from irrigation water by 4 to 19 g/m(2). While the studied outcomes of bund sealing are positive and compelling, widespread implementation of the technique should consider other factors, such as effect on yields, financial costs, and impact on the hydrologic system. We provide an initial and preliminary assessment of these implementation factors.

Satellite Docking Simulator with Generic Contact Dynamics Capabilities

NASA Astrophysics Data System (ADS)

Ma, O.; Crabtree, D.; Carr, R.; Gonthier, Y.; Martin, E.; Piedboeuf, J.-C.

2002-01-01

Satellite docking (and capture) systems are critical for the servicing or salvage of satellites. Satellite servicing has comparatively recently become a realistic and promising space operation/mission. Satellite servicing includes several of the following operations: rendezvous; docking (capturing); inspection; towing (transporting); refueling; refurbishing (replacement of faulty or "used-up" modules/boxes); and un-docking (releasing). Because spacecraft servicing has been, until recently non-feasible or non-economical, spacecraft servicing technology has been neglected. Accordingly, spacecraft designs have featured self- contained systems without consideration for operational servicing. Consistent with this view, most spacecrafts were designed and built without docking interfaces. If, through some mishap, a spacecraft was rendered non-operational, it was simply considered expendable. Several feasibility studies are in progress on salvaging stranded satellites (which, in fact had led to this project). The task of the designer of the docking system for a salvaging task is difficult. He/she has to work with whatever it is on orbit, and this excludes any special docking interfaces, which might have made his/her task easier. As satellite servicing becomes an accepted design requirement, many future satellites will be equipped with appropriate docking interfaces. The designer of docking systems will be faced with slightly different challenges: reliable, cost-effective, docking (and re-supply) systems. Thus, the role of designers of docking systems will increase from one of a kind, ad-hoc interfaces intended for salvaging operations, to docking systems for satellites and "caretaker" spacecraft which are meant for servicing and are produced in larger numbers. As in any space system (for which full and representative ground hardware test-beds are very expensive and often impossible to develop), simulations are mandatory for the development of systems and operations for satellite servicing. Simulations are also instrumental in concept studies during proposals and early development stages. Finally, simulations are useful during the operational phase of satellite servicing: improving the operational procedures; training ground operators; command and control, etc. Hence the need exists for a Satellite Servicing Simulator, which will support a project throughout its lifecycle. The paper addresses a project to develop a Simulink-based Satellite Docking Simulator (SDS) with generic Contact Dynamics (CD) capabilities. The simulator is intended to meet immediate practical demands for development of complex docking systems and operations at MD Robotics. The docking phase is the most critical and complex phase of the entire servicing sequence, and without docking there is no servicing. Docking mechanisms are often quite complex, especially when built to dock with a satellite manufactured without special docking interfaces. For successful docking operations, the design of a docking system must take into consideration: complexity of 3D geometric shapes defining the contact interfaces; sophistication of the docking mechanism; friction and stiction at the contacting surfaces; compliance (stiffness) and damping, in all axes; positional (translation and rotation) misalignments and relative velocities, in all axes; inertial properties of the docking satellites (including their distribution); complexity of the drive mechanisms and control sub-systems for the overall docking system; fully autonomous or tele-operated docking from the ground; etc. The docking simulator, which makes use of the proven Contact Dynamics Toolkit (CDT) developed by MD Robotics, is thus practically indispensable for the docking system designer. The use of the simulator could greatly reduce the prototyping and development time of a docking interface. A special feature of the simulator, which required an update of CDT, is variable step-size integration. This new capability permits increases in speed to accomplish all the simulation tasks.

BP-Dock: A Flexible Docking Scheme for Exploring Protein–Ligand Interactions Based on Unbound Structures

PubMed Central

Bolia, Ashini; Gerek, Z. Nevin; Ozkan, S. Banu

2016-01-01

Molecular docking serves as an important tool in modeling protein–ligand interactions. However, it is still challenging to incorporate overall receptor flexibility, especially backbone flexibility, in docking due to the large conformational space that needs to be sampled. To overcome this problem, we developed a novel flexible docking approach, BP-Dock (Backbone Perturbation-Dock) that can integrate both backbone and side chain conformational changes induced by ligand binding through a multi-scale approach. In the BP-Dock method, we mimic the nature of binding-induced events as a first-order approximation by perturbing the residues along the protein chain with a small Brownian kick one at a time. The response fluctuation profile of the chain upon these perturbations is computed using the perturbation response scanning method. These response fluctuation profiles are then used to generate binding-induced multiple receptor conformations for ensemble docking. To evaluate the performance of BP-Dock, we applied our approach on a large and diverse data set using unbound structures as receptors. We also compared the BP-Dock results with bound and unbound docking, where overall receptor flexibility was not taken into account. Our results highlight the importance of modeling backbone flexibility in docking for recapitulating the experimental binding affinities, especially when an unbound structure is used. With BP-Dock, we can generate a wide range of binding site conformations realized in nature even in the absence of a ligand that can help us to improve the accuracy of unbound docking. We expect that our fast and efficient flexible docking approach may further aid in our understanding of protein–ligand interactions as well as virtual screening of novel targets for rational drug design. PMID:24380381

DockRank: Ranking docked conformations using partner-specific sequence homology-based protein interface prediction

PubMed Central

Xue, Li C.; Jordan, Rafael A.; EL-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2015-01-01

Selecting near-native conformations from the immense number of conformations generated by docking programs remains a major challenge in molecular docking. We introduce DockRank, a novel approach to scoring docked conformations based on the degree to which the interface residues of the docked conformation match a set of predicted interface residues. Dock-Rank uses interface residues predicted by partner-specific sequence homology-based protein–protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). In cases where it is possible to obtain partner-specific (PS) interface predictions from PS-HomPPI, DockRank consistently outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank that use predicted interface residues obtained from several protein interface predictors that do not take into account the binding partner in making interface predictions (improving success rate by up to 39-fold). The latter result underscores the importance of using partner-specific interface residues in scoring docked conformations. We show that DockRank, when used to re-rank the conformations returned by ClusPro, improves upon the original ClusPro rankings in terms of both Success Rate and Hit Rate. DockRank is available as a server at http://einstein.cs.iastate.edu/DockRank/. PMID:23873600

DockRank: ranking docked conformations using partner-specific sequence homology-based protein interface prediction.

PubMed

Xue, Li C; Jordan, Rafael A; El-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2014-02-01

Selecting near-native conformations from the immense number of conformations generated by docking programs remains a major challenge in molecular docking. We introduce DockRank, a novel approach to scoring docked conformations based on the degree to which the interface residues of the docked conformation match a set of predicted interface residues. DockRank uses interface residues predicted by partner-specific sequence homology-based protein-protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). In cases where it is possible to obtain partner-specific (PS) interface predictions from PS-HomPPI, DockRank consistently outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank that use predicted interface residues obtained from several protein interface predictors that do not take into account the binding partner in making interface predictions (improving success rate by up to 39-fold). The latter result underscores the importance of using partner-specific interface residues in scoring docked conformations. We show that DockRank, when used to re-rank the conformations returned by ClusPro, improves upon the original ClusPro rankings in terms of both Success Rate and Hit Rate. DockRank is available as a server at http://einstein.cs.iastate.edu/DockRank/. Copyright © 2013 Wiley Periodicals, Inc.

ConsDock: A new program for the consensus analysis of protein-ligand interactions.

PubMed

Paul, Nicodème; Rognan, Didier

2002-06-01

Protein-based virtual screening of chemical libraries is a powerful technique for identifying new molecules that may interact with a macromolecular target of interest. Because of docking and scoring limitations, it is more difficult to apply as a lead optimization method because it requires that the docking/scoring tool is able to propose as few solutions as possible and all of them with a very good accuracy for both the protein-bound orientation and the conformation of the ligand. In the present study, we present a consensus docking approach (ConsDock) that takes advantage of three widely used docking tools (Dock, FlexX, and Gold). The consensus analysis of all possible poses generated by several docking tools is performed sequentially in four steps: (i) hierarchical clustering of all poses generated by a docking tool into families represented by a leader; (ii) definition of all consensus pairs from leaders generated by different docking programs; (iii) clustering of consensus pairs into classes, represented by a mean structure; and (iv) ranking the different means starting from the most populated class of consensus pairs. When applied to a test set of 100 protein-ligand complexes from the Protein Data Bank, ConsDock significantly outperforms single docking with respect to the docking accuracy of the top-ranked pose. In 60% of the cases investigated here, ConsDock was able to rank as top solution a pose within 2 A RMSD of the X-ray structure. It can be applied as a postprocessing filter to either single- or multiple-docking programs to prioritize three-dimensional guided lead optimization from the most likely docking solution. Copyright 2002 Wiley-Liss, Inc.

GalaxyDock BP2 score: a hybrid scoring function for accurate protein-ligand docking

NASA Astrophysics Data System (ADS)

Baek, Minkyung; Shin, Woong-Hee; Chung, Hwan Won; Seok, Chaok

2017-07-01

Protein-ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein-ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein-ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

PPI4DOCK: large scale assessment of the use of homology models in free docking over more than 1000 realistic targets.

PubMed

Yu, Jinchao; Guerois, Raphaël

2016-12-15

Protein-protein docking methods are of great importance for understanding interactomes at the structural level. It has become increasingly appealing to use not only experimental structures but also homology models of unbound subunits as input for docking simulations. So far we are missing a large scale assessment of the success of rigid-body free docking methods on homology models. We explored how we could benefit from comparative modelling of unbound subunits to expand docking benchmark datasets. Starting from a collection of 3157 non-redundant, high X-ray resolution heterodimers, we developed the PPI4DOCK benchmark containing 1417 docking targets based on unbound homology models. Rigid-body docking by Zdock showed that for 1208 cases (85.2%), at least one correct decoy was generated, emphasizing the efficiency of rigid-body docking in generating correct assemblies. Overall, the PPI4DOCK benchmark contains a large set of realistic cases and provides new ground for assessing docking and scoring methodologies. Benchmark sets can be downloaded from http://biodev.cea.fr/interevol/ppi4dock/ CONTACT: guerois@cea.frSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

American & Soviet engineers examine ASTP docking set-up following tests

NASA Image and Video Library

1974-07-10

S74-25394 (10 July 1974) --- A group of American and Soviet engineers of the Apollo-Soyuz Test Project working group three examines an ASTP docking set-up following a docking mechanism fitness test conducted in Building 13 at the Johnson Space Center. Working Group No. 3 is concerned with ASTP docking problems and techniques. The joint U.S.-USSR ASTP docking mission in Earth orbit is scheduled for the summer of 1975. The Apollo docking mechanism is atop the Soyuz docking mechanism.

Comparative evaluation of several docking tools for docking small molecule ligands to DC-SIGN.

PubMed

Jug, Gregor; Anderluh, Marko; Tomašič, Tihomir

2015-06-01

Five docking tools, namely AutoDock, FRED, CDOCKER, FlexX and GOLD, have been critically examined, with the aim of selecting those most appropriate for use as docking tools for docking molecules to the lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This lectin has been selected for its rather non-druggable binding site, which enables complex interactions that guide the binding of the core monosaccharide. Since optimal orientation is crucial for forming coordination bonds, it was important to assess whether the selected docking tools could reproduce the optimal binding conformation for several oligosaccharides that are known to bind DC-SIGN. Our results show that even widely used docking programs have certain limitations when faced with a rather shallow and featureless binding site, as is the case of DC-SIGN. The FRED docking software (OpenEye Scientific Software, Inc.) was found to score as the best tool for docking ligands to DC-SIGN. The performance of FRED was further assessed on another lectin, Langerin. We have demonstrated that this validated docking protocol could be used for docking to other lectins similar to DC-SIGN.

Development and application of new composite grouting material for sealing groundwater inflow and reinforcing wall rock in deep mine.

PubMed

Jinpeng, Zhang; Limin, Liu; Futao, Zhang; Junzhi, Cao

2018-04-04

With cement, bentonite, water glass, J85 accelerator, retarder and water as raw materials, a new composite grouting material used to seal groundwater inflow and reinforce wall rock in deep fractured rock mass was developed in this paper. Based on the reaction mechanism of raw material, the pumpable time, stone rate, initial setting time, plastic strength and unconfined compressive strength of multi-group proportion grouts were tested by orthogonal experiment. Then, the optimum proportion of composite grouting material was selected and applied to the grouting engineering for sealing groundwater inflow and reinforcing wall rock in mine shaft lining. The results show the mixing proportion of the maximum pumpable time, maximum stone rate and minimum initial setting time of grout are A K4 B K1 C K4 D K2 , A K3 B K1 C K1 D K4 and A K3 B K3 C K4 D K1 , respectively. The mixing proportion of the maximum plastic strength and unconfined compressive strength of grouts concretion bodies are A K1 B K1 C K1 D K3 and A K1 B K1 C K1 D K1 , respectively. Balanced the above 5 indicators overall and determined the optimum proportion of grouts: bentonite-cement ratio of 1.0, water-solid ratio of 3.5, accelerator content of 2.9% and retarder content of 1.45%. This new composite grouting material had good effect on the grouting engineering for sealing groundwater inflow and reinforcing wall rock in deep fractured rock mass.

Optimizing cyanobacteria growth conditions in a sealed environment to enable chemical inhibition tests with volatile chemicals.

PubMed

Johnson, Tylor J; Zahler, Jacob D; Baldwin, Emily L; Zhou, Ruanbao; Gibbons, William R

2016-07-01

Cyanobacteria are currently being engineered to photosynthetically produce next-generation biofuels and high-value chemicals. Many of these chemicals are highly toxic to cyanobacteria, thus strains with increased tolerance need to be developed. The volatility of these chemicals may necessitate that experiments be conducted in a sealed environment to maintain chemical concentrations. Therefore, carbon sources such as NaHCO3 must be used for supporting cyanobacterial growth instead of CO2 sparging. The primary goal of this study was to determine the optimal initial concentration of NaHCO3 for use in growth trials, as well as if daily supplementation of NaHCO3 would allow for increased growth. The secondary goal was to determine the most accurate method to assess growth of Anabaena sp. PCC 7120 in a sealed environment with low biomass titers and small sample volumes. An initial concentration of 0.5g/L NaHCO3 was found to be optimal for cyanobacteria growth, and fed-batch additions of NaHCO3 marginally improved growth. A separate study determined that a sealed test tube environment is necessary to maintain stable titers of volatile chemicals in solution. This study also showed that a SYTO® 9 fluorescence-based assay for cell viability was superior for monitoring filamentous cyanobacterial growth compared to absorbance, chlorophyll α (chl a) content, and biomass content due to its accuracy, small sampling size (100μL), and high throughput capabilities. Therefore, in future chemical inhibition trials, it is recommended that 0.5g/L NaHCO3 is used as the carbon source, and that culture viability is monitored via the SYTO® 9 fluorescence-based assay that requires minimum sample size. Copyright © 2016 Elsevier B.V. All rights reserved.

Accessible transportation technologies research initiative (ATTRI) : online dialogue.

DOT National Transportation Integrated Search

2014-08-01

In coordination with Easter Seals Project ACTION (ESPA) and with support from Noblis, ATTRI held an online dialogue from May 15-June 6, 2014 to garner input on mobility and transportation technology for travelers with disabilities. Participants were ...

AutoDockFR: Advances in Protein-Ligand Docking with Explicitly Specified Binding Site Flexibility

PubMed Central

Ravindranath, Pradeep Anand; Forli, Stefano; Goodsell, David S.; Olson, Arthur J.; Sanner, Michel F.

2015-01-01

Automated docking of drug-like molecules into receptors is an essential tool in structure-based drug design. While modeling receptor flexibility is important for correctly predicting ligand binding, it still remains challenging. This work focuses on an approach in which receptor flexibility is modeled by explicitly specifying a set of receptor side-chains a-priori. The challenges of this approach include the: 1) exponential growth of the search space, demanding more efficient search methods; and 2) increased number of false positives, calling for scoring functions tailored for flexible receptor docking. We present AutoDockFR–AutoDock for Flexible Receptors (ADFR), a new docking engine based on the AutoDock4 scoring function, which addresses the aforementioned challenges with a new Genetic Algorithm (GA) and customized scoring function. We validate ADFR using the Astex Diverse Set, demonstrating an increase in efficiency and reliability of its GA over the one implemented in AutoDock4. We demonstrate greatly increased success rates when cross-docking ligands into apo receptors that require side-chain conformational changes for ligand binding. These cross-docking experiments are based on two datasets: 1) SEQ17 –a receptor diversity set containing 17 pairs of apo-holo structures; and 2) CDK2 –a ligand diversity set composed of one CDK2 apo structure and 52 known bound inhibitors. We show that, when cross-docking ligands into the apo conformation of the receptors with up to 14 flexible side-chains, ADFR reports more correctly cross-docked ligands than AutoDock Vina on both datasets with solutions found for 70.6% vs. 35.3% systems on SEQ17, and 76.9% vs. 61.5% on CDK2. ADFR also outperforms AutoDock Vina in number of top ranking solutions on both datasets. Furthermore, we show that correctly docked CDK2 complexes re-create on average 79.8% of all pairwise atomic interactions between the ligand and moving receptor atoms in the holo complexes. Finally, we show that down-weighting the receptor internal energy improves the ranking of correctly docked poses and that runtime for AutoDockFR scales linearly when side-chain flexibility is added. PMID:26629955

Microgravity experiments of nano-satellite docking mechanism for final rendezvous approach and docking phase

NASA Astrophysics Data System (ADS)

Ui, Kyoichi; Matunaga, Saburo; Satori, Shin; Ishikawa, Tomohiro

2005-09-01

Laboratory for Space Systems (LSS), Tokyo Institute of Technology (Tokyo Tech) conducted three-dimensional microgravity environment experiments about a docking mechanism for mothership-daughtership (MS-DS) nano-satellite using the facility of Japan Micro Gravity Center (JAMIC) with Hokkaido Institute of Technology (HIT). LSS has studied and developed a docking mechanism for MS-DS nano-satellite system in final rendezvous approach and docking phase since 2000. Consideration of the docking mechanism is to mate a nano-satellite stably while remaining control error of relative velocity and attitude because it is difficult for nano-satellite to have complicated attitude control and mating systems. Objective of the experiments is to verify fundamental grasping function based on our proposed docking methodology. The proposed docking sequence is divided between approach/grasping phase and guiding phase. In the approach/grasping phase, the docking mechanism grasps the nano-satellite even though the nano-satellite has relative position and attitude control errors as well as relative velocity in a docking space. In the guiding function, the docking mechanism guides the nano-satellite to a docking port while adjusting its attitude in order to transfer electrical power and fuel to the nano-satellite. In the paper, we describe the experimental system including the docking mechanism, control system, the daughtership system and the release mechanism, and describe results of microgravity experiments in JAMIC.

Explosive Bolt Dual-Initiated from One Side

NASA Technical Reports Server (NTRS)

Snow, Eric

2011-01-01

An explosive bolt has been developed that has a one-sided dual initiation train all the way down to the pyro charge for high reliability, while still allowing the other side of the bolt to remain in place after actuation to act as a thermal seal in an extremely high-temperature environment. This lightweight separation device separates at a single fracture plane, and has as much redundancy/reliability as possible. The initiation train comes into the explosive bolt from one side.

Automatic spacecraft detumbling by internal mass motion

NASA Technical Reports Server (NTRS)

Edwards, T. L.; Kaplan, M. H.

1974-01-01

In the operation of future manned space vehicles, there will always be a finite probability that an accident will occur which results in uncontrolled tumbling of a craft. Hard docking by a manned rescue vehicle is not acceptable because of the hazardous environment to which rescue crewmen would be exposed and excessive maneuvering accelerations during docking operations. A movable-mass control concept, which is activated upon initiation of tumbling and is autonomous, can convert tumbling motion into simple spin. The complete equations of motion for an asymmetric rigid spacecraft containing a movable mass are presented, and appropriate control law and system parameters are selected to minimize kinetic energy, resulting in simple spin about the major principal axis. Simulations indicate that for a large space station experiencing a collision, which results in tumbling, a 1% movable mass is capable of stabilizing motion in 2 hr.

Long-term storage facility for reactor compartments in Sayda Bay - German support for utilization of nuclear submarines in Russia

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

Wolff, Dietmar; Voelzke, Holger; Weber, Wolfgang

2007-07-01

The German-Russian project that is part of the G8 initiative on Global Partnership Against the Spread of Weapons and Materials of Mass Destruction focuses on the speedy construction of a land-based interim storage facility for nuclear submarine reactor compartments at Sayda Bay near Murmansk. This project includes the required infrastructure facilities for long-term storage of about 150 reactor compartments for a period of about 70 years. The interim storage facility is a precondition for effective activities of decommissioning and dismantlement of almost all nuclear-powered submarines of the Russian Northern Fleet. The project also includes the establishment of a computer-assisted wastemore » monitoring system. In addition, the project involves clearing Sayda Bay of other shipwrecks of the Russian navy. On the German side the project is carried out by the Energiewerke Nord GmbH (EWN) on behalf of the Federal Ministry of Economics and Labour (BMWi). On the Russian side the Kurchatov Institute holds the project management of the long-term interim storage facility in Sayda Bay, whilst the Nerpa Shipyard, which is about 25 km away from the storage facility, is dismantling the submarines and preparing the reactor compartments for long-term interim storage. The technical monitoring of the German part of this project, being implemented by BMWi, is the responsibility of the Federal Institute for Materials Research and Testing (BAM). This paper gives an overview of the German-Russian project and a brief description of solutions for nuclear submarine disposal in other countries. At Nerpa shipyard, being refurbished with logistic and technical support from Germany, the reactor compartments are sealed by welding, provided with biological shielding, subjected to surface treatment and conservation measures. Using floating docks, a tugboat tows the reactor compartments from Nerpa shipyard to the interim storage facility at Sayda Bay where they will be left on the on-shore concrete storage space to allow the radioactivity to decay. For transport of reactor compartments at the shipyard, at the dock and at the storage facility, hydraulic keel blocks, developed and supplied by German subcontractors, are used. In July 2006 the first stage of the reactor compartment storage facility was commissioned and the first seven reactor compartments have been delivered from Nerpa shipyard. Following transports of reactor compartments to the storage facility are expected in 2007. (authors)« less

Initial experience using a femtosecond laser cataract surgery system at a UK National Health Service cataract surgery day care centre

PubMed Central

Dhallu, Sandeep K; Maurino, Vincenzo; Wilkins, Mark R

2016-01-01

Objectives To describe the initial outcomes following installation of a cataract surgery laser system. Setting National Health Service cataract surgery day care unit in North London, UK. Participants 158 eyes of 150 patients undergoing laser-assisted cataract surgery. Interventions Laser cataract surgery using the AMO Catalys femtosecond laser platform. Primary and secondary outcome measures Primary outcome measure: intraoperative complications including anterior and posterior capsule tears. Secondary outcome measures: docking to the laser platform, successful treatment delivery, postoperative visual acuities. Results Mean case age was 67.7±10.8 years (range 29–88 years). Docking was successful in 94% (148/158 cases), and in 4% (6/148 cases) of these, the laser delivery was aborted part way during delivery due to patient movement. A total of 32 surgeons, of grades from junior trainee to consultant, performed the surgeries. Median case number per surgeon was 3 (range from 1–20). The anterior capsulotomy was complete in 99.3% of cases, there were no anterior capsule tears (0%). There were 3 cases with posterior capsule rupture requiring anterior vitrectomy, and 1 with zonular dialysis requiring anterior vitrectomy (4/148 eyes, 2.7%). These 4 cases were performed by trainee surgeons, and were either their first laser cataract surgery (2 surgeons) or their first and second laser cataract surgeries (1 surgeon). Conclusions Despite the learning curve, docking and laser delivery were successfully performed in almost all cases, and surgical complication rates and visual outcomes were similar to those expected based on national data. Complications were predominately confined to trainee surgeons, and with the exception of intraoperative pupil constriction appeared unrelated to the laser-performed steps. PMID:27466243

STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among the HGF receptor family.

PubMed Central

Iwama, A; Yamaguchi, N; Suda, T

1996-01-01

STK/RON tyrosine kinase, a member of the hepatocyte growth factor (HGF) receptor family, is a receptor for macrophage-stimulating protein (MSP). To examine the STK/RON signalling pathway, we generated STK/ RON transfectants showing opposite features in growth. STK/RON-expressing Ba/F3 pro-B cells (BaF/STK) exhibited MSP-dependent growth, whereas STK/ RON-expressing mouse erythroleukaemia cells (MEL/ STK) displayed MSP-induced apoptosis. This apoptosis was accompanied by the prolonged activation of c-Jun N-terminal kinase (JNK), which has recently been implicated in the initiation of apoptosis. Co-immunoprecipitation analyses showed that autophosphorylated STK/RON associated with PLC-gamma, P13-kinase, Shc and Grb2 in both transfectants. However, major tyrosine-phosphorylated proteins, p61 and p65, specifically associated with STK/RON in MEL/STK cells. Mutations at two C-terminal tyrosine residues, Y1330 and Y1337, in the counterpart of the multifunctional docking site of the HGF receptor abolished both MSP-induced growth and apoptosis. Analyses of these mutants and in vitro association revealed that signalling proteins including p61 and p65 directly bound to the phosphotyrosines in the multifunctional docking site. These results demonstrate that positive or negative signals toward cell growth are generated through the multifunctional docking site and suggest the involvement of p61 and p65 as well as JNK in apoptosis. Our findings provide the first evidence for apoptosis via a receptor tyrosine kinase. Images PMID:8918464

Phosphoric acid electric utility fuel cell technology development

NASA Astrophysics Data System (ADS)

Breault, R. D.; Briggs, T. A.; Congdon, J. V.; Gelting, R. L.; Goller, G. J.; Luoma, W. L.; McCloskey, M. W.; Mientek, A. P.; Obrien, J. J.; Randall, S. A.

1985-07-01

Improved cross pressure tolerance has been demonstrated for electrodes containing impregnated seals. Electrodes, cooler assemblies, separator plates and reactant manifolds for the third 10-ft(2) short stack were completed. Assembly of the third 10-ft(2) short stack was initiated.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus.

PubMed

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-12-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na(+) (Na(v)) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of approximately 5 m s(-1) and approximately 0.7 m s(-1), respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na(+)] ACSF or the selective Na(v) channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Na(v) channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABA(A) receptors regulates the axonal initiation of action potentials.

Autonomous initiation and propagation of action potentials in neurons of the subthalamic nucleus

PubMed Central

Atherton, Jeremy F; Wokosin, David L; Ramanathan, Sankari; Bevan, Mark D

2008-01-01

The activity of the subthalamic nucleus (STN) is intimately related to movement and is generated, in part, by voltage-dependent Na+ (Nav) channels that drive autonomous firing. In order to determine the principles underlying the initiation and propagation of action potentials in STN neurons, 2-photon laser scanning microscopy was used to guide tight-seal whole-cell somatic and loose-seal cell-attached axonal/dendritic patch-clamp recordings and compartment-selective ion channel manipulation in rat brain slices. Action potentials were first detected in a region that corresponded most closely to the unmyelinated axon initial segment, as defined by Golgi and ankyrin G labelling. Following initiation, action potentials propagated reliably into axonal and somatodendritic compartments with conduction velocities of ∼5 m s−1 and ∼0.7 m s−1, respectively. Action potentials generated by neurons with axons truncated within or beyond the axon initial segment were not significantly different. However, axon initial segment and somatic but not dendritic or more distal axonal application of low [Na+] ACSF or the selective Nav channel blocker tetrodotoxin consistently depolarized action potential threshold. Finally, somatodendritic but not axonal application of GABA evoked large, rapid inhibitory currents in concordance with electron microscopic analyses, which revealed that the somatodendritic compartment was the principal target of putative inhibitory inputs. Together the data are consistent with the conclusions that in STN neurons the axon initial segment and soma express an excess of Nav channels for the generation of autonomous activity, while synaptic activation of somatodendritic GABAA receptors regulates the axonal initiation of action potentials. PMID:18832425

1. Full SW side of dock as viewed from shore ...

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

1. Full SW side of dock as viewed from shore at the Oil/Creosote Unloading Dock. This view formed a panorama with photo WA-131-H-5, which shows the Oil/Creosote Unloading Dock. - Pacific Creosoting Plant, West Dock, 5350 Creosote Place, Northeast, Bremerton, Kitsap County, WA

Optical Docking Aid Containing Fresnel Lenses

NASA Technical Reports Server (NTRS)

Pierce, Cole J.

1995-01-01

Proposed device provides self-contained visual cues to aid in docking. Similar to devices used to guide pilots in landing on aircraft carriers. Positions and directions of beams of light give observer visual cues of position relative to docking target point. Optical assemblies generate directed, diverging beams of light that, together, mark approach path to docking point. Conceived for use in docking spacecraft at Space Station Freedom, device adapted to numerous industrial docking and alignment applications.

pyDockWEB: a web server for rigid-body protein-protein docking using electrostatics and desolvation scoring.

PubMed

Jiménez-García, Brian; Pons, Carles; Fernández-Recio, Juan

2013-07-01

pyDockWEB is a web server for the rigid-body docking prediction of protein-protein complex structures using a new version of the pyDock scoring algorithm. We use here a new custom parallel FTDock implementation, with adjusted grid size for optimal FFT calculations, and a new version of pyDock, which dramatically speeds up calculations while keeping the same predictive accuracy. Given the 3D coordinates of two interacting proteins, pyDockWEB returns the best docking orientations as scored mainly by electrostatics and desolvation energy. The server does not require registration by the user and is freely accessible for academics at http://life.bsc.es/servlet/pydock. Supplementary data are available at Bioinformatics online.

Multi-Conformer Ensemble Docking to Difficult Protein Targets

DOE PAGES

Ellingson, Sally R.; Miao, Yinglong; Baudry, Jerome; ...

2014-09-08

We investigate large-scale ensemble docking using five proteins from the Directory of Useful Decoys (DUD, dud.docking.org) for which docking to crystal structures has proven difficult. Molecular dynamics trajectories are produced for each protein and an ensemble of representative conformational structures extracted from the trajectories. Docking calculations are performed on these selected simulation structures and ensemble-based enrichment factors compared with those obtained using docking in crystal structures of the same protein targets or random selection of compounds. We also found simulation-derived snapshots with improved enrichment factors that increased the chemical diversity of docking hits for four of the five selected proteins.more » A combination of all the docking results obtained from molecular dynamics simulation followed by selection of top-ranking compounds appears to be an effective strategy for increasing the number and diversity of hits when using docking to screen large libraries of chemicals against difficult protein targets.« less

Prevention of Over-Pressurization During Combustion in a Sealed Chamber

NASA Technical Reports Server (NTRS)

Gokoglu, Suleyman A.; Niehaus, Justin E.; Olson, Sandra L.; Dietrich, Daniel L.; Ruff, Gary A.; Johnston, Michael C.

2012-01-01

The combustion of flammable material in a sealed chamber invariably leads to an initial pressure rise in the volume. The pressure rise is due to the increase in the total number of gaseous moles (condensed fuel plus chamber oxygen combining to form gaseous carbon dioxide and water vapor) and, most importantly, the temperature rise of the gas in the chamber. Though the rise in temperature and pressure would reduce with time after flame extinguishment due to the absorption of heat by the walls and contents of the sealed spacecraft, the initial pressure rise from a fire, if large enough, could lead to a vehicle over-pressure and the release of gas through the pressure relief valve. This paper presents a simple lumped-parameter model of the pressure rise in a sealed chamber resulting from the heat release during combustion. The transient model considers the increase in gaseous moles due to combustion, and heat transfer to the chamber walls by convection and radiation and to the fuel-sample holder by conduction, as a function of the burning rate of the material. The results of the model are compared to the pressure rise in an experimental chamber during flame spread tests as well as to the pressure falloff after flame extinguishment. The experiments involve flame spread over thin solid fuel samples. Estimates of the heat release rate profiles for input to the model come from the assumed stoichiometric burning of the fuel along with the observed flame spread behavior. The sensitivity of the model to predict maximum chamber pressure is determined with respect to the uncertainties in input parameters. Model predictions are also presented for the pressure profile anticipated in the Fire Safety-1 experiment, a material flammability and fire safety experiment proposed for the European Space Agency (ESA) Automated Transfer Vehicle (ATV). Computations are done for a range of scenarios including various initial pressures and sample sizes. Based on these results, various mitigation approaches are suggested to prevent vehicle over-pressurization and help guide the definition of the space experiment.

System for Packaging Planetary Samples for Return to Earth

NASA Technical Reports Server (NTRS)

Badescu, Mircea; Bar-Cohen, Yoseph; Backes, paul G.; Sherrit, Stewart; Bao, Xiaoqi; Scott, James S.

2010-01-01

A system is proposed for packaging material samples on a remote planet (especially Mars) in sealed sample tubes in preparation for later return to Earth. The sample tubes (Figure 1) would comprise (1) tubes initially having open tops and closed bottoms; (2) small, bellows-like collapsible bodies inside the tubes at their bottoms; and (3) plugs to be eventually used to close the tops of the tubes. The top inner surface of each tube would be coated with solder. The side of each plug, which would fit snugly into a tube, would feature a solder-filled ring groove. The system would include equipment for storing, manipulating, filling, and sealing the tubes. The containerization system (see Figure 2) will be organized in stations and will include: the storage station, the loading station, and the heating station. These stations can be structured in circular or linear pattern to minimize the manipulator complexity, allowing for compact design and mass efficiency. The manipulation of the sample tube between stations is done by a simple manipulator arm. The storage station contains the unloaded sample tubes and the plugs before sealing as well as the sealed sample tubes with samples after loading and sealing. The chambers at the storage station also allow for plug insertion into the sample tube. At the loading station the sample is poured or inserted into the sample tube and then the tube is topped off. At the heating station the plug is heated so the solder ring melts and seals the plug to the sample tube. The process is performed as follows: Each tube is filled or slightly overfilled with sample material and the excess sample material is wiped off the top. Then, the plug is inserted into the top section of the tube packing the sample material against the collapsible bellowslike body allowing the accommodation of the sample volume. The plug and the top of the tube are heated momentarily to melt the solder in order to seal the tube.

Biofilm-induced calcium carbonate precipitation: application in the subsurface

NASA Astrophysics Data System (ADS)

Phillips, A. J.; Eldring, J.; Lauchnor, E.; Hiebert, R.; Gerlach, R.; Mitchell, A. C.; Esposito, R.; Cunningham, A. B.; Spangler, L.

2012-12-01

We have investigated mitigation strategies for sealing high permeability regions, like fractures, in the subsurface. This technology has the potential to, for example, improve the long-term security of geologically-stored carbon dioxide (CO2) by sealing fractures in cap rocks or to mitigate leakage pathways to prevent contamination of overlying aquifers from hydraulic fracturing fluids. Sealing technologies using low-viscosity fluids are advantageous since they potentially reduce the necessary injection pressures and increase the radius of influence around injection wells. In this technology, aqueous solutions and suspensions are used to promote microbially-induced mineral precipitation which can be applied in subsurface environments. To this end, a strategy was developed to twice seal a hydraulically fractured, 74 cm (2.4') diameter Boyles Sandstone core, collected in North-Central Alabama, with biofilm-induced calcium carbonate (CaCO3) precipitates under ambient pressures. Sporosarcina pasteurii biofilms were established and calcium and urea containing reagents were injected to promote saturation conditions favorable for CaCO3 precipitation followed by growth reagents to resuscitate the biofilm's ureolytic activity. Then, in order to evaluate this process at relevant deep subsurface pressures, a novel high pressure test vessel was developed to house the 74 cm diameter core under pressures as high as 96 bar (1,400 psi). After determining that no impact to the fracture permeability occurred due to increasing overburden pressure, the fractured core was sealed under subsurface relevant pressures relating to 457 meters (1,500 feet) below ground surface (44 bar (650 psi) overburden pressure). After fracture sealing under both ambient and subsurface relevant pressure conditions, the sandstone core withstood three times higher well bore pressure than during the initial fracturing event, which occurred prior to biofilm-induced CaCO3 mineralization. These studies suggest biofilm-induced CaCO3 precipitation technologies may potentially seal and strengthen high permeability regions or fractures (either natural or induced) in the subsurface. Novel high pressure test vessel to investigate biogeochemical processes under relevant subsurface scales and pressures.

Exposure of natural rubber to personal lubricants--swelling and stress relaxation as potential indicators of reduced seal integrity of non-lubricated male condoms.

PubMed

Sarkar Das, Srilekha; Coburn, James C; Tack, Charles; Schwerin, Matthew R; Richardson, D Coleman

2014-07-01

Male condoms act as mechanical barriers to prevent passage of body fluids. For effective use of condoms the mechanical seal is also expected to remain intact under reasonable use conditions, including with personal lubricants. Absorption of low molecular weight lubricant components into the material of male condoms may initiate material changes leading to swelling and stress relaxation of the polymer network chains that could affect performance of the sealing function of the device. Swelling indicates both a rubber-solvent interaction and stress relaxation, the latter of which may indicate and/or result in a reduced seal pressure in the current context. Swelling and stress relaxation of natural rubber latex condoms were assessed in a laboratory model in the presence of silicone-, glycol-, and water-based lubricants. Within 15 minutes, significant swelling (≥6 %) and stress reduction (≥12 %) of condoms were observed with 2 out of 4 silicone-based lubricants tested, but neither was observed with glycol- or water-based lubricants tested. Under a given strain, reduction in stress was prominent during the swelling processes, but not after the process was complete. Lubricant induced swelling and stress relaxation may loosen the circumferential stress responsible for the mechanical seal. Swelling and stress relaxation behavior of latex condoms in the presence of personal lubricants may be useful tests to identify lubricant-rooted changes in condom-materials. For non-lubricated latex condoms, material characteristics--which are relevant to failure--may change in the presence of a few silicone-based personal lubricants. These changes may in turn induce a loss of condom seal during use, specifically at low strain conditions. Published by Elsevier Inc.

3-D analysis of a containment equipment hatch

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

Greimann, L.; Fanous, F.

1985-01-01

There are at least two models used to characterize the possible leakage of a containment during a severe accident: (1) the threshold model in which the containment is assumed to be leak-tight until certain pressure/temperature conditions are reached and a very large rupture occurs; and (2) the leak-before-break model in which small leak paths are hypothesized to develop at levels below the threshold. The objective of this work is to investigate the leak-before-break potential of a typical equipment hatch seal. The relative deformations of the sealing surfaces during pressurization are of interest, especially if any buckling of the hatch occurs.more » A three-dimensional finite element model of the equipment hatch assembly was developed. The model included: shell elements for the containment shell, containment stiffeners, penetration sleeve and hatch shell; prestressed bar elements for the swing bolts which hold the hatch closed; and interface elements for the sliding or opening which can occur at the seal surfaces. The nonlinear material properties were approximated by a piecewise linear curve with a proportional limit equal to one-half the yield strength. Geometric nonlinearities were also included in the model. As pressure increments were added to the finite element model, the seal surfaces tended to move together initially. The dominate observable behavior in this range was ''ovaling'' of the penetration sleeve relative to the hatch cover. Since the hatch itself tended to remain circular, there was a mismatch at the sealing surface. Friction reduces but does not eliminate this relative motion. As the containment reached a higher pressure level, the hatch began to buckle at the idealized imperfection. The finite element solution was incremented through the snapthrough. As this postbuckling occurred, additional seal interface distortion was observed.« less

Influence of various bonding techniques on the fracture strength of thin CAD/CAM-fabricated occlusal glass-ceramic veneers.

PubMed

Yazigi, Christine; Kern, Matthias; Chaar, Mohamed Sad

2017-11-01

To evaluate the efficiency of immediate dentin sealing and the effects of different bonding protocols on the fracture strength of CAD/CAM occlusal veneers bonded to exposed dentin. Ninety-six extracted maxillary premolars were initially divided into three main groups with 32 specimens each: without immediate dentin sealing, immediate dentin sealing/total etching and immediate dentin sealing/selective etching. Teeth were identically prepared in the dentin to receive occlusal veneers of 0.8mm thickness, milled from lithium disilicate ceramic blocks (IPS e.max CAD). Each main group was later subdivided, according to the pre-cementation surface etching protocol (total/selective), into two subgroups with 16 specimens each. All restorations were adhesively bonded using a resin cement (Variolink Esthetic). Half of the specimens of each subgroup were subjected to thermo-dynamic loading in a chewing simulator with 1,200,000 cycles at 10kg load. The other half and the surviving specimens were subjected to quasi-static loading until failure. Statistical analysis was performed using three-way ANOVA and Tukey's post-hoc tests. All specimens except one survived the artificial aging. A significantly higher fracture strength of restorations (p ≤ 0.001) was obtained when immediate dentin sealing was followed regardless of the etching method with values ranging from a minimum of 1122 ± 336N to a maximum of 1853 ± 333N. Neither the pre-cementation treatment nor the artificial aging had a statistical significant effect on the fracture strength. Immediate dentin sealing protocol is recommended whenever dentin is exposed during the preparation for thin glass-ceramic occlusal veneers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Core Certification of Data Repositories: Trustworthiness and Long-Term Stewardship

NASA Astrophysics Data System (ADS)

de Sherbinin, A. M.; Mokrane, M.; Hugo, W.; Sorvari, S.; Harrison, S.

2017-12-01

Scientific integrity and norms dictate that data created and used by scientists should be managed, curated, and archived in trustworthy data repositories thus ensuring that science is verifiable and reproducible while preserving the initial investment in collecting data. Research stakeholders including researchers, science funders, librarians, and publishers must also be able to establish the trustworthiness of data repositories they use to confirm that the data they submit and use remain useful and meaningful in the long term. Data repositories are increasingly recognized as a key element of the global research infrastructure and the importance of establishing their trustworthiness is recognised as a prerequisite for efficient scientific research and data sharing. The Core Trustworthy Data Repository Requirements are a set of universal requirements for certification of data repositories at the core level (see: https://goo.gl/PYsygW). They were developed by the ICSU World Data System (WDS: www.icsu-wds.org) and the Data Seal of Approval (DSA: www.datasealofapproval.org)—the two authoritative organizations responsible for the development and implementation of this standard to be further developed under the CoreTrustSeal branding . CoreTrustSeal certification of data repositories involves a minimally intensive process whereby repositories supply evidence that they are sustainable and trustworthy. Repositories conduct a self-assessment which is then reviewed by community peers. Based on this review CoreTrustSeal certification is granted by the CoreTrustSeal Standards and Certification Board. Certification helps data communities—producers, repositories, and consumers—to improve the quality and transparency of their processes, and to increase awareness of and compliance with established standards. This presentation will introduce the CoreTrustSeal certification requirements for repositories and offer an opportunity to discuss ways to improve the contribution of certified data repositories to sustain open data for open scientific research.

The role of glycosaminoglycans in tissue adhesion during energy-based vessel sealing

NASA Astrophysics Data System (ADS)

Kramer, Eric A.; Anderson, Nicholas S.; Taylor, Kenneth D.; Ferguson, Virginia L.; Rentschler, Mark E.

2015-03-01

Energy-based vessel sealing remains a common alternative to traditional mechanical ligation procedures, despite considerable uncertainty as to the origin and stability of vascular adhesion forces. Evidence of conformal changes in Collagen IA has fostered support of denatured collagen as the origin of tissue adhesion; experimental observation suggests that while pure collagen fails to adhere, remaining vascular constituents play a critical adhesive role. This study initiates a constitutive model of adhesion forces in thermal fusion by determining the effects of glycosaminoglycan (GAG) content on the bursting pressure of thermally sealed vessels. GAG content of porcine splenic arteries was progressively altered via pre-fusion treatment in Chondroitinase ABC (ChABC) for 0-5h at 1U/mL (n=10/gp.), followed by fusion with the ConMed ALTRUS® thermal fusion device and subsequent strength testing. Sulfated GAG (sGAG) concentrations as quantified by the Dimethylmethylene Blue (DMMB) assay were reduced in ChABC-treated vessels (5h) by 73.8 +/- 4.2 % as compared with untreated tissue. Bursting pressures of ChABC-treated vessels (5h) were significantly greater than those of control vessels (800.33 +/- 54.34 mmHg and 438.40 +/- 51.81 mmHg respectively, p=2.0e-04). Histology enabled qualitative visualization of the treated arterial cross-section and of the bonding interface. The negative correlation between GAG content and arterial seal strengths suggests that by resisting water transport, arterial GAG presence may inhibit adhesive interactions between adjacent cellular tissue layers during energy-based vessel sealing. By elucidating the components which facilitate or inhibit adhesion in thermal vessel sealing, this study provides an important step towards understanding the chemistry underlying fusion and evaluating its potential for expansion to avascular tissues.

Synergistic Development, Test, and Qualification Approaches for the Ares I and V Launch Vehicles

NASA Technical Reports Server (NTRS)

Cockrell, Charles E.; Taylor, James L.; Patterson, Alan; Stephens, Samuel E.; Tuma, Margaret; Bartolotta, Paul; Huetter, Uwe; Kaderback, Don; Goggin, David

2009-01-01

The U.S. National Aeronautics and Space Administration (NASA) initiated plans to develop the Ares I and Ares V launch vehicles in 2005 to meet the mission objectives for future human exploration of space. Ares I is designed to provide the capability to deliver the Orion crew exploration vehicle (CEV) to low-Earth orbit (LEO), either for docking to the International Space Station (ISS) or docking with an Earth departure stage (EDS) and lunar lander for transit to the Moon. Ares V provides the heavy-lift capability to deliver the EDS and lunar lander to orbit. An integrated test plan was developed for Ares I that includes un-crewed flight validation testing and ground testing to qualify structural components and propulsion systems prior to operational deployment. The overall test program also includes a single development test flight conducted prior to the Ares I critical design review (CDR). Since the Ares V concept was formulated to maximize hardware commonality between the Ares V and Ares I launch vehicles, initial test planning for Ares V has considered the extensibility of test approaches and facilities from Ares I. The Ares V test plan was part of a successful mission concept review (MCR) in 2008.

Multilevel Parallelization of AutoDock 4.2.

PubMed

Norgan, Andrew P; Coffman, Paul K; Kocher, Jean-Pierre A; Katzmann, David J; Sosa, Carlos P

2011-04-28

Virtual (computational) screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelization of AutoDock 4.2 (mpAD4). Using MPI and OpenMP, AutoDock 4.2 was parallelized for use on MPI-enabled systems and to multithread the execution of individual docking jobs. In addition, code was implemented to reduce input/output (I/O) traffic by reusing grid maps at each node from docking to docking. Performance of mpAD4 was examined on two multiprocessor computers. Using MPI with OpenMP multithreading, mpAD4 scales with near linearity on the multiprocessor systems tested. In situations where I/O is limiting, reuse of grid maps reduces both system I/O and overall screening time. Multithreading of AutoDock's Lamarkian Genetic Algorithm with OpenMP increases the speed of execution of individual docking jobs, and when combined with MPI parallelization can significantly reduce the execution time of virtual screens. This work is significant in that mpAD4 speeds the execution of certain molecular docking workloads and allows the user to optimize the degree of system-level (MPI) and node-level (OpenMP) parallelization to best fit both workloads and computational resources.

Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE).

PubMed

Mohan, Jasna Jagan; Narayan, Prashanth; Padmanabhan, Renjini Ambika; Joseph, Selin; Kumar, Pradeep G; Laloraya, Malini

2018-07-01

Dedicator of cytokinesis (DOCK 180) involved in cytoskeletal reorganization is primarily a cytosolic molecule. It is recently shown to be nuclear in HeLa cells but its nuclear function is not known. The spatiotemporal distribution of DOCK180 in uterus was studied in uterine cytoplasmic and nuclear compartments during the "window of implantation." The functional significance of nuclear DOCK180 was explored by homology modeling, co-immunoprecipitation assays, and mass spectrometric analysis. Dock180's role in early pregnancy was ascertained by Dock 180 silencing and subsequent quantitative real-time PCR and Western blotting analysis. Our study shows a nuclear DOCK180 in the uterus during "window of implantation." Estrogen and progesterone mediate expression and nuclear translocation of DOCK180. The nuclear function of DOCK180 is attributed to its ability to import autoimmune regulator (AIRE) into the nucleus. Silencing of Dock180 inhibited AIRE nuclear shuttling which influenced its downstream targets, thereby affecting decidualization with AIRE and HOXA-10 as the major players as well as lack of implantation site formation due to impact on angiogenesis-associated genes. DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

InterEvDock: a docking server to predict the structure of protein–protein interactions using evolutionary information

PubMed Central

Yu, Jinchao; Vavrusa, Marek; Andreani, Jessica; Rey, Julien; Tufféry, Pierre; Guerois, Raphaël

2016-01-01

The structural modeling of protein–protein interactions is key in understanding how cell machineries cross-talk with each other. Molecular docking simulations provide efficient means to explore how two unbound protein structures interact. InterEvDock is a server for protein docking based on a free rigid-body docking strategy. A systematic rigid-body docking search is performed using the FRODOCK program and the resulting models are re-scored with InterEvScore and SOAP-PP statistical potentials. The InterEvScore potential was specifically designed to integrate co-evolutionary information in the docking process. InterEvDock server is thus particularly well suited in case homologous sequences are available for both binding partners. The server returns 10 structures of the most likely consensus models together with 10 predicted residues most likely involved in the interface. In 91% of all complexes tested in the benchmark, at least one residue out of the 10 predicted is involved in the interface, providing useful guidelines for mutagenesis. InterEvDock is able to identify a correct model among the top10 models for 49% of the rigid-body cases with evolutionary information, making it a unique and efficient tool to explore structural interactomes under an evolutionary perspective. The InterEvDock web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock/. PMID:27131368

Predictions of vacuum loss of evacuated vials from initial air leak rates.

PubMed

Prisco, Michael R; Ochoa, Jorge A; Yardimci, Atif M

2013-08-01

Container closure integrity is a critical factor for maintaining product sterility and stability. Therefore, closure systems (found in vials, syringes, and cartridges) are designed to provide a seal between rubber stoppers and glass containers. To ensure that the contained product has maintained its sterility and stability at the time of deployment, the seal must remain intact within acceptable limits. To this end, a mathematical model has been developed to describe vacuum loss in evacuated drug vials. The model computes equivalent leak diameter corresponding to initial air leak rate as well as vacuum loss as a function of time and vial size. The theory accounts for three flow regimes that may be encountered. Initial leak rates from 10(-8) to 10(3) sccm (standard cubic centimeters per minute) were investigated for vials ranging from 1 to 100 mL. Corresponding leak diameters of 0.25-173 μm were predicted. The time for a vial to lose half of its vacuum, the T50 value, ranged from many years at the lowest leak rates and largest vials, to fractions of a second at the highest leak rates and smallest vials. These results may be used to determine what level of initial vacuum leak is acceptable for a given product. Copyright © 2013 Wiley Periodicals, Inc.

Dry dock no. 4. Service Building between dry docks 4 ...

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

Dry dock no. 4. Service Building between dry docks 4 and 5. Floor plans (Navy Yard Public Works Office 1941). In files of Cushman & Wakefield, building 501. Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

Docking system for spacecraft

NASA Technical Reports Server (NTRS)

Kahn, Jon B. (Inventor)

1988-01-01

A mechanism is disclosed for the docking of a spacecraft to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a spacecraft and a passive docking structure on the station. The passive structure includes a docking ring mounted on a tunnel structure fixed to the space station. The active structure includes a docking ring carried by an actuator-attenuator devices, each attached at one end to the ring and at its other end in the spacecraft payload bay. The devices respond to command signals for moving the docking ring between a stowed position in the spacecraft to a deployed position suitable for engagement with the docking ring. The devices comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled spacecraft and station into final docked configuration and moving the tunnel structure to a berthed position in the spacecraft. Latches couple the spacecraft and space station upon contact of the docking rings and latches establish a structural tie between the spacecraft when retracted.

Expanded study of feasibility of measuring in-flight 747/JT9D loads, performance, clearance, and thermal data

NASA Technical Reports Server (NTRS)

Sallee, G. P.; Martin, R. L.

1980-01-01

The JT9D jet engine exhibits a TSFC loss of about 1 percent in the initial 50 flight cycles of a new engine. These early losses are caused by seal-wear induced opening of running clearances in the engine gas path. The causes of this seal wear have been identified as flight induced loads which deflect the engine cases and rotors, causing the rotating blades to rub against the seal surfaces, producing permanent clearance changes. The real level of flight loads encountered during airplane acceptance testing and revenue service and the engine's response in the dynamic flight environment were investigated. The feasibility of direct measurement of these flight loads and their effects by concurrent measurement of 747/JT9D propulsion system aerodynamic and inertia loads and the critical engine clearance and performance changes during 747 flight and ground operations was evaluated. A number of technical options were examined in relation to the total estimated program cost to facilitate selection of the most cost effective option. It is concluded that a flight test program meeting the overall objective of determining the levels of aerodynamic and inertia load levels to which the engine is exposed during the initial flight acceptance test and normal flight maneuvers is feasible and desirable. A specific recommended flight test program, based on the evaluation of cost effectiveness, is defined.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS).

PubMed

Whiteley, Chris G; Lee, Duu-Jong

2016-09-09

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the 'docking', first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one 'final' probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial 'orientation' of the AgNP with the enzyme is the same as the 'final' AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

A Hadoop-based Molecular Docking System

NASA Astrophysics Data System (ADS)

Dong, Yueli; Guo, Quan; Sun, Bin

2017-10-01

Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

SealSim Version 1.1

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

SealSim 1.1 is a state-of-the-art, Microsoft Windows based computer program developed for the U.S. Department of Energy by Aspen Research Corporation with Contracted support from TNO TPD. It is intended to be used by manufacturers, engineers, educators, students, architects, and others to help determine the relative durability of Insulating Glass Units (IGU). As a function of time, SealSim 1.1 simulates the behaviour of an Insulating Glass Unit, exposed to realistic or user-defined weather climates. Stresses and strains in the IGU are calculated as a function of time, together with temperature distributions, gas permeation effects (gas loss, desiccant loading), dew pointmore » temperature, U-factor, etc. The current version of SealSim 1.1 supports double-glazing Units. where the spacer system is either a Thermo Plastic Spacer (TPS) or Box type spacer. For the determination of solar properties of glazing systems, SealSim 1.1 uses the Tntemational Glazing Database of LBNL, which is also used by OPTICS and WINDOW. The goal of the SealSim 1.1 simulations is to predict the IGU's average lifetime, expressed in terms of the "Durability Index", together with the associated failure mechanisms. The Durability Index of a particular IGU and its most probable failure mechanism can be compared with other IGU's. How the predicted Durability Index relates to the actual durability of an IGU is not known, simply because sufficient experimental data is lacking for describing the behaviour of IG Units over extended periods of time together with a lack of knowledge of the conditions it is subjected to and initial state of the CU at the time of manufacturing. In order to simulate the IGU behaviour in time, the conditions of the IGU must be defined; together with the weather and or climate that the IGU is subjected to. Using physical models of the IGU, SealSim 1.1 calculates tte response of the CU in time. These physical models are described in more detail in separate documents provided with the SealSim 1.1 program. Though much care was taken to test the correct implementation of physical sub models in SealSim 1.1, make the graphical user interface intuitive, making it robust, and to check all options that are available in SealSim 1.1, it will certainly suffer from the deficiencies of a first release. Aspen Research Corporation 1700 Buerkle Road St Paul, Minnesota 55110« less

GPU.proton.DOCK: Genuine Protein Ultrafast proton equilibria consistent DOCKing.

PubMed

Kantardjiev, Alexander A

2011-07-01

GPU.proton.DOCK (Genuine Protein Ultrafast proton equilibria consistent DOCKing) is a state of the art service for in silico prediction of protein-protein interactions via rigorous and ultrafast docking code. It is unique in providing stringent account of electrostatic interactions self-consistency and proton equilibria mutual effects of docking partners. GPU.proton.DOCK is the first server offering such a crucial supplement to protein docking algorithms--a step toward more reliable and high accuracy docking results. The code (especially the Fast Fourier Transform bottleneck and electrostatic fields computation) is parallelized to run on a GPU supercomputer. The high performance will be of use for large-scale structural bioinformatics and systems biology projects, thus bridging physics of the interactions with analysis of molecular networks. We propose workflows for exploring in silico charge mutagenesis effects. Special emphasis is given to the interface-intuitive and user-friendly. The input is comprised of the atomic coordinate files in PDB format. The advanced user is provided with a special input section for addition of non-polypeptide charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. The output is comprised of docked complexes in PDB format as well as interactive visualization in a molecular viewer. GPU.proton.DOCK server can be accessed at http://gpudock.orgchm.bas.bg/.

CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site

PubMed Central

Kurcinski, Mateusz; Jamroz, Michal; Blaszczyk, Maciej; Kolinski, Andrzej; Kmiecik, Sebastian

2015-01-01

Protein–peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein–peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein–peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. PMID:25943545

AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.

PubMed

Ben-Shimon, Avraham; Niv, Masha Y

2015-05-05

The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protein-protein docking with binding site patch prediction and network-based terms enhanced combinatorial scoring.

PubMed

Gong, Xinqi; Wang, Panwen; Yang, Feng; Chang, Shan; Liu, Bin; He, Hongqiu; Cao, Libin; Xu, Xianjin; Li, Chunhua; Chen, Weizu; Wang, Cunxin

2010-11-15

Protein-protein docking has made much progress in recent years, but challenges still exist. Here we present the application of our docking approach HoDock in CAPRI. In this approach, a binding site prediction is implemented to reduce docking sampling space and filter out unreasonable docked structures, and a network-based enhanced combinatorial scoring function HPNCscore is used to evaluate the decoys. The experimental information was combined with the predicted binding site to pick out the most likely key binding site residues. We applied the HoDock method in the recent rounds of the CAPRI experiments, and got good results as predictors on targets 39, 40, and 41. We also got good results as scorers on targets 35, 37, 40, and 41. This indicates that our docking approach can contribute to the progress of protein-protein docking methods and to the understanding of the mechanism of protein-protein interactions. © 2010 Wiley-Liss, Inc.

STATUS REPORT FOR AGING STUDIES OF EPDM O-RING MATERIAL FOR THE H1616 SHIPPING PACKAGE

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

Stefek, T.; Daugherty, W.; Skidmore, E.

This is an interim status report for tasks carried out per Task Technical Plan SRNL-STI-2011-00506. A series of tasks/experiments are being performed at the Savannah River National Laboratory to monitor the aging performance of ethylene propylene diene monomer (EPDM) Orings used in the H1616 shipping package. The data will support the technical basis to extend the annual maintenance of the EPDM O-rings in the H1616 shipping package and to predict the life of the seals at bounding service conditions. Current expectations are that the O-rings will maintain a seal at bounding normal temperatures in service (152 F) for at leastmore » 12 months. The baseline aging data review suggests that the EPDM O-rings are likely to retain significant mechanical properties and sealing force at bounding service temperatures to provide a service life of at least 2 years. At lower, more realistic temperatures, longer service life is likely. Parallel compression stress relaxation and vessel leak test efforts are in progress to further validate this assessment and quantify a more realistic service life prediction. The H1616 shipping package O-rings were evaluated for baseline property data as part of this test program. This was done to provide a basis for comparison of changes in material properties and performance parameters as a function of aging. This initial characterization was limited to physical and mechanical properties, namely hardness, thickness and tensile strength. These properties appear to be consistent with O-ring specifications. Three H1616-1 Containment Vessels were placed in test conditions and are aging at temperatures ranging from 160 to 300 F. The vessels were Helium leak-tested initially and have been tested at periodic intervals after cooling to room temperature to determine if they meet the criterion of leaktightness defined in ANSI standard N14.5-97 (< 1E-07 std cc air/sec at room temperature). To date, no leak test failures have occurred. The cumulative time at temperature ranges from 174 days for the 300 F vessel to 189 days for the 160 F vessel as of 8/1/2012. The compression stress-relaxation (CSR) behavior of H1616 shipping package O-rings is being evaluated to develop an aging model based on material properties. O-ring segments were initially aged at four temperatures (175 F, 235 F, 300 F and 350 F). These temperatures were selected to bound normal service temperatures and to challenge the seals within a reasonable aging period. Currently, samples aging at 300 F and 350 F have reached the mechanical failure point (end of life) which is defined in this study as 90% loss of initial sealing force. As a result, additional samples more recently began aging at {approx}270 F to provide additional data for the aging model. Aging and periodic leak testing of the full containment vessels, as well as CSR testing of O-ring segments is ongoing. Continued testing per the Task Technical Plan is recommended in order to validate the assumptions outlined in this status report and to quantify and validate the long-term performance of O-ring seals under actual service conditions.« less

Structural analysis of a bolted joint concept for the space shuttle's solid rocket motor casing

NASA Technical Reports Server (NTRS)

Lindell, Michael C.; Stalnaker, Winifred A.

1987-01-01

The Space Shuttle Challenger accident is thought to have been caused by the failure of one of the tang-clevis joints joining together the casing segments of the Solid Rocket Motors (SRM). Excessive displacement between the tang and clevis, possibly unseating the O-ring seals, may have initiated the resulting accident. An effort was made at NASA Langley Research Center to design an alternative concept for mating the casing segments. A bolted flange joint concept was designed and analyzed to determine if the concept would effectively maintain a seal while minimizing joint weight and controlling stress levels. It is shown that under the loading conditions analyzed the seal area of the joint remains seated. The only potential stress problem is a stress concentration in the flange at the edge of the bolt hole, which is highly localized. While heavier than the existing joint, this concept does have some advantages making the bolted joint an attractive alternative.

Electrostatics in protein–protein docking

PubMed Central

Heifetz, Alexander; Katchalski-Katzir, Ephraim; Eisenstein, Miriam

2002-01-01

A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule. Thus, the electrostatic character of the molecule is represented as patches of positive, neutral, or negative values. The potential for each molecule is calculated only once and stored as potential spheres adequate for exhaustive rotation/translation scans. The geometric-electrostatic docking algorithm is applied to 17 systems, starting form the structures of the unbound molecules. The results—in terms of the complementarity scores of the nearly correct solutions, their ranking in the lists of sorted solutions, and their statistical uniqueness—are compared with those of geometric docking, showing that the inclusion of electrostatic complementarity in docking is very important, in particular in docking of unbound structures. Based on our results, we formulate several "good electrostatic docking rules": The geometric-electrostatic docking procedure is more successful than geometric docking when the potential patches are large and when the potential extends away from the molecular surface and protrudes into the solvent. In contrast, geometric docking is recommended when the electrostatic potential around the molecules to be docked appears homogenous, that is, with a similar sign all around the molecule. PMID:11847280

Magnetic docking aid for orbiter to ISS docking

NASA Technical Reports Server (NTRS)

Schneider, William C.; Nagy, Kornel; Schliesing, John A.

1996-01-01

The present docking system for the Orbiter uses mechanical capture latches that are actuated by contact forces. The forces are generated when the two approaching masses collide at the docking mechanism. There is always a trade-off between having high enough momentum to effect capture and low enough momentum to avoid structural overload or unacceptable angular displacements. The use of the present docking system includes a contact thrusting maneuver that causes high docking loads to be included into Space Station. A magnetic docking aid has been developed to reduce the load s during docking. The magnetic docking aid is comprised of two extendible booms that are attached adjacent to the docking structure with electromagnets attached on the end of the boom. On the mating vehicle, two steel plates are attached. As the Orbiter approaches Space Station, the booms are extended, and the magnets attach to the actuated (without thrusting), by slowly driving the extendible booms to the stowed position, thus reacting the load into the booms. This results in a docking event that has lower loads induced into Space Station structure. This method also greatly simplifies the Station berthing tasks, since the Shuttle Remote Manipulation System (SRMS) arm need only place the element to be berthed on the magnets (no load required), rather than firing the Reaction Control System (RCS) jets to provide the required force for capture latch actuation. The Magnetic Docking Aid was development testing on a six degree-of-freedom (6 DOF) system at JSC.

Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations.

PubMed

Liu, Kai; Watanabe, Etsurou; Kokubo, Hironori

2017-02-01

The binding mode prediction is of great importance to structure-based drug design. The discrimination of various binding poses of ligand generated by docking is a great challenge not only to docking score functions but also to the relatively expensive free energy calculation methods. Here we systematically analyzed the stability of various ligand poses under molecular dynamics (MD) simulation. First, a data set of 120 complexes was built based on the typical physicochemical properties of drug-like ligands. Three potential binding poses (one correct pose and two decoys) were selected for each ligand from self-docking in addition to the experimental pose. Then, five independent MD simulations for each pose were performed with different initial velocities for the statistical analysis. Finally, the stabilities of ligand poses under MD were evaluated and compared with the native one from crystal structure. We found that about 94% of the native poses were maintained stable during the simulations, which suggests that MD simulations are accurate enough to judge most experimental binding poses as stable properly. Interestingly, incorrect decoy poses were maintained much less and 38-44% of decoys could be excluded just by performing equilibrium MD simulations, though 56-62% of decoys were stable. The computationally-heavy binding free energy calculation can be performed only for these survived poses.

Deciphering the complexation process of a fluoroquinolone antibiotic, levofloxacin, with bovine serum albumin in the presence of additives

NASA Astrophysics Data System (ADS)

Kaur, Amandeep; Khan, Imran Ahmd; Banipal, Parampaul Kaur; Banipal, Tarlok Singh

2018-02-01

The current work aims to explore the thermodynamic and conformational aspects for the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible, fluorescence, circular dichroism, and 1H NMR), dynamic light scattering (DLS) and computational methods (molecular docking). The binding of LFC with BSA at two sequential sites with higher affinity ( 103 M- 1) at the first site has been explored by calorimetry whereas the binding at a single site with affinity of the order of 104 M- 1 has been observed from fluorescence spectroscopy. The calorimetric study in the presence of additives along with docking analysis reveals the significant role of electrostatic, hydrogen bonding, and hydrophobic interactions in the association process. The slight conformational changes in protein as well as the changes in the water network structure around the binding cavity of protein have been observed from spectroscopic and DLS measurements. The LFC induced quenching of BSA fluorescence was observed to be initiated mainly through the static quenching process and this suggests the formation of ground state LFC-BSA association complex. The stronger interactions of LFC in the cavity of Sudlow site I (subdomain IIA) of protein have been explored from site marker calorimetric and molecular docking study.

Topology and dynamics of the interaction between 5-nitroimidazole radiosensitizers and duplex DNA studied by a combination of docking, molecular dynamic simulations and NMR spectroscopy

NASA Astrophysics Data System (ADS)

Ramalho, Teodorico C.; França, Tanos C. C.; Cortopassi, Wilian A.; Gonçalves, Arlan S.; da Silva, Alan W. S.; da Cunha, Elaine F. F.

2011-04-01

In spite of recent progress, cancer is still one of the most serious health problems of mankind. Recently, it has been discovered that tumor hypoxia can be exploited for selective anticancer treatment using radiosensitizers that are activated only under hypoxic conditions. The most commonly used radiosensitizers are the 5-nitroimidazole derivatives. The toxicity of bioreductive anticancer drugs, such as radiosensitizers is associated to their interaction with DNA. In this work, we have investigated the interaction between the model radiosensitizers metronizole, nimorazole and secnidazole with salmon DNA in order to get insights on the drug-macromolecule interactions. To this end, we have employed NMR techniques (PFG NMR spectra and spin-lattice relaxation rates) in combination with theoretical tools, such as docking calculations and MD simulations. Initially, results show that the δ values are not the most appropriated NMR parameters to map the interaction topology of drug-macromolecule complexes. Furthermore our data indicate that radiosensitizers, in the inactive form, interact considerably with DNA, significantly increasing its toxicity. In fact, we obtained a good agreement between that technique and docking and MD simulations. This suggests that improvements in the structures of these molecules in order to achieve new and more selective bioreductive anticancer drugs are still necessary.

Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

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

Chung, Le Thi Kim, E-mail: ngocanh@nutr.med.tokushima-u.ac.jp; Hosaka, Toshio; Harada, Nagakatsu

2010-01-01

In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4more » to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.« less

A modular docking mechanism for in-orbit assembly and spacecraft servicing

NASA Technical Reports Server (NTRS)

Gampe, F.; Priesett, K.; Bentall, R. H.

1985-01-01

A Docking Mechanism concept is described which is suitable for use with autonomous docking systems. The central feature of using simple cylindrical handles on one side and a type of prism seating on the other is offered as a practical method of achieving a standardized structural interface without freezing continued development of the latches, either technically or commercially. The main emphasis in docking mechanism concepts is in two directions: (1) a very simple docking mechanism, involving mainly the latch mechanism to achieve a structural link; and (2) a sophisticated Docking Mechanism, where the latch mechanism is designed for nonrigid spacecraft and the achievement of very low dynamic interactions between spacecraft during the docking process.

76 FR 27309 - Union Electric Company, dba AmerenUE; Notice of Application for Amendment of License and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... brief comments up to 6,000 characters, without prior registration, using the eComment system at http... docks, and add 1,330 feet of breakwater. The completed development would have 18 docks (16 boat docks, 1 swim dock, and 1 fishing dock) with 240 boat slips and 156 personal watercraft lifts; boat fueling...

Docking system for spacecraft

NASA Technical Reports Server (NTRS)

Kahn, Jon B. (Inventor)

1990-01-01

A mechanism for the docking of a space vehicle to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a space vehicle 10 and a passive docking structure on a station 11. The passive structure includes a docking ring 50 mounted on a tunnel structure 35 fixed to the space station. The active structure including a docking ring 18 carried by actuator-attenuator devices 20, each attached at one end to the ring 18 and at its other end in the vehicle's payload bay 12. The devices 20 respond to command signals for moving the docking ring 18 between a stowed position in the space vehicle to a deployed position suitable for engagement with the docking ring 50. The devices 20 comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled space vehicle and station into final docked configuration and moving the tunnel structure to a berthed position in the space vehicle 10. Latches 60 couple the space vehicle and space station upon contact of docking rings 18 and 50 and latches 41-48 establish a structural tie between the spacecraft when retracted.

Multiple grid arrangement improves ligand docking with unknown binding sites: Application to the inverse docking problem.

PubMed

Ban, Tomohiro; Ohue, Masahito; Akiyama, Yutaka

2018-04-01

The identification of comprehensive drug-target interactions is important in drug discovery. Although numerous computational methods have been developed over the years, a gold standard technique has not been established. Computational ligand docking and structure-based drug design allow researchers to predict the binding affinity between a compound and a target protein, and thus, they are often used to virtually screen compound libraries. In addition, docking techniques have also been applied to the virtual screening of target proteins (inverse docking) to predict target proteins of a drug candidate. Nevertheless, a more accurate docking method is currently required. In this study, we proposed a method in which a predicted ligand-binding site is covered by multiple grids, termed multiple grid arrangement. Notably, multiple grid arrangement facilitates the conformational search for a grid-based ligand docking software and can be applied to the state-of-the-art commercial docking software Glide (Schrödinger, LLC). We validated the proposed method by re-docking with the Astex diverse benchmark dataset and blind binding site situations, which improved the correct prediction rate of the top scoring docking pose from 27.1% to 34.1%; however, only a slight improvement in target prediction accuracy was observed with inverse docking scenarios. These findings highlight the limitations and challenges of current scoring functions and the need for more accurate docking methods. The proposed multiple grid arrangement method was implemented in Glide by modifying a cross-docking script for Glide, xglide.py. The script of our method is freely available online at http://www.bi.cs.titech.ac.jp/mga_glide/. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Magnet-Based System for Docking of Miniature Spacecraft

NASA Technical Reports Server (NTRS)

Howard, Nathan; Nguyen, Hai D.

2007-01-01

A prototype system for docking a miniature spacecraft with a larger spacecraft has been developed by engineers at the Johnson Space Center. Engineers working on Mini AERCam, a free-flying robotic camera, needed to find a way to successfully dock and undock their miniature spacecraft to refuel the propulsion and recharge the batteries. The subsystems developed (see figure) include (1) a docking port, designed for the larger spacecraft, which contains an electromagnet, a ball lock mechanism, and a service probe; and (2) a docking cluster, designed for the smaller spacecraft, which contains either a permanent magnet or an electromagnet. A typical docking operation begins with the docking spacecraft maneuvering into position near the docking port on the parent vehicle. The electromagnet( s) are then turned on, and, if necessary, the docking spacecraft is then maneuvered within the capture envelope of the docking port. The capture envelope for this system is approximated by a 5-in. (12.7-cm) cube centered on the front of the docking-port electromagnet and within an angular misalignment of <30 . Thereafter, the magnetic forces draw the smaller spacecraft toward the larger one and this brings the spacecraft into approximate alignment prior to contact. Mechanical alignment guides provide the final rotational alignment into one of 12 positions. Once the docking vehicle has been captured magnetically in the docking port, the ball-lock mechanism is activated, which locks the two spacecraft together. At this point the electromagnet( s) are turned off, and the service probe extended if recharge and refueling are to be performed. Additionally, during undocking, the polarity of one electromagnet can be reversed to provide a gentle push to separate the two spacecraft. This system is currently being incorporated into the design of Mini AERCam vehicle.

Why are most EU pigs tail docked? Economic and ethical analysis of four pig housing and management scenarios in the light of EU legislation and animal welfare outcomes.

PubMed

D'Eath, R B; Niemi, J K; Vosough Ahmadi, B; Rutherford, K M D; Ison, S H; Turner, S P; Anker, H T; Jensen, T; Busch, M E; Jensen, K K; Lawrence, A B; Sandøe, P

2016-04-01

To limit tail biting incidence, most pig producers in Europe tail dock their piglets. This is despite EU Council Directive 2008/120/EC banning routine tail docking and allowing it only as a last resort. The paper aims to understand what it takes to fulfil the intentions of the Directive by examining economic results of four management and housing scenarios, and by discussing their consequences for animal welfare in the light of legal and ethical considerations. The four scenarios compared are: 'Standard Docked', a conventional housing scenario with tail docking meeting the recommendations for Danish production (0.7 m2/pig); 'Standard Undocked', which is the same as 'Standard Docked' but with no tail docking, 'Efficient Undocked' and 'Enhanced Undocked', which have increased solid floor area (0.9 and 1.0 m2/pig, respectively) provision of loose manipulable materials (100 and 200 g/straw per pig per day) and no tail docking. A decision tree model based on data from Danish and Finnish pig production suggests that Standard Docked provides the highest economic gross margin with the least tail biting. Given our assumptions, Enhanced Undocked is the least economic, although Efficient Undocked is better economically and both result in a lower incidence of tail biting than Standard Undocked but higher than Standard Docked. For a pig, being bitten is worse for welfare (repeated pain, risk of infections) than being docked, but to compare welfare consequences at a farm level means considering the number of affected pigs. Because of the high levels of biting in Standard Undocked, it has on average inferior welfare to Standard Docked, whereas the comparison of Standard Docked and Enhanced (or Efficient) Undocked is more difficult. In Enhanced (or Efficient) Undocked, more pigs than in Standard Docked suffer from being tail bitten, whereas all the pigs avoid the acute pain of docking endured by the pigs in Standard Docked. We illustrate and discuss this ethical balance using numbers derived from the above-mentioned data. We discuss our results in the light of the EU Directive and its adoption and enforcement by Member States. Widespread use of tail docking seems to be accepted, mainly because the alternative steps that producers are required to take before resorting to it are not specified in detail. By tail docking, producers are acting in their own best interests. We suggest that for the practice of tail docking to be terminated in a way that benefits animal welfare, changes in the way pigs are housed and managed may first be required.

Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

NASA Technical Reports Server (NTRS)

Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

2015-01-01

The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

13. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN ...

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

13. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN BUILT IN 1911-1912, THIS WAS THE LARGEST ORE-UNLOADING DOCK ON THE GREAT LAKES. THE DOCK FEATURED FOUR HULETT UNLOADERS, EACH WITH A BUCKET CAPACITY OF 17 TONS; A 15-TON CAPACITY ORE STOCKING AND REHANDLING BRIDGE; AND A ONE-MILLION-TON CAPACITY ORE STORAGE YARD. THE WILLIAM-SEAVER-MORGAN COMPANY OF CLEVELAND BUILT THE DOCK EQUIPMENT. - Pennsylvania Railway Ore Dock, Lake Erie at Whiskey Island, approximately 1.5 miles west of Public Square, Cleveland, Cuyahoga County, OH

Novel Bonding Technology for Hermetically Sealed Silicon Micropackage

NASA Astrophysics Data System (ADS)

Lee, Duck-Jung; Ju, Byeong-Kwon; Choi, Woo-Beom; Jeong, Jee-Won; Lee, Yun-Hi; Jang, Jin; Lee, Kwang-Bae; Oh, Myung-Hwan

1999-01-01

We performed glass-to-silicon bonding and fabricated a hermetically sealed silicon wafer using silicon direct bonding followed by anodic bonding (SDAB). The hydrophilized glass and silicon wafers in solution were dried and initially bonded in atmosphere as in the silicon direct bonding (SDB) process, but annealing at high temperature was not performed. Anodic bonding was subsequently carried out for the initially bonded specimens. Then the wafer pairs bonded by the SDAB method were different from those bonded by the anodic bonding process only. The effects of the bonding process on the bonded area and tensile strength were investigated as functions of bonding temperature and voltage. Using scanning electron microscopy (SEM), the cross-sectional view of the bonded interface region was observed. In order to investigate the migration of the sodium ions in the bonding process, the concentration of the bonded glass was compared with that of standard glass. The specimen bonded using the SDAB process had higher efficiency than that using the anodic bonding process only.

Soft Modular Robotic Cubes: Toward Replicating Morphogenetic Movements of the Embryo

PubMed Central

Mendoza-Garcia, Ricardo-Franco; Zagal, Juan Cristóbal

2017-01-01

In this paper we present a new type of simple, pneumatically actuated, soft modular robotic system that can reproduce fundamental cell behaviors observed during morphogenesis; the initial shaping stage of the living embryo. The fabrication method uses soft lithography for producing composite elastomeric hollow cubes and permanent magnets as passive docking mechanism. Actuation is achieved by controlling the internal pressurization of cubes with external micro air pumps. Our experiments show how simple soft robotic modules can serve to reproduce to great extend the overall mechanics of collective cell migration, delamination, invagination, involution, epiboly and even simple forms of self-reconfiguration. Instead of relying in complex rigid onboard docking hardware, we exploit the coordinated inflation/deflation of modules as a simple mechanism to detach/attach modules and even rearrange the spatial position of components. Our results suggest new avenues for producing inexpensive, yet functioning, synthetic morphogenetic systems and provide new tangible models of cell behavior. PMID:28060878

Modeling, docking and dynamics simulations of a non-specific lipid transfer protein from Peganum harmala L.

PubMed

Shi, Zheng; Wang, Zi-jie; Xu, Huai-long; Tian, Yang; Li, Xin; Bao, Jin-ku; Sun, Su-rong; Yue, Bi-song

2013-12-01

Non-specific lipid transfer proteins (ns-LTPs), ubiquitously found in various types of plants, have been well-known to transfer amphiphilic lipids and promote the lipid exchange between mitochondria and microbody. In this study, an in silico analysis was proposed to study ns-LTP in Peganum harmala L., which may belong to ns-LTP1 family, aiming at constructing its three-dimensional structure. Moreover, we adopted MEGA to analyze ns-LTPs and other species phylogenetically, which brought out an initial sequence alignment of ns-LTPs. In addition, we used molecular docking and molecular dynamics simulations to further investigate the affinities and stabilities of ns-LTP with several ligands complexes. Taken together, our results about ns-LTPs and their ligand-binding activities can provide a better understanding of the lipid-protein interactions, indicating some future applications of ns-LTP-mediated transport. Copyright © 2013 Elsevier Ltd. All rights reserved.

High performance transcription factor-DNA docking with GPU computing

PubMed Central

2012-01-01

Background Protein-DNA docking is a very challenging problem in structural bioinformatics and has important implications in a number of applications, such as structure-based prediction of transcription factor binding sites and rational drug design. Protein-DNA docking is very computational demanding due to the high cost of energy calculation and the statistical nature of conformational sampling algorithms. More importantly, experiments show that the docking quality depends on the coverage of the conformational sampling space. It is therefore desirable to accelerate the computation of the docking algorithm, not only to reduce computing time, but also to improve docking quality. Methods In an attempt to accelerate the sampling process and to improve the docking performance, we developed a graphics processing unit (GPU)-based protein-DNA docking algorithm. The algorithm employs a potential-based energy function to describe the binding affinity of a protein-DNA pair, and integrates Monte-Carlo simulation and a simulated annealing method to search through the conformational space. Algorithmic techniques were developed to improve the computation efficiency and scalability on GPU-based high performance computing systems. Results The effectiveness of our approach is tested on a non-redundant set of 75 TF-DNA complexes and a newly developed TF-DNA docking benchmark. We demonstrated that the GPU-based docking algorithm can significantly accelerate the simulation process and thereby improving the chance of finding near-native TF-DNA complex structures. This study also suggests that further improvement in protein-DNA docking research would require efforts from two integral aspects: improvement in computation efficiency and energy function design. Conclusions We present a high performance computing approach for improving the prediction accuracy of protein-DNA docking. The GPU-based docking algorithm accelerates the search of the conformational space and thus increases the chance of finding more near-native structures. To the best of our knowledge, this is the first ad hoc effort of applying GPU or GPU clusters to the protein-DNA docking problem. PMID:22759575

Docking of small molecules to farnesoid X receptors using AutoDock Vina with the Convex-PL potential: lessons learned from D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Kadukova, Maria; Grudinin, Sergei

2018-01-01

The 2016 D3R Grand Challenge 2 provided an opportunity to test multiple protein-ligand docking protocols on a set of ligands bound to farnesoid X receptor that has many available experimental structures. We participated in the Stage 1 of the Challenge devoted to the docking pose predictions, with the mean RMSD value of our submission poses of 2.9 Å. Here we present a thorough analysis of our docking predictions made with AutoDock Vina and the Convex-PL rescoring potential by reproducing our submission protocol and running a series of additional molecular docking experiments. We conclude that a correct receptor structure, or more precisely, the structure of the binding pocket, plays the crucial role in the success of our docking studies. We have also noticed the important role of a local ligand geometry, which seems to be not well discussed in literature. We succeed to improve our results up to the mean RMSD value of 2.15-2.33 Å dependent on the models of the ligands, if docking these to all available homologous receptors. Overall, for docking of ligands of diverse chemical series we suggest to perform docking of each of the ligands to a set of multiple receptors that are homologous to the target.

CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site.

PubMed

Kurcinski, Mateusz; Jamroz, Michal; Blaszczyk, Maciej; Kolinski, Andrzej; Kmiecik, Sebastian

2015-07-01

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

An Alternative Approach for Treating a Type Ia Endoleak after Conventional EVAR Using the Nellix Endovascular Aneurysm Sealing.

PubMed

Martinelli, Ombretta; Fresilli, Mauro; Irace, Luigi; Venosi, Salvatore; Jabbour, Jihad; Picone, Veronica; Maruca, Debora; Di Girolamo, Alessia; Gossetti, Bruno

2018-05-01

To report the use of a Nellix endovascular aneurysm sealing (EVAS) device, to successfully treat a type Ia endoleak (EL) after an endovascular aortic repair (EVAR). A 70-year-old man was diagnosed with a 90-mm aortic aneurysm, suspicious for being inflammatory. It was initially treated successfully, with a Medtronic Endurant (Medtronic, Minneapolis, MN, USA). Five years after the index endovascular repair, an asymptomatic type Ia EL was detected on duplex ultrasound and computed tomographic angiogram. Other endovascular solutions in the form of proximal cuff, chimney was considered difficult to execute due to challenges in planning, manipulation, and renal cannulation caused by the short proximal sealing zone above the existing stent graft and the constraints of the previous endograft. Thus, a relining of the previous endoprothesis was performed using the Nellix system (Endologix, Inc., Irvine, CA, USA). One-year follow-up imaging demonstrated successful resolution of the EL and persistent sealing of the Nellix device. Nellix EVAS system can be an alternative and safe option for relining a stent graft with a type Ia EL. Nellix platform can be added to the clinician's armamentarium for treating type Ia EL after conventional EVAR of infrarenal abdominal aortic aneurysm (AAA). Copyright © 2018 Elsevier Inc. All rights reserved.

The implications of developments on the Atlantic Frontier for marine mammals

NASA Astrophysics Data System (ADS)

Harwood, John; Wilson, Ben

2001-05-01

We review the available information on the distribution and abundance of marine mammals in the Atlantic Frontier area, and the literature on the potential effects of oil exploration and extraction on these species. Reliable estimates of seal abundance are only available for two species (grey and harbour seals). For grey seals and hooded seals there is also information from telemetry studies on their distribution at sea. Data on cetaceans comes from a variety of sources including whaling statistics, dedicated surveys, observers placed on vessels of opportunity, and from bottom-mounted hydrophone arrays. These indicate that the Atlantic Frontier region is of national, and possibly international, importance for a number of cetacean species. The most abundant small cetacean is likely to be the white-sided dolphin; however, smaller numbers of large whales, including endangered blue, right, fin and sei whales, and vulnerable humpback and sperm whales are also likely to be present in summer. There is growing evidence that a number of marine mammal species respond to the acoustic and physical disturbance associated with exploration for oil and gas resources, although the ecological impact of these responses is unclear. We describe how risk assessment frameworks, initially developed for evaluating the environmental impacts of hazardous chemicals, can be used to address this problem.

Alaska harbor seal (Phoca vitulina) contaminants: A review with annotated bibliography

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

Papa, R.S.; Becker, P.R.

1998-10-01

The numbers of harbor seals (Phoca vitulina) have declined steadily and substantially over the last two decades in the Central and Western Gulf of Alaska, including Prince William Sound. Although the reasons for this decline have not been identified, hypotheses have included fishery interactions, changes in availability of food resources, human harvests, disease, increase in predation, increase in disturbance, and pollution. Although the presence of contaminants has been suggested as one possible causative factor in the decline of both the harbor seal and Steller sea lion, very little information is readily available on contaminant concentrations in these animals. As anmore » initial step in the development of a database that can be used to define the types of studies needed to address the possible role of anthropogenic contaminants in the decline of this species, existing data and information on levels of contaminants in the harbor seals of Alaska, the contiguous U.S., and other areas of the world were reviewed. This report provides references and current scientific literature, as well as gray literature and unpublished databases. This report is divided into three sections: (1) a synthesis of information based on the review, (2) tables that summarize the published data, and (3) an annotated bibliography.« less

STS-74 view of MIR Docking module at Pad 39A

NASA Technical Reports Server (NTRS)

1995-01-01

Workers at Launch Pad 39A are preparing to close the payload bay doors on the Space Shuttle Atlantis for its upcoming launch on Mission STS-74 and the second docking with the Russian Space Station Mir. Uppermost in the payload bay is the Orbiter Docking System (ODS), which also flew on the first docking flight between the Space Shuttle and MIR. Lowermost is the primary payload of STS-74, the Russian-built Docking Module. During the mission, the Docking Module will first be attached to ODS and then to Mir. It will be left attached to Mir to become a permanent extension that will afford adequate clearance between the orbiter and the station during future dockings. At left in the payload bay, looking like a very long pole, is the Canadian-built Remote Manipulator System arm that will be used by the crew to hoist the Docking Module and attach it to the ODS.

The SH2/SH3 adaptor protein dock interacts with the Ste20-like kinase misshapen in controlling growth cone motility.

PubMed

Ruan, W; Pang, P; Rao, Y

1999-11-01

Recent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals.

Comparison of neural histomorphology in tail tips from pigs docked using clippers or cautery iron.

PubMed

Kells, N J; Beausoleil, N J; Johnson, C B; Sutherland, M A; Morrison, R S; Roe, W

2017-07-01

Tail docking of pigs is commonly performed to reduce the incidence of unwanted tail-biting behaviour. Two docking methods are commonly used: blunt trauma cutting (i.e. using side clippers), or cutting and concurrent cauterisation using a hot cautery iron. A potential consequence of tail amputation is the development of neuromas at the docking site. Neuromas have been linked to neuropathic pain, which can influence the longer-term welfare of affected individuals. To determine whether method of tail docking influences the extent of neuroma formation, 75 pigs were allocated to one of three treatments at birth: tail docked using clippers; tail docked using cautery iron; tail left intact. Tail docking was performed at 2 days of age and pigs were kept under conventional conditions until slaughter at 21 weeks of age. Tails were removed following slaughter and subjected to histological examination. Nerve histomorphology was scored according to the following scale: 1=discrete well-organised nerve bundles; 2=moderate neural proliferation and disorganisation affecting more than half of the circumference of the tail; 3=marked neural proliferation to form almost continuous disorganised bundles or non-continuous enlarged bundles compressing the surrounding connective tissue. Scores of 2 or 3 indicated neuroma formation. Scores were higher in docked pigs than undocked pigs (P<0.001), but did not differ between pigs docked using clippers and those docked using cautery (P=0.23). The results indicate that tail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

Human and Server Docking Prediction for CAPRI Round 30–35 Using LZerD with Combined Scoring Functions

PubMed Central

Peterson, Lenna X.; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

2016-01-01

We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues’ spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, i.e. whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. PMID:27654025

Seals Having Textured Portions for Protection in Space Environments

NASA Technical Reports Server (NTRS)

Daniels, Christopher (Inventor); Garafolo, Nicholas (Inventor)

2016-01-01

A sealing construct for a space environment includes a seal-bearing object, a seal on the seal-bearing object, and a seal-engaging object. The seal includes a seal body having a sealing surface, and a textured pattern at the sealing surface, the textured pattern defining at least one shaded channel surface. The seal-engaging object is selectively engaged with the seal-bearing object through the seal. The seal-engaging object has a sealing surface, wherein, when the seal-engaging object is selectively engaged with the seal-bearing object, the sealing surface of the seal-engaging object engages the sealing surface of the seal, and the seal is compressed between the seal-bearing object and the seal-engaging object such that at least one shaded channel surface engages the sealing surface of the seal-engaging object.

A web interface for easy flexible protein-protein docking with ATTRACT.

PubMed

de Vries, Sjoerd J; Schindler, Christina E M; Chauvot de Beauchêne, Isaure; Zacharias, Martin

2015-02-03

Protein-protein docking programs can give valuable insights into the structure of protein complexes in the absence of an experimental complex structure. Web interfaces can facilitate the use of docking programs by structural biologists. Here, we present an easy web interface for protein-protein docking with the ATTRACT program. While aimed at nonexpert users, the web interface still covers a considerable range of docking applications. The web interface supports systematic rigid-body protein docking with the ATTRACT coarse-grained force field, as well as various kinds of protein flexibility. The execution of a docking protocol takes up to a few hours on a standard desktop computer. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

DockQ: A Quality Measure for Protein-Protein Docking Models

PubMed Central

Basu, Sankar

2016-01-01

The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å) might still qualify as 'acceptable' with a descent Fnat (>0.50) and iRMS (<3.0Å). This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by combining Fnat, LRMS, and iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for protein structure prediction, and DockQ should be useful in a similar development in the protein docking field. DockQ is available at http://github.com/bjornwallner/DockQ/ PMID:27560519

NMR Model of PrgI-SipD Interaction and its Implications in the Needle-Tip Assembly of the Salmonella Type III Secretion System

PubMed Central

Rathinavelan, Thenmalarchelvi; Lara-Tejero, Maria; Lefebre, Matthew; Chatterjee, Srirupa; McShan, Andrew C.; Guo, Da-Chuan; Tang, Chun; Galan, Jorge E.; De Guzman, Roberto N.

2014-01-01

Salmonella and other pathogenic bacteria use the type III secretion system (T3SS) to inject virulence proteins into human cells to initiate infections. The structural component of the T3SS contains a needle and a needle tip. The needle is assembled from PrgI needle protomers and the needle tip is capped with several copies of the SipD tip protein. How a tip protein docks on the needle is unclear. A crystal structure of a PrgI-SipD fusion protein docked on the PrgI needle results in steric clash of SipD at the needle tip when modeled on the recent atomic structure of the needle. Thus, there is currently no good model of how SipD is docked on the PrgI needle tip. Previously, we showed by NMR paramagnetic relaxation enhancement (PRE) methods that a specific region in the SipD coiled-coil is the binding site for PrgI. Others have hypothesized that a domain of the tip protein – the N-terminal α-helical hairpin, has to swing away during the assembly of the needle apparatus. Here, we show by PRE methods that a truncated form of SipD lacking the α-helical hairpin domain binds more tightly to PrgI. Further, PRE-based structure calculations revealed multiple PrgI binding sites on the SipD coiled-coil. Our PRE results together with the recent NMR-derived atomic structure of the Salmonella needle suggest a possible model of how SipD might dock at the PrgI needle tip. SipD and PrgI are conserved in other bacterial T3SSs, thus our results have wider implication in understanding other needle-tip complexes. PMID:24951833

Combining self- and cross-docking as benchmark tools: the performance of DockBench in the D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2018-01-01

Molecular docking is a powerful tool in the field of computer-aided molecular design. In particular, it is the technique of choice for the prediction of a ligand pose within its target binding site. A multitude of docking methods is available nowadays, whose performance may vary depending on the data set. Therefore, some non-trivial choices should be made before starting a docking simulation. In the same framework, the selection of the target structure to use could be challenging, since the number of available experimental structures is increasing. Both issues have been explored within this work. The pose prediction of a pool of 36 compounds provided by D3R Grand Challenge 2 organizers was preceded by a pipeline to choose the best protein/docking-method couple for each blind ligand. An integrated benchmark approach including ligand shape comparison and cross-docking evaluations was implemented inside our DockBench software. The results are encouraging and show that bringing attention to the choice of the docking simulation fundamental components improves the results of the binding mode predictions.

jMetalCpp: optimizing molecular docking problems with a C++ metaheuristic framework.

PubMed

López-Camacho, Esteban; García Godoy, María Jesús; Nebro, Antonio J; Aldana-Montes, José F

2014-02-01

Molecular docking is a method for structure-based drug design and structural molecular biology, which attempts to predict the position and orientation of a small molecule (ligand) in relation to a protein (receptor) to produce a stable complex with a minimum binding energy. One of the most widely used software packages for this purpose is AutoDock, which incorporates three metaheuristic techniques. We propose the integration of AutoDock with jMetalCpp, an optimization framework, thereby providing both single- and multi-objective algorithms that can be used to effectively solve docking problems. The resulting combination of AutoDock + jMetalCpp allows users of the former to easily use the metaheuristics provided by the latter. In this way, biologists have at their disposal a richer set of optimization techniques than those already provided in AutoDock. Moreover, designers of metaheuristic techniques can use molecular docking for case studies, which can lead to more efficient algorithms oriented to solving the target problems.  jMetalCpp software adapted to AutoDock is freely available as a C++ source code at http://khaos.uma.es/AutodockjMetal/.

SAMPL4 & DOCK3.7: lessons for automated docking procedures

NASA Astrophysics Data System (ADS)

Coleman, Ryan G.; Sterling, Teague; Weiss, Dahlia R.

2014-03-01

The SAMPL4 challenges were used to test current automated methods for solvation energy, virtual screening, pose and affinity prediction of the molecular docking pipeline DOCK 3.7. Additionally, first-order models of binding affinity were proposed as milestones for any method predicting binding affinity. Several important discoveries about the molecular docking software were made during the challenge: (1) Solvation energies of ligands were five-fold worse than any other method used in SAMPL4, including methods that were similarly fast, (2) HIV Integrase is a challenging target, but automated docking on the correct allosteric site performed well in terms of virtual screening and pose prediction (compared to other methods) but affinity prediction, as expected, was very poor, (3) Molecular docking grid sizes can be very important, serious errors were discovered with default settings that have been adjusted for all future work. Overall, lessons from SAMPL4 suggest many changes to molecular docking tools, not just DOCK 3.7, that could improve the state of the art. Future difficulties and projects will be discussed.

Orbital docking system centerline color television camera system test

NASA Technical Reports Server (NTRS)

Mongan, Philip T.

1993-01-01

A series of tests was run to verify that the design of the centerline color television camera (CTVC) system is adequate optically for the STS-71 Space Shuttle Orbiter docking mission with the Mir space station. In each test, a mockup of the Mir consisting of hatch, docking mechanism, and docking target was positioned above the Johnson Space Center's full fuselage trainer, which simulated the Orbiter with a mockup of the external airlock and docking adapter. Test subjects viewed the docking target through the CTVC under 30 different lighting conditions and evaluated target resolution, field of view, light levels, light placement, and methods of target alignment. Test results indicate that the proposed design will provide adequate visibility through the centerline camera for a successful docking, even with a reasonable number of light failures. It is recommended that the flight deck crew have individual switching capability for docking lights to provide maximum shadow management and that centerline lights be retained to deal with light failures and user preferences. Procedures for light management should be developed and target alignment aids should be selected during simulated docking runs.

Overall view of test set-up in bldg 13 at JSC during docking set-up tests

NASA Image and Video Library

1974-08-04

S74-27049 (4 Aug. 1974) --- Overall view of test set-up in Building 23 at the Johnson Space Center during testing of the docking mechanisms for the joint U.S.-USSR Apollo-Soyuz Test Project. The cinematic check was being made when this picture was taken. The test control room is on the right. The Soviet-developed docking system is atop the USA-NASA developed docking system. Both American and Soviet engineers can be seen taking part in the docking testing. The ASTP docking mission in Earth orbit is scheduled for July 1975.

Kotov practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006656 (22 Nov. 2013) --- Russian cosmonaut Oleg Kotov, Expedition 38 commander, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Kotov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070857 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

Tyurin practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006663 (22 Nov. 2013) --- Russian cosmonaut Mikhail Tyurin, Expedition 38 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Tyurin, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070859 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

Monte Carlo replica-exchange based ensemble docking of protein conformations.

PubMed

Zhang, Zhe; Ehmann, Uwe; Zacharias, Martin

2017-05-01

A replica-exchange Monte Carlo (REMC) ensemble docking approach has been developed that allows efficient exploration of protein-protein docking geometries. In addition to Monte Carlo steps in translation and orientation of binding partners, possible conformational changes upon binding are included based on Monte Carlo selection of protein conformations stored as ordered pregenerated conformational ensembles. The conformational ensembles of each binding partner protein were generated by three different approaches starting from the unbound partner protein structure with a range spanning a root mean square deviation of 1-2.5 Å with respect to the unbound structure. Because MC sampling is performed to select appropriate partner conformations on the fly the approach is not limited by the number of conformations in the ensemble compared to ensemble docking of each conformer pair in ensemble cross docking. Although only a fraction of generated conformers was in closer agreement with the bound structure the REMC ensemble docking approach achieved improved docking results compared to REMC docking with only the unbound partner structures or using docking energy minimization methods. The approach has significant potential for further improvement in combination with more realistic structural ensembles and better docking scoring functions. Proteins 2017; 85:924-937. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DOCKSCORE: a webserver for ranking protein-protein docked poses.

PubMed

Malhotra, Sony; Mathew, Oommen K; Sowdhamini, Ramanathan

2015-04-24

Proteins interact with a variety of other molecules such as nucleic acids, small molecules and other proteins inside the cell. Structure-determination of protein-protein complexes is challenging due to several reasons such as the large molecular weights of these macromolecular complexes, their dynamic nature, difficulty in purification and sample preparation. Computational docking permits an early understanding of the feasibility and mode of protein-protein interactions. However, docking algorithms propose a number of solutions and it is a challenging task to select the native or near native pose(s) from this pool. DockScore is an objective scoring scheme that can be used to rank protein-protein docked poses. It considers several interface parameters, namely, surface area, evolutionary conservation, hydrophobicity, short contacts and spatial clustering at the interface for scoring. We have implemented DockScore in form of a webserver for its use by the scientific community. DockScore webserver can be employed, subsequent to docking, to perform scoring of the docked solutions, starting from multiple poses as inputs. The results, on scores and ranks for all the poses, can be downloaded as a csv file and graphical view of the interface of best ranking poses is possible. The webserver for DockScore is made freely available for the scientific community at: http://caps.ncbs.res.in/dockscore/ .

Spacecraft capture and docking system

NASA Technical Reports Server (NTRS)

Kong, Kinyuen (Inventor); Rafeek, Shaheed (Inventor); Myrick, Thomas (Inventor)

2001-01-01

A system for capturing and docking an active craft to a passive craft has a first docking assembly on the active craft with a first contact member and a spike projecting outwardly, a second docking assembly on the passive craft having a second contact member and a flexible net deployed over a target area with an open mesh for capturing the end of the spike of the active craft, and a motorized net drive for reeling in the net and active craft to mate with the passive craft's docking assembly. The spike has extendable tabs to allow it to become engaged with the net. The net's center is coupled to a net spool for reeling in. An alignment funnel has inclined walls to guide the net and captured spike towards the net spool. The passive craft's docking assembly includes circumferentially spaced preload wedges which are driven to lock the wedges against the contact member of the active craft. The active craft's docking assembly includes a rotary table and drive for rotating it to a predetermined angular alignment position, and mating connectors are then engaged with each other. The system may be used for docking spacecraft in zero or low-gravity environments, as well as for docking underwater vehicles, docking of ancillary craft to a mother craft in subsonic flight, in-flight refueling systems, etc.

The Drosophila SH2-SH3 adapter protein Dock is expressed in embryonic axons and facilitates synapse formation by the RP3 motoneuron.

PubMed

Desai, C J; Garrity, P A; Keshishian, H; Zipursky, S L; Zinn, K

1999-04-01

The Dock SH2-SH3 domain adapter protein, a homolog of the mammalian Nck oncoprotein, is required for axon guidance and target recognition by photoreceptor axons in Drosophila larvae. Here we show that Dock is widely expressed in neurons and at muscle attachment sites in the embryo, and that this expression pattern has both maternal and zygotic components. In motoneurons, Dock is concentrated in growth cones. Loss of zygotic dock function causes a selective delay in synapse formation by the RP3 motoneuron at the cleft between muscles 7 and 6. These muscles often completely lack innervation in late stage 16 dock mutant embryos. RP3 does form a synapse later in development, however, because muscles 7 and 6 are normally innervated in third-instar mutant larvae. The absence of zygotically expressed Dock also results in subtle defects in a longitudinal axon pathway in the embryonic central nervous system. Concomitant loss of both maternally and zygotically derived Dock dramatically enhances these central nervous system defects, but does not increase the delay in RP3 synaptogenesis. These results indicate that Dock facilitates synapse formation by the RP3 motoneuron and is also required for guidance of some interneuronal axons The involvement of Dock in the conversion of the RP3 growth cone into a presynaptic terminal may reflect a role for Dock-mediated signaling in remodeling of the growth cone's cytoskeleton.

Structural Interface Parameters Are Discriminatory in Recognising Near-Native Poses of Protein-Protein Interactions

PubMed Central

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets. PMID:24498255

Structural interface parameters are discriminatory in recognising near-native poses of protein-protein interactions.

PubMed

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets.

Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy.

PubMed

Erickson, Jon A; Jalaie, Mehran; Robertson, Daniel H; Lewis, Richard A; Vieth, Michal

2004-01-01

The key to success for computational tools used in structure-based drug design is the ability to accurately place or "dock" a ligand in the binding pocket of the target of interest. In this report we examine the effect of several factors on docking accuracy, including ligand and protein flexibility. To examine ligand flexibility in an unbiased fashion, a test set of 41 ligand-protein cocomplex X-ray structures were assembled that represent a diversity of size, flexibility, and polarity with respect to the ligands. Four docking algorithms, DOCK, FlexX, GOLD, and CDOCKER, were applied to the test set, and the results were examined in terms of the ability to reproduce X-ray ligand positions within 2.0A heavy atom root-mean-square deviation. Overall, each method performed well (>50% accuracy) but for all methods it was found that docking accuracy decreased substantially for ligands with eight or more rotatable bonds. Only CDOCKER was able to accurately dock most of those ligands with eight or more rotatable bonds (71% accuracy rate). A second test set of structures was gathered to examine how protein flexibility influences docking accuracy. CDOCKER was applied to X-ray structures of trypsin, thrombin, and HIV-1-protease, using protein structures bound to several ligands and also the unbound (apo) form. Docking experiments of each ligand to one "average" structure and to the apo form were carried out, and the results were compared to docking each ligand back to its originating structure. The results show that docking accuracy falls off dramatically if one uses an average or apo structure. In fact, it is shown that the drop in docking accuracy mirrors the degree to which the protein moves upon ligand binding.

Ground Demonstration on the Autonomous Docking of Two 3U CubeSats Using a Novel Permanent-Magnet Docking Mechanism

NASA Technical Reports Server (NTRS)

Pei, Jing; Murchison, Luke; BenShabat, Adam; Stewart, Victor; Rosenthal, James; Follman, Jacob; Branchy, Mark; Sellers, Drew; Elandt, Ryan; Elliott, Sawyer;

Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions.

PubMed

Peterson, Lenna X; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

2017-03-01

We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Validation studies of the site-directed docking program LibDock.

PubMed

Rao, Shashidhar N; Head, Martha S; Kulkarni, Amit; LaLonde, Judith M

2007-01-01

The performance of the site-features docking algorithm LibDock has been evaluated across eight GlaxoSmithKline targets as a follow-up to a broad validation study of docking and scoring software (Warren, G. L.; Andrews, W. C.; Capelli, A.; Clarke, B.; Lalonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Walls, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. J. Med. Chem. 2006, 49, 5912-5931). Docking experiments were performed to assess both the accuracy in reproducing the binding mode of the ligand and the retrieval of active compounds in a virtual screening protocol using both the DJD (Diller, D. J.; Merz, K. M., Jr. Proteins 2001, 43, 113-124) and LigScore2 (Krammer, A. K.; Kirchoff, P. D.; Jiang, X.; Venkatachalam, C. M.; Waldman, M. J. Mol. Graphics Modell. 2005, 23, 395-407) scoring functions. This study was conducted using DJD scoring, and poses were rescored using all available scoring functions in the Accelrys LigandFit module, including LigScore2. For six out of eight targets at least 30% of the ligands were docked within a root-mean-square difference (RMSD) of 2.0 A for the crystallographic poses when the LigScore2 scoring function was used. LibDock retrieved at least 20% of active compounds in the top 10% of screened ligands for four of the eight targets in the virtual screening protocol. In both studies the LigScore2 scoring function enhanced the retrieval of crystallographic poses or active compounds in comparison with the results obtained using the DJD scoring function. The results for LibDock accuracy and ligand retrieval in virtual screening are compared to 10 other docking and scoring programs. These studies demonstrate the utility of the LigScore2 scoring function and that LibDock as a feature directed docking method performs as well as docking programs that use genetic/growing and Monte Carlo driven algorithms.

Protein-protein docking using region-based 3D Zernike descriptors

PubMed Central

2009-01-01

Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods. PMID:20003235

Protein-protein docking using region-based 3D Zernike descriptors.

PubMed

Venkatraman, Vishwesh; Yang, Yifeng D; Sael, Lee; Kihara, Daisuke

2009-12-09

Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-alphaRMSD < or = 2.5 A) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

6. Looking west showing top of dock: steaming frozen ore ...

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

6. Looking west showing top of dock: steaming frozen ore which had been put in pockets in December 1959, May 6, 1990. Photographer: unknown - Marquette Ore Dock No. 6, Ore Dock, On pilings in Marquette City Lower Harbor, Marquette, Marquette County, MI

Fast and accurate grid representations for atom-based docking with partner flexibility.

PubMed

de Vries, Sjoerd J; Zacharias, Martin

2017-06-30

Macromolecular docking methods can broadly be divided into geometric and atom-based methods. Geometric methods use fast algorithms that operate on simplified, grid-like molecular representations, while atom-based methods are more realistic and flexible, but far less efficient. Here, a hybrid approach of grid-based and atom-based docking is presented, combining precalculated grid potentials with neighbor lists for fast and accurate calculation of atom-based intermolecular energies and forces. The grid representation is compatible with simultaneous multibody docking and can tolerate considerable protein flexibility. When implemented in our docking method ATTRACT, grid-based docking was found to be ∼35x faster. With the OPLSX forcefield instead of the ATTRACT coarse-grained forcefield, the average speed improvement was >100x. Grid-based representations may allow atom-based docking methods to explore large conformational spaces with many degrees of freedom, such as multiple macromolecules including flexibility. This increases the domain of biological problems to which docking methods can be applied. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Phillips CO-oxidation catalyts for long-lived CO2 lasers: Activity and initial characterization studies

NASA Technical Reports Server (NTRS)

Kolts, J. H.; Elliott, D. J.; Pennella, F.

1990-01-01

Four different catalysts have been developed specifically for use in sealed carbon dioxide lasers. The catalysts have been designed to be low dusting, stable to shock and vibration, have high activity at low temperatures and have long active lifetimes. Measured global CO oxidation rates range from 1.4 to 2.2 cc CO converted per minute per gram of catalyst at ambient temperature. The catalysts also retain substantial activity at temperatures as low as -35 C. The Phillips laser catalysts are prepared in a variety of different shapes to meet the different pressure drop and gas flow profiles present in the many different styles of lasers. Each catalyst has been tested in sealed TEA lasers and has been shown to substantially increase the sealed life of the laser. Activity measurements made on the precious metal catalysts which were prepared with and without activity promoters showed that the promoter materials increase catalyst CO oxidation activity at least an order of magnitude at ambient temperature. Initial studies using H2 and CO chemisorption, X ray diffraction (XRD) and X ray photoelectron spectroscopy (XPS) have shown that the activity promoters do not significantly affect the precious metal crystallite size or the electronic structure around the precious metal. In addition, the formation or lack of formation of solid solutions between the precious metal and promoters has also been shown not to affect the activity of the promoted catalyst.

Surflex-Dock: Docking benchmarks and real-world application

NASA Astrophysics Data System (ADS)

Spitzer, Russell; Jain, Ajay N.

2012-06-01

Benchmarks for molecular docking have historically focused on re-docking the cognate ligand of a well-determined protein-ligand complex to measure geometric pose prediction accuracy, and measurement of virtual screening performance has been focused on increasingly large and diverse sets of target protein structures, cognate ligands, and various types of decoy sets. Here, pose prediction is reported on the Astex Diverse set of 85 protein ligand complexes, and virtual screening performance is reported on the DUD set of 40 protein targets. In both cases, prepared structures of targets and ligands were provided by symposium organizers. The re-prepared data sets yielded results not significantly different than previous reports of Surflex-Dock on the two benchmarks. Minor changes to protein coordinates resulting from complex pre-optimization had large effects on observed performance, highlighting the limitations of cognate ligand re-docking for pose prediction assessment. Docking protocols developed for cross-docking, which address protein flexibility and produce discrete families of predicted poses, produced substantially better performance for pose prediction. Performance on virtual screening performance was shown to benefit by employing and combining multiple screening methods: docking, 2D molecular similarity, and 3D molecular similarity. In addition, use of multiple protein conformations significantly improved screening enrichment.

Extracellular domains play different roles in gap junction formation and docking compatibility.

PubMed

Bai, Donglin; Wang, Ao Hong

2014-02-15

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

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

Wang, Lei; Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp; Kimura, Taichi

2010-04-23

DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines,more » Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.« less

Shaft sealing issue in CO2 storage sites

NASA Astrophysics Data System (ADS)

Dieudonné, A.-C.; Charlier, R.; Collin, F.

2012-04-01

Carbon capture and storage is an innovating approach to tackle climate changes through the reduction of greenhouse gas emissions. Deep saline aquifers, depleted oil and gas reservoirs and unmineable coal seams are among the most studied reservoirs. However other types of reservoir, such as abandonned coal mines, could also be used for the storage of carbon dioxide. In this case, the problem of shaft sealing appears to be particularly critical regarding to the economic, ecologic and health aspects of geological storage. The purpose of the work is to study shaft sealing in the framework of CO2 storage projects in abandoned coal mines. The problem of gas transfers around a sealing system is studied numerically using the finite elements code LAGAMINE, which has been developped for 30 years at the University of Liege. A coupled hydro-mechanical model of unsaturated geomaterials is used for the analyses. The response of the two-phase flow model is first studied through a simple synthetic problem consisting in the injection of gas in a concrete-made column. It stands out of this first modeling that the advection of the gas phase represents the main transfer mechanism of CO2 in highly unsaturated materials. Furthermore the setting of a bentonite barrier seal limits considerably the gas influx into the biosphere. A 2D axisymetric hydromechanical modeling of the Anderlues natural gas storage site is then performed. The geological and hydrogeological contexts of the site are used to define the problem, for the initial and boundary conditions, as well as the material properties. In order to reproduce stress and water saturation states in the shale before CO2 injection in the mine, different phases corresponding to the shaft sinking, the mining and the set up of the sealing system are simulated. The system efficiency is then evaluated by simulating the CO2 injection with the imposed pressure at the shaft wall. According to the modeling, the low water saturation of concrete and its higher intrinsic permeability give the concrete a higher gas permeability than the one of the rock. Thus, the major part of CO2 fluxes flows through concrete elements. Moreover, the hydraulic seal of bentonite doesn't contribute to the reduction of CO2 fluxes to the atmosphere since it is in contact with the concrete shaft support. Indeed, in the present case, CO2 fluxes bypass the seal, going through the more permeable concrete. Consequently, the design of the shaft sealing system contributes significantly to a loss in performance and appears to be a significant parameter to evaluate the risks of CO2 leakage.

Chlorinated hydrocarbon contaminants in arctic marine mammals.

PubMed

Norstrom, R J; Muir, D C

1994-09-16

By 1976, the presence of chlorinated hydrocarbon contaminants (CHCs) had been demonstrated in fur seal (Callorhinus ursinus), ringed seal (Phoca hispida), hooded seal (Cystophora cristata), bearded seal (Erignathus barbatus), walrus (Obdobenus rosmarus divergens), beluga (Delphinapterus leucas), porpoise (Phocoena phocoena) and polar bear (Ursus maritimus) in various parts of the Arctic. In spite of this early interest, very little subsequent research on contaminants in Arctic marine mammals was undertaken until the mid-1980s. Since that time, there has been an explosion of interest, resulting in a much expanded data base on contaminants in Arctic marine mammals. Except in the Russian Arctic, data have now been obtained on the temporospatial distribution of PCBs and other contaminants in ringed seal, beluga and polar bear. Contaminants in narwhal (Monodon monoceros) have also now been measured. On a fat weight basis, the sum of DDT-related compounds (S-DDT) and PCB levels are lowest in walrus (< 0.1 microgram/g), followed by ringed seal, (0.1-1 microgram/g range). Levels are an order of magnitude higher in beluga and narwhal (1-10 micrograms/g range). It appears that metabolism and excretion of S-DDT and PCBs may be less efficient in cetaceans, leading to greater biomagnification. Polar bears have similar levels of PCBs as cetaceans (1-10 micrograms/g), but with a much simpler congener pattern. DDE levels are lowest in polar bear, indicating rapid metabolism. Effects of age and sex on residue levels are found for all species where this was measured. Among cetaceans and ringed seal, sexually mature females have lower levels than males due to lactation. Although PCB levels in adult male polar bears are about twice as high as females, there is only a trivial age effect in either sex apart from an initial decrease from birth to sexual maturity (age 0-5). Comparison of levels of S-DDT and PCBs in Arctic beluga and ringed seal with those in beluga in the Gulf of St. Lawrence and ringed seal in the Baltic Sea, indicate that overall contamination of the Arctic marine ecosystem is 10-50 times less than the most highly contaminated areas in the northern hemisphere temperate latitude marine environment. Geographic distribution of residue levels in polar bears indicates a gradual increase from Alaska east to Svalbard, except PCB levels are significantly higher in eastern Greenland and Svalbard. Information on temporal trends is somewhat contradictory.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth Kinematics of Opening-Mode Fractures

NASA Astrophysics Data System (ADS)

Eichhubl, P.; Alzayer, Y.; Laubach, S.; Fall, A.

2014-12-01

Fracture aperture is a primary control on flow in fractured reservoirs of low matrix permeability including unconventional oil and gas reservoirs and most geothermal systems. Guided by principles of linear elastic fracture mechanics, fracture aperture is generally assumed to be a linear function of fracture length and elastic material properties. Natural opening-mode fractures with significant preserved aperture are observed in core and outcrop indicative of fracture opening strain accommodated by permanent solution-precipitation creep. Fracture opening may thus be decoupled from length growth if the material effectively weakens after initial elastic fracture growth by either non-elastic deformation processes or changes in elastic properties. To investigate the kinematics of fracture length and aperture growth, we reconstructed the opening history of three opening-mode fractures that are bridged by crack-seal quartz cement in Travis Peak Sandstone of the SFOT-1 well, East Texas. Similar crack-seal cement bridges had been interpreted to form by repeated incremental fracture opening and subsequent precipitation of quartz cement. We imaged crack-seal cement textures for bridges sampled at varying distance from the tips using scanning electron microscope cathodoluminescence, and determined the number and thickness of crack-seal cement increments as a function of position along the fracture length and height. Observed trends in increment number and thickness are consistent with an initial stage of fast fracture propagation relative to aperture growth, followed by a stage of slow propagation and pronounced aperture growth. Consistent with fluid inclusion observations indicative of fracture opening and propagation occurring over 30-40 m.y., we interpret the second phase of pronounced aperture growth to result from fracture opening strain accommodated by solution-precipitation creep and concurrent slow, possibly subcritical, fracture propagation. Similar deformation mechanisms are envisioned to govern fracture growth over shorter timescales in reactive chemical subsurface environments including CO2 reservoirs, organic-rich shales, and geothermal systems.

In Silico Screening for Biothreat Countermeasures

DTIC Science & Technology

2006-02-03

drug candidates to each kinase structure using the well-known docking algorithm LibDock . This population of 1200 ligands includes ~400 ligands with...mentioned previously, each of the known p38 inhibitors in the population was docked to its target using the LibDock application. This method resulted

Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

PubMed

LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C

2014-01-01

Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number of CPUs to tens of thousands of protein targets and millions of potential drug candidates.

Suspended sediment concentration in the Lower Sea Scheldt (Belgium): long term trends and relation to mud disposal

NASA Astrophysics Data System (ADS)

Depreiter, Davy; van Holland, Gijsbert; Lanckriet, Thijs; Beirinckx, Kirsten; Vanlede, Joris; Maris, Tom

2015-04-01

In this presentation, results from different monitoring and research projects (OMES, MONEOS, Flexible Disposal and Marine-Fluvial mud ratio) will be integrated to increase the insight in the trends and relation between mud disposal and the increasing sediment concentrations (SSC) in the Lower Sea Scheldt. In the Scheldt Estuary, major projects have been carried out in the past decade, among which the third deepening of the navigation channel and the opening of the Deurganck dock. Maintenance dredging is carried out to guarantee a minimum navigation depth. A rising trend in the volume of mud dredged in the Lower Sea Scheldt is observed since 2006, the year after the opening of the Deurganck Dock. The trend is explained by increasing mud volumes dredged in this dock and on a nearby sill. This volume culminated in 2011 (4.8 million m³) when the depth of this dock was increased to its design depth. The dredged mud is disposed upstream, quickly to be resuspended. Near the mud disposal location, yearly averaged SSC (measured at 4.5 m above bed) tripled between 2005 and 2011 (108 to 348 mg/L), and SSC peaks increased even stronger. A multivariate regression model indicated a strong correlation between mud disposal volumes and timing and observed SSC. Mud disposal volumes and SSC where somewhat lower again after 2011. The SSC increase raises an alert with regard to the risk for a regime shift towards a hyperturbid system. Increasing SSC may indeed decrease the hydraulic resistance initiating a feedback mechanism that results in further increasing SSC values. It thus appears that more mud is being circulated: the Deurganck dock acts as mud sink, from which the mud is - after dredging and disposal - resuspended. The mud may have different sources: fluvial or marine influx. The increasing SSC might not only be related to the mud disposal, but also to changing tidal characteristics that enhance the influx of marine suspended sediments. To elucidate this, an analysis of the marine fraction in soil and suspended sediments has also been performed.

76 FR 70976 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... proposes to make changes to the DD Form 441 and SF 328. The requirement for execution of the corporate ``Certificate'' section and the use of a corporate seal is being deleted. Currently the government does not... Agreement,'' which is the initial agreement between the contractor and the government regarding security...

21 CFR 113.87 - Operations in the thermal processing room.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED... should be made. (c) The initial temperature of the contents of the containers to be processed shall be accurately determined and recorded with sufficient frequency to ensure that the temperature of the product is...

21 CFR 113.87 - Operations in the thermal processing room.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (CONTINUED) FOOD FOR HUMAN CONSUMPTION THERMALLY PROCESSED LOW-ACID FOODS PACKAGED IN HERMETICALLY SEALED... should be made. (c) The initial temperature of the contents of the containers to be processed shall be accurately determined and recorded with sufficient frequency to ensure that the temperature of the product is...

Blubber and buoyancy: monitoring the body condition of free-ranging seals using simple dive characteristics.

PubMed

Biuw, Martin; McConnell, Bernie; Bradshaw, Corey J A; Burton, Harry; Fedak, Mike

2003-10-01

Elephant seals regularly perform dives during which they spend a large proportion of time drifting passively through the water column. The rate of vertical change in depth during these "drift" dives is largely a result of the proportion of lipid tissue in the body, with fatter seals having higher (more positive or less negative) drift rates compared with leaner seals. We examined the temporal changes in drift rates of 24 newly weaned southern elephant seal (Mirounga leonina) pups during their first trip to sea to determine if this easily recorded dive characteristic can be used to continuously monitor changes in body composition of seals throughout their foraging trips. All seals demonstrated a similar trend over time: drift rates were initially positive but decreased steadily over the first 30-50 days after departure (Phase 1), corresponding to seals becoming gradually less buoyant. Over the following approximately 100 days (Phase 2), drift rates again increased gradually, while during the last approximately 20-45 days (Phase 3) drift rates either remained constant or decreased slightly. The daily rate of change in drift rate was negatively related to the daily rate of horizontal displacement (daily travel rate), and daily travel rates of more than approximately 80 km were almost exclusively associated with negative changes in drift rate. We developed a mechanistic model based on body compositions and morphometrics measured in the field, published values for the density of seawater and various body components, and values of drag coefficients for objects of different shapes. We used this model to examine the theoretical relationships between drift rate and body composition and carried out a sensitivity analysis to quantify errors and biases caused by varying model parameters. While variations in seawater density and uncertainties in estimated body surface area and volume are unlikely to result in errors in estimated lipid content of more than +/-2.5%, variations in drag coefficient can lead to errors of >or =10%. Finally, we compared the lipid contents predicted by our model with the lipid contents measured using isotopically labelled water and found a strong positive correlation. The best-fitting model suggests that the drag coefficient of seals while drifting passively is between approximately 0.49 (roughly corresponding to a sphere-shaped object) and 0.69 (a prolate spheroid), and we were able to estimate relative lipid content to within approximately +/-2% lipid. Our results suggest that this simple method can be used to estimate the changes in lipid content of free-ranging seals while at sea and may help improve our understanding of the foraging strategies of these important marine predators.

NASA Docking System (NDS) Technical Integration Meeting

NASA Technical Reports Server (NTRS)

Lewis, James L.

2010-01-01

This slide presentation reviews the NASA Docking System (NDS) as NASA's implementation of the International Docking System Standard (IDSS). The goals of the NDS, is to build on proven technologies previously demonstrated in flight and to advance the state of the art of docking systems by incorporating Low Impact Docking System (LIDS) technology into the NDS. A Hardware Demonstration was included in the meeting, and there was discussion about software, NDS major system interfaces, integration information, schedule, and future upgrades.

HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy

PubMed Central

Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong

2017-01-01

Abstract Protein–protein and protein–DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein–protein and protein–DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10–20 min for a docking run. Tested on the cases with weakly homologous complexes of <30% sequence identity from five docking benchmarks, the HDOCK pipeline tied with template-based modeling on the protein–protein and protein–DNA benchmarks and performed better than template-based modeling on the three protein–RNA benchmarks when the top 10 predictions were considered. The performance of HDOCK became better when more predictions were considered. Combining the results of HDOCK and template-based modeling by ranking first of the template-based model further improved the predictive power of the server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. PMID:28521030

Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

PubMed

Feinstein, Wei P; Brylinski, Michal

2015-01-01

Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to improve the ranking accuracy in production virtual screening simulations. Importantly, the optimized search space systematically yields better results than the default method not only for experimental pockets, but also for those predicted from protein structures. A script for calculating the optimal docking box size is freely available at www.brylinski.org/content/docking-box-size. Graphical AbstractWe developed a procedure to optimize the box size in molecular docking calculations. Left panel shows the predicted binding pose of NADP (green sticks) compared to the experimental complex structure of human aldose reductase (blue sticks) using a default protocol. Right panel shows the docking accuracy using an optimized box size.

NASA Docking System (NDS) Interface Definitions Document (IDD). Revision F, Dec. 15, 2011

NASA Technical Reports Server (NTRS)

Lewis, James

2011-01-01

The NASA Docking System (NDS) mating system supports low approach velocity docking and provides a modular and reconfigurable standard interface, supporting crewed and autonomous vehicles during mating and assembly operations. The NDS is NASA s implementation for the International Docking System Standard (IDSS) using low impact docking technology. All NDS configurations can mate with the configuration specified in the IDSS Interface Definition Document (IDD), Revision A, released May 13, 2011. The NDS evolved from the Low Impact Docking System (LIDS). The term (and its associated acronym), international Low Impact Docking System (iLIDS) is also used to describe this system. NDS and iLIDS may be used interchangeability. Some of the heritage documentation and implementations (e.g., software command names) used on the NDS will continue to use the LIDS acronym.

Stimulation of insulin release by glucose is associated with an increase in the number of docked granules in the beta-cells of rat pancreatic islets.

PubMed

Straub, Susanne G; Shanmugam, Geetha; Sharp, Geoffrey W G

2004-12-01

Electron microscopy and quantitative stereological techniques were used to study the dynamics of the docked granule pool in the rat pancreatic beta-cell. The mean number of granules per beta-cell was 11,136. After equilibration in RPMI containing 5.6 mmol/l glucose, 6.4% of the granules (approximately 700) were docked at the plasma membrane (also measured as [means +/- SE] 4.3 +/- 0.6 docked granules per 10 microm of plasma membrane at the perimeter of the cell sections). After a 40-min exposure to 16.7 mmol/l glucose, 10.2% of the granules (approximately 1,060) were docked (6.4 +/- 0.8 granules per 10 microm of plasma membrane). Thus, the docked pool increased by 50% during stimulation with glucose. Islets were also exposed to 16.7 mmol/l glucose in the absence or presence of 10 micromol/l nitrendipine. In the absence and presence of nitrendipine, there were 6.1 +/- 0.7 and 6.3 +/- 0.6 granules per 10 microm of membrane, respectively. Thus, glucose increased granule docking independently of increased [Ca2+]i and exocytosis. The data suggest a limit to the number of docking sites. As the rate of docking exceeded the rate of exocytosis, docking is not rate limiting for insulin release. Only with extremely high release rates, glucose stimulation after a 4-h incubation with a high concentration of fatty acid-free BSA, was the docked granule pool reduced in size.

The robotic Whipple: operative strategy and technical considerations.

PubMed

MacKenzie, Shawn; Kosari, Kambiz; Sielaff, Timothy; Johnson, Eric

2011-03-01

Advances in robotic surgery have allowed the frontiers of minimally invasive pancreatic surgery to expand. We present a step-by-step approach to the robotic Whipple procedure. The discussion includes port setting and robotic docking, kocherization and superior mesenteric vein identification, portal dissection, releasing the ligament of Treitz, uncinate dissection, and reconstruction. A brief report of our initial 2-year experience with the robotic Whipple procedure is also presented.

An epigenetically distinct breast cancer cell subpopulation promotes collective invasion

PubMed Central

Westcott, Jill M.; Prechtl, Amanda M.; Maine, Erin A.; Dang, Tuyen T.; Esparza, Matthew A.; Sun, Han; Zhou, Yunyun; Xie, Yang; Pearson, Gray W.

2015-01-01

Tumor cells can engage in a process called collective invasion, in which cohesive groups of cells invade through interstitial tissue. Here, we identified an epigenetically distinct subpopulation of breast tumor cells that have an enhanced capacity to collectively invade. Analysis of spheroid invasion in an organotypic culture system revealed that these “trailblazer” cells are capable of initiating collective invasion and promote non-trailblazer cell invasion, indicating a commensal relationship among subpopulations within heterogenous tumors. Canonical mesenchymal markers were not sufficient to distinguish trailblazer cells from non-trailblazer cells, suggesting that defining the molecular underpinnings of the trailblazer phenotype could reveal collective invasion-specific mechanisms. Functional analysis determined that DOCK10, ITGA11, DAB2, PDFGRA, VASN, PPAP2B, and LPAR1 are highly expressed in trailblazer cells and required to initiate collective invasion, with DOCK10 essential for metastasis. In patients with triple-negative breast cancer, expression of these 7 genes correlated with poor outcome. Together, our results indicate that spontaneous conversion of the epigenetic state in a subpopulation of cells can promote a transition from in situ to invasive growth through induction of a cooperative form of collective invasion and suggest that therapeutic inhibition of trailblazer cell invasion may help prevent metastasis. PMID:25844900

Voss with docking probe in Service module

NASA Image and Video Library

2001-05-30

ISS002-E-6478 (30 May 2001) --- James S. Voss, Expedition Two flight engineer, handles a spacecraft docking probe in the Service Module. The docking probe assists with the docking of the Soyuz and Progress vehicles to the International Space Station. The image was taken with a digital still camera.

Tyurin packs the docking probe in Node 1 during Expedition Three

NASA Image and Video Library

2001-09-17

ISS003-E-5634 (17 September 2001) --- Cosmonaut Mikhail Tyurin, Expedition Three flight engineer, packs the docking probe in a stowage bag in Unity. The docking probe successfully guided the arrival of the Russian-built Pirs docking compartment to the International Space Station (ISS). Tyurin represents Rosaviakosmos.

9 CFR 355.15 - Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly...

Code of Federal Regulations, 2012 CFR

2012-01-01

... storage rooms; outer premises, docks, driveways, etc.; fly-breeding material; nuisances. 355.15 Section....15 Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly... departments where certified products are prepared, handled, or stored. Docks and areas where cars and vehicles...

9 CFR 355.15 - Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly...

Code of Federal Regulations, 2014 CFR

2014-01-01

... storage rooms; outer premises, docks, driveways, etc.; fly-breeding material; nuisances. 355.15 Section....15 Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly... departments where certified products are prepared, handled, or stored. Docks and areas where cars and vehicles...

9 CFR 355.15 - Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly...

Code of Federal Regulations, 2013 CFR

2013-01-01

... storage rooms; outer premises, docks, driveways, etc.; fly-breeding material; nuisances. 355.15 Section....15 Inedible material operating and storage rooms; outer premises, docks, driveways, etc.; fly... departments where certified products are prepared, handled, or stored. Docks and areas where cars and vehicles...

17. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN ...

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

17. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN BUILT IN 1911-1912, THIS WAS THE LARGEST ORE-UNLOADING DOCK ON THE GREAT LAKES. - Pennsylvania Railway Ore Dock, Lake Erie at Whiskey Island, approximately 1.5 miles west of Public Square, Cleveland, Cuyahoga County, OH

Vinogradov practices docking procedures of the Progress 21 in the SM during Expedition 13

NASA Image and Video Library

2006-04-26

ISS013-E-10225 (26 April 2006) --- Cosmonaut Pavel V. Vinogradov, Expedition 13 commander representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 21 spacecraft. Vinogradov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system.

Evolution of the Proximal Sealing Rings of the Anaconda Stent-Graft After Endovascular Aneurysm Repair.

PubMed

Koenrades, Maaike A; Klein, Almar; Leferink, Anne M; Slump, Cornelis H; Geelkerken, Robert H

2018-04-01

To provide insight into the evolution of the saddle-shaped proximal sealing rings of the Anaconda stent-graft after endovascular aneurysm repair (EVAR). Eighteen abdominal aortic aneurysm patients were consecutively enrolled in a single-center, prospective, observational cohort study (LSPEAS; Trialregister.nl identifier NTR4276). The patients were treated electively using an Anaconda stent-graft with a mean 31% oversizing (range 17-47). According to protocol, participants were to be followed for 2 years, during which 5 noncontrast electrocardiogram-gated computed tomography scans would be conducted. Three patients were eliminated within 30 days (1 withdrew, 1 died, and a third was converted before stent-graft deployment), leaving 15 patients (mean age 72.8±3.7 years; 14 men) for this analysis. Evolution in size and shape (symmetry) of both proximal infrarenal sealing rings were assessed from discharge to 24 months using dedicated postprocessing algorithms. At 24 months, the mean diameters of the first and second ring stents had increased significantly (first ring: 2.2±1.0 mm, p<0.001; second ring: 2.7±1.1 mm, p<0.001). At 6 months, the first and second rings had expanded to a mean 96.6%±2.1% and 94.8%±2.7%, respectively, of their nominal diameter, after which the rings expanded slowly; ring diameters stabilized to near nominal size (first ring, 98.3%±1.1%; second ring, 97.2%±1.4%) at 24 months irrespective of initial oversizing. No type I or III endoleaks or aneurysm-, device-, or procedure-related adverse events were noted in follow-up. The difference in the diametric distances between the peaks and valleys of the saddle-shaped rings was marked at discharge but became smaller after 24 months for both rings (first ring: median 2.0 vs 1.2 mm, p=0.191; second ring: median 2.8 vs 0.8 mm; p=0.013). Irrespective of initial oversizing, the Anaconda proximal sealing rings radially expanded to near nominal size within 6 months after EVAR. Initial oval-shaped rings conformed symmetrically and became nearly circular through 24 months. These findings should be taken into account in planning and follow-up.

Space Shuttle RCS Oxidizer Leak Repair for STS-26

NASA Technical Reports Server (NTRS)

Delventhal, R. A.; Faget, N. M.

1989-01-01

Following propellant loading of the Space Shuttle's reaction control system (RCS) for mission STS 26, an oxidizer leak was detected in the left orbital maneuvering system (OMS) pod, where the RCS is located. Subsequent investigation determined that the leak was isolated at a mechanical Dynatube fitting near the RCS nitrogen tetroxide tank. An intense effort was initiated to design, fabricate, and qualify a sealing device to stop the oxidizer leak externally so that the Space Shuttle launch could proceed. It was discovered that sealing devices called clamshells were widely used throughout the petrochemical and power generation industries to stop leaks developed in large diameter pipes which carry steam or other hazardous fluids. These clamshells are available in different diameters and strengths and are placed around the pipe at the location of the leak. A sealing compound is then injected under high pressure into the clamshell to stop the leak. This technology was scaled down and applied to the problem of stopping the leak on the Orbiter, which was on a half-inch diameter line in a nearly inaccessible location. Many obstacles had to be overcome such as determining that the sealing material would be compatible with the nitrogen tetroxide and ensuring that the clamshell would actually fit around the Dynatube fitting without interfering with other lines which were in close proximity. The effort at the NASA Johnson Space Center included materials compatibility testing of several sealants, design of a clamshell to fit in the confined compartment, and manufacture and qualification of the flight hardware. A clamshell was successfully placed around the Dynatube fitting on the Orbiter and the oxidizer leak was terminated. Then it was decided to apply this technology further and design clamshells for other mechanical fittings onboard the Orbiter and develop sealing compounds which will be compatible with fuels such as monomethyl hydrazine (MMH). The potential exists for using this type of sealing device in numerous other applications throughout the aerospace industry.

Numerical Modeling of the Hydrothermal System at East Pacific Rise 9°50'N Including Anhydrite Precipitation

NASA Astrophysics Data System (ADS)

Kolandaivelu, K. P.; Lowell, R. P.

2015-12-01

To better understand the effects of anhydrite precipitation on mid-ocean ridge hydrothermal systems, we conducted 2-D numerical simulations of two-phase hydrothermal circulation in a NaCl-H2O fluid at the East Pacific Rise 9°50'N. The simulations were constrained by key observational thermal data and seismicity that suggests the fluid flow is primarily along axis with recharge focused into a small zone near a 4th order discontinuity. The simulations considered an open-top square box with a fixed seafloor pressure of 25 MPa, and nominal seafloor temperature of 10 °C. The sides of the box were assumed to be impermeable and insulated. We considered two models: a homogeneous model with a permeability of 10-13 m2 and a heterogeneous model in which layer 2A extrusives were given a higher permeability. Both models had a fixed bottom temperature distribution and initial porosity of 0.1. Assuming that anhydrite precipitation resulted from the decrease in solubility with increasing temperature as downwelling fluid gets heated, we calculated the rate of porosity decrease and sealing times in each cell at certain time snapshots in the simulations. The results showed that sealing would occur most rapidly in limited regions near the base of the high-temperature plumes, where complete sealing could occur on decadal time scales. Though more detailed analysis is needed, it appeared that the areas of rapid sealing would likely have negligible impact on the overall circulation pattern and hydrothermal vent temperatures. The simulations also indicated that sealing due to anhydrite precipitation would occur more slowly at the margins of the ascending plumes. The sealing times in the deep recharge zone determined in these simulations were considerably greater than estimated from 1D analytical calculations, suggesting that with a 2D model, focused recharge at the EPR 9°50'N site may occur, at least on a decadal time scale.

Ceramic Borehole Seals for Nuclear Waste Disposal Applications

NASA Astrophysics Data System (ADS)

Lowry, B.; Coates, K.; Wohletz, K.; Dunn, S.; Patera, E.; Duguid, A.; Arnold, B.; Zyvoloski, G.; Groven, L.; Kuramyssova, K.

2015-12-01

Sealing plugs are critical features of the deep borehole system design. They serve as structural platforms to bear the weight of the backfill column, and as seals through their low fluid permeability and bond to the borehole or casing wall. High hydrostatic and lithostatic pressures, high mineral content water, and elevated temperature due to the waste packages and geothermal gradient challenge the long term performance of seal materials. Deep borehole nuclear waste disposal faces the added requirement of assuring performance for thousands of years in large boreholes, requiring very long term chemical and physical stability. A high performance plug system is being developed which capitalizes on the energy of solid phase reactions to form a ceramic plug in-situ. Thermites are a family of self-oxidized metal/oxide reactions with very high energy content and the ability to react under water. When combined with engineered additives the product exhibits attractive structural, sealing, and corrosion properties. In the initial phase of this research, exploratory and scaled tests demonstrated formulations that achieved controlled, fine grained, homogeneous, net shape plugs composed predominantly of ceramic material. Laboratory experiments produced plug cores with confined fluid permeability as low as 100 mDarcy, compressive strength as high as 70 MPa (three times the strength of conventional well cement), with the inherent corrosion resistance and service temperature of ceramic matrices. Numerical thermal and thermal/structural analyses predicted the in-situ thermal performance of the reacted plugs, showing that they cooled to ambient temperature (and design strength) within 24 to 48 hours. The current development effort is refining the reactant formulations to achieve desired performance characteristics, developing the system design and emplacement processes to be compatible with conventional well service practices, and understanding the thermal, fluid, and structural effects the plug will have on surrounding media. This paper will report on the state of the development effort and plans for a field demonstration in early 2016 in a cased well with traditional plug seal and strength measurements.

Safety in earth orbit study. Volume 2: Analysis of hazardous payloads, docking, on-board survivability

NASA Technical Reports Server (NTRS)

1972-01-01

Detailed and supporting analyses are presented of the hazardous payloads, docking, and on-board survivability aspects connected with earth orbital operations of the space shuttle program. The hazards resulting from delivery, deployment, and retrieval of hazardous payloads, and from handling and transport of cargo between orbiter, sortie modules, and space station are identified and analyzed. The safety aspects of shuttle orbiter to modular space station docking includes docking for assembly of space station, normal resupply docking, and emergency docking. Personnel traffic patterns, escape routes, and on-board survivability are analyzed for orbiter with crew and passenger, sortie modules, and modular space station, under normal, emergency, and EVA and IVA operations.

Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

PubMed

Evangelista, Wilfredo; Weir, Rebecca L; Ellingson, Sally R; Harris, Jason B; Kapoor, Karan; Smith, Jeremy C; Baudry, Jerome

2016-10-15

This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Drosophila photoreceptor axon guidance and targeting requires the dreadlocks SH2/SH3 adapter protein.

PubMed

Garrity, P A; Rao, Y; Salecker, I; McGlade, J; Pawson, T; Zipursky, S L

1996-05-31

Mutations in the Drosophila gene dreadlocks (dock) disrupt photoreceptor cell (R cell) axon guidance and targeting. Genetic mosaic analysis and cell-type-specific expression of dock transgenes demonstrate dock is required in R cells for proper innervation. Dock protein contains one SH2 and three SH3 domains, implicating it in tyrosine kinase signaling, and is highly related to the human proto-oncogene Nck. Dock expression is detected in R cell growth cones in the target region. We propose Dock transmits signals in the growth cone in response to guidance and targeting cues. These findings provide an important step for dissection of signaling pathways regulating growth cone motility.

Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets.

PubMed

Lulu, S Sajitha; Thabitha, A; Vino, S; Priya, A Mohana; Rout, Madhusmita

2016-01-01

Nonstructural proteins of hepatitis C virus had drawn much attention for the scientific fraternity in drug discovery due to its important role in the disease. 3D structure of the protein was predicted using molecular modelling protocol. Docking studies of 10 medicinal plant compounds and three drugs available in the market (control) with NS2 protease were employed by using rigid docking approach of AutoDock 4.2. Among the molecules tested for docking study, naringenin and quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2 protease. All the ligands were docked deeply within the binding pocket region of the protein. The docking study results showed that these compounds are potential inhibitors of the target; and also all these docked compounds have good inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

STS-74 view of ODS from Payload Changout Room

NASA Technical Reports Server (NTRS)

1995-01-01

Workers at Launch Pad 39A are preparing to close the payload bay doors on the Space Shuttle Atlantis for its upcoming launch on Mission STS-74 and the second docking with the Russian Space Station Mir. Uppermost in the payload bay is the Orbiter Docking System (ODS), which also flew on the first docking flight between the Space Shuttle and MIR. Lowermost is the primary payload of STS-74, the Russian-built Docking Module. During the mission, the Docking Module will first be attached to ODS and then to Mir. It will be left attached to Mir to become a permanent extension that will afford adequate clearance between the orbiter and the station during future dockings. At left in the payload bay, looking like a very long pole, is the Canadian-built Remote Manipulator System arm that will be used by the crew to hoist the Docking Module and attach it to the ODS.

Pak functions downstream of Dock to regulate photoreceptor axon guidance in Drosophila.

PubMed

Hing, H; Xiao, J; Harden, N; Lim, L; Zipursky, S L

1999-06-25

The SH2/SH3 adaptor protein Dock has been proposed to transduce signals from guidance receptors to the actin cytoskeleton in Drosophila photoreceptor (R cell) growth cones. Here, we demonstrate that Drosophila p21-activated kinase (Pak) is required in a Dock pathway regulating R cell axon guidance and targeting. Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable. Normal patterns of R cell connectivity require Pak's kinase activity and binding sites for both Dock and Cdc42/Rac. A membrane-tethered form of Pak (Pak(myr) acts as a dominant gain-of-function protein. Retinal expression of Pak(myr) rescues the R cell connectivity phenotype in dock mutants. These data establish Pak as a critical regulator of axon guidance and a downstream effector of Dock in vivo.

A machine learning approach for ranking clusters of docked protein‐protein complexes by pairwise cluster comparison

PubMed Central

Pfeiffenberger, Erik; Chaleil, Raphael A.G.; Moal, Iain H.

2017-01-01

ABSTRACT Reliable identification of near‐native poses of docked protein–protein complexes is still an unsolved problem. The intrinsic heterogeneity of protein–protein interactions is challenging for traditional biophysical or knowledge based potentials and the identification of many false positive binding sites is not unusual. Often, ranking protocols are based on initial clustering of docked poses followed by the application of an energy function to rank each cluster according to its lowest energy member. Here, we present an approach of cluster ranking based not only on one molecular descriptor (e.g., an energy function) but also employing a large number of descriptors that are integrated in a machine learning model, whereby, an extremely randomized tree classifier based on 109 molecular descriptors is trained. The protocol is based on first locally enriching clusters with additional poses, the clusters are then characterized using features describing the distribution of molecular descriptors within the cluster, which are combined into a pairwise cluster comparison model to discriminate near‐native from incorrect clusters. The results show that our approach is able to identify clusters containing near‐native protein–protein complexes. In addition, we present an analysis of the descriptors with respect to their power to discriminate near native from incorrect clusters and how data transformations and recursive feature elimination can improve the ranking performance. Proteins 2017; 85:528–543. © 2016 Wiley Periodicals, Inc. PMID:27935158

Ligand- and structure-based in silico studies to identify kinesin spindle protein (KSP) inhibitors as potential anticancer agents.

PubMed

Balakumar, Chandrasekaran; Ramesh, Muthusamy; Tham, Chuin Lean; Khathi, Samukelisiwe Pretty; Kozielski, Frank; Srinivasulu, Cherukupalli; Hampannavar, Girish A; Sayyad, Nisar; Soliman, Mahmoud E; Karpoormath, Rajshekhar

2017-11-29

Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule-based motor proteins. KSP is responsible for the establishment of the bipolar mitotic spindle which mediates cell division. Inhibition of KSP expedites the blockade of the normal cell cycle during mitosis through the generation of monoastral MT arrays that finally cause apoptotic cell death. As KSP is highly expressed in proliferating/cancer cells, it has gained considerable attention as a potential drug target for cancer chemotherapy. Therefore, this study envisaged to design novel KSP inhibitors by employing computational techniques/tools such as pharmacophore modelling, virtual database screening, molecular docking and molecular dynamics. Initially, the pharmacophore models were generated from the data-set of highly potent KSP inhibitors and the pharmacophore models were validated against in house test set ligands. The validated pharmacophore model was then taken for database screening (Maybridge and ChemBridge) to yield hits, which were further filtered for their drug-likeliness. The potential hits retrieved from virtual database screening were docked using CDOCKER to identify the ligand binding landscape. The top-ranked hits obtained from molecular docking were progressed to molecular dynamics (AMBER) simulations to deduce the ligand binding affinity. This study identified MB-41570 and CB-10358 as potential hits and evaluated these experimentally using in vitro KSP ATPase inhibition assays.

Post processing of protein-compound docking for fragment-based drug discovery (FBDD): in-silico structure-based drug screening and ligand-binding pose prediction.

PubMed

Fukunishi, Yoshifumi

2010-01-01

For fragment-based drug development, both hit (active) compound prediction and docking-pose (protein-ligand complex structure) prediction of the hit compound are important, since chemical modification (fragment linking, fragment evolution) subsequent to the hit discovery must be performed based on the protein-ligand complex structure. However, the naïve protein-compound docking calculation shows poor accuracy in terms of docking-pose prediction. Thus, post-processing of the protein-compound docking is necessary. Recently, several methods for the post-processing of protein-compound docking have been proposed. In FBDD, the compounds are smaller than those for conventional drug screening. This makes it difficult to perform the protein-compound docking calculation. A method to avoid this problem has been reported. Protein-ligand binding free energy estimation is useful to reduce the procedures involved in the chemical modification of the hit fragment. Several prediction methods have been proposed for high-accuracy estimation of protein-ligand binding free energy. This paper summarizes the various computational methods proposed for docking-pose prediction and their usefulness in FBDD.

Apollo Rendezvous Docking Simulator

NASA Image and Video Library

1964-11-02

Originally the Rendezvous was used by the astronauts preparing for Gemini missions. The Rendezvous Docking Simulator was then modified and used to develop docking techniques for the Apollo program. The pilot is shown maneuvering the LEM into position for docking with a full-scale Apollo Command Module. From A.W. Vogeley, Piloted Space-Flight Simulation at Langley Research Center, Paper presented at the American Society of Mechanical Engineers, 1966 Winter Meeting, New York, NY, November 27 - December 1, 1966. The Rendezvous Docking Simulator and also the Lunar Landing Research Facility are both rather large moving-base simulators. It should be noted, however, that neither was built primarily because of its motion characteristics. The main reason they were built was to provide a realistic visual scene. A secondary reason was that they would provide correct angular motion cues (important in control of vehicle short-period motions) even though the linear acceleration cues would be incorrect. Apollo Rendezvous Docking Simulator: Langley s Rendezvous Docking Simulator was developed by NASA scientists to study the complex task of docking the Lunar Excursion Module with the Command Module in Lunar orbit.

Commercial Fishing Port Development in North Florida. [Escambia, Bay, Gulf, Franklin, Wakulla, Nassau, and Duval Counties

NASA Technical Reports Server (NTRS)

Mathis, K. (Principal Investigator); Cato, J. C.; Degner, P. D.; Landrum, P. D.; Prochaska, F. J.

1978-01-01

The author has identified the following significant results. Seven major counties were examined: Escambia, Bay, Gulf, Franklin, Wakulla, Nassau, and Duval. Population and economic activity were reviewed, along with commercial fishing and port facilities. Recommendations for five northwest Florida counties were based on interpretation of aerial photographs, satellite imagery, an aerial survey site visit, and published data. Major needs in Pensacola included docking, ice supply, and net and engine repair services. Costs for additional docks, an ice plant, and gear storage were estimated at $3,658,600. Port users in Panama City identified additional docking and gear storage as primary needs, along with gear repair and a marine railway. Estimated costs for dock and gear storage were $2,860,000. Added docking, gear storage, and ice supply, as well as gear electronics and diesel repair were needed in Port St. Joe. Costs were calculated at $1,231,500. Franklin County has three ports (Apalachicola - $1,107,000 for docks and gear storage, Eastpoint - $420,000 for additional docks, and Carrabella - $2,824,100 for docks, gear storage, and ice plant).

Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design.

PubMed

Pevzner, Yuri; Frugier, Emilie; Schalk, Vinushka; Caflisch, Amedeo; Woodcock, H Lee

2014-09-22

Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure analysis, dynamics, multiscale modeling, and other techniques commonly used by computational life scientists. We have extended CHARMMing's capabilities to include a fragment-based docking protocol that allows users to perform molecular docking and virtual screening calculations either directly via the CHARMMing Web server or on computing resources using the self-contained job scripts generated via the Web interface. The docking protocol was evaluated by performing a series of "re-dockings" with direct comparison to top commercial docking software. Results of this evaluation showed that CHARMMing's docking implementation is comparable to many widely used software packages and validates the use of the new CHARMM generalized force field for docking and virtual screening.

DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015

NASA Astrophysics Data System (ADS)

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2016-09-01

Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015.

PubMed

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2016-09-01

Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

Flexible CDOCKER: Development and application of a pseudo-explicit structure-based docking method within CHARMM

PubMed Central

Gagnon, Jessica K.; Law, Sean M.; Brooks, Charles L.

2016-01-01

Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an inter-converting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs. PMID:26691274

Flexible CDOCKER: Development and application of a pseudo-explicit structure-based docking method within CHARMM.

PubMed

Gagnon, Jessica K; Law, Sean M; Brooks, Charles L

2016-03-30

Protein-ligand docking is a commonly used method for lead identification and refinement. While traditional structure-based docking methods represent the receptor as a rigid body, recent developments have been moving toward the inclusion of protein flexibility. Proteins exist in an interconverting ensemble of conformational states, but effectively and efficiently searching the conformational space available to both the receptor and ligand remains a well-appreciated computational challenge. To this end, we have developed the Flexible CDOCKER method as an extension of the family of complete docking solutions available within CHARMM. This method integrates atomically detailed side chain flexibility with grid-based docking methods, maintaining efficiency while allowing the protein and ligand configurations to explore their conformational space simultaneously. This is in contrast to existing approaches that use induced-fit like sampling, such as Glide or Autodock, where the protein or the ligand space is sampled independently in an iterative fashion. Presented here are developments to the CHARMM docking methodology to incorporate receptor flexibility and improvements to the sampling protocol as demonstrated with re-docking trials on a subset of the CCDC/Astex set. These developments within CDOCKER achieve docking accuracy competitive with or exceeding the performance of other widely utilized docking programs. © 2015 Wiley Periodicals, Inc.

PSOVina: The hybrid particle swarm optimization algorithm for protein-ligand docking.

PubMed

Ng, Marcus C K; Fong, Simon; Siu, Shirley W I

2015-06-01

Protein-ligand docking is an essential step in modern drug discovery process. The challenge here is to accurately predict and efficiently optimize the position and orientation of ligands in the binding pocket of a target protein. In this paper, we present a new method called PSOVina which combined the particle swarm optimization (PSO) algorithm with the efficient Broyden-Fletcher-Goldfarb-Shannon (BFGS) local search method adopted in AutoDock Vina to tackle the conformational search problem in docking. Using a diverse data set of 201 protein-ligand complexes from the PDBbind database and a full set of ligands and decoys for four representative targets from the directory of useful decoys (DUD) virtual screening data set, we assessed the docking performance of PSOVina in comparison to the original Vina program. Our results showed that PSOVina achieves a remarkable execution time reduction of 51-60% without compromising the prediction accuracies in the docking and virtual screening experiments. This improvement in time efficiency makes PSOVina a better choice of a docking tool in large-scale protein-ligand docking applications. Our work lays the foundation for the future development of swarm-based algorithms in molecular docking programs. PSOVina is freely available to non-commercial users at http://cbbio.cis.umac.mo .

A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance.

PubMed

Clemens, J C; Ursuliak, Z; Clemens, K K; Price, J V; Dixon, J E

1996-07-19

We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (dock) (Garrity, P. A., Rao, Y., Salecker, I., and Zipursky, S. L.(1996) Cell 85, 639-650). Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain. The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments. A sequence containing five PXXP motifs from the non-catalytic domain of the PTP is sufficient for interaction with Dock. This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co-precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain. These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.

The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo

PubMed Central

Laurin, Mélanie; Dumouchel, Annie; Fukui, Yoshinori; Côté, Jean-François

2013-01-01

Podocytes are specialized kidney cells that form the kidney filtration barrier through the connection of their foot processes. Nephrin and Neph family transmembrane molecules at the surface of podocytes interconnect to form a unique type of cell-cell junction, the slit diaphragm, which acts as a molecular sieve. The cytoplasmic tails of Nephrin and Neph mediate cytoskeletal rearrangement that contributes to the maintenance of the filtration barrier. Nephrin and Neph1 orthologs are essential to regulate cell-cell adhesion and Rac-dependent actin rearrangement during Drosophila myoblast fusion. We hypothesized here that molecules regulating myoblast fusion in Drosophila could contribute to signaling downstream of Nephrin and Neph1 in podocytes. We found that Nephrin engagement promoted recruitment of the Rac exchange factor Dock1 to the membrane. Furthermore, Nephrin overexpression led to lamellipodia formation that could be blocked by inhibiting Rac1 activity. We generated in vivo mouse models to investigate whether Dock1 and Dock5 contribute to the formation and maintenance of the kidney filtration barrier. Our results indicate that while Dock1 and Dock5 are expressed in podocytes, their functions are not essential for the development of the glomerular filtration barrier. Furthermore, mice lacking Dock1 were not protected from LPS-induced podocyte effacement. Our data suggest that Dock1 and Dock5 are not the important exchange factors regulating Rac activity during the establishment and maintenance of the glomerular barrier. PMID:24365888

AutoDock-GIST: Incorporating Thermodynamics of Active-Site Water into Scoring Function for Accurate Protein-Ligand Docking.

PubMed

Uehara, Shota; Tanaka, Shigenori

2016-11-23

Water plays a significant role in the binding process between protein and ligand. However, the thermodynamics of water molecules are often underestimated, or even ignored, in protein-ligand docking. Usually, the free energies of active-site water molecules are substantially different from those of waters in the bulk region. The binding of a ligand to a protein causes a displacement of these waters from an active site to bulk, and this displacement process substantially contributes to the free energy change of protein-ligand binding. The free energy of active-site water molecules can be calculated by grid inhomogeneous solvation theory (GIST), using molecular dynamics (MD) and the trajectory of a target protein and water molecules. Here, we show a case study of the combination of GIST and a docking program and discuss the effectiveness of the displacing gain of unfavorable water in protein-ligand docking. We combined the GIST-based desolvation function with the scoring function of AutoDock4, which is called AutoDock-GIST. The proposed scoring function was assessed employing 51 ligands of coagulation factor Xa (FXa), and results showed that both scoring accuracy and docking success rate were improved. We also evaluated virtual screening performance of AutoDock-GIST using FXa ligands in the directory of useful decoys-enhanced (DUD-E), thus finding that the displacing gain of unfavorable water is effective for a successful docking campaign.

HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.

PubMed

Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong; Huang, Sheng-You

2017-07-03

Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein-protein and protein-DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10-20 min for a docking run. Tested on the cases with weakly homologous complexes of <30% sequence identity from five docking benchmarks, the HDOCK pipeline tied with template-based modeling on the protein-protein and protein-DNA benchmarks and performed better than template-based modeling on the three protein-RNA benchmarks when the top 10 predictions were considered. The performance of HDOCK became better when more predictions were considered. Combining the results of HDOCK and template-based modeling by ranking first of the template-based model further improved the predictive power of the server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system.

PubMed

Kantardjiev, Alexander A

2012-07-01

Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html.

Application of a post-docking procedure based on MM-PBSA and MM-GBSA on single and multiple protein conformations.

PubMed

Sgobba, Miriam; Caporuscio, Fabiana; Anighoro, Andrew; Portioli, Corinne; Rastelli, Giulio

2012-12-01

In the last decades, molecular docking has emerged as an increasingly useful tool in the modern drug discovery process, but it still needs to overcome many hurdles and limitations such as how to account for protein flexibility and poor scoring function performance. For this reason, it has been recognized that in many cases docking results need to be post-processed to achieve a significant agreement with experimental activities. In this study, we have evaluated the performance of MM-PBSA and MM-GBSA scoring functions, implemented in our post-docking procedure BEAR, in rescoring docking solutions. For the first time, the performance of this post-docking procedure has been evaluated on six different biological targets (namely estrogen receptor, thymidine kinase, factor Xa, adenosine deaminase, aldose reductase, and enoyl ACP reductase) by using i) both a single and a multiple protein conformation approach, and ii) two different software, namely AutoDock and LibDock. The assessment has been based on two of the most important criteria for the evaluation of docking methods, i.e., the ability of known ligands to enrich the top positions of a ranked database with respect to molecular decoys, and the consistency of the docking poses with crystallographic binding modes. We found that, in many cases, MM-PBSA and MM-GBSA are able to yield higher enrichment factors compared to those obtained with the docking scoring functions alone. However, for only a minority of the cases, the enrichment factors obtained by using multiple protein conformations were higher than those obtained by using only one protein conformation. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Strain-Life Assessment of Grainex Mar-M 247 for NASA's Turbine Seal Test Facility

NASA Technical Reports Server (NTRS)

Delgado, Irebert R.; Halford, Gary R.; Steinetz, Bruce M.; Rimnac, Clare M.

2004-01-01

NASA s Turbine Seal Test Facility is used to test air-to-air seals for use primarily in advanced jet engine applications. Combinations of high temperature, high speed, and high pressure limit the disk life, due to the concern of crack initiation in the bolt holes of the Grainex Mar-M 247 disk. The primary purpose of this current work is to determine an inspection interval to ensure safe operation. The current work presents high temperature fatigue strain-life data for test specimens cut from an actual Grainex Mar-M 247 disk. Several different strain-life models were compared to the experimental data including the Manson-Hirschberg Method of Universal Slopes, the Halford-Nachtigall Mean Stress Method, and the Modified Morrow Method. The Halford-Nachtigall Method resulted in only an 18 percent difference between predicted and experimental results. Using the experimental data at a 99.95 percent prediction level and the presence of 6 bolt holes it was found that the disk should be inspected after 665 cycles based on a total strain of 0.5 percent at 649 C.

Optimization of Turbine Rim Seals

NASA Technical Reports Server (NTRS)

Wagner, J. H.; Tew, D. E.; Stetson, G. M.; Sabnis, J. S.

2006-01-01

Experiments are being conducted to gain an understanding of the physics of rim scale cavity ingestion in a turbine stage with the high-work, single-stage characteristics envisioned for Advanced Subsonic Transport (AST) aircraft gas turbine engines fo the early 21st century. Initial experimental measurements to be presented include time-averaged turbine rim cavity and main gas path static pressure measurements for rim seal coolant to main gas path mass flow ratios between 0 and 0.02. The ultimate objective of this work is develop improved rim seal design concepts for use in modern high-work, single sage turbines n order to minimize the use of secondary coolant flow. Toward this objective the time averaged and unsteady data to be obtained in these experiments will be used to 1) Quantify the impact of the rim cavity cooling air on the ingestion process. 2) Quantify the film cooling benefits of the rim cavity purge flow in the main gas path. 3) Quantify the impact of the cooling air on turbine efficiency. 4) Develop/evaluate both 3D CFD and analytical models of the ingestion/cooling process.

The development of diving in marine endotherms: preparing the skeletal muscles of dolphins, penguins, and seals for activity during submergence.

PubMed

Noren, S R; Williams, T M; Pabst, D A; McLellan, W A; Dearolf, J L

2001-03-01

Myoglobin is an important oxygen store for supporting aerobic diving in endotherms, yet little is known about its role during postnatal development. Therefore, we compared the postnatal development of myoglobin in marine endotherms that develop at sea (cetaceans) to those that develop on land (penguins and pinnipeds). We measured myoglobin concentrations in the major locomotor muscles of mature and immature bottlenose dolphins (Tursiops truncatus) and king penguins (Aptenodytes patagonicus) and compared the data to previously reported values for northern elephant seals (Mirounga angustirostris). Neonatal dolphins, penguins, and seals lack the myoglobin concentrations required for prolonged dive durations, having 10%, 9%, and 31% of adult values, respectively. Myoglobin contents increased significantly during subsequent development. The increases in myoglobin content with age may correspond to increases in activity levels, thermal demands, and time spent in apnea during swimming and diving. Across these phylogenetically diverse taxa (cetaceans, penguins, and pinnipeds), the final stage of postnatal development of myoglobin occurs during the initiation of independent foraging, regardless of whether development takes place at sea or on land.

FlexAID: Revisiting Docking on Non-Native-Complex Structures.

PubMed

Gaudreault, Francis; Najmanovich, Rafael J

2015-07-27

Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The pairwise energy parameters were derived from a large dataset of true positive poses and negative decoys from the PDBbind database through an iterative process using Monte Carlo simulations. The prediction of binding poses is tested using the widely used Astex dataset as well as the HAP2 dataset, while performance in virtual screening is evaluated using a subset of the DUD dataset. We compare FlexAID to AutoDock Vina, FlexX, and rDock in an extensive number of scenarios to understand the strengths and limitations of the different programs as well as to reported results for Glide, GOLD, and DOCK6 where applicable. The most relevant among these scenarios is that of docking on flexible non-native-complex structures where as is the case in reality, the target conformation in the bound form is not known a priori. We demonstrate that FlexAID, unlike other programs, is robust against increasing structural variability. FlexAID obtains equivalent sampling success as GOLD and performs better than AutoDock Vina or FlexX in all scenarios against non-native-complex structures. FlexAID is better than rDock when there is at least one critical side-chain movement required upon ligand binding. In virtual screening, FlexAID results are lower on average than those of AutoDock Vina and rDock. The higher accuracy in flexible targets where critical movements are required, intuitive PyMOL-integrated graphical user interface and free source code as well as precompiled executables for Windows, Linux, and Mac OS make FlexAID a welcome addition to the arsenal of existing small-molecule protein docking methods.

istar: a web platform for large-scale protein-ligand docking.

PubMed

Li, Hongjian; Leung, Kwong-Sak; Ballester, Pedro J; Wong, Man-Hon

2014-01-01

Protein-ligand docking is a key computational method in the design of starting points for the drug discovery process. We are motivated by the desire to automate large-scale docking using our popular docking engine idock and thus have developed a publicly-accessible web platform called istar. Without tedious software installation, users can submit jobs using our website. Our istar website supports 1) filtering ligands by desired molecular properties and previewing the number of ligands to dock, 2) monitoring job progress in real time, and 3) visualizing ligand conformations and outputting free energy and ligand efficiency predicted by idock, binding affinity predicted by RF-Score, putative hydrogen bonds, and supplier information for easy purchase, three useful features commonly lacked on other online docking platforms like DOCK Blaster or iScreen. We have collected 17,224,424 ligands from the All Clean subset of the ZINC database, and revamped our docking engine idock to version 2.0, further improving docking speed and accuracy, and integrating RF-Score as an alternative rescoring function. To compare idock 2.0 with the state-of-the-art AutoDock Vina 1.1.2, we have carried out a rescoring benchmark and a redocking benchmark on the 2,897 and 343 protein-ligand complexes of PDBbind v2012 refined set and CSAR NRC HiQ Set 24Sept2010 respectively, and an execution time benchmark on 12 diverse proteins and 3,000 ligands of different molecular weight. Results show that, under various scenarios, idock achieves comparable success rates while outperforming AutoDock Vina in terms of docking speed by at least 8.69 times and at most 37.51 times. When evaluated on the PDBbind v2012 core set, our istar platform combining with RF-Score manages to reproduce Pearson's correlation coefficient and Spearman's correlation coefficient of as high as 0.855 and 0.859 respectively between the experimental binding affinity and the predicted binding affinity of the docked conformation. istar is freely available at http://istar.cse.cuhk.edu.hk/idock.

Performance characteristics of a laser initiated microdetonator

NASA Technical Reports Server (NTRS)

Yang, L. C.

1981-01-01

The test results of 320 units of a laser initiated microdetonator are summarized. The commercially fabricated units used a lead styphnate/lead azide/HMX (1 mg/13.5 mg) explosive train design contained in a miniature aluminum can that was capped with a glass-metal seal window. The test parameters were the laser energy, temperature, laser pulse duration, laser wavelength and nuclear radiation (5,000,000 rad of 1 MeV gamma rays). The performance parameters were the laser energy for ignition and the actuation response time.

Seal assembly with anti-rotation pin for high pressure supercritical fluids

DOEpatents

Wright, Steven A.; Fuller, Robert L.

2014-08-05

A seal assembly for sealing a machine with a first chamber and a second chamber is provided. A rotating shaft extends through the first and second chambers, and rotates therein. The seal assembly has a seal housing, a seal ring and a seal pin. The seal housing is positionable in the machine housing. The seal housing has a seal pocket extending into a fluid side thereof, and a housing receptacle extending into an inner diameter thereof at the seal pocket. The seal ring is positionable in the seal pocket of the seal housing for forming a seal therewith. The seal ring has a ring receptacle extending into an outer diameter thereof. The ring receptacle is positionable adjacent to the housing receptacle for defining a pin hole therebetween. The seal pin is loosely positionable in the pin hole whereby movement about the seal ring is accommodated while preventing rotation thereof.

Design guide for helicopter transmission seals

NASA Technical Reports Server (NTRS)

Hayden, T. S.; Keller, C. H., Jr.

1974-01-01

A detailed approach for the selection and design of seals for helicopter transmissions is presented. There are two major types of seals presently being used and they are lip type seals and mechanical type seals. Lip type seals can be divided in conventional lip seals and hydrodynamic lip seals. Conventional lip seals can be used for slow-speed, low-pressure, low-temperature sealing. Hydrodynamic lip seals although they are as pressure and temperature limited as conventional lip seals, can operate at a higher speed. Mechanical types seals are comprised of face seals and circumferential seals. Face seals are capable of high speed, high pressure, and high temperature. Circumferential seals can be used in high-speed and high-temperature applications, but will leak excessively at moderate pressures. The performance goals of transmission seals are a life that is at least equal to the scheduled overhaul interval of the gearbox component and a leakage rate of near zero.

Service building. Cross section thru dry dock nos. 4 & ...

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

Service building. Cross section thru dry dock nos. 4 & 5 showing service bldg & 20-75-150 ton cranes (dry dock associates, May 23, 1941). In files of Cushman & Wakefield, building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

21. ORE DOCK, LOOKING SOUTHWEST. THIS VIEW SHOWS THE WEST ...

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

21. ORE DOCK, LOOKING SOUTHWEST. THIS VIEW SHOWS THE WEST END OF THE DOCK. EMPTY CARS ARE MOVED IN FROM THE WEST BY 'SHUNT CARS,' PUT INTO PLACE AS NEEDED BENEATH THE HULETTS, FILLED, THEN SHUNTED TO THE EAST END OF THE YARD WHERE THEY ARE MADE UP INTO TRAINS. THE POWER HOUSE (WITH TALL ARCHED WINDOWS) AND THE TWO-STORY DOCK OFFICE CAN BE SEEN HERE. - Pennsylvania Railway Ore Dock, Lake Erie at Whiskey Island, approximately 1.5 miles west of Public Square, Cleveland, Cuyahoga County, OH

Kotov in SM during Progress 37P Docking

NASA Image and Video Library

2010-05-01

ISS023-E-031743 (1 May 2010) --- Russian cosmonaut Oleg Kotov, Expedition 23 commander, is pictured at the manual TORU docking system controls in the Zvezda Service Module of the International Space Station just before conducting a manual control docking of the Progress 37 due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan.

Ensemble-based docking: From hit discovery to metabolism and toxicity predictions

DOE PAGES

Evangelista, Wilfredo; Weir, Rebecca; Ellingson, Sally; ...

2016-07-29

The use of ensemble-based docking for the exploration of biochemical pathways and toxicity prediction of drug candidates is described. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials.

GENIUS In Silico Screening Technology for HCV Drug Discovery.

PubMed

Patil, Vaishali M; Masand, Neeraj; Gupta, Satya P

2016-01-01

The various reported in silico screening protocols such as molecular docking are associated with various drawbacks as well as benefits. In molecular docking, on interaction with ligand, the protein or receptor molecule gets activated by adopting conformational changes. These conformational changes cannot be utilized to predict the 3D structure of a protein-ligand complex from unbound protein conformations rigid docking, which necessitates the demand for understanding protein flexibility. Therefore, efficiency and accuracy of docking should be achieved and various available/developed protocols may be adopted. One such protocol is GENIUS induced-fit docking and it is used effectively for the development of anti-HCV NS3-4A serine protease inhibitors. The present review elaborates the GENIUS docking protocol along with its benefits and drawbacks.

Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx.

PubMed

Bharatham, Nagakumar; Finch, Kristin E; Min, Jaeki; Mayasundari, Anand; Dyer, Michael A; Guy, R Kiplin; Bashford, Donald

2017-06-01

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used. Published by Elsevier Inc.

Syn-Fuel reciprocating charge pump improvement program. Quarterly technical project report, April-June 1984

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

Not Available

1984-01-01

Major accomplishments during the second quarter of 1984 were completion of the Diaphragm Separation Seal clear liquid testing, and initiation of Phase III Field Testing. Diaphragm operational testing was conducted on a clear water test loop. The test goals were to ensure; mechanical reliability of the Diaphragm Seal, safe operation with simulated component failure, and proper operation of the Diaphragm Buffer Volume Control System. This latter system is essential in controlling the phasing of the diaphragm with its driving plunger. These tests were completed successfully. All operational problems were solved. However, it must be emphasized that the Diaphragm Seal wouldmore » be damaged by allowing the pump to operate in a cavitating condition for an extended period of time. A change in the Field Test phase of the program was made regarding choice of field test site. There is no operating Syn-Fuel pilot plant capable of inexpensively producing the slurry stream required for the reciprocating pump testing. The Field Tests will now be conducted by first testing the prototype pump and separation seals in an ambient temperature sand water slurry. This will determine resistence to abrasive wear and determine any operation problems at pressure over a lengthy period of time. After successful conclusion of these tests the pump and seals will be operated with a high temperature oil, but without solids, to identify any problems associated with thermal gradients, thermal shock and differential growth. After successful completion of the high temperature clean oil tests the pump will be deemed ready for in-line installation at a designated Syn-Fuel pilot plant. The above approach avoids the expense and complications of a separate hot slurry test loop. It also reduces risk of operational problems while in-line at the pilot plant. 5 figs.« less

Retention and penetration of a conventional resin-based sealant and a photochromatic flowable composite resin placed on occlusal pits and fissures.

PubMed

Aguilar, F G; Drubi-Filho, B; Casemiro, L A; Watanabe, M G C; Pires-de-Souza, F C P

2007-01-01

This study compares the retention and penetration of a conventional resin-based sealant (Fluroshield) and a photochromatic flowable composite resin (Tetric Flow Chroma) placed on occlusal pits and fissures and submitted to thermal or chemical cycling regimens. Penetration assessment--ten premolars were sealed with each material, isolated (except for the sealed surface) and immersed in 0.2% Rhodamine B. The teeth were serially sectioned in a mesiodistal direction. The images of the sections were digitized and analyzed (ImageLab). The distance between the most superficial and the deepest points on the occlusal central groove was calculated to determine the groove's total depth. The length of the central groove filled with the sealant was divided by its total depth to obtain the percentage of sealing of the occlusal groove. Retention assessment--30 premolars were sealed, their occlusal surfaces were photographed and the area occupied by the sealing materials was demarcated (ImageLab). The teeth were submitted to different treatments: thermocycled, stored in artificial saliva and immersed in acetic acid and saliva (10 cycles/day protocol for 30 days). New photographs were taken to assess the final area occupied by the materials. The difference between the final and initial area was calculated to obtain the material loss. The data was analyzed (two-way ANOVA and Tukey's test P<0.05). Both materials presented similar penetration of the occlusal central groove. After thermal and chemical cycling, the materials did not differ with respect to retention, except for immersion in acetic acid. In this case, Tetric Flow Chroma presented greater retention than Fluoroshield.

Influence of elastomeric seal plate surface chemistry on interface integrity in biofouling-prone systems: Evaluation of a hydrophobic "easy-release" silicone-epoxy coating for maintaining water seal integrity of a sliding neoprene/steel interface

NASA Astrophysics Data System (ADS)

Andolina, Vincent L.

The scientific hypothesis of this work is that modulation of the properties of hard materials to exhibit abrasion-reducing and low-energy surfaces will extend the functional lifetimes of elastomeric seals pressed against them in abrasive underwater systems. The initial motivation of this work was to correct a problem noted in the leaking of seals at major hydropower generating facilities subject to fouling by abrasive zebra mussel shells and extensive corrosion. Similar biofouling-influenced problems can develop at seals in medical devices and appliances from regulators in anesthetic machines and SCUBA diving oxygen supply units to autoclave door seals, injection syringe gaskets, medical pumps, drug delivery components, and feeding devices, as well as in food handling equipment like pasteurizers and transfer lines. Maritime and many other heavy industrial seal interfaces could also benefit from this coating system. Little prior work has been done to elucidate the relationship of seal plate surface properties to the friction and wear of elastomeric seals during sliding contacts of these articulating materials, or to examine the secondary influence of mineralized debris within the contacting interfaces. This investigation utilized the seal materials relevant to the hydropower application---neoprene elastomer against carbon steel---with and without the application of a silicone-epoxy coating (WearlonRTM 2020.98) selected for its wear-resistance, hydrophobicity, and "easy-release" capabilities against biological fouling debris present in actual field use. Analytical techniques applied to these materials before and after wear-producing processes included comprehensive Contact Angle measurements for Critical Surface Tension (CA-CST) determination, Scanning Electron Microscopic inspections, together with Energy Dispersive X-ray Spectroscopy (SEM-EDS) and X-Ray Fluorescence (XRF) measurements for determination of surface texture and inorganic composition, Multiple Attenuated Internal Reflection (MAIR-IR) and Microscopic Infrared Spectroscopy for organic surface compositional details, light microscopy for wear area quantification, and profilometry for surface roughness estimation and wear depth quantification. Pin-on-disc dynamic Coefficient of Friction (CoF) measurements provided data relevant to forecasts of seal integrity in dry, wet and biofouling-influenced sliding contact. Actual wear of neoprene seal material against uncoated and coated steel surfaces, wet and dry, was monitored after both rotary and linear cyclic wear testing, demonstrating significant reductions in elastomer wear areas and depths (and resultant volumes) when the coating was present. Coating the steel eliminated a 270% increase in neoprene surface area wear and an 11-fold increase in seal abrasive volume loss associated with underwater rusting in rotary experiments. Linear testing results confirm coating efficacy by reducing wear area in both loading regimes by about half. No coating delamination was observed, apparently due to a differential distribution of silicone and epoxy ingredients at the air-exposed vs. steel-bonded interfaces demonstrated by IR and EDS methods. Frictional testing revealed higher Coefficients of Friction (CoF) associated with the low-speed sliding of Neoprene over coated rather than uncoated steel surfaces in a wet environment, indicating better potential seal adhesion between the hydrophobic elastomer and coating than between the elastomer and intrinsically hydrophilic uncoated steel. When zebra mussel biofouling debris was present in the articulating joints, CoF was reduced as a result of a water channel path produced between the articulating surfaces by the retained biological matter. Easier release of the biofouling from the low-CST coated surfaces restored the seal integrity more rapidly with further water rinsing. Rapid sliding diminished these biofouling-related differences, but revealed a significant advantage in reducing the CoF of the elastomer-on-coating couples to less than 50% of the elastomer-on-steel couples in all conditions. These consolidated results indicate that general improvements in maintenance of seal integrity and functional lifetimes for other sliding joints exposed to potentially abrasive biofouling media can be obtained by coating the more-rigid seal-plate surfaces with low-CST, hydrophobic, wear-resistant materials such as the silicone-epoxy system characterized here.

40 CFR 63.3171 - How do I demonstrate initial compliance?

Code of Federal Regulations, 2013 CFR

2013-07-01

... of electrodeposition bake oven emissions. You must show that the electrodeposition bake oven meets... of the exhaust gases from the bake oven to an add-on control device. For purposes of this showing, an electrodeposition bake oven air seal is not considered a natural draft opening provided you demonstrate that the...

40 CFR 63.3171 - How do I demonstrate initial compliance?

Code of Federal Regulations, 2012 CFR

2012-07-01

... of electrodeposition bake oven emissions. You must show that the electrodeposition bake oven meets... of the exhaust gases from the bake oven to an add-on control device. For purposes of this showing, an electrodeposition bake oven air seal is not considered a natural draft opening provided you demonstrate that the...

40 CFR 63.3171 - How do I demonstrate initial compliance?

Code of Federal Regulations, 2011 CFR

2011-07-01

... of electrodeposition bake oven emissions. You must show that the electrodeposition bake oven meets... of the exhaust gases from the bake oven to an add-on control device. For purposes of this showing, an electrodeposition bake oven air seal is not considered a natural draft opening provided you demonstrate that the...

40 CFR 63.3171 - How do I demonstrate initial compliance?

Code of Federal Regulations, 2014 CFR

2014-07-01

... of electrodeposition bake oven emissions. You must show that the electrodeposition bake oven meets... of the exhaust gases from the bake oven to an add-on control device. For purposes of this showing, an electrodeposition bake oven air seal is not considered a natural draft opening provided you demonstrate that the...

40 CFR 63.3171 - How do I demonstrate initial compliance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of electrodeposition bake oven emissions. You must show that the electrodeposition bake oven meets... of the exhaust gases from the bake oven to an add-on control device. For purposes of this showing, an electrodeposition bake oven air seal is not considered a natural draft opening provided you demonstrate that the...

49 CFR Appendix B to Part 209 - Federal Railroad Administration Guidelines for Initial Hazardous Materials Assessments

Code of Federal Regulations, 2010 CFR

2010-10-01

... hazardous materials are only safe for transportation when they are securely sealed in a proper package...) that a container or package for transportation of a hazardous material is safe, certified, or in.... —Listing an unauthorized, incorrect, non-working, or unmonitored (24 hrs. a day) emergency response...

Turbine with radial acting seal

DOEpatents

Eng, Darryl S; Ebert, Todd A

2016-11-22

A floating brush seal in a rim cavity of a turbine in a gas turbine engine, where the floating brush seal includes a seal holder in which the floating brush seal floats, and a expandable seal that fits within two radial extending seal slots that maintains a seal with radial displacement of the floating brush seal and the seal holder.

Surface conforming thermal/pressure seal. [tail assemblies of space shuttle orbiters

NASA Technical Reports Server (NTRS)

Stevens, M. L. (Inventor)

1981-01-01

An assembly is disclosed for sealing a variable gap between the surface of element and a second element in movable relation to it. A seal housing is attached to the second element for movement therewith and has a sealing surface. At least one elongated seal member carried by the housing has first and second conjugate sealing surfaces. The first sealing surface is for rubbing and sealing engagement with the first element surface and the second sealing surface is for sliding and sealing engagement with the housing sealing surface. A biasing assembly may be carried by the housing for biasing the first and second conjugate sealing surfaces of the sealing member toward sealing engagement with the first element surface and housing sealing surface, respectively.

Fuel cell manifold sealing system

DOEpatents

Grevstad, Paul E.; Johnson, Carl K.; Mientek, Anthony P.

1980-01-01

A manifold-to-stack seal and sealing method for fuel cell stacks. This seal system solves the problem of maintaining a low leak rate manifold seal as the fuel cell stack undergoes compressive creep. The seal system eliminates the problem of the manifold-to-stack seal sliding against the rough stack surface as the stack becomes shorter because of cell creep, which relative motion destroys the seal. The seal system described herein utilizes a polymer seal frame firmly clamped between the manifold and the stack such that the seal frame moves with the stack. Thus, as the stack creeps, the seal frame creeps with it, and there is no sliding at the rough, tough to seal, stack-to-seal frame interface. Here the sliding is on a smooth easy to seal location between the seal frame and the manifold.

Method for producing a fuel cell manifold seal

DOEpatents

Grevstad, Paul E.; Johnson, Carl K.; Mientek, Anthony P.

1982-01-01

A manifold-to-stack seal and sealing method for fuel cell stacks. This seal system solves the problem of maintaining a low leak rate manifold seal as the fuel cell stack undergoes compressive creep. The seal system eliminates the problem of the manifold-to-stack seal sliding against the rough stack surface as the stack becomes shorter because of cell creep, which relative motion destroys the seal. The seal system described herein utilizes a polymer seal frame firmly clamped between the manifold and the stack such that the seal frame moves with the stack. Thus, as the stack creeps, the seal frame creeps with it, and there is no sliding at the rough, tough to seal, stack-to-seal frame interface. Here the sliding is on a smooth easy to seal location between the seal frame and the manifold.

Discovery of binding proteins for a protein target using protein-protein docking-based virtual screening.

PubMed

Zhang, Changsheng; Tang, Bo; Wang, Qian; Lai, Luhua

2014-10-01

Target structure-based virtual screening, which employs protein-small molecule docking to identify potential ligands, has been widely used in small-molecule drug discovery. In the present study, we used a protein-protein docking program to identify proteins that bind to a specific target protein. In the testing phase, an all-to-all protein-protein docking run on a large dataset was performed. The three-dimensional rigid docking program SDOCK was used to examine protein-protein docking on all protein pairs in the dataset. Both the binding affinity and features of the binding energy landscape were considered in the scoring function in order to distinguish positive binding pairs from negative binding pairs. Thus, the lowest docking score, the average Z-score, and convergency of the low-score solutions were incorporated in the analysis. The hybrid scoring function was optimized in the all-to-all docking test. The docking method and the hybrid scoring function were then used to screen for proteins that bind to tumor necrosis factor-α (TNFα), which is a well-known therapeutic target for rheumatoid arthritis and other autoimmune diseases. A protein library containing 677 proteins was used for the screen. Proteins with scores among the top 20% were further examined. Sixteen proteins from the top-ranking 67 proteins were selected for experimental study. Two of these proteins showed significant binding to TNFα in an in vitro binding study. The results of the present study demonstrate the power and potential application of protein-protein docking for the discovery of novel binding proteins for specific protein targets. © 2014 Wiley Periodicals, Inc.

Addressing recent docking challenges: A hybrid strategy to integrate template-based and free protein-protein docking.

PubMed

Yan, Yumeng; Wen, Zeyu; Wang, Xinxiang; Huang, Sheng-You

2017-03-01

Protein-protein docking is an important computational tool for predicting protein-protein interactions. With the rapid development of proteomics projects, more and more experimental binding information ranging from mutagenesis data to three-dimensional structures of protein complexes are becoming available. Therefore, how to appropriately incorporate the biological information into traditional ab initio docking has been an important issue and challenge in the field of protein-protein docking. To address these challenges, we have developed a Hybrid DOCKing protocol of template-based and template-free approaches, referred to as HDOCK. The basic procedure of HDOCK is to model the structures of individual components based on the template complex by a template-based method if a template is available; otherwise, the component structures will be modeled based on monomer proteins by regular homology modeling. Then, the complex structure of the component models is predicted by traditional protein-protein docking. With the HDOCK protocol, we have participated in the CPARI experiment for rounds 28-35. Out of the 25 CASP-CAPRI targets for oligomer modeling, our HDOCK protocol predicted correct models for 16 targets, ranking one of the top algorithms in this challenge. Our docking method also made correct predictions on other CAPRI challenges such as protein-peptide binding for 6 out of 8 targets and water predictions for 2 out of 2 targets. The advantage of our hybrid docking approach over pure template-based docking was further confirmed by a comparative evaluation on 20 CASP-CAPRI targets. Proteins 2017; 85:497-512. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Low Impact Docking System (LIDS)

NASA Technical Reports Server (NTRS)

LaBauve, Tobie E.

2009-01-01

Since 1996, NASA has been developing a docking system that will simplify operations and reduce risks associated with mating spacecraft. This effort has focused on developing and testing an original, reconfigurable, active, closed-loop, force-feedback controlled docking system using modern technologies. The primary objective of this effort has been to design a docking interface that is tunable to the unique performance requirements for all types of mating operations (i.e. docking and berthing, autonomous and piloted rendezvous, and in-space assembly of vehicles, modules and structures). The docking system must also support the transfer of crew, cargo, power, fluid, and data. As a result of the past 10 years of docking system advancement, the Low Impact Docking System or LIDS was developed. The current LIDS design incorporates the lessons learned and development experiences from both previous and existing docking systems. LIDS feasibility was established through multiple iterations of prototype hardware development and testing. Benefits of LIDS include safe, low impact mating operations, more effective and flexible mission implementation with an anytime/anywhere mating capability, system level redundancy, and a more affordable and sustainable mission architecture with reduced mission and life cycle costs. In 1996 the LIDS project, then known as the Advanced Docking Berthing System (ADBS) project, launched a four year developmental period. At the end of the four years, the team had built a prototype of the soft-capture hardware and verified the control system that will be used to control the soft-capture system. In 2001, the LIDS team was tasked to work with the X- 38 Crew Return Vehicle (CRV) project and build its first Engineering Development Unit (EDU).

PtdIns(4,5)P2 is not required for secretory granule docking.

PubMed

Omar-Hmeadi, Muhmmad; Gandasi, Nikhil R; Barg, Sebastian

2018-06-01

Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution total internal reflection imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules. We also observed rapid accumulation of syntaxin-1 at sites where granules arrived to dock. Acute depletion of plasma membrane phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P 2 ) by recruitment of a 5'-phosphatase strongly inhibited Ca 2+ -dependent exocytosis, but had no effect on docked granules or the distribution and clustering of syntaxin-1. Cell permeabilization by α-toxin or formaldehyde-fixation caused PtdIns marker to slowly cluster, in part near docked granules. In summary, our data indicate that PtdIns(4,5)P 2 accelerates granule priming, but challenge a role of PtdIns in secretory granule docking or clustering of syntaxin-1 at the release site. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

PubMed

Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

2005-02-22

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

Tyurin packs the docking probe in Node 1 during Expedition Three

NASA Image and Video Library

2001-09-17

ISS003-E-5632 (17 September 2001) --- Cosmonaut Mikhail Tyurin, Expedition Three flight engineer, packs the docking probe in a stowage bag in Unity. Cosmonaut Vladimir Dezhurov, flight engineer, videotapes the event. The docking probe successfully guided the arrival of the Russian-built Pirs docking compartment to the International Space Station (ISS). Tyurin and Dezhurov represent Rosaviakosmos.

Dezhurov removes the docking probe in Zvezda during Expedition Three

NASA Image and Video Library

2001-09-17

ISS003-E-5621 (17 September 2001) --- Cosmonaut Vladimir Dezhurov, Expedition Three flight engineer, prepares to remove the docking probe in the Zvezda Service Module's pressurized adapter. The docking probe successfully guided the arrival of the Russian-built Pirs docking compartment to the International Space Station (ISS). Mikhail Tyurin, flight engineer, is visible in the background. Tyurin and Dezhurov represent Rosaviakosmos.

Orion Handling Qualities During ISS Proximity Operations and Docking

NASA Technical Reports Server (NTRS)

Stephens, John-Paul; Vos, Gordon A.; Bilimoria, Karl D.; Mueller, Eric R.; Brazzel, Jack; Spehar, Pete

2011-01-01

NASA's Orion spacecraft is designed to autonomously rendezvous and dock with many vehicles including the International Space Station. However, the crew is able to assume manual control of the vehicle s attitude and flight path. In these instances, Orion must meet handling qualities requirements established by NASA. Two handling qualities assessments were conducted at the Johnson Space Center to evaluate preliminary designs of the vehicle using a six degree of freedom, high-fidelity guidance, navigation, and control simulation. The first assessed Orion s handling qualities during the last 20 ft before docking, and included both steady and oscillatory motions of the docking target. The second focused on manual acquisition of the docking axis during the proximity operations phase and subsequent station-keeping. Cooper-Harper handling qualities ratings, workload ratings and comments were provided by 10 evaluation pilots for the docking study and 5 evaluation pilots for the proximity operations study. For the docking task, both cases received 90% Level 1 (satisfactory) handling qualities ratings, exceeding NASA s requirement. All ratings for the ProxOps task were Level 1. These evaluations indicate that Orion is on course to meet NASA's handling quality requirements for ProxOps and docking.

STS-112 Flight Day 3 Highlights

NASA Technical Reports Server (NTRS)

2002-01-01

During the third flight day of STS-112 (Commander Jeff Ashby, Pilot Pam Melroy and Mission Specialists Sandy Magnus, Piers Sellers, David Wolf and Fyodor Yurchikhin), the Space Shuttle Atlantis begins its final approach to the International Space Station (ISS) with which it will dock. The Chinese mainland is seen, at night, at a height of 242 statute miles. In one section of video from a camera onboard the ISS, Atlantis can be seen to be almost directly below the station, at a distance of several hundred feet. The orbiter's docking system is shown, as it is slowly guided by Ashby towards the forward docking port on the ISS's Destiny Laboratory Module and its forward docking port. Above the docking port, the S0 truss structure can be seen, to which the S1 truss structure in Atlantis' payload bay will be attached during this mission. Also seen are the Unity airlock and other modules. Following the completion of docking, in which an excellent shot of the docking system in hard dock is visible, the hatches between the two crafts are opened and the members of Atlantis are greeted by the very excited members of Expedition 5, who have been aboard the ISS for several months.

Tail docking in horses: a review of the issues.

PubMed

Lefebvre, D; Lips, D; Odberg, F O; Giffroy, J M

2007-09-01

Routinely performed painful procedures are of increasing interest and, in 2001 (Royal Order, May 17), Belgium prohibited docking in several vertebrates including horses. In 2004, opponents to this decision submitted a Bill (Doc51 0969/001) to Parliament, intending to obtain derogation for Belgian draught horses, which were traditionally docked. The Animal Welfare Council of Belgium, an official body advising the Minister of Public Health, was asked to evaluate this complex question, including biological, ethical and socio-economic aspects, on the basis of the available peer-reviewed studies. In this context, this study reviews legal aspects (overview of the European legislation), zootechnic aspects (uses of the Belgian draught horse) and biological aspects (pain potentially related to docking; horses' welfare linked to insect harassment and hygiene, communication and reproduction) of tail docking in draught horses. We conclude that (1) there is no benefit for horses in tail docking, including Belgian draught horses, (2) potential advantages of docking are essentially in favour of humans and these advantages could be scrupulously re-evaluated, taking into account practices of other countries. Therefore, there is no need to dock any horse other than for veterinary reasons.

HSYMDOCK: a docking web server for predicting the structure of protein homo-oligomers with Cn or Dn symmetry.

PubMed

Yan, Yumeng; Tao, Huanyu; Huang, Sheng-You

2018-05-26

A major subclass of protein-protein interactions is formed by homo-oligomers with certain symmetry. Therefore, computational modeling of the symmetric protein complexes is important for understanding the molecular mechanism of related biological processes. Although several symmetric docking algorithms have been developed for Cn symmetry, few docking servers have been proposed for Dn symmetry. Here, we present HSYMDOCK, a web server of our hierarchical symmetric docking algorithm that supports both Cn and Dn symmetry. The HSYMDOCK server was extensively evaluated on three benchmarks of symmetric protein complexes, including the 20 CASP11-CAPRI30 homo-oligomer targets, the symmetric docking benchmark of 213 Cn targets and 35 Dn targets, and a nonredundant test set of 55 transmembrane proteins. It was shown that HSYMDOCK obtained a significantly better performance than other similar docking algorithms. The server supports both sequence and structure inputs for the monomer/subunit. Users have an option to provide the symmetry type of the complex, or the server can predict the symmetry type automatically. The docking process is fast and on average consumes 10∼20 min for a docking job. The HSYMDOCK web server is available at http://huanglab.phys.hust.edu.cn/hsymdock/.

Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

NASA Technical Reports Server (NTRS)

Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

2002-01-01

The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins.

PubMed

Nguyen, Phuong T V; Yu, Haibo; Keller, Paul A

2017-03-11

The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported examples, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational sampling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for example Gly91 and His230, are identified as possessing important roles in the fusion process.

ART CONCEPTS - ASTP

NASA Image and Video Library

1975-04-01

S75-27289 (May 1975) --- An artist?s concept depicting the American Apollo spacecraft docked with a Soviet Soyuz spacecraft in Earth orbit. During the joint U.S.-USSR Apollo-Soyuz Test Project mission, scheduled for July 1975, the American and Soviet crews will visit one another?s spacecraft while the Soyuz and Apollo are docked for a maximum period of two days. The mission is designed to test equipment and techniques that will establish international crew rescue capability in space, as well as permit future cooperative scientific missions. Each nation has developed separately docking systems based on a mutually agreeable single set of interface design specifications. The major new U.S. program elements are the docking module and docking system necessary to achieve compatibility of rendezvous and docking systems with the USSR-developed hardware to be used on the Soyuz spacecraft. The DM and docking system together with an Apollo Command/Service Module will be launched by a Saturn 1B launch vehicle. This artwork is by Paul Fjeld.

Russian Docking Module is lowered

NASA Technical Reports Server (NTRS)

1995-01-01

The Russian-built Docking Module (DM) is lowered for installation into the payload bay of the Space Shuttle Orbiter Atlantis while the spaceplane is in Orbiter Processing Facility bay 2. The module will fly as a primary payload on the second Space Shuttle/Mir space station docking mission, STS-74, which is now scheduled for liftoff in the fall of 1995. During the mission, the module will first be attached with the orbiter's robot arm to the Orbiter Docking System (ODS) in the payload bay of the orbiter Atlantis and then be docked with the Mir. When Atlantis undocks from the Mir, it will leave the new docking module permanently attached to the space station for use during future Shuttle Mir docking missions. The new module will simplify future Shuttle linkups with Mir by improving orbiter clearances when it serves as a bridge between the two space vehicles. The white structures attached to the module's sides are solar panels that will be attached to the Mir after the conclusion of the STS-74 mission.

A cross docking pipeline for improving pose prediction and virtual screening performance

NASA Astrophysics Data System (ADS)

Kumar, Ashutosh; Zhang, Kam Y. J.

2018-01-01

Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.

A magnetic fluid seal for rotary blood pumps: effects of seal structure on long-term performance in liquid.

PubMed

Mitamura, Yoshinori; Takahashi, Sayaka; Amari, Shuichi; Okamoto, Eiji; Murabayashi, Shun; Nishimura, Ikuya

2011-03-01

A magnetic fluid (MF) seal enables mechanical contact-free rotation of the shaft and hence has excellent durability. The performance of an MF seal, however, has been reported to decrease in liquids. We developed an MF seal that has a "shield" mechanism, and a new MF with a higher magnetization of 47.9 kA/m. The sealing performance of the MF seal installed in a rotary blood pump was studied. Three types of MF seals were used. Seal A was a conventional seal without a shield. Seal B had the same structure as that of Seal A, but the seal was installed at 1 mm below liquid level. Seal C was a seal with a shield and the MF was set at 1 mm below liquid level. Seal A failed after 6 and 11 days. Seal B showed better results (20 and 73 days). Seal C showed long-term durability (217 and 275 days). The reason for different results in different seal structures was considered to be different flow conditions near the magnetic fluid. Fluid dynamics near the MF in the pump were analyzed using computational fluid dynamics (CFD) software. We have developed an MF seal with a shield that works in liquid for >275 days. The MF seal is promising as a shaft seal for rotary blood pumps.

CovalentDock Cloud: a web server for automated covalent docking.

PubMed

Ouyang, Xuchang; Zhou, Shuo; Ge, Zemei; Li, Runtao; Kwoh, Chee Keong

2013-07-01

Covalent binding is an important mechanism for many drugs to gain its function. We developed a computational algorithm to model this chemical event and extended it to a web server, the CovalentDock Cloud, to make it accessible directly online without any local installation and configuration. It provides a simple yet user-friendly web interface to perform covalent docking experiments and analysis online. The web server accepts the structures of both the ligand and the receptor uploaded by the user or retrieved from online databases with valid access id. It identifies the potential covalent binding patterns, carries out the covalent docking experiments and provides visualization of the result for user analysis. This web server is free and open to all users at http://docking.sce.ntu.edu.sg/.

Developing a cross-docking network design model under uncertain environment

NASA Astrophysics Data System (ADS)

Seyedhoseini, S. M.; Rashid, Reza; Teimoury, E.

2015-06-01

Cross-docking is a logistic concept, which plays an important role in supply chain management by decreasing inventory holding, order packing, transportation costs and delivery time. Paying attention to these concerns, and importance of the congestion in cross docks, we present a mixed-integer model to optimize the location and design of cross docks at the same time to minimize the total transportation and operating costs. The model combines queuing theory for design aspects, for that matter, we consider a network of cross docks and customers where two M/M/c queues have been represented to describe operations of indoor trucks and outdoor trucks in each cross dock. To prepare a perfect illustration for performance of the model, a real case also has been examined that indicated effectiveness of the proposed model.

CovalentDock Cloud: a web server for automated covalent docking

PubMed Central

Ouyang, Xuchang; Zhou, Shuo; Ge, Zemei; Li, Runtao; Kwoh, Chee Keong

2013-01-01

Covalent binding is an important mechanism for many drugs to gain its function. We developed a computational algorithm to model this chemical event and extended it to a web server, the CovalentDock Cloud, to make it accessible directly online without any local installation and configuration. It provides a simple yet user-friendly web interface to perform covalent docking experiments and analysis online. The web server accepts the structures of both the ligand and the receptor uploaded by the user or retrieved from online databases with valid access id. It identifies the potential covalent binding patterns, carries out the covalent docking experiments and provides visualization of the result for user analysis. This web server is free and open to all users at http://docking.sce.ntu.edu.sg/. PMID:23677616

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

PubMed

Duffy, Bryan C; Liu, Shuang; Martin, Gregory S; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F; Kharenko, Olesya A; Norek, Karen; Gesner, Emily M; Young, Peter R; McLure, Kevin G; Wagner, Gregory S; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K; Hansen, Henrik C; Kitchen, Douglas B

2015-07-15

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low μM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Cosmetic tail docking: an overview of abuse and report of an interesting case.

PubMed

Eyarefe, Oghenemega David; Oguntoye, Cecilia O

2016-02-29

This paper presents an overview of the global controversies surrounding cosmetic tail docking in puppies, some observed inconsistent practices among dog breeders and Veterinarians in West Africa, and the need for the African Veterinary Profession to take a decisive position on the cosmetic docking procedure. An interesting report of observed complications associated with cosmetic tail docking in a 3 week old male Boerboel is reported alongside the management of the ensuing complications. This paper highlights the still prevalent practice of cosmetic tail docking and seeks to enlighten clinicians towards stemming its abuse in Africa.

Binding site and affinity prediction of general anesthetics to protein targets using docking.

PubMed

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G

2012-05-01

The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explored whether a computational method, AutoDock, could serve as such a tool. High-resolution crystal data of water-soluble proteins (cytochrome C, apoferritin, and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus [GLIC]) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (http://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants were compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent cocrystallization data. Docking calculations for 6 general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known 50% effective concentration (EC(50)) values were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC(50) values and octanol/water partition coefficients for the 6 general anesthetics. All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (P = 0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site located in the extracellular domain of GLIC. The predicted affinities correlated significantly with the known EC(50) values for the 6 frequently used anesthetics in GLIC for the site identified in the experimental crystal data (P = 0.006). However, predicted affinities in apoferritin, human serum albumin, and cytochrome C did not correlate with these 6 anesthetics' known experimental EC(50) values. A weak correlation between the predicted affinities and the octanol/water partition coefficients was observed for the sites in GLIC. We demonstrated that anesthetic binding sites and relative affinities can be predicted using docking calculations in an automatic docking server (AutoDock) for both water-soluble and membrane proteins. Correlation of predicted affinity and EC(50) for 6 frequently used general anesthetics was only observed in GLIC, a member of a protein family relevant to anesthetic mechanism.

Continued Investigation of Leakage and Power Loss Test Results for Competing Turbine Engine Seals

NASA Technical Reports Server (NTRS)

Delgado, Irebert R.; Proctor, Margaret P.

2007-01-01

Seal leakage decreases with increasing surface speed due to reduced clearances from disk centrifugal growth. Annular and labyrinth seal leakage are 2-3 times greater than brush and finger seal leakage. Seal leakage rates increase with increasing temperature because of seal clearance growth due to different coefficients of thermal expansion between the seal and test disk. Seal power loss is not strongly affected by inlet temperature. Seal power loss increases with increasing surface speed, seal pressure differential, mass flow rate or flow factor, and radial clearance. The brush and finger seals had nearly the same power loss. Annular and labyrinth seal power loss were higher than finger or brush seal power loss. The brush seal power loss was the lowest and 15-30% lower than annular and labyrinth seal power loss.

Analyses of the dynamic docking test system for advanced mission docking system test programs. [Apollo Soyuz Test Project

NASA Technical Reports Server (NTRS)

Gates, R. M.; Williams, J. E.

1974-01-01

Results are given of analytical studies performed in support of the design, implementation, checkout and use of NASA's dynamic docking test system (DDTS). Included are analyses of simulator components, a list of detailed operational test procedures, a summary of simulator performance, and an analysis and comparison of docking dynamics and loads obtained by test and analysis.

NASA Docking System (NDS) Interface Definitions Document (IDD)

NASA Technical Reports Server (NTRS)

Tabakman, Alexander; England, Warren

2013-01-01

The contents of this document define the integrated performance and interface design for NASA Docking System (NDS) Block 1 and the International Docking Adapter. The intent of this IDD is to provide the interface design for using, installing, and interfacing to the NDS Block 1 that will enable successful docking to the IDA. This document is under the control of the ISS Development Projects Office (OG).

Recovery of spinning satellites

NASA Technical Reports Server (NTRS)

Coppey, J. M.; Mahaffey, W. R.

1977-01-01

The behavior of a space tug and a spinning satellite in a coupled configuration was simulated and analyzed. A docking concept was developed to investigate the requirements pertaining to the design of a docking interface. Sensing techniques and control requirements for the chase vehicle were studied to assess the feasibility of an automatic docking. The effects of nutation dampers and liquid propellant slosh motion upon the docking transient were investigated.

Turbine interstage seal with self-balancing capability

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

Mills, Jacob A; Jones, Russell B; Sexton, Thomas D

An interstage seal for a turbine of a gas turbine engine, the interstage seal having a seal carrier with an axial extending seal tooth movable with a stator of the engine, and a rotor with a seal surface that forms the interstage seal with the seal tooth, where a magnetic force produced by two magnets and a gas force produced by a gas pressure acting on the seal carrier forms a balancing force to maintain a close clearance of the seal without the seal tooth contacting the rotor seal surfaces during engine operation. In other embodiments, two pairs of magnetsmore » produce first and second magnetic forces that balance the seal in the engine.« less

Exploring the Stability of Ligand Binding Modes to Proteins by Molecular Dynamics Simulations: A Cross-docking Study.

PubMed

Liu, Kai; Kokubo, Hironori

2017-10-23

Docking has become an indispensable approach in drug discovery research to predict the binding mode of a ligand. One great challenge in docking is to efficiently refine the correct pose from various putative docking poses through scoring functions. We recently examined the stability of self-docking poses under molecular dynamics (MD) simulations and showed that equilibrium MD simulations have some capability to discriminate between correct and decoy poses. Here, we have extended our previous work to cross-docking studies for practical applications. Three target proteins (thrombin, heat shock protein 90-alpha, and cyclin-dependent kinase 2) of pharmaceutical interest were selected. Three comparable poses (one correct pose and two decoys) for each ligand were then selected from the docking poses. To obtain the docking poses for the three target proteins, we used three different protocols, namely: normal docking, induced fit docking (IFD), and IFD against the homology model. Finally, five parallel MD equilibrium runs were performed on each pose for the statistical analysis. The results showed that the correct poses were generally more stable than the decoy poses under MD. The discrimination capability of MD depends on the strategy. The safest way was to judge a pose as being stable if any one run among five parallel runs was stable under MD. In this case, 95% of the correct poses were retained under MD, and about 25-44% of the decoys could be excluded by the simulations for all cases. On the other hand, if we judge a pose as being stable when any two or three runs were stable, with the risk of incorrectly excluding some correct poses, approximately 31-53% or 39-56% of the two decoys could be excluded by MD, respectively. Our results suggest that simple equilibrium simulations can serve as an effective filter to exclude decoy poses that cannot be distinguished by docking scores from the computationally expensive free-energy calculations.

Effects of Compression, Staging, and Braid Angle on Braided Rope Seal Performance

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Adams, Michael L.

1997-01-01

Future turbine engines and industrial systems will be operating at increased temperatures to achieve more demanding efficiency and performance goals. In the highest temperature sections of the engine new material systems such as ceramics and intermetallics are being considered to withstand the harsh thermal environment. Components constructed of these low expansion-rate materials experience thermal strains and a resulting reduction of life when rigidly attached to high expansion-rate, superalloy support structures. Seals are being designed to both seal and to serve as compliant mounts allowing for relative thermal growths between high temperature but brittle primary structures and the surrounding support structures. Previous seal research yielded several braided rope seal designs which demonstrated the ability to both seal and serve as a compliant mount. The hybrid seal was constructed of an all-ceramic (alumina-silica) core overbraided with a superalloy wire sheath (cobalt based superalloy). The all ceramic seal was constructed of an all-ceramic (alumina-silica) core overbraided with multiple ceramic (alumina-silica) sheath layers. Program goals for braided rope seals are to improve flow resistance and/or seal resilience. To that end, the current report studies the test results of: baseline and modified hybrid seals; two stage hybrid and two stage all-ceramic seal configurations; and single stage hybrid and single stage all-ceramic seal configurations for a range of seal crush conditions. Hybrid seal modifications include increasing the sheath braid angle and core coverage. For the same percent seal cross-sectional crush, results show that increasing the hybrid seal braid angle increased seal stiffness and seal unit load, resulting in flows approximately one third of the baseline hybrid seal flows. For both hybrid and all-ceramic seals, two stage seal configurations significantly outperformed single stage configurations. Two stage seal flows were at least 30% less than the single stage seal flows for the same seal crush. Furthermore, test results of single stage seals indicate that for both all-ceramic and hybrid seals, a specific seal crush condition exists at which minimum flows are achieved (i.e. increasing seal crush beyond a certain point does not result in better flow performance). Flow results are presented for a range of pressures and temperatures from ambient to 1300 F, before and after scrubbing. Compression tests results show that for both all-ceramic and hybrid seals, seal preload and stiffness increase with seal crush, but residual seal interference remains constant.

GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

PubMed Central

Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

2016-01-01

Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300