Sample records for functional cargo block
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Dynamic Properties of the International Space Station throughout the Assembly Process
1998-06-29
with the launch of the Russian-built FGB, or Functional Cargo Block (most fitting translation) atop a Russian Proton rocket in June of 1998. Phase Two...experiments were conducted in areas of plant growth, life sciences, and microgravity science. But more importantly, Mir-Shuttle operations presented...Configuration Rationale/Comments 30Jun 1998 1 A/R Russian Proton • Functional Cargo Block (FGB) • FGB is a self-supporting active vehicle. • It provides
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EVA view of the Zenith (-ZA/FGB Plane III) side of the Functional Cargo Block (FGB).
1998-12-12
STS088-353-006 (4 -15 Dec. 1998) --- Astronaut James H. Newman, mission specialist, holds onto a handrail on Zarya while conducting a space walk at the top of the Unity-Zarya stack in the cargo bay of the Earth-orbiting Space Shuttle Endeavour. The open payload doors and part of the cargo bay, including the Ku-band antenna, are seen in upper left.
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Ando, David; Gopinathan, Ajay
2017-01-01
Nucleocytoplasmic transport is highly selective, efficient, and is regulated by a poorly understood mechanism involving hundreds of disordered FG nucleoporin proteins (FG nups) lining the inside wall of the nuclear pore complex (NPC). Previous research has concluded that FG nups in Baker’s yeast (S. cerevisiae) are present in a bimodal distribution, with the “Forest Model” classifying FG nups as either di-block polymer like “trees” or single-block polymer like “shrubs”. Using a combination of coarse-grained modeling and polymer brush modeling, the function of the di-block FG nups has previously been hypothesized in the Di-block Copolymer Brush Gate (DCBG) model to form a higher-order polymer brush architecture which can open and close to regulate transport across the NPC. In this manuscript we work to extend the original DCBG model by first performing coarse grained simulations of the single-block FG nups which confirm that they have a single block polymer structure rather than the di-block structure of tree nups. Our molecular simulations also demonstrate that these single-block FG nups are likely cohesive, compact, collapsed coil polymers, implying that these FG nups are generally localized to their grafting location within the NPC. We find that adding a layer of single-block FG nups to the DCBG model increases the range of cargo sizes which are able to translocate the pore through a cooperative effect involving single-block and di-block FG nups. This effect can explain the puzzling connection between single-block FG nup deletion mutants in S. cerevisiae and the resulting failure of certain large cargo transport through the NPC. Facilitation of large cargo transport via single-block and di-block FG nup cooperativity in the nuclear pore could provide a model mechanism for designing future biomimetic pores of greater applicability. PMID:28068389
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Xpo7 is a broad-spectrum exportin and a nuclear import receptor.
Aksu, Metin; Pleiner, Tino; Karaca, Samir; Kappert, Christin; Dehne, Heinz-Jürgen; Seibel, Katharina; Urlaub, Henning; Bohnsack, Markus T; Görlich, Dirk
2018-05-10
Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future. © 2018 Aksu et al.
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Wang, Cynthia X; Utech, Stefanie; Gopez, Jeffrey D; Mabesoone, Mathijs F J; Hawker, Craig J; Klinger, Daniel
2016-07-06
Well-defined microgel particles were prepared by combining coacervate-driven cross-linking of ionic triblock copolymers with the ability to control particle size and encapsulate functional cargos inherent in microfluidic devices. In this approach, the efficient assembly of PEO-based triblock copolymers with oppositely charged end-blocks allows for bioinspired cross-linking under mild conditions in dispersed aqueous droplets. This strategy enables the integration of charged cargos into the coacervate domains (e.g., the loading of anionic model compounds through electrostatic association with cationic end-blocks). Distinct release profiles can be realized by systematically varying the chemical nature of the payload and the microgel dimensions. This mild and noncovalent assembly method represents a promising new approach to tunable microgels as scaffolds for colloidal biomaterials in therapeutics and regenerative medicine.
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Strela boom, FGB, PMA3, U.S. Lab, and SSRMS as seen during Expedition 8 EVA operations
2004-02-26
ISS008-E-22399 (28 February 2004) --- This view, taken during Expedition 8 extravehicular activity (EVA), shows the Strela Cargo Boom at left; and the functional cargo block (FGB) or Zarya; Pressurized Mating Adapter (PMA-3); Destiny laboratory and Canadarm2, or Space Station Remote Manipulator System (SSRMS), at right, backdropped against Earths horizon and the blackness of space.
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Creamer uses communication equipment in the FGB during Expedition 22
2010-01-14
ISS022-E-025400 (14 Jan. 2010) --- NASA astronaut T.J. Creamer, Expedition 22 flight engineer, uses a communication system in the Zarya Functional Cargo Block (FGB) of the International Space Station.
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2010-05-18
ISS023-E-047527 (18 May 2010) --- In the grasp of the station?s robotic Canadarm2, the Russian-built Mini-Research Module 1 (MRM-1) is attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB) of the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia. Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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STS-88 Onboard Photograph - Unity and Zarya Modules
NASA Technical Reports Server (NTRS)
1998-01-01
This photograph, taken during the STS-88 mission, shows the cornected Unity Module or Node 1 and Zarya or the Functional Cargo Block (FGB) after having been released from the Orbiter Endeavour's cargo bay. The Unity (also called Node 1), the first U.S. Module for the International Space Station (ISS), is a six-sided connector to which all future U.S. Station modules will attach. It was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity Module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.
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2010-05-18
ISS023-E-047488 (18 May 2010) --- In the grasp of the station?s robotic Canadarm2, the Russian-built Mini-Research Module 1 (MRM-1) is moved to be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB) of the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia. Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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2010-05-18
ISS023-E-047462 (18 May 2010) --- In the grasp of the station?s robotic Canadarm2, the Russian-built Mini-Research Module 1 (MRM-1) is moved to be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB) of the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia. Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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2010-05-18
S132-E-008114 (18 May 2010) --- In the grasp of the Canadarm2, the Russian-built Mini-Research Module 1 (MRM-1) is transferred from space shuttle Atlantis’ payload bay to be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB) of the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia. Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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Ooi, Cher-Pheng; Smith, Terry K; Gluenz, Eva; Wand, Nadina Vasileva; Vaughan, Sue; Rudenko, Gloria
2018-06-01
The predominant secretory cargo of bloodstream form Trypanosoma brucei is variant surface glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of endoplasmic reticulum exit sites (ERES) in post-mitotic cells dropped from 3.9 ± 0.6 to 2.7 ± 0.1 eight hours after blocking VSG synthesis. The secretory pathway was still functional in these stalled cells, as monitored using Cathepsin L. Rates of phospholipid and glycosylphosphatidylinositol-anchor biosynthesis remained relatively unaffected, except for the level of sphingomyelin which increased. However, both endoplasmic reticulum and Golgi morphology became distorted, with the Golgi cisternae becoming significantly dilated, particularly at the trans-face. Membrane accumulation in these structures is possibly caused by reduced budding of nascent vesicles due to the drastic reduction in the total amount of secretory cargo, that is, VSG. These data argue that the total flux of secretory cargo impacts upon the biogenesis and maintenance of secretory structures and organelles in T. brucei, including the ERES and Golgi. © 2018 The Authors. Traffic published by John Wiley & Sons Ltd.
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Helms in FGB/Zarya with cameras
2001-06-08
ISS002-E-6526 (8 June 2001) --- Astronaut Susan J. Helms, Expedition Two flight engineer, mounts a video camera onto a bracket in the Zarya or Functional Cargo Block (FGB) of the International Space Station (ISS). The image was recorded with a digital still camera.
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29 CFR 1918.84 - Bulling cargo.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo... from padeyes, straps, or beam clamps. Snatch blocks or straps shall not be made fast to batten cleats...
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External view of Zarya and Zvezda taken during the STS-106 mission
2000-09-11
S106-E-5116 (11 September 2000) --- This view of the International Space Station (ISS) was taken while it was docked with the Space Shuttle Atlantis and shows parts of all but one of the current components. From the top are the Progress supply vehicle, the Zvezda service module, and the Zarya functional cargo block (FGB). The Unity, now linked to the docking system of the Atlantis in the cargo bay, is out of view at bottom. A multicolored layer signals a sunset or sunrise on Earth at bottom left.
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External Survey from Windows in Mini-Research Modules and Pirs Docking Compartment
2013-04-03
Survey view of a portion of the Zarya Functional Cargo Block (FGB) taken through a window in the Russian segment of the ISS during Expedition 35. Portions of the S0 and Z1 Truss segments are also in view.
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Burbank exits the MRM1 hatch area into the FGB Transfer Compartment
2012-01-27
ISS030-E-050953 (27 Jan. 2012) --- NASA astronaut Dan Burbank, Expedition 30 commander, is pictured in a hatch as he exits the Rassvet Mini-Research Module 1 (MRM-1) into the Zarya Functional Cargo Block (FGB) transfer compartment of the International Space Station.
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Reiter during maintenance tasks in the FGB
2006-08-10
ISS013-E-65721 (10 Aug. 2006) --- European Space Agency (ESA) astronaut Thomas Reiter, Expedition 13 flight engineer, replaces the number two replaceable pump panel (SPN) in the number one loop (VGK1) of the International Space Station's Zarya functional cargo block (FGB) thermal control system with a new spare from stowage.
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Pettit uses a Grab Sample Container in the FGB during Expedition Six
2003-01-22
ISS006-E-20835 (22 January 2003) --- Astronaut Donald R. Pettit, Expedition 6 NASA ISS science officer, holds a Grab Sample Container (GSC) in the functional cargo block (FGB), or Zarya, on the International Space Station (ISS). GSC is used for collecting air samples as part of ISS environmental monitoring.
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NASA Technical Reports Server (NTRS)
1998-01-01
Designed by the STS-88 crew members, this patch commemorates the first assembly flight to carry United States-built hardware for constructing the International Space Station (ISS). This flight's primary task was to assemble the cornerstone of the Space Station: the Node with the Functional Cargo Block (FGB). The rising sun symbolizes the dawning of a new era of international cooperation in space and the beginning of a new program: the International Space Station. The Earth scene outlines the countries of the Station Partners: the United States, Russia, those of the European Space Agency (ESA), Japan, and Canada. Along with the Pressurized Mating Adapters (PMA) and the Functional Cargo Block, the Node is shown in the final mated configuration while berthed to the Space Shuttle during the STS-88/2A mission. The Big Dipper Constellation points the way to the North Star, a guiding light for pioneers and explorers for generations. In the words of the crew, These stars symbolize the efforts of everyone, including all the countries involved in the design and construction of the International Space Station, guiding us into the future.
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International Space Station (ISS)
1998-11-08
Designed by the STS-88 crew members, this patch commemorates the first assembly flight to carry United States-built hardware for constructing the International Space Station (ISS). This flight's primary task was to assemble the cornerstone of the Space Station: the Node with the Functional Cargo Block (FGB). The rising sun symbolizes the dawning of a new era of international cooperation in space and the beginning of a new program: the International Space Station. The Earth scene outlines the countries of the Station Partners: the United States, Russia, those of the European Space Agency (ESA), Japan, and Canada. Along with the Pressurized Mating Adapters (PMA) and the Functional Cargo Block, the Node is shown in the final mated configuration while berthed to the Space Shuttle during the STS-88/2A mission. The Big Dipper Constellation points the way to the North Star, a guiding light for pioneers and explorers for generations. In the words of the crew, These stars symbolize the efforts of everyone, including all the countries involved in the design and construction of the International Space Station, guiding us into the future.
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International Space Station (ISS)
2000-12-01
This image of the International Space Station in orbit was taken from the Space Shuttle Endeavour prior to docking. Most of the Station's components are clearly visible in this photograph. They are the Node 1 or Unity Module docked with the Functional Cargo Block or Zarya (top) that is linked to the Zvezda Service Module. The Soyuz spacecraft is at the bottom.
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International Space Station (ISS)
2000-09-01
This image of the International Space Station (ISS) was taken during the STS-106 mission. The ISS component nearest the camera is the U.S. built Node 1 or Unity module, which cornected with the Russian built Functional Cargo Block (FGB) or Zarya. The FGB was linked with the Service Module or Zvezda. On the far end is the Russian Progress supply ship.
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Active colloids as mobile microelectrodes for unified label-free selective cargo transport.
Boymelgreen, Alicia M; Balli, Tov; Miloh, Touvia; Yossifon, Gilad
2018-02-22
Utilization of active colloids to transport both biological and inorganic cargo has been widely examined in the context of applications ranging from targeted drug delivery to sample analysis. In general, carriers are customized to load one specific target via a mechanism distinct from that driving the transport. Here we unify these tasks and extend loading capabilities to include on-demand selection of multiple nano/micro-sized targets without the need for pre-labelling or surface functionalization. An externally applied electric field is singularly used to drive the active cargo carrier and transform it into a mobile floating electrode that can attract (trap) or repel specific targets from its surface by dielectrophoresis, enabling dynamic control of target selection, loading and rate of transport via the electric field parameters. In the future, dynamic selectivity could be combined with directed motion to develop building blocks for bottom-up fabrication in applications such as additive manufacturing and soft robotics.
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Yu, Ziyi; Zheng, Yu; Parker, Richard M; Lan, Yang; Wu, Yuchao; Coulston, Roger J; Zhang, Jing; Scherman, Oren A; Abell, Chris
2016-04-06
Bottom-up hierarchical assembly has emerged as an elaborate and energy-efficient strategy for the fabrication of smart materials. Herein, we present a hierarchical assembly process, whereby linear amphiphilic block copolymers are self-assembled into micelles, which in turn are accommodated at the interface of microfluidic droplets via cucurbit[8]uril-mediated host-guest chemistry to form supramolecular microcapsules. The monodisperse microcapsules can be used for simultaneous carriage of both organic (Nile Red) and aqueous-soluble (fluorescein isothiocyanate-dextran) cargo. Furthermore, the well-defined compartmentalized structure benefits from the dynamic nature of the supramolecular interaction and offers synergistic delivery of cargos with triggered release or through photocontrolled porosity. This demonstration of premeditated hierarchical assembly, where interactions from the molecular to microscale are designed, illustrates the power of this route toward accessing the next generation of functional materials and encapsulation strategies.
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International Space Station (ISS)
2001-06-08
Astronaut Susan J. Helms, Expedition Two flight engineer, mounts a video camera onto a bracket in the Russian Zarya or Functional Cargo Block (FGB) of the International Space Station (ISS). Launched by a Russian Proton rocket from the Baikonu Cosmodrome on November 20, 1998, the Unites States-funded and Russian-built Zarya was the first element of the ISS, followed by the U.S. Unity Node.
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EVA view of the Zenith (-ZA/FGB Plane III) side of the Functional Cargo Block (FGB).
1998-12-12
STS088-353-008 (4-15 Dec. 1998) --- Astronaut James H. Newman, mission specialist, translates along a hand rail on the Russian-built Zarya Module in this Extravehicular Activity (EVA) photograph taken by astronaut Jerry L. Ross, mission specialist. Ross and Newman shared three space walks altogether to perform cable connection tasks and to put finishing touches on the exteriors of the recently-joined Zarya and the United States-built Unity (Node 1) modules. Unity is partially visible beneath Zarya, as is most of the cargo bay of the Space Shuttle Endeavour. The Canadian-built Remote Manipulator System (RMS) arm is partially visible, also.
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2010-05-14
STS132-S-006 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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2010-05-14
STS132-S-009 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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2010-05-14
STS132-S-008 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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2010-05-14
STS132-S-007 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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NASA Technical Reports Server (NTRS)
Jenkins, George
1986-01-01
Prelaunch, launch, mission, and landing distribution of RF and hardline uplink/downlink information between Space Shuttle Orbiter/cargo elements, tracking antennas, and control centers at JSC, KSC, MSFC, GSFC, ESMC/RCC, and Sunnyvale are presented as functional block diagrams. Typical mismatch problems encountered during spacecraft-to-project control center telemetry transmissions are listed along with new items for future support enhancement.
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MS Lonchakov and MS Phillips work with an IMAX film magazine bag in Zarya
2001-04-23
S100-E-5345 (23 April 2001) --- Cosmonaut Yuri V. Lonchakov, STS-100 mission specialist representing Rosaviakosmos, changes out a film magazine on an IMAX camera in the Functional Cargo Block (FGB) or Zarya aboard the International Space Station (ISS). Astronaut John L. Phillips, mission specialist, is in the background. The scene was recorded with a digital still camera.
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NASA Astrophysics Data System (ADS)
Jenkins, George
Prelaunch, launch, mission, and landing distribution of RF and hardline uplink/downlink information between Space Shuttle Orbiter/cargo elements, tracking antennas, and control centers at JSC, KSC, MSFC, GSFC, ESMC/RCC, and Sunnyvale are presented as functional block diagrams. Typical mismatch problems encountered during spacecraft-to-project control center telemetry transmissions are listed along with new items for future support enhancement.
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International Space Station (ISS)
2000-09-01
This image of the International Space Station (ISS) was taken when Space Shuttle Atlantis (STS-106 mission) approached the ISS for docking. At the top is the Russian Progress supply ship that is linked with the Russian built Service Module or Zvezda. The Zvezda is cornected with the Russian built Functional Cargo Block (FGB) or Zarya. The U.S. built Node 1 or Unity module is seen at the bottom.
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-08-06
...., Malta) (vessel) [CUBA]. 3. ALAMINOS (f.k.a. RUBY ISLANDS) (P32C3) General Cargo 15,088DWT 8,909GRT Cyprus flag (Alaminos Shipping Co. Ltd.) (vessel) [CUBA]. 4. CARIBBEAN PRINCESS (C4GL) General Cargo 24... (C4JO) General Cargo 24,106DWT 16,794GRT Cyprus flag (CARIBBEAN QUEEN SHIPPING (SDN)) (vessel) [CUBA]. 6...
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2010-05-18
ISS023-E-047431 (18 May 2010) --- Intersecting the thin line of Earth's atmosphere, the docked space shuttle Atlantis is featured in this image photographed by an Expedition 23 crew member on the International Space Station. The Russian-built Mini-Research Module 1 (MRM-1) is visible in the payload bay as the shuttle robotic arm prepares to unberth the module from Atlantis and position it for handoff to the station robotic arm. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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Astronaut Susan J. Helms Mounts a Videao Camera in Zarya
NASA Technical Reports Server (NTRS)
2001-01-01
Astronaut Susan J. Helms, Expedition Two flight engineer, mounts a video camera onto a bracket in the Russian Zarya or Functional Cargo Block (FGB) of the International Space Station (ISS). Launched by a Russian Proton rocket from the Baikonu Cosmodrome on November 20, 1998, the Unites States-funded and Russian-built Zarya was the first element of the ISS, followed by the U.S. Unity Node.
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Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport
Guichard, Annabel; Jain, Prashant; Moayeri, Mahtab; Cruz-Moreno, Beatriz; Leppla, Stephen H.; Nizet, Victor
2017-01-01
Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies. PMID:28945820
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Anthrax edema toxin disrupts distinct steps in Rab11-dependent junctional transport.
Guichard, Annabel; Jain, Prashant; Moayeri, Mahtab; Schwartz, Ruth; Chin, Stephen; Zhu, Lin; Cruz-Moreno, Beatriz; Liu, Janet Z; Aguilar, Bernice; Hollands, Andrew; Leppla, Stephen H; Nizet, Victor; Bier, Ethan
2017-09-01
Various bacterial toxins circumvent host defenses through overproduction of cAMP. In a previous study, we showed that edema factor (EF), an adenylate cyclase from Bacillus anthracis, disrupts endocytic recycling mediated by the small GTPase Rab11. As a result, cargo proteins such as cadherins fail to reach inter-cellular junctions. In the present study, we provide further mechanistic dissection of Rab11 inhibition by EF using a combination of Drosophila and mammalian systems. EF blocks Rab11 trafficking after the GTP-loading step, preventing a constitutively active form of Rab11 from delivering cargo vesicles to the plasma membrane. Both of the primary cAMP effector pathways -PKA and Epac/Rap1- contribute to inhibition of Rab11-mediated trafficking, but act at distinct steps of the delivery process. PKA acts early, preventing Rab11 from associating with its effectors Rip11 and Sec15. In contrast, Epac functions subsequently via the small GTPase Rap1 to block fusion of recycling endosomes with the plasma membrane, and appears to be the primary effector of EF toxicity in this process. Similarly, experiments conducted in mammalian systems reveal that Epac, but not PKA, mediates the activity of EF both in cell culture and in vivo. The small GTPase Arf6, which initiates endocytic retrieval of cell adhesion components, also contributes to junctional homeostasis by counteracting Rab11-dependent delivery of cargo proteins at sites of cell-cell contact. These studies have potentially significant practical implications, since chemical inhibition of either Arf6 or Epac blocks the effect of EF in cell culture and in vivo, opening new potential therapeutic avenues for treating symptoms caused by cAMP-inducing toxins or related barrier-disrupting pathologies.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-074 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-080 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-076 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-072 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-075 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-077 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-081 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-073 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-078 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-079 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-071 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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Cheng, Yilong; Sellers, Drew L; Tan, James-Kevin Y; Peeler, David J; Horner, Philip J; Pun, Suzie H
2017-05-01
Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)-b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery. Copyright © 2017 Elsevier Ltd. All rights reserved.
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1997-07-26
International Space Station (ISS) contractors erect access scaffolding around the Pressurized Mating Adapter-1 (PMA-1) for the ISS in KSC’s Space Station Processing Facility. A PMA is a cone-shaped connector that will be attached to Node 1, the space station’s structural building block, during ground processing. The white flight cables around PMA-1 will assist in connecting the node to the U.S.-financed, Russian-built Functional Cargo Block, a component that supplies early power and propulsion systems for the station. Node 1 with two adapters attached will be the first element of the station to be launched aboard the Space Shuttle Endeavour on STS-88 in July 1998
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1997-07-26
The first of two Pressurized Mating Adapters, or PMAs, for the International Space Station arrive in KSC’s Space Station Processing Facility in July. A PMA is a cone-shaped connector that will be attached to Node 1, the space station’s structural building block, during ground processing. The adapter will house space station computers and various electrical support equipment and eventually will serve as the passageway for astronauts between the node and the U.S-financed, Russian-built Functional Cargo Block. Node 1 with two adapters attached will be the first element of the station to be launched aboard the Space Shuttle Endeavour on STS-88 in July 1998
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1997-07-26
The first of two Pressurized Mating Adapters, or PMAs, for the International Space Station arrive in KSC’s Space Station Processing Facility in July. A PMA is a cone-shaped connector that will be attached to Node 1, the space station’s structural building block, during ground processing. The adapter will house space station computers and various electrical support equipment and eventually will serve as the passageway for astronauts between the node and the U.S-financed, Russian-built Functional Cargo Block. Node 1 with two adapters attached will be the first element of the station to be launched aboard the Space Shuttle Endeavour on STS-88 in July 1998
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1997-07-26
International Space Station (ISS) contractors erect access scaffolding around the Pressurized Mating Adapter-1 (PMA-1) for the ISS in KSC’s Space Station Processing Facility. A PMA is a cone-shaped connector that will be attached to Node 1, the space station’s structural building block, during ground processing. The white flight cables around PMA-1 will assist in connecting the node to the U.S.-financed, Russian-built Functional Cargo Block, a component that supplies early power and propulsion systems for the station. Node 1 with two adapters attached will be the first element of the station to be launched aboard the Space Shuttle Endeavour on STS-88 in July 1998
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Investigating Block-Copolymer Micelle Dynamics for Tunable Cargo Delivery
NASA Astrophysics Data System (ADS)
Li, Xiuli; Kidd, Bryce; Cooksey, Tyler; Robertson, Megan; Madsen, Louis
Block-copolymer micelles (BCPMs) can carry molecular cargo in a nanoscopic package that is tunable using polymer structure in combination with cargo properties, as well as with external stimuli such as temperature or pH. For example, BCPMs can be used in targeted anticancer drug delivery due to their biocompatibility, in vivo degradability and prolonged circulation time. We are using NMR spectroscopy and diffusometry as well as SANS to investigate BCPMs. Here we study a diblock poly(ethylene oxide)-b-(caprolactone) (PEO-PCL) that forms spherical micelles at 1% (w/v) in the mixed solvent D2O/THF-d8. We quantify the populations and diffusion coefficients of coexisting micelles and free unimers over a range of temperatures and solvent compositions. We use temperature as a stimulus to enhance unimer exchange and hence trigger cargo release, in some cases at a few degrees above body temperature. We present evidence for dominance of the insertion-expulsion mechanism of unimer exchange in these systems, and we map phase diagrams versus temperature and solvent composition. This study sheds light on how intermolecular interactions fundamentally affect cargo release, unimer exchange, and overall micelle tunability.
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Padalka holds packages of food unloaded from the Progress 15P vehicle during Expedition 9
2004-08-15
ISS009-E-18558 (15 August 2004) --- Cosmonaut Gennady I. Padalka, Expedition 9 commander representing Russia's Federal Space Agency, holds packages of food, as two apples float freely near him, in the Unity node of the International Space Station (ISS). The food was recently unloaded from the Progress 15 supply vehicle docked to the Station. The functional cargo block (FGB) or Zarya hatchway is visible in the background.
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Stowage bags in FGB/Zarya module
2005-07-31
S114-E-5945 (31 July 2005) --- This scene in Zarya, the functional cargo block for the International Space Station, serves witness to the primary current emphasis onboard the orbital outpost. Transfers of additional water and supplies to the International Space Station continues on this Sunday as the crew aboard Space Shuttle Discovery begins Flight Day 6. Cosmonaut Sergei Krikalev of Russia's Federal Space Agency can be seen at the far end of the cluttered hallway.
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2010-05-18
ISS023-E-046806 (18 May 2010) --- Backdropped by Earth?s horizon and the blackness of space, the docked space shuttle Atlantis is featured in this image photographed by an Expedition 23 crew member on the International Space Station. The Russian-built Mini-Research Module 1 (MRM-1) is visible in the payload bay as the shuttle robotic arm prepares to unberth the module from Atlantis and position it for handoff to the station robotic arm (visible at right). Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station.
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Klayman, Lauren M; Wedegaertner, Philip B
2017-02-03
Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
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Klayman, Lauren M.; Wedegaertner, Philip B.
2017-01-01
Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. PMID:27994056
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2010-05-14
STS132-S-005 (14 May 2010) --- Witnessed by news media representatives and STS-132 Tweet-up participants on hand by the countdown clock at the Press Site, Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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2010-05-14
STS132-S-011 (14 May 2010) --- Witnessed by news media representatives and STS-132 Tweet-up participants on hand by the countdown clock at the Press Site, Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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STS-132 Space Shuttle Atlantis Launch
2010-05-14
STS132-S-015 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Jack Pfaller
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STS-132 Space Shuttle Atlantis Launch
2010-05-14
STS132-S-016 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Jack Pfaller
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2010-05-14
STS132-S-010 (14 May 2010) --- Witnessed by news media representatives and STS-132 Tweet-up participants on hand by the countdown clock at the Press Site, Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis.
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STS-132 Space Shuttle Atlantis Launch
2010-05-14
STS132-S-017 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Jack Pfaller
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Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin
Ganguly, Archan; Han, Xuemei; Das, Utpal; Caillol, Ghislaine
2017-01-01
Soluble cytosolic proteins vital to axonal and presynaptic function are synthesized in the neuronal soma and conveyed via slow axonal transport. Our previous studies suggest that the overall slow transport of synapsin is mediated by dynamic assembly/disassembly of cargo complexes followed by short-range vectorial transit (the “dynamic recruitment” model). However, neither the composition of these complexes nor the mechanistic basis for the dynamic behavior is understood. In this study, we first examined putative cargo complexes associated with synapsin using coimmunoprecipitation and multidimensional protein identification technology mass spectrometry (MS). MS data indicate that synapsin is part of a multiprotein complex enriched in chaperones/cochaperones including Hsc70. Axonal synapsin–Hsc70 coclusters are also visualized by two-color superresolution microscopy. Inhibition of Hsc70 ATPase activity blocked the slow transport of synapsin, disrupted axonal synapsin organization, and attenuated Hsc70–synapsin associations, advocating a model where Hsc70 activity dynamically clusters cytosolic proteins into cargo complexes, allowing transport. Collectively, our study offers insight into the molecular organization of cytosolic transport complexes and identifies a novel regulator of slow transport. PMID:28559423
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Kin5 Knockdown in Tetrahymena thermophila Using RNAi Blocks Cargo Transport of Gef1
Awan, Aashir; Bell, Aaron J.; Satir, Peter
2009-01-01
A critical process that builds and maintains the eukaryotic cilium is intraflagellar transport (IFT). This process utilizes members of the kinesin-2 superfamily to transport cargo into the cilium (anterograde transport) and a dynein motor for the retrograde traffic. Using a novel RNAi knockdown method, we have analyzed the function of the homodimeric IFT kinesin-2, Kin5, in Tetrahymena ciliary transport. In RNAi transformants, Kin5 was severely downregulated and disappeared from the cilia, but cilia did not resorb, although tip structure was affected. After deciliation of the knockdown cell, cilia regrew and cells swam, which suggested that Kin5 is not responsible for the trafficking of axonemal precursors to build the cilium, but could be transporting molecules that act in ciliary signal transduction, such as guanine nucleotide exchange proteins (GEFs). Gef1 is a Tetrahymena ciliary protein, and current coimmunoprecipitation and immunofluorescence studies showed that it is absent in regrowing cilia of the knockdown cells lacking ciliary Kin5. We suggest that one important cargo of Kin5 is Gef1 and knockdown of Kin5 results in cell lethality. PMID:19290045
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Lee, Seongju; Chang, Jaerak; Blackstone, Craig
2016-01-01
The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27–retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27–retromer–WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi. PMID:26956659
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Lee, Seongju; Chang, Jaerak; Blackstone, Craig
2016-03-09
The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27-retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27-retromer-WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi.
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Expedition 26 Crewmembers pose with European Matroshka-R Phantom Experiment
2011-03-11
ISS026-E-033131 (11 March 2011) --- Russian cosmonauts Alexander Kaleri (left foreground), Oleg Skripochka (right foreground), Dmitry Kondratyev (left background) and European Space Agency astronaut Paolo Nespoli, all Expedition 26 flight engineers, pose for a photo with the European Matroshka-R Phantom experiment in the Zarya Functional Cargo Block (FGB) of the International Space Station. Matroshka, the name for the traditional Russian set of nestling dolls, is an antroph-amorphous model of a human torso designed for radiation studies.
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-035 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-051 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-053 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-061 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-036 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Visitors during STS-132 Space Shuttle Atlantis Launch
2010-05-14
STS132-S-013 (14 May 2010) --- As visitors watch, the space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Ben Cooper
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-060 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-039 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-040 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-056 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-044 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-063 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-062 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-050 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-064 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-058 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-052 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-038 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-042 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-055 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-065 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Visitors during STS-132 Space Shuttle Atlantis Launch
2010-05-14
STS132-S-014 (14 May 2010) --- With visitors looking on, the space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Ben Cooper
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-037 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-057 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-059 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-033 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell..
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-066 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-054 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-067 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo Credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-047 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-030 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-048 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-045 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-041 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-049 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-043 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-068 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-034 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-069 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Rusty Backer and Michael Gayle
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-046 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Tony Gray and Tom Farrar
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Launch of Space Shuttle Atlantis STS-132
2010-05-14
STS132-S-031 (14 May 2010) --- Space shuttle Atlantis and its six-member STS-132 crew head toward Earth orbit and rendezvous with the International Space Station. Liftoff was at 2:20 p.m. (EDT) on May 14, 2010, from launch pad 39A at NASA's Kennedy Space Center. Onboard are NASA astronauts Ken Ham, commander; Tony Antonelli, pilot; Garrett Reisman, Michael Good, Steve Bowen and Piers Sellers, all mission specialists. The crew will deliver the Russian-built Mini-Research Module 1 (MRM-1) to the International Space Station. Named Rassvet, Russian for "dawn," the module is the second in a series of new pressurized components for Russia and will be permanently attached to the Earth-facing port of the Zarya Functional Cargo Block (FGB). Rassvet will be used for cargo storage and will provide an additional docking port to the station. Also aboard Atlantis is an Integrated Cargo Carrier, or ICC, an unpressurized flat bed pallet and keel yoke assembly used to support the transfer of exterior cargo from the shuttle to the station. STS-132 is the 34th mission to the station and the last scheduled flight for Atlantis. For more information on the STS-132 mission objectives, payload and crew, visit www.nasa.gov/mission_pages/shuttle/shuttlemissions/sts132/index.html. Photo credit: NASA/Sandra Joseph and Kevin O'Connell
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1998-09-01
STS088-S-001 (September 1998) --- Designed by the crew members, this STS-88 patch commemorates the first assembly flight to carry United States-built hardware for constructing the International Space Station (ISS). This flight's primary task is to assemble the cornerstone of the space station: the Node with the Functional Cargo Block (FGB). The rising sun symbolizes the dawning of a new era of international cooperation in space and the beginning of a new program: the International Space Station. The Earth scene outlines the countries of the Station Partners: the United States, Russia, those of the European Space Agency (ESA), Japan, and Canada. Along with the Pressurized Mating Adapters (PMA) and the Functional Cargo Block, the Node is shown in the final mated configuration while berthed to the space shuttle during the STS-88/2A mission. The Big Dipper Constellation points the way to the North Star, a guiding light for pioneers and explorers for generations. In the words of the crew, "These stars symbolize the efforts of everyone, including all the countries involved in the design and construction of the International Space Station, guiding us into the future." The NASA insignia design for space shuttle flights is reserved for use by the astronauts and for other official use as the NASA Administrator may authorize. Public availability has been approved only in the forms of illustrations by the various news media. When and if there is any change in this policy, which is not anticipated, the change will be publicly announced. Photo credit: NASA
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Thubagere, Anupama J; Li, Wei; Johnson, Robert F; Chen, Zibo; Doroudi, Shayan; Lee, Yae Lim; Izatt, Gregory; Wittman, Sarah; Srinivas, Niranjan; Woods, Damien; Winfree, Erik; Qian, Lulu
2017-09-15
Two critical challenges in the design and synthesis of molecular robots are modularity and algorithm simplicity. We demonstrate three modular building blocks for a DNA robot that performs cargo sorting at the molecular level. A simple algorithm encoding recognition between cargos and their destinations allows for a simple robot design: a single-stranded DNA with one leg and two foot domains for walking, and one arm and one hand domain for picking up and dropping off cargos. The robot explores a two-dimensional testing ground on the surface of DNA origami, picks up multiple cargos of two types that are initially at unordered locations, and delivers them to specified destinations until all molecules are sorted into two distinct piles. The robot is designed to perform a random walk without any energy supply. Exploiting this feature, a single robot can repeatedly sort multiple cargos. Localization on DNA origami allows for distinct cargo-sorting tasks to take place simultaneously in one test tube or for multiple robots to collectively perform the same task. Copyright © 2017, American Association for the Advancement of Science.
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Zhao, Junwei; He, Zhaoshuai; Li, Biao; Cheng, Tanyu; Liu, Guohua
2017-04-01
Recently, the controlled drug delivery system has become a potential platform for biomedical application. Herein, we developed a pH and light-dual controlled cargo release system exhibiting AND logic based on MCM-41 mesoporous silica nanoparticles, which was surface modified using β-cyclodextrin (β-CD) with imine bond and azobenzene derivative. The complex of β-CD and azobenzene derivative effectively blocked the cargo delivery in pH=7.0 phosphate buffered saline (PBS) solution without 365nm UV light irradiation. The cargo was fully released when both factors of acidic environment (pH=5.0 PBS) and 365nm UV light irradiation were satisfied, meanwhile only very little cargo was delivered if one factor was satisfied. The result also demonstrates that the opening/closing of the gate and the release of the cargo in small portions can be controlled. Copyright © 2016 Elsevier B.V. All rights reserved.
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Job Grading Standard for Blocker and Bracer WG-4602.
ERIC Educational Resources Information Center
Civil Service Commission, Washington, DC. Bureau of Policies and Standards.
The standard is used to grade nonsupervisor's work involved in blocking, bracing, staying, and securing cargo for shipment by land, sea, or air. It requires skill in constructing, placing, and installing wooden blocks, wedges, bracing structures and other staying devices, as well as skill in securing items using wires, ropes, chains, cables,…
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Hierarchically assembled theranostic nanostructures for siRNA delivery and imaging applications.
Shrestha, Ritu; Elsabahy, Mahmoud; Luehmann, Hannah; Samarajeewa, Sandani; Florez-Malaver, Stephanie; Lee, Nam S; Welch, Michael J; Liu, Yongjian; Wooley, Karen L
2012-10-24
Dual functional hierarchically assembled nanostructures, with two unique functions of carrying therapeutic cargo electrostatically and maintaining radiolabeled imaging agents covalently within separate component building blocks, have been developed via the supramolecular assembly of several spherical cationic shell cross-linked nanoparticles clustered around a central anionic shell cross-linked cylinder. The shells of the cationic nanoparticles and the hydrophobic core domain of the anionic central cylindrical nanostructure of the assemblies were utilized to complex negatively charged nucleic acids (siRNA) and to undergo radiolabeling, respectively, for potential theranostic applications. The assemblies exhibited exceptional cell transfection and radiolabeling efficiencies, providing an overall advantage over the individual components, which could each facilitate only one or the other of the functions.
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Eggenberger, Kai; Mink, Christian; Wadhwani, Parvesh; Ulrich, Anne S; Nick, Peter
2011-01-03
The delivery of externally applied macromolecules or nanoparticles into living cells still represents a critically limiting step before the full capabilities of chemical engineering can be explored. Molecular transporters such as cell-penetrating peptides, peptoids, and other mimetics can be used to carry cargo across the cellular membrane, but it is still difficult to find suitable sequences that operate efficiently for any particular type of cell. Here we report that BP100 (KKLFKKILKYL-amide), originally designed as an antimicrobial peptide against plant pathogens, can be employed as a fast and efficient cell-penetrating agent to transport fluorescent test cargoes into the cytosol of walled plant cells. The uptake of BP100 proceeds slightly more slowly than the endocytosis of fluorescent dextranes, but BP100 accumulates more efficiently and to much higher levels (by an order of magnitude). The entry of BP100 can be efficiently blocked by latrunculin B; this suggests that actin filaments are essential to the uptake mechanism. To test whether this novel transporter can also be used to deliver functional cargoes, we designed a fusion construct of BP100 with the actin-binding Lifeact peptide (MGVADLIKKFESISKEE). We demonstrated that the short BP100 could transport the attached 17-residue sequence quickly and efficiently into tobacco cells. The Lifeact construct retained its functionality as it successfully labeled the actin bundles that tether the nucleus in the cell center.
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Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm
NASA Astrophysics Data System (ADS)
Kassem, Salma; Lee, Alan T. L.; Leigh, David A.; Markevicius, Augustinas; Solà, Jordi
2016-02-01
Modern-day factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. The idea of manipulating molecular fragments in a similar way has to date only been explored using biological building blocks (specifically DNA). Here, we report on a wholly artificial small-molecule robotic arm capable of selectively transporting a molecular cargo in either direction between two spatially distinct, chemically similar, sites on a molecular platform. The arm picks up/releases a 3-mercaptopropanehydrazide cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry controls the cargo binding to the platform. Transport is controlled by selectively inducing conformational and configurational changes within an embedded hydrazone rotary switch that steers the robotic arm. In a three-stage operation, 79-85% of 3-mercaptopropanehydrazide molecules are transported in either (chosen) direction between the two platform sites, without the cargo at any time fully dissociating from the machine nor exchanging with other molecules in the bulk.
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Pick-up, transport and release of a molecular cargo using a small-molecule robotic arm.
Kassem, Salma; Lee, Alan T L; Leigh, David A; Markevicius, Augustinas; Solà, Jordi
2016-02-01
Modern-day factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. The idea of manipulating molecular fragments in a similar way has to date only been explored using biological building blocks (specifically DNA). Here, we report on a wholly artificial small-molecule robotic arm capable of selectively transporting a molecular cargo in either direction between two spatially distinct, chemically similar, sites on a molecular platform. The arm picks up/releases a 3-mercaptopropanehydrazide cargo by formation/breakage of a disulfide bond, while dynamic hydrazone chemistry controls the cargo binding to the platform. Transport is controlled by selectively inducing conformational and configurational changes within an embedded hydrazone rotary switch that steers the robotic arm. In a three-stage operation, 79-85% of 3-mercaptopropanehydrazide molecules are transported in either (chosen) direction between the two platform sites, without the cargo at any time fully dissociating from the machine nor exchanging with other molecules in the bulk.
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Art concept of STS-88 RMS capture of the FGB
1998-06-23
S98-09020 (21 July 1997) --- The Space Shuttle Endeavour prepares to capture the Functional Cargo Block (FGB) using the shuttle's mechanical arm in this artist's depiction of the first Space Shuttle assembly flight for the International Space Station (ISS), mission STS-88 scheduled to launch in July 1998. The shuttle will carry the first United States-built component for the station, a connecting module called Node 1, and attach it to the already orbiting FGB, which supplies early electrical power and propulsion. The FGB will have been launched about two weeks earlier on a Russian Proton rocket from the Baikonur Cosmodrome, Kazahkstan. Once the FGB is captured using the mechanical arm, astronaut Nancy J. Currie will maneuver the arm to dock the FGB to the conical mating adapter at the top of Node 1 in the Shuttle's cargo bay. In ensuing days, three Extravehicular Activity?s (EVA) by astronauts Jerry L. Ross and James H. Newman will be performed to make power, data and utility connections between the two modules.
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A Voltage-Responsive Free-Blockage Controlled-Release System Based on Hydrophobicity Switching.
Jiao, Xiangyu; Sun, Ruijuan; Cheng, Yaya; Li, Fengyu; Du, Xin; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji
2017-05-19
Controlled-release systems based on mesoporous silica nanomaterials (MSNs) have drawn great attention owing to their potential biomedical applications. Various switches have been designed to control the release of cargoes through the construction of physical blocking units on the surface of MSNs. However, such physical blockages are limited by poor sealing ability and low biocompatibility, and most of them lack closure ability. Herein, a voltage-responsive controlled-release system was constructed by functionalizing the nanopore of MSNs with ferrocene. The system realized free-blockage controlled release and achieved pulsatile release. The nanopores of the ferrocene-functionalized MSNs were hydrophobic enough to prevent invasion of the solution. Once a suitable voltage was applied, the nanopores became hydrophilic, which was followed by invasion of the solution and the release of the cargos. Moreover, pulsatile release was realized, which avoided unexpected release after the stimulus disappeared. Thus, we believe that our studies provide new insight into highly effective blockage for MSNs. Furthermore, the voltage-responsive release system is expected to find use in electrical stimulation combination therapy and bioelectricity-responsive release. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Bis-polymer lipid-peptide conjugates and nanoparticles thereof
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Ting; Dong, He; Shu, Jessica
The present invention provides bis-polymer lipid-peptide conjugates containing a hydrophobic block and headgroup containing a helical peptide and two polymer blocks. The conjugates can self-assemble to form helix bundle subunits, which in turn assemble to provide micellar nanocarriers for drug cargos and other agents. Particles containing the conjugates and methods for forming the particles are also disclosed.
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Physical modeling of geometrically confined disordered protein assemblies
NASA Astrophysics Data System (ADS)
Ando, David
2015-08-01
The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature and uncertainty regarding the properties of individual nucleoporins. We first study the defining characteristics of the amino acid sequences of nucleoporins through bioinformatics techniques, although bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of FG motif containing nucleoporins (FG nups). The biophysical mechanism by which the critical FG nups regulate nucleocytoplasmic transport has remained elusive, yet our analysis revealed a set of highly conserved spatial features in the sequence structure of individual FG nups, such as the separation, localization, and ordering of FG motifs and charged residues along the protein chain. These sequence features are likely conserved due to a common functionality between species regarding how FG nups functionally regulate traffic, therefore these results constrain current models and eliminate proposed biophysical mechanisms responsible for regulation of nucleocytoplasmic traffic in the NPC which would not result in such a conserved amino acid sequence structure. Additionally, this method allows us to identify potentially functionally analogous disordered proteins across distantly related species. To understand the physical implications of the sequence features on structure and dynamics of the nucleoporins, we performed coarse-grained simulations of nucleoporins to understand their individual polymer properties. Our results indicate that different regions or blocks of an individual NPC protein can have distinctly different forms of disorder and that this property appears to be a conserved functional feature, consistent with the results of our physical bioinformatic analysis. Further simulations of grafted rings of FG nups mimicking the in vivo geometry of the NPC were performed and supplemented with polymer brush modeling to understand how aggregates of FG nups regulate transport in vivo. We found that the block structure at the individual protein level in terms of polymer properties is critical to the formation of a unique higher-order polymer brush architecture that can exist in distinct morphologies depending on the effective interaction energy between the phenylalanine glycine (FG) domains of different nups. Because the interactions between FG domains may be modulated by certain forms of transport factors, our results indicate that transitions between brush morphologies that correspond to open and closed states could play an important role in regulating transport across the NPC, suggesting novel forms of gated transport across membrane pores with wide biomimetic applicability in our Diblock Copolymer Brush Gate model. Previous experimental research has concluded that FG nups from S. cerevisiae are present in a bimodal distribution, with the "Forest Model" classifying FG nups as either diblock polymer like "trees" or single block polymer like "shrubs." Our simulation and polymer brush modeling results indicated that the function of the tree FG nups in the Diblock Copolymer Brush Gate (DCBG) model is to form a higher-order polymer brush architecture which can open and close to regulate transport across the NPC. Here we perform coarse grained simulations of the shrub FG nups which confirm that they have a single block polymer structure rather than the diblock structure of tree nups. Our molecular simulations also demonstrate that these single block FG nups are likely compact collapsed coil polymers, implying that shrubs are generally localized to their grafting location within the NPC. We find that adding a layer of shrub FG nups to the DCBG model increases the range of cargo sizes which are able to translocate the pore through a cooperative effect involving shrub and tree nups. This effect can explain the puzzling connection between shrub FG nup deletion mutants in S. cerevisiae and the resulting failure of certain large cargo transport through the NPC. Facilitation of large cargo transport via single block and diblock FG nup cooperativity in the nuclear pore could provide a model mechanism for designing future biomimetic pores of greater applicability. In summary, this dissertation presents a cohesive body of research that uses a combination of techniques including bioinformatics, coarse grained molecular modeling, and polymer brush theory to understand the properties of individual FG nups and how they behave in aggregate, strongly constraining possible biophysical mechanisms which may play a role in regulating traffic through the NPC. Our results are observed across different species and are consistent with many experimental observations which have been reported. Finally, our DCBG model for NPC function provides testable predictions for future experimental investigation and provides a foundation for the design and commercialization of biomimetic pores for filtering applications in vitro and industrial use.
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NASA Astrophysics Data System (ADS)
Madsen, Louis; Kidd, Bryce; Li, Xiuli; Miller, Katherine; Cooksey, Tyler; Robertson, Megan
Our team seeks to understand dynamic behaviors of block copolymer micelles and their interplay with encapsulated cargo molecules. Quantifying unimer and cargo exchange rates micelles can provide critical information for determining mechanisms of unimer exchange as well as designing systems for specific cargo release dynamics. We are exploring the utility of NMR spectroscopy and diffusometry techniques as complements to existing SANS and fluorescence methods. One promising new method involves time-resolved NMR spin relaxation measurements, wherein mixing of fully protonated and 2H-labeled PEO-b-PCL micelles solutions shows an increase in spin-lattice relaxation time (T1) with time after mixing. This is due to a weakening in magnetic environment surrounding 1H spins as 2H-bearing unimers join fully protonated micelles. We are measuring time constants for unimer exchange of minutes to hours, and we expect to resolve times of <1 min. This method can work on any solution NMR spectrometer and with minimal perturbation to chemical structure (as in dye-labelled fluorescence methods). Multimodal NMR can complement existing characterization tools, expanding and accelerating dynamics measurements for polymer micelle, nanogel, and nanoparticle developers.
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Improved Tumor Targeting of Polymer-based Nanovesicles Using Polymer-Lipid Blends
Cheng, Zhiliang; Elias, Drew R.; Kamat, Neha P.; Johnston, Eric D.; Poloukhtine, Andrei; Popik, Vladimir; Hammer, Daniel A.; Tsourkas, Andrew
2011-01-01
Block copolymer-based vesicles have recently garnered a great deal of interest as nanoplatforms for drug delivery and molecular imaging applications due to their unique structural properties. These nanovesicles have been shown to direct their cargo to disease sites either through enhanced permeability and retention or even more efficiently via active targeting. Here we show that the efficacy of nanovesicle targeting can be significantly improved when prepared from polymer-lipid blends compared with block copolymer alone. Polymer-lipid hybrid nanovesicles were produced from the aqueous co-assembly of the diblock copolymer, poly(ethylene oxide)-block-polybutadiene (PEO-PBD), and the phospholipid, hydrogenated soy phosphatidylcholine (HSPC). The PEG-based vesicles, 117 nm in diameter, were functionalized with either folic acid or anti-HER2/neu affibodies as targeting ligands to confer specificity for cancer cells. Our results revealed that nanovesicles prepared from polymer-lipid blends led to significant improvement in cell binding compared to nanovesicles prepared from block copolymer alone in both in vitro cell studies and murine tumor models. Therefore, it is envisioned that nanovesicles composed of polymer-lipid blends may constitute a preferred embodiment for targeted drug delivery and molecular imaging applications. PMID:21899335
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NASA Astrophysics Data System (ADS)
Sawczuk, Wojciech
2017-06-01
Due to their wide range of friction characteristics resulting from the application of different friction materials and good heat dissipation conditions, railway disc brakes have long replaced block brakes in many rail vehicles. A block brake still remains in use, however, in low speed cargo trains. The paper presents the assessment of the braking process through the analysis of vibrations generated by the components of the brake system during braking. It presents a possibility of a wider application of vibroacoustic diagnostics (VA), which aside from the assessment of technical conditions (wear of brake pads) also enables the determination of the changes of the average friction coefficient as a function of the braking onset speed. Vibration signals of XYZ were measured and analyzed. The analysis of the results has shown that there is a relation between the values of the point measures and the wear of the brake pads.
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Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement
NASA Astrophysics Data System (ADS)
Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping
2016-09-01
Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10-100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer-polymer and polymer-cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.
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Wang, Shunzhi; McGuirk, C Michael; Ross, Michael B; Wang, Shuya; Chen, Pengcheng; Xing, Hang; Liu, Yuan; Mirkin, Chad A
2017-07-26
Metal-organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality of MOF nanoparticles are less developed. A generalizable approach to modify their surfaces would allow one to impart chemical functionality onto the particle surface that is independent of the bulk MOF structure. Moreover, the use of a chemically programmable ligand, such as DNA, would allow for the manipulation of interparticle interactions. Herein, we report a coordination chemistry-based strategy for the surface functionalization of the external metal nodes of MOF nanoparticles with terminal phosphate-modified oligonucleotides. The external surfaces of nine distinct archetypical MOF particles containing four different metal species (Zr, Cr, Fe, and Al) were successfully functionalized with oligonucleotides, illustrating the generality of this strategy. By taking advantage of the programmable and specific interactions of DNA, 11 distinct MOF particle-inorganic particle core-satellite clusters were synthesized. In these hybrid nanoclusters, the relative stoichiometry, size, shape, and composition of the building blocks can all be independently controlled. This work provides access to a new set of nucleic acid-nanoparticle conjugates, which may be useful as programmable material building blocks and as probes for measuring and manipulating intracellular processes.
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Herzog, Christian; Yang, Cheng; Holmes, Alexandrea
2012-01-01
Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI. PMID:22896037
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46 CFR 151.45-2 - Special operating requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... conditions. (c) No cargo tank hatch, ullage hole, or tank cleaning openings shall be opened or remain open... shown in black block style letters and numerals (characters) at least 3 inches high on a white...
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46 CFR 151.45-2 - Special operating requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... conditions. (c) No cargo tank hatch, ullage hole, or tank cleaning openings shall be opened or remain open... shown in black block style letters and numerals (characters) at least 3 inches high on a white...
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46 CFR 151.45-2 - Special operating requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... conditions. (c) No cargo tank hatch, ullage hole, or tank cleaning openings shall be opened or remain open... shown in black block style letters and numerals (characters) at least 3 inches high on a white...
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Selectivity Mechanism of the Nuclear Pore Complex Characterized by Single Cargo Tracking
Lowe, Alan R.; Siegel, Jake J.; Kalab, Petr; Siu, Merek; Weis, Karsten; Liphardt, Jan T.
2010-01-01
The Nuclear Pore Complex (NPC) mediates all exchange between the cytoplasm and the nucleus. Small molecules can passively diffuse through the NPC, while larger cargos require transport receptors to translocate1. How the NPC facilitates the translocation of transport receptor/cargo complexes remains unclear. Here, we track single protein-functionalized Quantum Dot (QD) cargos as they translocate the NPC. Import proceeds by successive sub-steps comprising cargo capture, filtering and translocation, and release into the nucleus. The majority of QDs are rejected at one of these steps and return to the cytoplasm including very large cargos that abort at a size-selective barrier. Cargo movement in the central channel is subdiffusive and cargos that can bind more transport receptors diffuse more freely. Without Ran, cargos still explore the entire NPC, but have a markedly reduced probability of exit into the nucleus, suggesting that NPC entry and exit steps are not equivalent and that the pore is functionally asymmetric to importing cargos. The overall selectivity of the NPC appears to arise from the cumulative action of multiple reversible sub-steps and a final irreversible exit step. PMID:20811366
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Santra, Santimukul; Kaittanis, Charalambos; Perez, J. Manuel
2009-01-01
Herein we report the design and synthesis of multifunctional hyperbranched polyester-based nanoparticles and nanocomposites with properties ranging from magnetic, fluorescence, antioxidant and X-ray contrast. The fabrication of these nanostructures was achieved using a novel aliphatic and biodegradable hyperbranched polyester (HBPE) synthesized from readily available diethylmalonate. The polymer’s globular structure with functional surface carboxylic groups and hydrophobic cavities residing in the polymer’s interior allows for the formation of multifunctional polymeric nanoparticles, which are able to encapsulate a diversity of hydrophobic cargos. Via simple surface chemistry modifications, the surface carboxylic acid groups were modified to yield nanoparticles with a variety of surface functionalizations, such as amino, azide and propargyl groups, which mediated the conjugation of small molecules. This capability achieved the engineering of the HBPE nanoparticle surface for specific cell internalization studies and the formation of nanoparticle assemblies for the creation of novel nanocomposites that retained, and in some cases enhanced, the properties of the parental nanoparticle building blocks. Considering these results, the HBPE polymer, nanoparticles and composites should be ideal for biomedical, pharmaceutical, nanophotonics and material applications. PMID:19957939
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Wang, Jing; Fresquez, Theresa; Kandachar, Vasundhara; Deretic, Dusanka
2017-12-01
The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that during the carrier biogenesis from the photoreceptor Golgi/ trans -Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory N-terminal dimerization and cyclophillin-binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is essential for GBF1-Arf4 complex formation in vivo Notably, GBF1 interacts with the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that converging signals on GBF1 from the influx of cargo into the Golgi/TGN and the feedback from Arf4, combined with input from ASAP1, control Arf4 activation during sensory membrane trafficking to primary cilia. © 2017. Published by The Company of Biologists Ltd.
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Intracellular cargo delivery by virus capsid protein-based vehicles: From nano to micro.
Gao, Ding; Lin, Xiu-Ping; Zhang, Zhi-Ping; Li, Wei; Men, Dong; Zhang, Xian-En; Cui, Zong-Qiang
2016-02-01
Cellular delivery is an important concern for the efficiency of medicines and sensors for disease diagnoses and therapy. However, this task is quite challenging. Self-assembly virus capsid proteins might be developed as building blocks for multifunctional cellular delivery vehicles. In this work, we found that SV40 VP1 (Simian virus 40 major capsid protein) could function as a new cell-penetrating protein. The VP1 protein could carry foreign proteins into cells in a pentameric structure. A double color structure, with red QDs (Quantum dots) encapsulated by viral capsids fused with EGFP, was created for imaging cargo delivery and release from viral capsids. The viral capsids encapsulating QDs were further used for cellular delivery of micron-sized iron oxide particles (MPIOs). MPIOs were efficiently delivered into live cells and controlled by a magnetic field. Therefore, our study built virus-based cellular delivery systems for different sizes of cargos: protein molecules, nanoparticles, and micron-sized particles. Much research is being done to investigate methods for efficient and specific cellular delivery of drugs, proteins or genetic material. In this article, the authors describe their approach in using self-assembly virus capsid proteins SV40 VP1 (Simian virus 40 major capsid protein). The cell-penetrating behavior provided excellent cellular delivery and should give a new method for biomedical applications. Copyright © 2015 Elsevier Inc. All rights reserved.
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Structure of block copolymer micelles in the presence of co-solvents
NASA Astrophysics Data System (ADS)
Robertson, Megan; Wang, Shu; Le, Kim Mai; Piemonte, Rachele; Madsen, Louis
2015-03-01
Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using scattering experiments and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.
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Influencing the structure of block copolymer micelles with small molecule additives
NASA Astrophysics Data System (ADS)
Robertson, Megan; Singh, Avantika; Cooksey, Tyler; Kidd, Bryce; Piemonte, Rachele; Wang, Shu; Mai Le, Kim; Madsen, Louis
Amphiphilic block copolymer micelles in water are under broad exploration for drug delivery applications due to their high loading capacity and targeted drug delivery. We aim to understand the kinetic and thermodynamic processes that underlie the self-assembly of diblock copolymer micelle systems. The present work focuses on diblock copolymers containing poly(ethylene oxide) (a hydrophilic polymer) and polycaprolactone (a hydrophobic polymer), which spontaneously self-assemble into spherical micelles in water. Addition of a common good solvent (a co-solvent) for both of the constituting blocks, such as tetrahydrofuran (THF), reduces the interfacial tension at the core-corona interface. We are currently investigating the effect of this phenomenon on the micelle structural properties, using small-angle scattering and nuclear magnetic resonance. We have characterized the hydrodynamic radius, core radius, corona thickness, aggregation number, degree of swelling of the micelle core with the co-solvent, and unimer (free chain) concentration, as a function of the co-solvent concentration. Fundamental knowledge from these studies will inform design of drug delivery systems by allowing us to tailor micelle properties for optimal cargo loading.
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The Vehicle Control Systems Branch at the Marshall Space Flight Center
NASA Technical Reports Server (NTRS)
Barret, Chris
1990-01-01
This paper outlines the responsibility of the Vehicle Control Systems Branch at the Marshall Space Flight Center (MSFC) to analyze, evaluate, define, design, verify, and specify requirements for advanced launch vehicles and related space projects, and to conduct research in advanced flight control concepts. Attention is given to branch responsibilities which include Shuttle-C, Shuttle-C Block II, Shuttle-Z, lunar cargo launch vehicles, Mars cargo launch vehicles, orbital maneuvering vehicle, automatic docking, tethered satellite, aeroassisted flight experiment, and solid rocket booster parachute recovery system design.
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Documentation of STS-88 Node evaluation
1997-09-08
S97-11949 (8 Sept 1997) --- Wearing training versions of the Shuttle Extravehicular Mobility Unit (EMU) space suit, astronauts Jerry L. Ross (left), and James Newman perform the first training session in the Neutral Buoyancy Laboratory (NBL) of the Sonny Carter Training Facility. The training was actually a dress rehearsal of three Extravehicular Activity?s (EVA) the pair will conduct during the July 1998 flight (STS-88) -- the first International Space Station (ISS) assembly mission. During the six-hour training session, the crew practiced hooking up power and data cables between full-scale mockups of the Functional Cargo Block and the United States-built Node 1 (foreground).
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05075 (8 Apr. 1998) --- Astronaut Nancy J. Currie, assigned as a mission specialist for the mission, uses hardware in the virtual reality lab at the Johnson Space Center (JSC) to train for her duties aboard the Space Shuttle Endeavour. This type computer interface paired with virtual reality training hardware for the assigned space-walking astronauts -- in this case, Jerry L. Ross and James H. Newman -- helps to prepare the entire team for dealing with International Space Station (ISS) elements. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Endeavour?s cargo bay. In ensuing days, three Extravehicular Activity?s (EVA) by Ross and Newman will be performed to make power, data and utility connections between the two modules.
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Stringer, Daniel K.
2011-01-01
ESCRTs (endosomal sorting complexes required for transport) bind and sequester ubiquitinated membrane proteins and usher them into multivesicular bodies (MVBs). As Ubiquitin (Ub)-binding proteins, ESCRTs themselves become ubiquitinated. However, it is unclear whether this regulates a critical aspect of their function or is a nonspecific consequence of their association with the Ub system. We investigated whether ubiquitination of the ESCRTs was required for their ability to sort cargo into the MVB lumen. Although we found that Rsp5 was the main Ub ligase responsible for ubiquitination of ESCRT-0, elimination of Rsp5 or elimination of the ubiquitinatable lysines within ESCRT-0 did not affect MVB sorting. Moreover, by fusing the catalytic domain of deubiquitinating peptidases onto ESCRTs, we could block ESCRT ubiquitination and the sorting of proteins that undergo Rsp5-dependent ubiquitination. Yet, proteins fused to a single Ub moiety were efficiently delivered to the MVB lumen, which strongly indicates that a single Ub is sufficient in sorting MVBs in the absence of ESCRT ubiquitination. PMID:21242292
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Art concept, line drawing and Service Module of the ISS
1998-04-13
S98-04904 (21 July 1997) --- The Space Shuttle Endeavour prepares to capture the Functional Cargo Block (FGB) using the shuttle's mechanical arm in this artist's depiction of the first Space Shuttle assembly flight for the International Space Station (ISS), mission STS-88 scheduled to launch in December 1998. The shuttle will carry the first United States-built component for the station, a connecting module called Node 1 or Unity, and attach it to the already orbiting FGB, which supplies early electrical power and propulsion. The FGB, Zarya, will have been launched about two weeks earlier on a Russian Proton rocket from the Baikonur Cosmodrome, Kazahkstan. Once the FGB is captured using the mechanical arm, astronaut Nancy J. Currie will maneuver the arm to dock the FGB to the conical mating adapter at the top of Node 1 in the Shuttle's cargo bay. In ensuing days, three Extravehicular Activity?s (EVA) by astronauts Jerry L. Ross and James H. Newman will be performed to make power, data and utility connections between the two modules.
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29 CFR 1919.90 - Documentation.
Code of Federal Regulations, 2011 CFR
2011-07-01
...(f) Test Supervision .10(b) Annual Examinations: (see Examinations). Assistant Secretary .2(d) Blocks...). Cargo Gear: Braking Devices .22 Chains .25 Damaged Components .20 Definition .2(b) Derrick Attachment...: (see Gear Certification). Shore-Based Materials Handling Devices .70(a) Chains, Limitations .25...
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29 CFR 1919.90 - Documentation.
Code of Federal Regulations, 2012 CFR
2012-07-01
...(f) Test Supervision .10(b) Annual Examinations: (see Examinations). Assistant Secretary .2(d) Blocks...). Cargo Gear: Braking Devices .22 Chains .25 Damaged Components .20 Definition .2(b) Derrick Attachment...: (see Gear Certification). Shore-Based Materials Handling Devices .70(a) Chains, Limitations .25...
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2017-01-01
Metal–organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality of MOF nanoparticles are less developed. A generalizable approach to modify their surfaces would allow one to impart chemical functionality onto the particle surface that is independent of the bulk MOF structure. Moreover, the use of a chemically programmable ligand, such as DNA, would allow for the manipulation of interparticle interactions. Herein, we report a coordination chemistry-based strategy for the surface functionalization of the external metal nodes of MOF nanoparticles with terminal phosphate-modified oligonucleotides. The external surfaces of nine distinct archetypical MOF particles containing four different metal species (Zr, Cr, Fe, and Al) were successfully functionalized with oligonucleotides, illustrating the generality of this strategy. By taking advantage of the programmable and specific interactions of DNA, 11 distinct MOF particle–inorganic particle core–satellite clusters were synthesized. In these hybrid nanoclusters, the relative stoichiometry, size, shape, and composition of the building blocks can all be independently controlled. This work provides access to a new set of nucleic acid–nanoparticle conjugates, which may be useful as programmable material building blocks and as probes for measuring and manipulating intracellular processes. PMID:28718644
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Versatile Loading of Diverse Cargo into Functional Polymer Capsules.
Richardson, Joseph J; Maina, James W; Ejima, Hirotaka; Hu, Ming; Guo, Junling; Choy, Mei Y; Gunawan, Sylvia T; Lybaert, Lien; Hagemeyer, Christoph E; De Geest, Bruno G; Caruso, Frank
2015-02-01
Polymer microcapsules are of particular interest for applications including self-healing coatings, catalysis, bioreactions, sensing, and drug delivery. The primary way that polymer capsules can exhibit functionality relevant to these diverse fields is through the incorporation of functional cargo in the capsule cavity or wall. Diverse functional and therapeutic cargo can be loaded into polymer capsules with ease using polymer-stabilized calcium carbonate (CaCO 3 ) particles. A variety of examples are demonstrated, including 15 types of cargo, yielding a toolbox with effectively 500+ variations. This process uses no harsh reagents and can take less than 30 min to prepare, load, coat, and form the hollow capsules. For these reasons, it is expected that the technique will play a crucial role across scientific studies in numerous fields.
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Bi-stability in cooperative transport by ants in the presence of obstacles
Pinkoviezky, Itai; Feinerman, Ofer
2018-01-01
To cooperatively carry large food items to the nest, individual ants conform their efforts and coordinate their motion. Throughout this expedition, collective motion is driven both by internal interactions between the carrying ants and a response to newly arrived informed ants that orient the cargo towards the nest. During the transport process, the carrying group must overcome obstacles that block their path to the nest. Here, we investigate the dynamics of cooperative transport, when the motion of the ants is frustrated by a linear obstacle that obstructs the motion of the cargo. The obstacle contains a narrow opening that serves as the only available passage to the nest, and through which single ants can pass but not with the cargo. We provide an analytical model for the ant-cargo system in the constrained environment that predicts a bi-stable dynamic behavior between an oscillatory mode of motion along the obstacle and a convergent mode of motion near the opening. Using both experiments and simulations, we show how for small cargo sizes, the system exhibits spontaneous transitions between these two modes of motion due to fluctuations in the applied force on the cargo. The bi-stability provides two possible problem solving strategies for overcoming the obstacle, either by attempting to pass through the opening, or take large excursions to circumvent the obstacle. PMID:29746457
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Bi-stability in cooperative transport by ants in the presence of obstacles.
Ron, Jonathan E; Pinkoviezky, Itai; Fonio, Ehud; Feinerman, Ofer; Gov, Nir S
2018-05-01
To cooperatively carry large food items to the nest, individual ants conform their efforts and coordinate their motion. Throughout this expedition, collective motion is driven both by internal interactions between the carrying ants and a response to newly arrived informed ants that orient the cargo towards the nest. During the transport process, the carrying group must overcome obstacles that block their path to the nest. Here, we investigate the dynamics of cooperative transport, when the motion of the ants is frustrated by a linear obstacle that obstructs the motion of the cargo. The obstacle contains a narrow opening that serves as the only available passage to the nest, and through which single ants can pass but not with the cargo. We provide an analytical model for the ant-cargo system in the constrained environment that predicts a bi-stable dynamic behavior between an oscillatory mode of motion along the obstacle and a convergent mode of motion near the opening. Using both experiments and simulations, we show how for small cargo sizes, the system exhibits spontaneous transitions between these two modes of motion due to fluctuations in the applied force on the cargo. The bi-stability provides two possible problem solving strategies for overcoming the obstacle, either by attempting to pass through the opening, or take large excursions to circumvent the obstacle.
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Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis
Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi; ...
2017-11-13
The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from anmore » amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. As a result, this study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.« less
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Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis
Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi; Yang, Lin; Yoshimura, Hideyuki; Miettinen, Heini M.; LaFrance, Ben; Patterson, Dustin P.; Schwarz, Benjamin; Karty, Jonathan A.; Prevelige, Peter E.; Lee, Byeongdu; Douglas, Trevor
2018-01-01
The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy; the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from an amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles, and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. This study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales, and exhibits properties and function that arise from the interaction between individual building blocks. PMID:29131580
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Chaudhary, Suman; Smith, Carol Anne; del Pino, Pablo; de la Fuente, Jesus M.; Mullin, Margaret; Hursthouse, Andrew; Stirling, David; Berry, Catherine C.
2013-01-01
Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs) have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrin- medicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation) blocking particle uptake. Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake. PMID:24275948
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Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi
The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from anmore » amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. As a result, this study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.« less
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Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.
Kim, Dong-Hyun; Vitol, Elina A; Liu, Jing; Balasubramanian, Shankar; Gosztola, David J; Cohen, Ezra E; Novosad, Valentyn; Rozhkova, Elena A
2013-06-18
Hybrid nanoarchitectures are among the most promising nanotechnology-enabled materials for biomedical applications. Interfacing of nanoparticles with active materials gives rise to the structures with unique multiple functionality. Superparamagnetic iron oxide nanoparticles particles SPION are widely employed in the biology and in developing of advanced medical technologies. Polymeric micelles offer the advantage of multifunctional carriers which can serve as delivery vehicles carrying nanoparticles, hydrophobic chemotherapeutics and other functional materials and molecules. Stimuli-responsive polymers are especially attractive since their properties can be modulated in a controlled manner. Here we report on multifunctional thermo-responsive poly(N-isopropylacrylamide-co-acrylamide)-block-poly(ε-caprolactone) random block copolymer micelles as magnetic hyperthermia-mediated payload release and imaging agents. The combination of copolymers, nanoparticles and doxorubicin drug was tailored the way that the loaded micelles were cable to respond to magnetic heating at physiologically-relevant temperatures. A surface functionalization of the micelles with the integrin β4 antibody and consequent interfacing of the resulting nanobio hybrid with squamous head and neck carcinoma cells which is known to specifically over-express the A9 antigen resulted in concentration of the micelles on the surface of cells. No inherent cytotoxicity was detected for the magnetic micelles without external stimuli application. Furthermore, SPION-loaded micelles demonstrate significant MRI contrast enhancement abilities.
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31 CFR Appendixes to Chapter V - Note
Code of Federal Regulations, 2010 CFR
2010-07-01
.... Freight forwarders and shippers may not charter, book cargo on, or otherwise deal with blocked vessels. 7. References to regulatory parts in chapter V or other authorities: [BALKANS]: Western Balkans Stabilization... the economic sanctions programs in chapter V. (Please call OFAC Compliance Programs Division for...
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Transportation of Nanoscale Cargoes by Myosin Propelled Actin Filaments
Persson, Malin; Gullberg, Maria; Tolf, Conny; Lindberg, A. Michael; Månsson, Alf; Kocer, Armagan
2013-01-01
Myosin II propelled actin filaments move ten times faster than kinesin driven microtubules and are thus attractive candidates as cargo-transporting shuttles in motor driven lab-on-a-chip devices. In addition, actomyosin-based transportation of nanoparticles is useful in various fundamental studies. However, it is poorly understood how actomyosin function is affected by different number of nanoscale cargoes, by cargo size, and by the mode of cargo-attachment to the actin filament. This is studied here using biotin/fluorophores, streptavidin, streptavidin-coated quantum dots, and liposomes as model cargoes attached to monomers along the actin filaments (“side-attached”) or to the trailing filament end via the plus end capping protein CapZ. Long-distance transportation (>100 µm) could be seen for all cargoes independently of attachment mode but the fraction of motile filaments decreased with increasing number of side-attached cargoes, a reduction that occurred within a range of 10–50 streptavidin molecules, 1–10 quantum dots or with just 1 liposome. However, as observed by monitoring these motile filaments with the attached cargo, the velocity was little affected. This also applied for end-attached cargoes where the attachment was mediated by CapZ. The results with side-attached cargoes argue against certain models for chemomechanical energy transduction in actomyosin and give important insights of relevance for effective exploitation of actomyosin-based cargo-transportation in molecular diagnostics and other nanotechnological applications. The attachment of quantum dots via CapZ, without appreciable modulation of actomyosin function, is useful in fundamental studies as exemplified here by tracking with nanometer accuracy. PMID:23437074
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Non-amyloidogenic peptide tags for the regulatable self-assembling of protein-only nanoparticles.
Unzueta, Ugutz; Ferrer-Miralles, Neus; Cedano, Juan; Zikung, Xu; Pesarrodona, Mireia; Saccardo, Paolo; García-Fruitós, Elena; Domingo-Espín, Joan; Kumar, Pradeep; Gupta, Kailash C; Mangues, Ramón; Villaverde, Antonio; Vazquez, Esther
2012-11-01
Controlling the self-assembling of building blocks as nanoscale entities is a requisite for the generation of bio-inspired vehicles for nanomedicines. A wide spectrum of functional peptides has been incorporated to different types of nanoparticles for the delivery of conventional drugs and nucleic acids, enabling receptor-specific cell binding and internalization, endosomal escape, cytosolic trafficking, nuclear targeting and DNA condensation. However, the development of architectonic tags to induce the self-assembling of functionalized monomers has been essentially neglected. We have examined here the nanoscale architectonic capabilities of arginine-rich cationic peptides, that when displayed on His-tagged proteins, promote their self-assembling as monodisperse, protein-only nanoparticles. The scrutiny of the cross-molecular interactivity cooperatively conferred by poly-arginines and poly-histidines has identified regulatable electrostatic interactions between building blocks that can also be engineered to encapsulate cargo DNA. The combined use of cationic peptides and poly-histidine tags offers an unusually versatile approach for the tailored design and biofabrication of protein-based nano-therapeutics, beyond the more limited spectrum of possibilities so far offered by self-assembling amyloidogenic peptides. Copyright © 2012 Elsevier Ltd. All rights reserved.
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The Automated Logistics Element Planning System (ALEPS)
NASA Technical Reports Server (NTRS)
Schwaab, Douglas G.
1992-01-01
ALEPS, which is being developed to provide the SSF program with a computer system to automate logistics resupply/return cargo load planning and verification, is presented. ALEPS will make it possible to simultaneously optimize both the resupply flight load plan and the return flight reload plan for any of the logistics carriers. In the verification mode ALEPS will support the carrier's flight readiness reviews and control proper execution of the approved plans. It will also support the SSF inventory management system by providing electronic block updates to the inventory database on the cargo arriving at or departing the station aboard a logistics carrier. A prototype drawer packing algorithm is described which is capable of generating solutions for 3D packing of cargo items into a logistics carrier storage accommodation. It is concluded that ALEPS will provide the capability to generate and modify optimized loading plans for the logistics elements fleet.
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ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.
Sarapas, Joel M; Backlund, Coralie M; deRonde, Brittany M; Minter, Lisa M; Tew, Gregory N
2017-05-17
Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with diguanidinium norbornene molecules being polymerized to both 10 and 20 repeat units. Generally, homopolymer CPPMs delivered low amounts of siRNA into Jurkat T cells, with no apparent backbone dependence; however, by adding a short hydrophobic methyl methacrylate block to the guanidinium-rich methacrylate polymer, siRNA delivery to nearly the entire cell population was achieved. Protein internalization yielded similar results for most of the CPPMs, though the block polymer was unable to deliver proteins. In contrast, the styrene-based CPPM yielded the highest internalization for GFP (≈40 % of cells affected), showing that indeed backbone chemistry impacts protein delivery, specifically through the incorporation of an aromatic group. These results demonstrate that an understanding of how polymer structure affects cargo-dependent internalization is critical to designing new, more effective CPPMs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05079 (8 Apr. 1998) --- Astronaut Jerry L. Ross, assigned as a mission specialist for the mission, uses specialized gear to train for his duties aboard the Space Shuttle Endeavour. This type virtual reality training allows each of the assigned Extravehicular Activity (EVA) astronauts -- Ross and James H. Newman -- to wear a helmet and special gloves to look at computer displays simulating actual movements around the various locations on the International Space Station (ISS) hardware with which they'll be working. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, astronaut Nancy J. Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Shuttle's cargo bay. In ensuing days, three EVA space walks by Ross and Newman will be performed to make power, data and utility connections between the two modules. Currie also uses this same lab to train for her RMS controlling duties.
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05078 (8 Apr. 1998) --- With crew mates looking on, astronaut Nancy J. Currie, mission specialist, uses hardware in the virtual reality lab at the Johnson Space Center (JSC) to train for her duties aboard the Space Shuttle Endeavour. She is flanked by astronaut Robert Cabana (left), commander; and Frederick W. Sturckow (right), pilot. This type computer interface paired with virtual reality training hardware for the assigned space-walking astronauts -- Jerry L. Ross and James H. Newman -- helps to prepare the entire team for dealing with International Space Station (ISS) elements. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Endeavour's cargo bay. In ensuing days, three Extravehicular Activity?s (EVA) by Ross and Newman will be performed to make power, data and utility connections between the two modules. Looking on is Scott A. Bleisath (behind Currie), with the EVA Systems Group at JSC.
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05077 (8 Apr. 1998) --- With crew mates looking on, astronaut Nancy J. Currie, mission specialist, uses hardware in the virtual reality lab at the Johnson Space Center (JSC) to train for her duties aboard the Space Shuttle Endeavour. She is flanked by astronaut Robert Cabana (left), commander; and Frederick W. Sturckow (right), pilot. This type computer interface paired with virtual reality training hardware for the assigned space-walking astronauts -- Jerry L. Ross and James H. Newman -- helps to prepare the entire team for dealing with International Space Station (ISS) elements. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Endeavour's cargo bay. In ensuing days, three Extravehicular Activity?s (EVA) by Ross and Newman will be performed to make power, data and utility connections between the two modules. Looking on is Scott A. Bleisath (behind Currie), with the EVA Systems Group at JSC.
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05074 (8 Apr. 1998) --- Astronaut Jerry L. Ross, assigned as a mission specialist for the mission, uses special gear and software to train for his duties aboard the Space Shuttle Endeavour. This type virtual reality training supplements practice for each of the assigned space-walking astronauts -- Ross and James H. Newman -- during which they wear a helmet and special gloves to look at computer displays simulating actual movements around the various locations on the early International Space Station (ISS) hardware with which they'll be working. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, astronaut Nancy J. Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Shuttle's cargo bay. In ensuing days, three space walks by Ross and Newman will be performed to make power, data and utility connections between the two modules. Currie also uses this same lab to train for her RMS controlling duties.
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STS-88 crew use simulators and virtual reality in preflight training
1998-04-08
S98-05076 (8 Apr. 1998) --- Astronaut Jerry L. Ross, assigned as a mission specialist for the mission, uses special gear and software to train for his duties aboard the Space Shuttle Endeavour. This type virtual reality training supplements practice for each of the assigned space-walking astronauts -- Ross and James H. Newman -- during which they wear a helmet and special gloves to look at computer displays simulating actual movements around the various locations on the early International Space Station (ISS) hardware with which they'll be working. One of those elements will be the Functional Cargo Block (FGB), which will have been launched a couple of weeks prior to STS-88. Once the FGB is captured using the Remote Manipulator System (RMS) of the Endeavour, astronaut Nancy J. Currie will maneuver the robot arm to dock the FGB to the conical mating adapter at the top of Node 1, to be carried in the Shuttle's cargo bay. In ensuing days, three space walks by Ross and Newman will be performed to make power, data and utility connections between the two modules. Currie also uses this same lab to train for her RMS controlling duties.
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Human plasma platelet-derived exosomes: effects of aspirin.
Goetzl, Edward J; Goetzl, Laura; Karliner, Joel S; Tang, Norina; Pulliam, Lynn
2016-05-01
Platelet-derived exosomes mediate platelet atherogenic interactions with endothelial cells and monocytes. A new method for isolation of plasma platelet-derived exosomes is described and used to examine effects of aging and aspirin on exosome cargo proteins. Exosome secretion by purified platelets in vitro did not increase after exposure to thrombin or collagen, as assessed by exosome counts and quantification of the CD81 exosome marker. Thrombin and collagen increased exosome content of α-granule chemokines CXCL4 and CXCL7 and cytoplasmic high-mobility group box 1 (HMGB1) protein, but not membrane platelet glycoprotein VI (GPVI), with dependence on extracellular calcium. Aspirin consumption significantly blocked thrombin- and collagen-induced increases in exosome cargo levels of chemokines and HMGB1, without altering total exosome secretion or GPVI cargo. Plasma platelet-derived exosomes, enriched by absorption with mouse antihuman CD42b [platelet glycoprotein Ib (GPIb)] mAb, had sizes and cargo protein contents similar to those of exosomes from purified platelets. The plasma platelet-derived exosome number is lower and its chemokine and HMGB1 levels higher after age 65 yr. Aspirin consumption significantly suppressed cargo protein levels of plasma platelet-derived exosomes without altering total levels of exosomes. Cargo proteins of human plasma platelet-derived exosomes may biomark platelet abnormalities and in vivo effects of drugs.- Goetzl, E. J., Goetzl, L., Karliner, J. S., Tang, N., Pulliam, L. Human plasma platelet-derived exosomes: effects of aspirin. © FASEB.
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Lamch, Łukasz; Tylus, Włodzimierz; Jewgiński, Michał; Latajka, Rafał; Wilk, Kazimiera A
2016-12-15
Hydrophobic zinc(II) phthalocyanine-type derivatives, solubilized in polymeric micelles (PMs), provide a befitting group of so-called nanophotosensitizers, suitable for a variety of photodynamic therapy (PDT) protocols. The factors that influence the success of such products in PDT are the location of the active cargo in the PMs and the nanocarrier-enhanced ability to safely interact with biological systems and fulfill their therapeutic functions. Therefore, the aim of this work was to determine the solubilization loci of three phthalocyanines of varying hydrophobicity, i.e., zinc(II) phthalocyanine (ZnPc), along with its tetrasulfonic acid (ZnPc-sulfo 4 ) and perfluorinated (ZnPcF 16 ) derivatives, loaded in polymeric micelles of methoxy poly(ethylene oxide)-b-poly(l-lactide) (mPEG-b-PLLA), by means of 1 H nuclear magnetic resonance (NMR) and X-ray photoelectron spectroscopy (XPS) combined with ion sputtering. Furthermore, the microenvironment influence upon the chemical and physical status of the solubilized cargo in PMs, expressed by photobleaching and reactive oxygen species (ROS) generation comparing to the same properties of native cargoes in solution, was also evaluated and discussed in regards to the probing location data. The studied phthalocyanine-loaded PMs exhibited good physical stability, high drug-loading efficiency, and a size of less than ca. 150 nm with low polydispersity indices. The formation of polymeric micelles and the solubilization locus were investigated by 1 H NMR and XPS. ZnPc localized within the PM core, whereas both ZnPcF 16 and ZnPc-sulfo 4 - in the corona of PMs. We proved that the cargo locus is crucial for the photochemical properties of the studied phthalocyanines; the increase in photostability and ability to generate ROS in micellar solution compared to free photosensitizer was most significant for the photosensitizer in the PM core. Our results indicate the role of the cargo location in the PM microenvironment and demonstrate that such attempts are fundamental for improving the properties of photosensitizers and their assumed efficiency as nanophotosensitizers in PDT.
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Trans-Golgi network/early endosome: a central sorting station for cargo proteins in plant immunity.
LaMontagne, Erica D; Heese, Antje
2017-12-01
In plants, the trans-Golgi network (TGN) functionally overlaps with the early endosome (EE), serving as a central sorting hub to direct newly synthesized and endocytosed cargo to the cell surface or vacuole. Here, we focus on the emerging role of the TGN/EE in sorting of immune cargo proteins for effective plant immunity against pathogenic bacteria and fungi. Specific vesicle coat and regulatory components at the TGN/EE ensure that immune cargoes are correctly sorted and transported to the location of their cellular functions. Our understanding of the identity of immune cargoes and the underlying cellular mechanisms regulating their sorting are still rudimentary, but this knowledge is essential to understanding the physiological contribution of the TGN/EE to effective immune responses. Copyright © 2017. Published by Elsevier Ltd.
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Extensive cargo identification reveals distinct biological roles of the 12 importin pathways.
Kimura, Makoto; Morinaka, Yuriko; Imai, Kenichiro; Kose, Shingo; Horton, Paul; Imamoto, Naoko
2017-01-24
Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple parallel transport pathways that the receptors constitute is poorly understood because only limited numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 species of human import receptors with a high-throughput method that employs stable isotope labeling with amino acids in cell culture, an in vitro reconstituted transport system, and quantitative mass spectrometry. The identified cargoes illuminated the manner of cargo allocation to the receptors. The redundancies of the receptors vary widely depending on the cargo protein. Cargoes of the same receptor are functionally related to one another, and the predominant protein groups in the cargo cohorts differ among the receptors. Thus, the receptors are linked to distinct biological processes by the nature of their cargoes.
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46 CFR 31.10-16 - Inspection and certification of cargo gear-TB/ALL.
Code of Federal Regulations, 2010 CFR
2010-10-01
...; (4) Certification of the testing and examination of chains, rings, hooks, shackles, swivels, and blocks; (5) Certification of the testing and examination of wire rope; (6) Certification of the heat treatment of chains, rings, hooks, shackles, and swivels which require such treatment; and, (7...
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46 CFR 31.10-16 - Inspection and certification of cargo gear-TB/ALL.
Code of Federal Regulations, 2012 CFR
2012-10-01
...; (4) Certification of the testing and examination of chains, rings, hooks, shackles, swivels, and blocks; (5) Certification of the testing and examination of wire rope; (6) Certification of the heat treatment of chains, rings, hooks, shackles, and swivels which require such treatment; and, (7...
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46 CFR 31.10-16 - Inspection and certification of cargo gear-TB/ALL.
Code of Federal Regulations, 2013 CFR
2013-10-01
...; (4) Certification of the testing and examination of chains, rings, hooks, shackles, swivels, and blocks; (5) Certification of the testing and examination of wire rope; (6) Certification of the heat treatment of chains, rings, hooks, shackles, and swivels which require such treatment; and, (7...
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46 CFR 31.10-16 - Inspection and certification of cargo gear-TB/ALL.
Code of Federal Regulations, 2011 CFR
2011-10-01
...; (4) Certification of the testing and examination of chains, rings, hooks, shackles, swivels, and blocks; (5) Certification of the testing and examination of wire rope; (6) Certification of the heat treatment of chains, rings, hooks, shackles, and swivels which require such treatment; and, (7...
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46 CFR 31.10-16 - Inspection and certification of cargo gear-TB/ALL.
Code of Federal Regulations, 2014 CFR
2014-10-01
...; (4) Certification of the testing and examination of chains, rings, hooks, shackles, swivels, and blocks; (5) Certification of the testing and examination of wire rope; (6) Certification of the heat treatment of chains, rings, hooks, shackles, and swivels which require such treatment; and, (7...
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Characterizing Density and Complexity of Imported Cargos
DOE Office of Scientific and Technical Information (OSTI.GOV)
Birrer, Nathaniel; Divin, Charles; Glenn, Steven
X-ray inspection systems are used to detect radiological and nuclear threats in imported cargo. In order to better understand performance of these systems, system imaging capabilities and the characteristics of imported cargo need to be determined. This project involved calculation of the modulation transfer function as a metric of system imaging performance and a study of the density and inhomogeneity of imported cargos, which have been shown to correlate with human analysts, threat detection performance.
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Secondary barrier construction for low temperature liquefied gas storage tank carrying vessels
DOE Office of Scientific and Technical Information (OSTI.GOV)
Okamoto, T.; Nishimoto, T.; Sawada, K.
1978-12-05
A new LNG-cargo-tank secondary barrier developed by Japan's Hitachi Shipbuilding and Engineering Co., Ltd., offers ease of fabrication, simple construction, improved efficiency of installation, and protection against seawater ingress as well as LNG leakage. The secondary barrier, intended for use below spherical LNG tanks, consists of unit heat-insulating block plates adhesively secured to the bottom plate of the ship's hold, heat-insulating filling members stuffed into the joints between the block plates, and a protective layer formed on the entire surface of the block plates and the filling members. These unit block plates are in the form of heat-insulating members ofmore » the required thickness, preformed into a square or trapezoidal shape, particularly in the form of rigid-foam synthetic-resin plates.« less
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Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph
2015-05-07
A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.
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Polymer nano-particle hybrid micelles: Encapsulation of POSS into semi-fluorinated polymer micelles
NASA Astrophysics Data System (ADS)
Ratnaweera, Dilru; Perahia, Dvora; Iacono, Scott; Mabry, Joseph; Smith, Dennis
2012-02-01
Self-assembly of block copolymers in selective solvents was used to form a nanoparticle (NP)/polymer hybrid micelles. These micelles can be used as a cargo vehicle for other substances such as drug delivery, and as building blocks for polymer-nanocomposites with controlled NP distribution. Association of NPs into specific blocks of the copolymer depends on the compatibility between the NPs and the block as well as their preference to the solvent that micellization takes place. The current work introduces a small angle neutron scattering study of association of Polyhedral Oligomeric Silsesquioxane (POSS) NPs into micelles of a highly segregating random copolymer, Biphenyl Perfluorocyclobutane (BPh-PFCB), in toluene, which is a good solvent for BPh. Incompatibility between the blocks drives copolymer into micelles with PFCB in the core and BPh in swollen corona. Modification of NPs with polymer chains drives POSS cages into the micelle core and prevents the micelle dissociation at higher temperatures.
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Drive the Car(go)s-New Modalities to Control Cargo Trafficking in Live Cells.
Mondal, Payel; Khamo, John S; Krishnamurthy, Vishnu V; Cai, Qi; Zhang, Kai
2017-01-01
Synaptic transmission is a fundamental molecular process underlying learning and memory. Successful synaptic transmission involves coupled interaction between electrical signals (action potentials) and chemical signals (neurotransmitters). Defective synaptic transmission has been reported in a variety of neurological disorders such as Autism and Alzheimer's disease. A large variety of macromolecules and organelles are enriched near functional synapses. Although a portion of macromolecules can be produced locally at the synapse, a large number of synaptic components especially the membrane-bound receptors and peptide neurotransmitters require active transport machinery to reach their sites of action. This spatial relocation is mediated by energy-consuming, motor protein-driven cargo trafficking. Properly regulated cargo trafficking is of fundamental importance to neuronal functions, including synaptic transmission. In this review, we discuss the molecular machinery of cargo trafficking with emphasis on new experimental strategies that enable direct modulation of cargo trafficking in live cells. These strategies promise to provide insights into a quantitative understanding of cargo trafficking, which could lead to new intervention strategies for the treatment of neurological diseases.
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Live-cell imaging of retrograde transport initiation in primary neurons.
Nirschl, Jeffrey J; Holzbaur, Erika L F
2016-01-01
Axonal transport is an essential function in neurons, as mutations in either motor proteins or their adaptors cause neurodegeneration. While some mutations cause a complete block in axonal transport, other mutations affect transport more subtly. This is especially true of mutations identified in human patients, many of which impair but do not block motor function in the cell. Dissecting the pathogenic mechanisms of these more subtle mutations requires assays that can tease apart the distinct phases of axonal transport, including transport initiation, sustained/regulated motility, and cargo-specific sorting or delivery. Here, we describe a live-cell photobleaching assay to assess retrograde flux from the distal axon tip, a measure for distal transport initiation. We have previously used this method to show that the CAP-Gly domain of DCTN1 is required for efficient retrograde transport initiation in the distal axon, but it is not required to maintain retrograde flux along the mid-axon (Moughamian & Holzbaur, 2012). This approach has allowed us to examine the effects of disease-causing mutations in the axonal transport machinery, and in combination with other assays, will be useful in determining the mechanisms and regulation of axonal transport in normal and diseased conditions. Copyright © 2016 Elsevier Inc. All rights reserved.
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Proposed space shuttle cargo handling criteria at the operational site (preliminary)
NASA Technical Reports Server (NTRS)
Beck, P. E.
1972-01-01
The criteria for cargo handling at the operational site of space shuttles are presented, based on assumed program requirements. The concepts for the following functions are described: maintenance and checkout facility, transfer to launch pad, and launch pad. The requirements for the ground equipment are given along with the general sequences for cargo loading.
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Development of Test Article Building Block (TABB) for deployable platform systems
NASA Technical Reports Server (NTRS)
Greenberg, H. S.; Barbour, R. T.
1984-01-01
The concept of a Test Article Building Block (TABB) is described. The TABB is a ground test article that is representative of a future building block that can be used to construct LEO and GEO deployable space platforms for communications and scientific payloads. This building block contains a main housing within which the entire structure, utilities, and deployment/retraction mechanism are stowed during launch. The end adapter secures the foregoing components to the housing during launch. The main housing and adapter provide the necessary building-block-to-building-block attachments for automatically deployable platforms. Removal from the shuttle cargo bay can be accomplished with the remote manipulator system (RMS) and/or the handling and positioning aid (HAPA). In this concept, all the electrical connections are in place prior to launch with automatic latches for payload attachment provided on either the end adapters or housings. The housings also can contain orbiter docking ports for payload installation and maintenance.
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Structural Insights into Functional Overlapping and Differentiation among Myosin V Motors*
Nascimento, Andrey F. Z.; Trindade, Daniel M.; Tonoli, Celisa C. C.; de Giuseppe, Priscila O.; Assis, Leandro H. P.; Honorato, Rodrigo V.; de Oliveira, Paulo S. L.; Mahajan, Pravin; Burgess-Brown, Nicola A.; von Delft, Frank; Larson, Roy E.; Murakami, Mario T.
2013-01-01
Myosin V (MyoV) motors have been implicated in the intracellular transport of diverse cargoes including vesicles, organelles, RNA-protein complexes, and regulatory proteins. Here, we have solved the cargo-binding domain (CBD) structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the CBD dimerization process, which is unique for the MyoVc subclass. Moreover, the cargo- and motor-binding sites were structurally assigned, indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high resolution insights into motor domain inhibition by CBD. These results contribute to understanding the structural requirements for cargo transport, autoinhibition, and regulatory mechanisms in myosin V motors. PMID:24097982
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2011-01-01
Many bacterial species contain intracellular nano- and micro-compartments consisting of self-assembling proteins that form protein-only shells. These structures are built up by combinations of a reduced number of repeated elements, from 60 repeated copies of one unique structural element self-assembled in encapsulins of 24 nm to 10,000-20,000 copies of a few protein species assembled in a organelle of around 100-150 nm in cross-section. However, this apparent simplicity does not correspond to the structural and functional sophistication of some of these organelles. They package, by not yet definitely solved mechanisms, one or more enzymes involved in specific metabolic pathways, confining such reactions and sequestering or increasing the inner concentration of unstable, toxics or volatile intermediate metabolites. From a biotechnological point of view, we can use the self assembling properties of these particles for directing shell assembling and enzyme packaging, mimicking nature to design new applications in biotechnology. Upon appropriate engineering of the building blocks, they could act as a new family of self-assembled, protein-based vehicles in Nanomedicine to encapsulate, target and deliver therapeutic cargoes to specific cell types and/or tissues. This would provide a new, intriguing platform of microbial origin for drug delivery. PMID:22046962
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Yildiz, Ibrahim; Lee, Karin L.; Chen, Kevin; Shukla, Sourabh; Steinmetz, Nicole F.
2013-01-01
This work is focused on the development of a plant virus-based carrier system for cargo delivery, specifically 30 nm-sized cowpea mosaic virus (CPMV). Whereas previous reports described the engineering of CPMV through genetic or chemical modification, we report a non-covalent infusion technique that facilitates efficient cargo loading. Infusion and retention of 130–155 fluorescent dye molecules per CPMV using DAPI (4’,6-diamidino-2-phenylindole dihydrochloride), propidium iodide (3,8-diamino-5-[3-(diethylmethylammonio)propyl]-6-phenylphenanthridinium diiodide), and acridine orange (3,6-bis(dimethylamino)acridinium chloride), as well as 140 copies of therapeutic payload proflavine (PF, acridine-3,6-diamine hydrochloride), is reported. Loading is achieved through interaction of the cargo with the CPMV’s encapsidated RNA molecules. The loading mechanism is specific; empty RNA-free eCPMV nanoparticles could not be loaded. Cargo-infused CPMV nanoparticles remain chemically active, and surface lysine residues were covalent modified with dyes leading to the development of dual-functional CPMV carrier systems. We demonstrate cargo-delivery to a panel of cancer cells (cervical, breast, and colon): CPMV nanoparticles enter cells via the surface marker vimentin, the nanoparticles target the endolysosome, where the carrier is degraded and the cargo released allowing imaging and/or cell killing. In conclusion, we demonstrate cargo-infusion and delivery to cells; the methods discussed provide a useful means for functionalization of CPMV toward its application as drug and/or contrast agent delivery vehicle. PMID:23665254
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The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles
Topalidou, Irini; Cattin-Ortolá, Jérôme; MacCoss, Michael J.
2016-01-01
The dense-core vesicle is a secretory organelle that mediates the regulated release of peptide hormones, growth factors, and biogenic amines. Dense-core vesicles originate from the trans-Golgi of neurons and neuroendocrine cells, but it is unclear how this specialized organelle is formed and acquires its specific cargos. To identify proteins that act in dense-core vesicle biogenesis, we performed a forward genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We previously reported the identification of two conserved proteins that interact with the small GTPase RAB-2 to control normal dense-core vesicle cargo-sorting. Here we identify several additional conserved factors important for dense-core vesicle cargo sorting: the WD40 domain protein EIPR-1 and the endosome-associated recycling protein (EARP) complex. By assaying behavior and the trafficking of dense-core vesicle cargos, we show that mutants that lack EIPR-1 or EARP have defects in dense-core vesicle cargo-sorting similar to those of mutants in the RAB-2 pathway. Genetic epistasis data indicate that RAB-2, EIPR-1 and EARP function in a common pathway. In addition, using a proteomic approach in rat insulinoma cells, we show that EIPR-1 physically interacts with the EARP complex. Our data suggest that EIPR-1 is a new interactor of the EARP complex and that dense-core vesicle cargo sorting depends on the EARP-dependent trafficking of cargo through an endosomal sorting compartment. PMID:27191843
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Code of Federal Regulations, 2014 CFR
2014-07-01
... alarm and shutdown shown on the piping and instrumentation diagrams (P&IDs) and reviewed in the hazard... cleaning facility; and that (5) The automatic liquid block valve successfully stops flow of liquid to the... automatically stop the cargo flow to each transfer hose simultaneously, in the event an upset condition occurs...
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Herzig, Yonatan; Sharpe, Hayley J; Elbaz, Yael; Munro, Sean; Schuldiner, Maya
2012-01-01
The endoplasmic reticulum (ER) is the site of synthesis of secreted and membrane proteins. To exit the ER, proteins are packaged into COPII vesicles through direct interaction with the COPII coat or aided by specific cargo receptors. Despite the fundamental role of such cargo receptors in protein traffic, only a few have been identified; their cargo spectrum is unknown and the signals they recognize remain poorly understood. We present here an approach we term "PAIRS" (pairing analysis of cargo receptors), which combines systematic genetic manipulations of yeast with automated microscopy screening, to map the spectrum of cargo for a known receptor or to uncover a novel receptor for a particular cargo. Using PAIRS we followed the fate of ∼150 cargos on the background of mutations in nine putative cargo receptors and identified novel cargo for most of these receptors. Deletion of the Erv14 cargo receptor affected the widest range of cargo. Erv14 substrates have a wide array of functions and structures; however, they are all membrane-spanning proteins of the late secretory pathway or plasma membrane. Proteins residing in these organelles have longer transmembrane domains (TMDs). Detailed examination of one cargo supported the hypothesis that Erv14 dependency reflects the length rather than the sequence of the TMD. The PAIRS approach allowed us to uncover new cargo for known cargo receptors and to obtain an unbiased look at specificity in cargo selection. Obtaining the spectrum of cargo for a cargo receptor allows a novel perspective on its mode of action. The rules that appear to guide Erv14 substrate recognition suggest that sorting of membrane proteins at multiple points in the secretory pathway could depend on the physical properties of TMDs. Such a mechanism would allow diverse proteins to utilize a few receptors without the constraints of evolving location-specific sorting motifs.
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Pashkova, Natasha; Gakhar, Lokesh; Winistorfer, Stanley; Sunshine, Anna B.; Rich, Matthew; Dunham, Maitreya J.; Yu, Liping; Piper, Robert
2013-01-01
SUMMARY Sorting of ubiquitinated membrane proteins into lumenal vesicles of multivesicular bodies is mediated by the ESCRT apparatus and accessory proteins such as Bro1, which recruits the deubiquitinating enzyme Doa4 to remove ubiquitin from cargo. Here we propose that Bro1 works as a receptor for the selective sorting of ubiquitinated cargos. We found synthetic genetic interactions between BRO1 and ESCRT-0, suggesting Bro1 functions similarly to ESCRT-0. Multiple structural approaches demonstrated that Bro1 binds ubiquitin via the N-terminal trihelical arm of its middle V domain. Mutants of Bro1 that lack the ability to bind Ub were dramatically impaired in their ability to sort Ub-cargo membrane proteins, but only when combined with hypomorphic alleles of ESCRT-0. These data suggest that Bro1 and other Bro1 family members function in parallel with ESCRT-0 to recognize and sort Ub-cargos. PMID:23726974
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Yildiz, Ibrahim; Lee, Karin L; Chen, Kevin; Shukla, Sourabh; Steinmetz, Nicole F
2013-12-10
This work is focused on the development of a plant virus-based carrier system for cargo delivery, specifically 30nm-sized cowpea mosaic virus (CPMV). Whereas previous reports described the engineering of CPMV through genetic or chemical modification, we report a non-covalent infusion technique that facilitates efficient cargo loading. Infusion and retention of 130-155 fluorescent dye molecules per CPMV using DAPI (4',6-diamidino-2-phenylindole dihydrochloride), propidium iodide (3,8-diamino-5-[3-(diethylmethylammonio)propyl]-6-phenylphenanthridinium diiodide), and acridine orange (3,6-bis(dimethylamino)acridinium chloride), as well as 140 copies of therapeutic payload proflavine (PF, acridine-3,6-diamine hydrochloride), is reported. Loading is achieved through interaction of the cargo with the CPMV's encapsidated RNA molecules. The loading mechanism is specific; empty RNA-free eCPMV nanoparticles could not be loaded. Cargo-infused CPMV nanoparticles remain chemically active, and surface lysine residues were covalent modified with dyes leading to the development of dual-functional CPMV carrier systems. We demonstrate cargo-delivery to a panel of cancer cells (cervical, breast, and colon): CPMV nanoparticles enter cells via the surface marker vimentin, the nanoparticles target the endolysosome, where the carrier is degraded and the cargo is released allowing imaging and/or cell killing. In conclusion, we demonstrate cargo-infusion and delivery to cells; the methods discussed provide a useful means for functionalization of CPMV toward its application as drug and/or contrast agent delivery vehicle. Copyright © 2013 Elsevier B.V. All rights reserved.
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Tabujew, Ilja; Freidel, Christoph; Krieg, Bettina; Helm, Mark; Koynov, Kaloian; Müllen, Klaus; Peneva, Kalina
2014-07-01
Here, the preparation of a novel block copolymer consisting of a statistical copolymer N-(2-hydroxypropyl) methacrylamide-s-N-(3-aminopropyl) methacrylamide and a short terminal 3-guanidinopropyl methacrylamide block is reported. This polymer structure forms neutral but water-soluble nanosized complexes with siRNA. The siRNA block copolymer complexes are first analyzed using agarose gel electrophoresis and their size is determined with fluorescence correlation spectroscopy. The protective properties of the polymer against RNA degradation are investigated by treating the siRNA block copolymer complexes with RNase V1. Heparin competition assays confirm the efficient release of the cargo in vitro. In addition, the utilization of microscale thermophoresis is demonstrated for the determination of the binding strength between a fluorescently labeled polyanion and a polymer molecule. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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49 CFR 393.118 - What are the rules for securing dressed lumber or similar building products?
Code of Federal Regulations, 2010 CFR
2010-10-01
... Shifting and Falling Cargo Specific Securement Requirements by Commodity Type § 393.118 What are the rules... transported using no more than one tier. Bundles carried on one tier must be secured in accordance with the... one tier. Bundles carried in more than one tier must be either: (1) Blocked against lateral movement...
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Structural basis of cargo recognitions for class V myosins
Wei, Zhiyi; Liu, Xiaotian; Yu, Cong; Zhang, Mingjie
2013-01-01
Class V myosins (MyoV), the most studied unconventional myosins, recognize numerous cargos mainly via the motor’s globular tail domain (GTD). Little is known regarding how MyoV-GTD recognizes such a diverse array of cargos specifically. Here, we solved the crystal structures of MyoVa-GTD in its apo-form and in complex with two distinct cargos, melanophilin and Rab interacting lysosomal protein-like 2. The apo-MyoVa-GTD structure indicates that most mutations found in patients with Griscelli syndrome, microvillus inclusion disease, or cancers or in “dilute” rodents likely impair the folding of GTD. The MyoVa-GTD/cargo complex structure reveals two distinct cargo-binding surfaces, one primarily via charge–charge interaction and the other mainly via hydrophobic interactions. Structural and biochemical analysis reveal the specific cargo-binding specificities of various isoforms of mammalian MyoV as well as very different cargo recognition mechanisms of MyoV between yeast and higher eukaryotes. The MyoVa-GTD structures resolved here provide a framework for future functional studies of vertebrate class V myosins. PMID:23798443
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Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L; Lata, James P; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M; Bergkvist, Magnus; Sherwood, Robert W; Zhang, Sheng; Travis, Alexander J
2017-01-02
For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Mukai, Chinatsu; Gao, Lizeng; Nelson, Jacquelyn L.; Lata, James P.; Cohen, Roy; Wu, Lauren; Hinchman, Meleana M.; Bergkvist, Magnus; Sherwood, Robert W.; Zhang, Sheng; Travis, Alexander J.
2016-01-01
For nanobiotechnology to achieve its potential, complex organic-inorganic systems must grow to utilize the sequential functions of multiple biological components. Critical challenges exist: immobilizing enzymes can block substrate-binding sites or prohibit conformational changes, substrate composition can interfere with activity, and multistep reactions risk diffusion of intermediates. As a result, the most complex tethered reaction reported involves only 3 enzymes. Inspired by the oriented immobilization of glycolytic enzymes on the fibrous sheath of mammalian sperm, here we show a complex reaction of 10 enzymes tethered to nanoparticles. Although individual enzyme efficiency was higher in solution, the efficacy of the 10-step pathway measured by conversion of glucose to lactate was significantly higher when tethered. To our knowledge, this is the most complex organic-inorganic system described, and it shows that tethered, multi-step biological pathways can be reconstituted in hybrid systems to carry out functions such as energy production or delivery of molecular cargo. PMID:27901298
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Biogenesis and Function of Multivesicular Bodies
Piper, Robert C.; Katzmann, David J.
2010-01-01
The two major cellular sites for membrane protein degradation are the proteasome and the lysosome. Ubiquitin attachment is a sorting signal for both degradation routes. For lysosomal degradation, ubiquitination triggers the sorting of cargo proteins into the lumen of late endosomal multivesicular bodies (MVBs)/endosomes. MVB formation occurs when a portion of the limiting membrane of an endosome invaginates and buds into its own lumen. Intralumenal vesicles are degraded when MVBs fuse to lysosomes. The proper delivery of proteins to the MVB interior relies on specific ubiquitination of cargo, recognition and sorting of ubiquitinated cargo to endosomal subdomains, and the formation and scission of cargo-filled intralumenal vesicles. Over the past five years, a number of proteins that may directly participate in these aspects of MVB function and biogenesis have been identified. However, major questions remain as to exactly what these proteins do at the molecular level and how they may accomplish these tasks. PMID:17506697
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Amateur Radio on the International Space Station: The First Operational Payload on the ISS
NASA Technical Reports Server (NTRS)
Bauer, Frank H.; McFadin, Lou; Steiner, Mark D.; Conley, Carolynn L.
2002-01-01
As astronauts and cosmonauts have adapted to life on the International Space Station (ISS), they have found amateur radio and its connection to life on Earth to be a important on-board companion and a substantial psychological boost. Since its first use in November 2000, the first five expedition crews have utilized the amateur radio station in the Functional Cargo Block (also referred to as the FGB or Zarya module) to talk to thousands of students in schools, to their families on Earth, and to amateur radio operators around the world. This paper will discuss the development, qualification, installation and operation of the amateur radio system. It will also discuss some of the challenges that the amateur radio international team of volunteers overcame to bring its first phase of equipment on ISS to fruition.
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Li, Zixian; de Barros, Andre Luis Branco; Soares, Daniel Cristian Ferreira; Moss, Sara Nicole; Alisaraie, Laleh
2017-05-30
The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.
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NanoShuttles: Harnessing Motor Proteins to Transport Cargo in Synthetic Environments
NASA Astrophysics Data System (ADS)
Vogel, V.; Hess, H.
Motors have become a crucial commodity in our daily lives, from transportation to driving conveyor belts that enable the sequential assembly of cars and other industrial machines. For the sequential assembly of building blocks at the nanoscale that would not assemble spontaneously into larger functional systems, however, active transport systems are not yet available. In contrast, cells have evolved sophisticated molecular machinery that drives movement and active transport. Driven by the conversion of chemical into mechanical energy, namely through hydrolysis of the biological fuel ATP, molecular motors enable cells to operate far away from equilibrium by transporting organelles and molecules to designated locations within the cell, often against concentration gradients. Inspired by the biological concept of active transport, major efforts are underway to learn how to build nanoscale transport systems that are driven by molecular motors. Emerging engineering principles are discussed of how to build tracks and junctions to guide such nanoshuttles, how to load them with cargo and control their speed, how to use active transport to assemble mesoscopic structures that would otherwise not assemble spontaneously and what polymeric materials to choose to integrate motors into MEMS and other biohybrid devices. Finally, two applications that exploit the physical properties of microtubules are discussed, surface imaging by a swarm of microtubules and a self-assembled picoNewton force meter to probe receptor-ligand interactions.
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2016-12-01
laboratory. The transition of this function to the commercial sector under Firm Fixed-Price contracting has forced both NASA and commercial providers to...adjust to make this effort successful. Improving bag-level cargo launch manifests delivered from NASA to the provider more than a year in advance is...contracting has forced both NASA and commercial providers to adjust to make this effort successful. Improving bag-level cargo launch manifests delivered from
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Cargo crowding at actin-rich regions along axons causes local traffic jams.
Sood, Parul; Murthy, Kausalya; Kumar, Vinod; Nonet, Michael L; Menon, Gautam I; Koushika, Sandhya P
2018-03-01
Steady axonal cargo flow is central to the functioning of healthy neurons. However, a substantial fraction of cargo in axons remains stationary up to several minutes. We examine the transport of precursors of synaptic vesicles (pre-SVs), endosomes and mitochondria in Caenorhabditis elegans touch receptor neurons, showing that stationary cargo are predominantly present at actin-rich regions along the neuronal process. Stationary vesicles at actin-rich regions increase the propensity of moving vesicles to stall at the same location, resulting in traffic jams arising from physical crowding. Such local traffic jams at actin-rich regions are likely to be a general feature of axonal transport since they also occur in Drosophila neurons. Repeated touch stimulation of C. elegans reduces the density of stationary pre-SVs, indicating that these traffic jams can act as both sources and sinks of vesicles. This suggests that vesicles trapped in actin-rich regions are functional reservoirs that may contribute to maintaining robust cargo flow in the neuron. A video abstract of this article can be found at: Video S1; Video S2. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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LC3/GABARAP family proteins: autophagy-(un)related functions.
Schaaf, Marco B E; Keulers, Tom G; Vooijs, Marc A; Rouschop, Kasper M A
2016-12-01
From yeast to mammals, autophagy is an important mechanism for sustaining cellular homeostasis through facilitating the degradation and recycling of aged and cytotoxic components. During autophagy, cargo is captured in double-membraned vesicles, the autophagosomes, and degraded through lysosomal fusion. In yeast, autophagy initiation, cargo recognition, cargo engulfment, and vesicle closure is Atg8 dependent. In higher eukaryotes, Atg8 has evolved into the LC3/GABARAP protein family, consisting of 7 family proteins [LC3A (2 splice variants), LC3B, LC3C, GABARAP, GABARAPL1, and GABARAPL2]. LC3B, the most studied family protein, is associated with autophagosome development and maturation and is used to monitor autophagic activity. Given the high homology, the other LC3/GABARAP family proteins are often presumed to fulfill similar functions. Nevertheless, substantial evidence shows that the LC3/GABARAP family proteins are unique in function and important in autophagy-independent mechanisms. In this review, we discuss the current knowledge and functions of the LC3/GABARAP family proteins. We focus on processing of the individual family proteins and their role in autophagy initiation, cargo recognition, vesicle closure, and trafficking, a complex and tightly regulated process that requires selective presentation and recruitment of these family proteins. In addition, functions unrelated to autophagy of the LC3/GABARAP protein family members are discussed.-Schaaf, M. B. E., Keulers, T. G, Vooijs, M. A., Rouschop, K. M. A. LC3/GABARAP family proteins: autophagy-(un)related functions. © FASEB.
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Effect of fuel concentration on cargo transport by a team of Kinesin motors
NASA Astrophysics Data System (ADS)
Takshak, Anjneya; Mishra, Nirvantosh; Kulkarni, Aditi; Kunwar, Ambarish
2017-02-01
Eukaryotic cells employ specialized proteins called molecular motors for transporting organelles and vesicles from one location to another in a regulated and directed manner. These molecular motors often work collectively in a team while transporting cargos. Molecular motors use cytoplasmic ATP as fuel, which is hydrolyzed to generate mechanical force. While the effect of ATP concentration on cargo transport by single Kinesin motor function is well understood, it is still unexplored, both theoretically and experimentally, how ATP concentration would affect cargo transport by a team of Kinesin motors. For instance, how does fuel concentration affect the travel distances and travel velocities of cargo? How cooperativity of Kinesin motors engaged on a cargo is affected by ATP concentration? To answer these questions, here we develop mechano-chemical models of cargo transport by a team of Kinesin motors. To develop these models we use experimentally-constrained mechano-chemical model of a single Kinesin motor as well as earlier developed mean-field and stochastic models of load sharing for cargo transport. Thus, our new models for cargo transport by a team of Kinesin motors include fuel concentration explicitly, which was not considered in earlier models. We make several interesting predictions which can be tested experimentally. For instance, the travel distances of cargos are very large at limited ATP concentrations in spite of very small travel velocity. Velocities of cargos driven by multiple Kinesin have a Michaelis-Menten dependence on ATP concentration. Similarly, cooperativity among the engaged Kinesin motors on the cargo shows a Michaelis-Menten type dependence, which attains a maximum value near physiological ATP concentrations. Our new results can be potentially useful in controlling artificial nano-molecular shuttles precisely for targeted delivery in various nano-technological applications.
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Cargo-Delivery Platforms for Targeted Delivery of Inhibitor Cargos Against Botulism
Wilson, Brenda A.; Ho, Mengfei
2015-01-01
Delivering therapeutic cargos to specific cell types in vivo poses many technical challenges. There is currently a plethora of drug leads and therapies against numerous diseases, ranging from small molecule compounds to nucleic acids to peptides to proteins with varying binding or enzymatic functions. Many of these candidate therapies have documented potential for mitigating or reversing disease symptoms, if only a means for gaining access to the intracellular target were available. Recent advances in our understanding of the biology of cellular uptake and transport processes and the mode of action of bacterial protein toxins have accelerated the development of toxin-based cargo-delivery vehicle platforms. This review provides an updated survey of the status of available platforms for targeted delivery of therapeutic cargos, outlining various strategies that have been used to deliver different types of cargo into cells. Particular emphasis is placed on the application of toxin-based approaches, examining critical issues that have hampered realization of post-intoxication antitoxins against botulism. PMID:25335885
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Cargo-delivery platforms for targeted delivery of inhibitor cargos against botulism.
Wilson, Brenda A; Ho, Mengfei
2014-01-01
Delivering therapeutic cargos to specific cell types in vivo poses many technical challenges. There is currently a plethora of drug leads and therapies against numerous diseases, ranging from small molecule compounds to nucleic acids to peptides to proteins with varying binding or enzymatic functions. Many of these candidate therapies have documented potential for mitigating or reversing disease symptoms, if only a means for gaining access to the intracellular target were available. Recent advances in our understanding of the biology of cellular uptake and transport processes and the mode of action of bacterial protein toxins have accelerated the development of toxin-based cargo-delivery vehicle platforms. This review provides an updated survey of the status of available platforms for targeted delivery of therapeutic cargos, outlining various strategies that have been used to deliver different types of cargo into cells. Particular emphasis is placed on the application of toxin-based approaches, examining critical issues that have hampered realization of post-intoxication antitoxins against botulism.
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Rotational dynamics of cargos at pauses during axonal transport.
Gu, Yan; Sun, Wei; Wang, Gufeng; Jeftinija, Ksenija; Jeftinija, Srdija; Fang, Ning
2012-01-01
Direct visualization of axonal transport in live neurons is essential for our understanding of the neuronal functions and the working mechanisms of microtubule-based motor proteins. Here we use the high-speed single particle orientation and rotational tracking technique to directly visualize the rotational dynamics of cargos in both active directional transport and pausing stages of axonal transport, with a temporal resolution of 2 ms. Both long and short pauses are imaged, and the correlations between the pause duration, the rotational behaviour of the cargo at the pause, and the moving direction after the pause are established. Furthermore, the rotational dynamics leading to switching tracks are visualized in detail. These first-time observations of cargo's rotational dynamics provide new insights on how kinesin and dynein motors take the cargo through the alternating stages of active directional transport and pause.
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A multioutput cost function for port terminals : some guidelines for regulation
DOT National Transportation Integrated Search
2003-10-01
Cargo handling in ports is a multi-output activity, as freight can arrive in many forms such as containers, bulk, rolling stock, or non-containerized general cargo. Port regulation is not an easy task considering the diversity of activities that occu...
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Verification and Implementation of Operations Safety Controls for Flight Missions
NASA Technical Reports Server (NTRS)
Jones, Cheryl L.; Smalls, James R.; Carrier, Alicia S.
2010-01-01
Approximately eleven years ago, the International Space Station launched the first module from Russia, the Functional Cargo Block (FGB). Safety and Mission Assurance (S&MA) Operations (Ops) Engineers played an integral part in that endeavor by executing strict flight product verification as well as continued staffing of S&MA's console in the Mission Evaluation Room (MER) for that flight mission. How were these engineers able to conduct such a complicated task? They conducted it based on product verification that consisted of ensuring that safety requirements were adequately contained in all flight products that affected crew safety. S&MA Ops engineers apply both systems engineering and project management principles in order to gain a appropriate level of technical knowledge necessary to perform thorough reviews which cover the subsystem(s) affected. They also ensured that mission priorities were carried out with a great detail and success.
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Micromotors Spontaneously Neutralize Gastric Acid for pH-Responsive Payload Release.
Li, Jinxing; Angsantikul, Pavimol; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Thamphiwatana, Soracha; Xu, Mingli; Sandraz, Elodie; Wang, Xiaolei; Delezuk, Jorge; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph
2017-02-13
The highly acidic gastric environment creates a physiological barrier for using therapeutic drugs in the stomach. While proton pump inhibitors have been widely used for blocking acid-producing enzymes, this approach can cause various adverse effects. Reported herein is a new microdevice, consisting of magnesium-based micromotors which can autonomously and temporally neutralize gastric acid through efficient chemical propulsion in the gastric fluid by rapidly depleting the localized protons. Coating these micromotors with a cargo-containing pH-responsive polymer layer leads to autonomous release of the encapsulated payload upon gastric-acid neutralization by the motors. Testing in a mouse model demonstrate that these motors can safely and rapidly neutralize gastric acid and simultaneously release payload without causing noticeable acute toxicity or affecting the stomach function, and the normal stomach pH is restored within 24 h post motor administration. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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NASA Astrophysics Data System (ADS)
Molla, Mijanur Rahaman; Rangadurai, Poornima; Antony, Lucas; Swaminathan, Subramani; de Pablo, Juan J.; Thayumanavan, S.
2018-06-01
Nature has engineered exquisitely responsive systems where molecular-scale information is transferred across an interface and propagated over long length scales. Such systems rely on multiple interacting, signalling and adaptable molecular and supramolecular networks that are built on dynamic, non-equilibrium structures. Comparable synthetic systems are still in their infancy. Here, we demonstrate that the light-induced actuation of a molecularly thin interfacial layer, assembled from a hydrophilic- azobenzene -hydrophobic diblock copolymer, can result in a reversible, long-lived perturbation of a robust glassy membrane across a range of over 500 chemical bonds. We show that the out-of-equilibrium actuation is caused by the photochemical trans-cis isomerization of the azo group, a single chemical functionality, in the middle of the interfacial layer. The principles proposed here are implemented in water-dispersed nanocapsules, and have implications for on-demand release of embedded cargo molecules.
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STS-88 Onboard Photograph - The Unity Module and the Zarya
NASA Technical Reports Server (NTRS)
1998-01-01
This photograph taken during the STS-88 mission, shows the cornected Zarya (top with solar wings) and the Unity Module after having been released from the Orbiter Endeavour's cargo bay. The Unity (also called Node 1), the first U.S. Module for the International Space Station (ISS), is a six-sided connector to which all future U.S. Station modules will attach and was manufactured by the Boeing Company at the Marshall Space Flight Center from 1994 to 1997. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian built Functional Energy Block (FGB). The Zarya was launched on a Russian proton rocket prior to the launch of the Unity. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.
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2013-12-10
CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, three members of the STS-88 space shuttle crew speak to spaceport employees during a celebration commemorating the 15th anniversary of the start of assembly of the International Space Station. On stage, from the left, are mission specialist Nancy Currie and Jerry Ross, along with and mission commander Bob Cabana, who is Kennedy's director. The Russian Space Agency's Functional Cargo Block, named "Zarya," was launched from the Baikonur Cosmodrome in Kazakhstan on Nov. 20, 1998. Two weeks later, on Dec. 4, 1998, the space shuttle Endeavour lifted off from Kennedy on STS-88 with node 1, called "Unity." In addition to Cabana, Curie and Ross, the crew also included pilot Rick Sturckow, along with mission specialists Jim Newman and Sergei Krikalev, a Russian cosmonaut. For more information, visit: http://www.nasa.gov/mission_pages/station/main/index.html Photo credit: NASA/Jim Grossman
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Cytosolic delivery of multi-domain cargos by the N-terminus of Pasteurella multocida toxin.
Clemons, Nathan C; Bannai, Yuka; Haywood, Elizabeth E; Xu, Yiting; Buschbach, James D; Ho, Mengfei; Wilson, Brenda A
2018-05-21
The zoonotic pathogen Pasteurella multocida produces a 146-kDa modular toxin (PMT) that enters host cells and manipulates intracellular signaling through action on its Gα-protein targets. The N-terminus of PMT (PMT-N) mediates cellular uptake through receptor-mediated endocytosis, followed by delivery of the C-terminal catalytic domain from acidic endosomes into the cytosol. The putative native cargo of PMT consists of a 710-residue polypeptide of three distinct modular subdomains (C1-C2-C3), where C1 contains a membrane localization domain (MLD), C2 has as-of-yet undefined function, and C3 catalyzes deamidation of a specific active-site glutamine residue in Gα-protein targets. However, whether the three cargo subdomains are delivered intact or undergo further proteolytic processing during or after translocation from the late endosome is unclear. Here, we demonstrate that PMT-N mediates delivery of its native C-terminal cargo as a single polypeptide, corresponding to C1-C2-C3, including the MLD, with no evidence of cleavage between subdomains. We show that PMT-N also delivers into the cytosol non-native GFP cargo, further supporting that the receptor-binding and translocation functions reside within PMT-N. Our findings further show that PMT-N can deliver C1-C2 alone but that the presence of C1-C2 is important for cytosolic delivery of the catalytic C3 subdomain by PMT-N. In addition, we further refine the minimum C3 domain required for intracellular activity as comprising residues 1105-1278. These findings reinforce that PMT-N serves as the cytosolic delivery vehicle for C-terminal cargo and demonstrate that its native cargo is delivered intact as C1-C2-C3. Copyright © 2018 American Society for Microbiology.
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Cargo Logistics Airlift Systems Study (CLASS). Volume 2: Case study approach and results
NASA Technical Reports Server (NTRS)
Burby, R. J.; Kuhlman, W. H.
1978-01-01
Models of transportation mode decision making were developed. The user's view of the present and future air cargo systems is discussed. Issues summarized include: (1) organization of the distribution function; (2) mode choice decision making; (3) air freight system; and (4) the future of air freight.
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Dendritic trafficking faces physiologically critical speed-precision tradeoffs
Williams, Alex H.; O'Donnell, Cian; Sejnowski, Terrence J.; ...
2016-12-30
Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’. Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimatesmore » of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.« less
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Dendritic trafficking faces physiologically critical speed-precision tradeoffs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, Alex H.; O'Donnell, Cian; Sejnowski, Terrence J.
Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’. Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimatesmore » of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. In conclusion, these findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons.« less
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Targeting SQSTM1/p62 Induces Cargo Loading Failure and Converts Autophagy to Apoptosis via NBK/Bik
Chen, Shuang; Zhou, Liang; Zhang, Yu; Leng, Yun; Pei, Xin-Yan; Lin, Hui; Jones, Richard; Orlowski, Robert Z.
2014-01-01
In selective autophagy, the adaptor protein SQSTM1/p62 plays a critical role in recognizing/loading cargo (e.g., malfolded proteins) into autophagosomes for lysosomal degradation. Here we report that whereas SQSTM1/p62 levels fluctuated in a time-dependent manner during autophagy, inhibition or knockdown of Cdk9/cyclin T1 transcriptionally downregulated SQSTM1/p62 but did not affect autophagic flux. These interventions, or short hairpin RNA (shRNA) directly targeting SQSTM1/p62, resulted in cargo loading failure and inefficient autophagy, phenomena recently described for Huntington's disease neurons. These events led to the accumulation of the BH3-only protein NBK/Bik on endoplasmic reticulum (ER) membranes, most likely by blocking loading and autophagic degradation of NBK/Bik, culminating in apoptosis. Whereas NBK/Bik upregulation was further enhanced by disruption of distal autophagic events (e.g., autophagosome maturation) by chloroquine (CQ) or Lamp2 shRNA, it was substantially diminished by inhibition of autophagy initiation (e.g., genetically by shRNA targeting Ulk1, beclin-1, or Atg5 or pharmacologically by 3-methyladenine [3-MA] or spautin-1), arguing that NBK/Bik accumulation stems from inefficient autophagy. Finally, NBK/Bik knockdown markedly attenuated apoptosis in vitro and in vivo. Together, these findings identify novel cross talk between autophagy and apoptosis, wherein targeting SQSTM1/p62 converts cytoprotective autophagy to an inefficient form due to cargo loading failure, leading to NBK/Bik accumulation, which triggers apoptosis. PMID:25002530
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The Advanced Re-Entry Vehicle (ARV) A Development Step From ATV Toward Manned Transportation Systems
NASA Astrophysics Data System (ADS)
Bottacini, Massimiliano; Berthe, Philippe; Vo, Xavier; Pietsch, Klaus
2011-05-01
The Advanced Re-entry Vehicle (ARV) programme has been undertaken by Europe with the objective to contribute to the preparation of a future European crew transportation system, while providing a valuable logistic support to the ISS through an operational cargo return system. This development would allow: - the early acquisition of critical technologies; - the design, development and testing of elements suitable for the follow up human rated transportation system. These vehicles should also serve future LEO infrastructures and exploration missions. With the aim to satisfy the above objectives a team composed by major European industries and led by EADS Astrium Space Transportation is currently conducting the phase A of the programme under contract with the European Space Agency (ESA). Two vehicle versions are being investigated: a Cargo version, transporting cargo only to/from the ISS, and a Crew version, which will allow the transfer of both crew and cargo to/from the ISS. The ARV Cargo version, in its present configuration, is composed of three modules. The Versatile Service Module (VSM) provides to the system the propulsion/GNC for orbital manoeuvres and attitude control and the orbital power generation. Its propulsion system and GNC shall be robust enough to allow its use for different launch stacks and different LEO missions in the future. The Un-pressurised Cargo Module (UCM) provides the accommodation for about 3000 kg of unpressurised cargo and is to be sufficiently flexible to ensure the transportation of: - orbital infrastructure components (ORU’s); - scientific / technological experiments; - propellant for re-fuelling, re-boost (and de-orbiting) of the ISS. The Re-entry Module (RM) provides a pressurized volume to accommodate active/passive cargo (2000 kg upload/1500 kg download). It is conceived as an expendable conical capsule with spherical heat-shield, interfacing with the new docking standard of the ISS, i.e. it carries the IBDM docking system, on a dedicated adapter. Its thermo-mechanical design, GNC, descent & landing systems take into account its future evolution for crew transportation. The ARV Crew version is also composed of three main modules: - an Integrated Resource Module (IRM) providing the main propulsion and power functions during the on-orbit phases of the mission; - a Re-entry Module (RM) providing the re-entry function and a pressurized environment for four crew members and about 250 kg of passive / active cargo; - a Crew Escape System (CES) providing the function of emergency separation of the RM from the launcher (in case of failure of this latter). The paper presents an overview of the ARV Cargo and Crew versions requirements derived from the above objectives, their mission scenarios, system architectures and performances. The commonality aspects between the ARV Cargo version and future transportation systems (including also the ARV Crew version and logistic carriers) are also highlighted.
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The Advanced Re-Entry Vehicle (ARV) a Development Step from ATV Toward Manned Transportation Systems
NASA Astrophysics Data System (ADS)
Bottacini, M.; Berthe, P.; Vo, X.; Pietsch, K.
2011-08-01
The Advanced Re-entry Vehicle (ARV) programme has been undertaken by Europe with the objective to contribute to the preparation of a future European crew transportation system, while providing a valuable logistic support to the ISS through an operational cargo return system. This development would allow: - the early acquisition of critical technologies; - the design, development and testing of elements suitable for the follow up human rated transportation system. These vehicles should also serve future LEO infrastructures and exploration missions. With the aim to satisfy the above objectives a team composed by major European industries and led by EADS Astrium Space Transportation is currently conducting the phase A of the programme under contract with the European Space Agency (ESA). Two vehicle versions are being investigated: a Cargo version, transporting cargo only to/from the ISS, and a Crew version, which will allow the transfer of both crew and cargo to/from the ISS. The ARV Cargo version, in its present configuration, is composed of three modules. The Versatile Service Module (VSM) provides to the system the propulsion/GNC for orbital manoeuvres and attitude control and the orbital power generation. Its propulsion system and GNC shall be robust enough to allow its use for different launch stacks and different LEO missions in the future. The Un-pressurised Cargo Module (UCM) provides the accommodation for about 3000 kg of un-pressurised cargo and is to be sufficiently flexible to ensure the transportation of: - orbital infrastructure components (ORU's); - scientific / technological experiments; - propellant for re-fuelling, re-boost (and deorbiting) of the ISS. The Re-entry Module (RM) provides a pressurized volume to accommodate active/passive cargo (2000 kg upload/1500 kg download). It is conceived as an expendable conical capsule with spherical heat- hield, interfacing with the new docking standard of the ISS, i.e. it carries the IBDM docking system, on a dedicated adapter. Its thermo-mechanical design, GNC, descent & landing systems take into account its future evolution for crew transportation. The ARV Crew version is also composed of three main modules: - an Integrated Resource Module (IRM) providing the main propulsion and power functions during the on-orbit phases of the mission; - a Re-entry Module (RM) providing the re-entry function and a pressurized environment for four crew members and about 250 kg of passive / active cargo; - a Crew Escape System (CES) providing the function of emergency separation of the RM from the launcher (in case of failure of this latter). The paper presents an overview of the ARV Cargo and Crew versions requirements derived from the above objectives, their mission scenarios, system architectures and performances. The commonality aspects between the ARV Cargo version and future transportation systems (including also the ARV Crew version and logistic carriers) are also highlighted.
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Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling
Kurup, Naina; Yan, Dong; Goncharov, Alexandr; Jin, Yishi
2015-01-01
A striking neuronal connectivity change in C. elegans involves the coordinated elimination of existing synapses and formation of synapses at new locations, without altering neuronal morphology. Here, we investigate the tripartite interaction between dynamic microtubules (MTs), kinesin-1, and vesicular cargo during this synapse remodeling. We find that a reduction in the dynamic MT population in motor neuron axons, resulting from genetic interaction between loss of function in the conserved MAPKKK dlk-1 and an α-tubulin mutation, specifically blocks synapse remodeling. Using live imaging and pharmacological modulation of the MT cytoskeleton, we show that dynamic MTs are increased at the onset of remodeling and are critical for new synapse formation. DLK-1 acts during synapse remodeling, and its function involves MT catastrophe factors including kinesin-13/KLP-7 and spastin/SPAS-1. Through a forward genetic screen, we identify gain-of-function mutations in kinesin-1 that can compensate for reduced dynamic MTs to promote synaptic vesicle transport during remodeling. Our data provide in vivo evidence supporting the requirement of dynamic MTs for kinesin-1 dependent axonal transport and shed insight on the role of the MT cytoskeleton in facilitating neural circuit plasticity. PMID:26051896
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Integrin α8 and Pcdh15 act as a complex to regulate cilia biogenesis in sensory cells.
Goodman, Linda; Zallocchi, Marisa
2017-11-01
The way an organism perceives its surroundings depends on sensory systems and the highly specialized cilia present in the neurosensory cells. Here, we describe the existence of an integrin α8 (Itga8) and protocadherin-15a (Pcdh15a) ciliary complex in neuromast hair cells in a zebrafish model. Depletion of the complex via downregulation or loss-of-function mutation leads to a dysregulation of cilia biogenesis and endocytosis. At the molecular level, removal of the complex blocks the access of Rab8a into the cilia as well as normal recruitment of ciliary cargo by centriolar satellites. These defects can be reversed by the introduction of a constitutively active form of Rhoa, suggesting that Itga8-Pcdh15a complex mediates its effect through the activation of this small GTPase and probably by the regulation of actin cytoskeleton dynamics. Our data points to a novel mechanism involved in the regulation of sensory cilia development, with the corresponding implications for normal sensory function. © 2017. Published by The Company of Biologists Ltd.
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NASA Technical Reports Server (NTRS)
Toll, T. A.
1980-01-01
A parametric analysis was made to investigate the relationship between current cargo airplanes and possible future designs that may differ greatly in both size and configuration. The method makes use of empirical scaling laws developed from statistical studies of data from current and advanced airplanes and, in addition, accounts for payload density, effects of span distributed load, and variations in tail area ratio. The method is believed to be particularly useful for exploratory studies of design and technology options for large airplanes. The analysis predicts somewhat more favorable variations of the ratios of payload to gross weight and block fuel to payload as the airplane size is increased than has been generally understood from interpretations of the cube-square law. In terms of these same ratios, large all wing (spanloader) designs show an advantage over wing-fuselage designs.
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46 CFR 151.03-35 - Limiting draft.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Limiting draft. 151.03-35 Section 151.03-35 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-35 Limiting draft. Maximum allowable draft to which a barge may be loaded. Limiting draft is a function of hull type and cargo specific gravity...
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46 CFR 151.03-35 - Limiting draft.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Limiting draft. 151.03-35 Section 151.03-35 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-35 Limiting draft. Maximum allowable draft to which a barge may be loaded. Limiting draft is a function of hull type and cargo specific gravity...
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46 CFR 151.03-35 - Limiting draft.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Limiting draft. 151.03-35 Section 151.03-35 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-35 Limiting draft. Maximum allowable draft to which a barge may be loaded. Limiting draft is a function of hull type and cargo specific gravity...
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46 CFR 151.03-35 - Limiting draft.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Limiting draft. 151.03-35 Section 151.03-35 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-35 Limiting draft. Maximum allowable draft to which a barge may be loaded. Limiting draft is a function of hull type and cargo specific gravity...
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46 CFR 151.03-35 - Limiting draft.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Limiting draft. 151.03-35 Section 151.03-35 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-35 Limiting draft. Maximum allowable draft to which a barge may be loaded. Limiting draft is a function of hull type and cargo specific gravity...
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Diffusion-Limited Cargo Loading of an Engineered Protein Container.
Zschoche, Reinhard; Hilvert, Donald
2015-12-30
The engineered bacterial nanocompartment AaLS-13 is a promising artificial encapsulation system that exploits electrostatic interactions for cargo loading. In order to study its ability to take up and retain guests, a pair of fluorescent proteins was developed which allows spectroscopic determination of the extent of encapsulation by Förster resonance energy transfer (FRET). The encapsulation process is generally complete within a second, suggesting low energetic barriers for proteins to cross the capsid shell. Formation of intermediate aggregates upon mixing host and guest in vitro complicates capsid loading at low ionic strength, but can be sidestepped by increasing salt concentrations or diluting the components. Encapsulation of guests is completely reversible, and the position of the equilibrium is easily tuned by varying the ionic strength. These results, which challenge the notion that AaLS-13 is a continuous rigid shell, provide valuable information about cargo loading that will guide ongoing efforts to engineer functional host-guest complexes. Moreover, it should be possible to adapt the protein FRET pair described in this report to characterize functional capsid-cargo complexes generated by other encapsulation systems.
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Microfluidics and BIO-encapsulation for drug- and cell-therapy
NASA Astrophysics Data System (ADS)
Aloisi, A.; Toma, C. C.; Di Corato, R.; Rinaldi, R.
2017-08-01
We present the construction and the application of biocompatible micro- and nano-structures that can be administered systemically and transport in a targeted and effective way drugs, small molecules, stem cells or immune system cells. These polymeric nano-systems represent a primary goal for the treatment of a wide family of neurological/systemic disorders, as well as tumors and/or acute injuries. As natural, biocompatible, biodegradable and non-immunogenic building blocks, alginate and chitosan are been currently exploited. Ionotropic pre-gelation of the alginate core, followed by chitosan polyelectrolyte complexation, allows to encapsulate selected active molecules by means of physical entrapment and electrostatic interactions within sub-micron sized hydrogel vesicles. Here we present a microfluidicassisted assembly method of nano- and micro-vesicles -under sterile, closed environment and gas exchange adjustable conditions, which is a critical issue, when the cargo to be uploaded is very sensitive. Polymer/polymer and polymer/drug mass ratio relationship are crucial in order to attain the optimum in terms of shuttle size and cargo concentration. By modulating polymer reticulation conditions, it become possible to control drug loading efficiency as well as drug delivery dynamics. Recent results on the application of these vesicles for the encapsulation and delivery of Inhibin-A and Decorin, proteins involved in acute kidney injury (AKI), for Renal tubular cell regeneration will be presented. Finally, the impact of these polysaccharide sub-micron vesicles on Human Immune cells and the metabolic and functional activity of cells embedded in the assembled vesicles will be presented and discussed.
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Rosas-Santiago, Paul; Lagunas-Gomez, Daniel; Yáñez-Domínguez, Carolina; Vera-Estrella, Rosario; Zimmermannová, Olga; Sychrová, Hana; Pantoja, Omar
2017-10-01
The export of membrane proteins along the secretory pathway is initiated at the endoplasmic reticulum after proteins are folded and packaged inside this organelle by their recruiting into the coat complex COPII vesicles. It is proposed that cargo receptors are required for the correct transport of proteins to its target membrane, however, little is known about ER export signals for cargo receptors. Erv14/Cornichon belong to a well conserved protein family in Eukaryotes, and have been proposed to function as cargo receptors for many transmembrane proteins. Amino acid sequence alignment showed the presence of a conserved acidic motif in the C-terminal in homologues from plants and yeast. Here, we demonstrate that mutation of the C-terminal acidic motif from ScErv14 or OsCNIH1, did not alter the localization of these cargo receptors, however it modified the proper targeting of the plasma membrane transporters Nha1p, Pdr12p and Qdr2p. Our results suggest that mistargeting of these plasma membrane proteins is a consequence of a weaker interaction between the cargo receptor and cargo proteins caused by the mutation of the C-terminal acidic motif. Copyright © 2017 Elsevier B.V. All rights reserved.
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A fluid membrane enhances the velocity of cargo transport by small teams of kinesin-1
NASA Astrophysics Data System (ADS)
Li, Qiaochu; Tseng, Kuo-Fu; King, Stephen J.; Qiu, Weihong; Xu, Jing
2018-03-01
Kinesin-1 (hereafter referred to as kinesin) is a major microtubule-based motor protein for plus-end-directed intracellular transport in live cells. While the single-molecule functions of kinesin are well characterized, the physiologically relevant transport of membranous cargos by small teams of kinesins remains poorly understood. A key experimental challenge remains in the quantitative control of the number of motors driving transport. Here we utilized "motile fraction" to overcome this challenge and experimentally accessed transport by a single kinesin through the physiologically relevant transport by a small team of kinesins. We used a fluid lipid bilayer to model the cellular membrane in vitro and employed optical trapping to quantify the transport of membrane-enclosed cargos versus traditional membrane-free cargos under identical conditions. We found that coupling motors via a fluid membrane significantly enhances the velocity of cargo transport by small teams of kinesins. Importantly, enclosing a cargo in a fluid lipid membrane did not impact single-kinesin transport, indicating that membrane-dependent velocity enhancement for team-based transport arises from altered interactions between kinesins. Our study demonstrates that membrane-based coupling between motors is a key determinant of kinesin-based transport. Enhanced velocity may be critical for fast delivery of cargos in live cells.
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Gleason, Adenrele M.; Nguyen, Ken C. Q.; Hall, David H.; Grant, Barth D.
2016-01-01
Syndapin/pascin-family F-BAR domain proteins bind directly to membrane lipids and are associated with actin dynamics at the plasma membrane. Previous reports also implicated mammalian syndapin 2 in endosome function during receptor recycling, but precise analysis of a putative recycling function for syndapin in mammalian systems is difficult because of its effects on the earlier step of endocytic uptake and potential redundancy among the three separate genes that encode mammalian syndapin isoforms. Here we analyze the endocytic transport function of the only Caenorhabditis elegans syndapin, SDPN-1. We find that SDPN-1 is a resident protein of the early and basolateral recycling endosomes in the C. elegans intestinal epithelium, and sdpn-1 deletion mutants display phenotypes indicating a block in basolateral recycling transport. sdpn-1 mutants accumulate abnormal endosomes positive for early endosome and recycling endosome markers that are normally separate, and such endosomes accumulate high levels of basolateral recycling cargo. Furthermore, we observed strong colocalization of endosomal SDPN-1 with the F-actin biosensor Lifeact and found that loss of SDPN-1 greatly reduced Lifeact accumulation on early endosomes. Taken together, our results provide strong evidence for an in vivo function of syndapin in endocytic recycling and suggest that syndapin promotes transport via endosomal fission. PMID:27630264
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NASA Astrophysics Data System (ADS)
Yilmaz, M. Deniz; Xue, Min; Ambrogio, Michael W.; Buyukcakir, Onur; Wu, Yilei; Frasconi, Marco; Chen, Xinqi; Nassar, Majed S.; Stoddart, J. Fraser; Zink, Jeffrey I.
2014-12-01
A sugar and pH dual-responsive controlled release system, which is highly specific towards molecular stimuli, has been developed based on the binding between catechol and boronic acid on a platform of mesoporous silica nanoparticles (MSNs). By grafting phenylboronic acid stalks onto the silica surface, catechol-containing β-cyclodextrins can be attached to the orifices of the MSNs' nanopores through formation of boronate esters which block access to the nanopores. These esters are stable enough to prevent cargo molecules from escaping. The boronate esters disassociate in the presence of sugars, enabling the molecule-specific controlled-release feature of this hybrid system. The rate of release has been found to be tunable by varying both the structures and the concentrations of sugars, as a result of the competitive binding nature associated with the mechanism of its operation. Acidification also induces the release of cargo molecules. Further investigations show that the presence of both a low pH and sugar molecules provides cooperative effects which together control the rate of release.A sugar and pH dual-responsive controlled release system, which is highly specific towards molecular stimuli, has been developed based on the binding between catechol and boronic acid on a platform of mesoporous silica nanoparticles (MSNs). By grafting phenylboronic acid stalks onto the silica surface, catechol-containing β-cyclodextrins can be attached to the orifices of the MSNs' nanopores through formation of boronate esters which block access to the nanopores. These esters are stable enough to prevent cargo molecules from escaping. The boronate esters disassociate in the presence of sugars, enabling the molecule-specific controlled-release feature of this hybrid system. The rate of release has been found to be tunable by varying both the structures and the concentrations of sugars, as a result of the competitive binding nature associated with the mechanism of its operation. Acidification also induces the release of cargo molecules. Further investigations show that the presence of both a low pH and sugar molecules provides cooperative effects which together control the rate of release. Electronic supplementary information (ESI) available: Synthetic schemes, electron microscopy images and nitrogen adsorption/desorption isotherms of the nanoparticles, FT-IR spectra, isothermal titration calorimetry, X-ray photoelectron spectra and time-of-flight secondary ion mass spectra. DLS results for nanoparticle stability. See DOI: 10.1039/c4nr04796f
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Kim, Sung Hyun; Ryan, Timothy A.
2009-01-01
The mechanisms of how, following exocytosis, the approximately nine types of synaptic vesicle (SV) transmembrane proteins are accurately resorted to form SVs are poorly understood. The time course of SV endocytosis is very sensitive to perturbations in clathrin and dynamin, supporting the model that SV endocytosis occurs through a clathrin-mediated pathway. We recently demonstrated that removal of the clathrin adaptor protein AP-2, the key protein thought to coordinate cargo selection into clathrin-coated pits, results in a significant impairment in endocytosis kinetics. Endocytosis, however, still proceeds in the absence of AP-2, bringing into question the role of AP-2 in cargo sorting in this process. Using quantitative endocytosis assays at nerve terminals, we examined how endocytosis depends on the integrity of μ2 function. Our experiments indicate that no single perturbation in μ2 prevents restoration of endocytic function when mutated μ2 replaces native μ2, whereas introduction of multiple distributed mutations significantly impairs endocytosis. We also examined whether the presence of AP-2 is important for the functionality of the previously identified endocytic motif in an SV cargo protein, the dileucine motif in vGlut-1. These data show that while mutations in the dileucine motif slow the retrieval of vGlut-1, they only do so in the presence of AP-2. These data thus indicate that AP-2 plays a role in cargo selection but that no single aspect of μ2 function is critical, implying that a more distributed network of interactions supports AP-2 function in SV endocytosis. PMID:19762466
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In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.
Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom
2013-11-26
Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.
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Kinesin molecular motors: Transport pathways, receptors, and human disease
NASA Astrophysics Data System (ADS)
Goldstein, Lawrence S. B.
2001-06-01
Kinesin molecular motor proteins are responsible for many of the major microtubule-dependent transport pathways in neuronal and non-neuronal cells. Elucidating the transport pathways mediated by kinesins, the identity of the cargoes moved, and the nature of the proteins that link kinesin motors to cargoes are areas of intense investigation. Kinesin-II recently was found to be required for transport in motile and nonmotile cilia and flagella where it is essential for proper left-right determination in mammalian development, sensory function in ciliated neurons, and opsin transport and viability in photoreceptors. Thus, these pathways and proteins may be prominent contributors to several human diseases including ciliary dyskinesias, situs inversus, and retinitis pigmentosa. Kinesin-I is needed to move many different types of cargoes in neuronal axons. Two candidates for receptor proteins that attach kinesin-I to vesicular cargoes were recently found. One candidate, sunday driver, is proposed to both link kinesin-I to an unknown vesicular cargo and to bind and organize the mitogen-activated protein kinase components of a c-Jun N-terminal kinase signaling module. A second candidate, amyloid precursor protein, is proposed to link kinesin-I to a different, also unknown, class of axonal vesicles. The finding of a possible functional interaction between kinesin-I and amyloid precursor protein may implicate kinesin-I based transport in the development of Alzheimer's disease.
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A quantitative examination of the role of cargo-exerted forces in axonal transport
Mitchell, Cassie S.; Lee, Robert H.
2009-01-01
Axonal transport, via molecular motors kinesin and dynein, is a critical process in supplying the necessary constituents to maintain normal neuronal function. In this study, we predict the role of cooperativity by motors of the same polarity across the entire spectrum of physiological axonal transport. That is, we examined how the number of motors, either kinesin or dynein, working together to move a cargo, results in the experimentally determined velocity profiles seen in fast and slow anterograde and retrograde transport. We quantified the physiological forces exerted on a motor by a cargo as a function of cargo size, transport velocity, and transport type. Our results show that the force exerted by our base case neurofilament (DNF=10nm, LNF=1.6μm) is ~1.25pN at 600nm/s; additionally, the force exerted by our base case organelle (DOrg=1μm) at 1,000nm/s is ~5.7pN. Our results indicate that while a single motor can independently carry an average cargo, cooperativity is required to produce the experimental velocity profiles for fast transport. However, no cooperativity is required to produce the slow transport velocity profiles; thus, a single dynein or kinesin can carry the average neurofilament retrogradely or anterogradely, respectively. The potential role cooperativity may play in the hypothesized mechanisms of motoneuron transport diseases such as Amyotrophic Lateral Sclerosis (ALS) is discussed. PMID:19150364
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1980-12-01
NOTES 3 19. KEY WORDS (Continue on revere side If n.cessary d Identify by block number) Bulk cargo Market demand analysis Commodity resource inventory...The study included a Commodity Resource Inventory, a Modal Split Analysis and a Market Demand Analysis. The work included investigation and analyses...inventory, a modal split analysis and a market demand analysis. The work included investigation and analyses of the production, transportation, and
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Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration
Bernis, Cyril; Swift-Taylor, Beth; Nord, Matthew; Carmona, Sarah; Chook, Yuh Min; Forbes, Douglass J.
2014-01-01
The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. PMID:24478460
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REVIEW ARTICLE: Hither and yon: a review of bi-directional microtubule-based transport
NASA Astrophysics Data System (ADS)
Gross, Steven P.
2004-06-01
Active transport is critical for cellular organization and function, and impaired transport has been linked to diseases such as neuronal degeneration. Much long distance transport in cells uses opposite polarity molecular motors of the kinesin and dynein families to move cargos along microtubules. It is increasingly clear that many cargos are moved by both sets of motors, and frequently reverse course. This review compares this bi-directional transport to the more well studied uni-directional transport. It discusses some bi-directionally moving cargos, and critically evaluates three different physical models for how such transport might occur. It then considers the evidence for the number of active motors per cargo, and how the net or average direction of transport might be controlled. The likelihood of a complex linking the activities of kinesin and dynein is also discussed. The paper concludes by reviewing elements of apparent universality between different bi-directionally moving cargos and by briefly considering possible reasons for the existence of bi-directional transport.
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Tsai, Wen-Chyan; Rizvi, Syed S H
2017-06-01
A new technique of liposomal microencapsulation, consisting of supercritical fluid extraction followed by rapid expansion of the supercritical solution and vacuum-driven cargo loading, was successfully developed. It is a continuous flow-through process without usage of any toxic organic solvent. For use as a coating material, the solubility of soy phospholipids in supercritical carbon dioxide was first determined using a dynamic equilibrium system and the data was correlated with the Chrastil model with good agreement. Liposomes were made with D-(+)-glucose as a cargo and their properties were characterized as functions of expansion pressure, temperature, and cargo loading rates. The highest encapsulation efficiency attained was 31.7% at the middle expansion pressure of 12.41MPa, highest expansion temperature of 90°C, and lowest cargo loading rate of 0.25mL/s. The large unilamellar vesicles and multivesicular vesicles were observed to be a majority of the liposomes produced using this eco-friendly process. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Dendritic trafficking faces physiologically critical speed-precision tradeoffs
Williams, Alex H; O'Donnell, Cian; Sejnowski, Terrence J; O'Leary, Timothy
2016-01-01
Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons. DOI: http://dx.doi.org/10.7554/eLife.20556.001 PMID:28034367
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NASA Astrophysics Data System (ADS)
Franch, Oskar; Iacovelli, Federico; Falconi, Mattia; Juul, Sissel; Ottaviani, Alessio; Benvenuti, Claudia; Biocca, Silvia; Ho, Yi-Ping; Knudsen, Birgitta R.; Desideri, Alessandro
2016-07-01
In the present study we investigate the mechanism behind temperature controlled cargo uptake using a truncated octahedral DNA cage scaffold functionalized with one, two, three or four hairpin forming DNA strands inserted in one corner of the structure. This investigation was inspired by our previous demonstration of temperature controlled reversible encapsulation of the cargo enzyme, horseradish peroxidase, in the cage with four hairpin forming strands. However, in this previous study the mechanism of cargo uptake was not directly addressed (Juul, et al., Temperature-Controlled Encapsulation and Release of an Active Enzyme in the Cavity of a Self-Assembled DNA Nanocage, ACS Nano, 2013, 7, 9724-9734). In the present study we use a combination of molecular dynamics simulations and in vitro analyses to unravel the mechanism of cargo uptake in hairpin containing DNA cages. We find that two hairpin forming strands are necessary and sufficient to facilitate efficient cargo uptake, which argues against a full opening-closing of one corner of the structure being responsible for encapsulation. Molecular dynamics simulations were carried out to evaluate the atomistic motions responsible for encapsulation and showed that the two hairpin forming strands facilitated extension of at least one of the face surfaces of the cage scaffold, allowing entrance of the cargo protein into the cavity of the structure. Hence, the presented data demonstrate that cargo uptake does not involve a full opening of the structure. Rather, the uptake mechanism represents a feature of increased flexibility integrated in this nanocage structure upon the addition of at least two hairpin-forming strands.In the present study we investigate the mechanism behind temperature controlled cargo uptake using a truncated octahedral DNA cage scaffold functionalized with one, two, three or four hairpin forming DNA strands inserted in one corner of the structure. This investigation was inspired by our previous demonstration of temperature controlled reversible encapsulation of the cargo enzyme, horseradish peroxidase, in the cage with four hairpin forming strands. However, in this previous study the mechanism of cargo uptake was not directly addressed (Juul, et al., Temperature-Controlled Encapsulation and Release of an Active Enzyme in the Cavity of a Self-Assembled DNA Nanocage, ACS Nano, 2013, 7, 9724-9734). In the present study we use a combination of molecular dynamics simulations and in vitro analyses to unravel the mechanism of cargo uptake in hairpin containing DNA cages. We find that two hairpin forming strands are necessary and sufficient to facilitate efficient cargo uptake, which argues against a full opening-closing of one corner of the structure being responsible for encapsulation. Molecular dynamics simulations were carried out to evaluate the atomistic motions responsible for encapsulation and showed that the two hairpin forming strands facilitated extension of at least one of the face surfaces of the cage scaffold, allowing entrance of the cargo protein into the cavity of the structure. Hence, the presented data demonstrate that cargo uptake does not involve a full opening of the structure. Rather, the uptake mechanism represents a feature of increased flexibility integrated in this nanocage structure upon the addition of at least two hairpin-forming strands. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01806h
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Zhang, Xin; Yan, Qi; Mulatihan, Di Naer; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun
2018-06-22
The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.
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NASA Astrophysics Data System (ADS)
Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun
2018-06-01
The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.
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Meister, M; Bänfer, S; Gärtner, U; Koskimies, J; Amaddii, M; Jacob, R; Tikkanen, R
2017-01-01
Ubiquitin-dependent sorting of membrane proteins in endosomes directs them to lysosomal degradation. In the case of receptors such as the epidermal growth factor receptor (EGFR), lysosomal degradation is important for the regulation of downstream signalling. Ubiquitinated proteins are recognised in endosomes by the endosomal sorting complexes required for transport (ESCRT) complexes, which sequentially interact with the ubiquitinated cargo. Although the role of each ESCRT complex in sorting is well established, it is not clear how the cargo is passed on from one ESCRT to the next. We here show that flotillin-1 is required for EGFR degradation, and that it interacts with the subunits of ESCRT-0 and -I complexes (hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and Tsg101). Flotillin-1 is required for cargo recognition and sorting by ESCRT-0/Hrs and for its interaction with Tsg101. In addition, flotillin-1 is also required for the sorting of human immunodeficiency virus 1 Gag polyprotein, which mimics ESCRT-0 complex during viral assembly. We propose that flotillin-1 functions in cargo transfer between ESCRT-0 and -I complexes. PMID:28581508
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Nucleocytoplasmic Transport: A Paradigm for Molecular Logistics in Artificial Systems.
Vujica, Suncica; Zelmer, Christina; Panatala, Radhakrishnan; Lim, Roderick Y H
2016-01-01
Artificial organelles, molecular factories and nanoreactors are membrane-bound systems envisaged to exhibit cell-like functionality. These constitute liposomes, polymersomes or hybrid lipo-polymersomes that display different membrane-spanning channels and/or enclose molecular modules. To achieve more complex functionality, an artificial organelle should ideally sustain a continuous influx of essential macromolecular modules (i.e. cargoes) and metabolites against an outflow of reaction products. This would benefit from the incorporation of selective nanopores as well as specific trafficking factors that facilitate cargo selectivity, translocation efficiency, and directionality. Towards this goal, we describe how proteinaceous cargoes are transported between the nucleus and cytoplasm by nuclear pore complexes and the biological trafficking machinery in living cells (i.e. nucleocytoplasmic transport). On this basis, we discuss how biomimetic control may be implemented to selectively import, compartmentalize and accumulate diverse macromolecular modules against concentration gradients in artificial organelles.
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Ribeiro, Luís F; de Wit, Joris
2017-04-19
Accurate control of polarized cargo trafficking is essential for neuronal function. In this issue of Neuron, Gumy et al. (2017) show that MAP2 defines a pre-axonal filtering zone and controls axonal cargo transport by influencing the activities of distinct kinesin motors. Copyright © 2017 Elsevier Inc. All rights reserved.
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1980-12-01
SUPPLEMENTARY NOTES 19. KEY WORDS (Continue on reverse aide if neceeary aod identify by block number) Bulk cargo Market demand analysis Iron Commodity resource...shown below. The study included a Commodity Resource Inventory, a Modal Split Analysis and a Market Demand Analysis. The work included investigation...resource inventory, a modal split analysis and a market demand analysis. The work included investigation and analyses of the production
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Linear-Force Actuators for Use on Shipboard Weapons and Cargo Elevators.
1984-01-09
lock units an electro-mechanical brake is furnished so that when the unit stops at any position, its brake locks automatically , preventing any drift...NAME AND ADDRESS 12. REPORT DATE Naval Sea Systems Command (Code 56W4) f~nur 9, 1984 Washigton DC 03623. NUM4BER Of PAGES .9 ~, DC24 1.MONITORING...Hydraulic systems Weapons elevators a&. )TRACT (Couinsiu an ,evelee aide It nogceoy and fdentflr by block nunbov) "-Reports of hydraulic problems in
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Sitaram, Anand; Dennis, Megan K.; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Bonifacino, Juan S.; Marks, Michael S.
2012-01-01
Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. PMID:22718909
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NASA Astrophysics Data System (ADS)
Shumov, A. E.; Novikov, L. S.; Shaevich, S. K.; Aleksandrov, N. G.; Smirnova, T. N.; Nikishin, E. F.; Chernik, V. N.; Petukhov, V. P.; Voronina, E. N.; Sedov, V. V.; Salnikova, I. A.; Babaevskiy, P. G.; Kozlov, N. A.; Deev, I. S.; Startsev, O. V.; Shindo, D. J.; Golden, J. L.; Kravchenko, M.
2015-11-01
The Komplast materials experiment was designed by Khrunichev State Research and Production Space Center together with Skobeltsyn Institute of Nuclear Physics, Lomonosov Moscow State University and other Russian scientific institutes, and has been carried out by Mission Control Moscow since 1998. The purpose of this experiment is to study the complex effect of the low Earth orbit environment on samples of various spacecraft materials. On November 20, 1998 the Komplast experiment began with the launch of the first International Space Station module Zarya, or Functional Cargo Block (FGB). Eight Komplast panels with samples of materials and sensors were installed on the outer surface of FGB module. Two of eight experiment panels were retrieved during Russian extravehicular activity in February 2011 after 12 years of space exposure and were subsequently returned to Earth by Space Shuttle "Discovery" on the STS-133/ULF-5 mission in March 2011. The article presents the results obtained from this unique long-duration experiment on board of the International Space Station.
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1998-05-22
KENNEDY SPACE CENTER, FLA. -- The International Space Station's (ISS) Unity node, with Pressurized Mating Adapter (PMA)-2 attached, awaits further processing in the Space Station Processing Facility (SSPF). The Unity node is the first element of the ISS to be manufactured in the United States and is currently scheduled to lift off aboard the Space Shuttle Endeavour on STS-88 later this year. Unity has two PMAs attached to it now that this mate is completed. PMAs are conical docking adapters which will allow the docking systems used by the Space Shuttle and by Russian modules to attach to the node's hatches and berthing mechanisms. Once in orbit, Unity, which has six hatches, will be mated with the already orbiting Control Module and will eventually provide attachment points for the U.S. laboratory module; Node 3; an early exterior framework or truss for the station; an airlock; and a multi-windowed cupola. The Control Module, or Functional Cargo Block, is a U.S.-funded and Russian-built component that will be launched aboard a Russian rocket from Kazakstan
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1998-05-22
KENNEDY SPACE CENTER, FLA. -- The International Space Station's (ISS) Unity node, with Pressurized Mating Adapter (PMA)-2 attached, awaits further processing in the Space Station Processing Facility (SSPF). The Unity node is the first element of the ISS to be manufactured in the United States and is currently scheduled to lift off aboard the Space Shuttle Endeavour on STS-88 later this year. Unity has two PMAs attached to it now that this mate is completed. PMAs are conical docking adapters which will allow the docking systems used by the Space Shuttle and by Russian modules to attach to the node's hatches and berthing mechanisms. Once in orbit, Unity, which has six hatches, will be mated with the already orbiting Control Module and will eventually provide attachment points for the U.S. laboratory module; Node 3; an early exterior framework or truss for the station; an airlock; and a multi-windowed cupola. The Control Module, or Functional Cargo Block, is a U.S.-funded and Russian-built component that will be launched aboard a Russian rocket from Kazakstan
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2013-12-10
CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, the center's director, Bob Cabana, cuts a 15th anniversary cake during an employee celebration commemorating the start of assembly of the International Space Station. Cabana served as commander of STS-88, the space shuttle mission that launched the first American-built element of the space station, beginning the effort to construct the orbiting complex. Also participating in the ceremony were STS-88 mission specialists Nancy Currie and Jerry Ross. The Russian Space Agency's Functional Cargo Block, named "Zarya," was launched from the Baikonur Cosmodrome in Kazakhstan on Nov. 20, 1998. Two weeks later, on Dec. 4, 1998, the space shuttle Endeavour lifted off from Kennedy on STS-88 with node 1, called "Unity." In addition to Cabana, Curie and Ross, the crew also included pilot Rick Sturckow, along with mission specialists Jim Newman and Sergei Krikalev, a Russian cosmonaut. For more information, visit: http://www.nasa.gov/mission_pages/station/main/index.html Photo credit: NASA/Jim Grossman
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2013-12-10
CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, the center's director, Bob Cabana, speaks during an employee celebration commemorating the 15th anniversary of the start of assembly of the International Space Station. Cabana served as commander of STS-88, the space shuttle mission that launched the first American-built element of the space station, beginning the effort to construct the orbiting complex. Also participating in the ceremony were STS-88 mission specialists Nancy Currie and Jerry Ross. The Russian Space Agency's Functional Cargo Block, named "Zarya," was launched from the Baikonur Cosmodrome in Kazakhstan on Nov. 20, 1998. Two weeks later, on Dec. 4, 1998, the space shuttle Endeavour lifted off from Kennedy on STS-88 with node 1, called "Unity." In addition to Cabana, Curie and Ross, the crew also included pilot Rick Sturckow, along with mission specialists Jim Newman and Sergei Krikalev, a Russian cosmonaut. For more information, visit: http://www.nasa.gov/mission_pages/station/main/index.html Photo credit: NASA/Jim Grossman
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2013-12-10
CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, the center's director, Bob Cabana, right, speaks during an employee celebration commemorating the 15th anniversary of the start of assembly of the International Space Station. Cabana served as commander of STS-88, the space shuttle mission that launched the first American-built element of the space station, beginning the effort to construct the orbiting complex. Participating in the presentation, from the left, are STS-88 crew members Nancy Currie, Jerry Ross and Cabana. The Russian Space Agency's Functional Cargo Block, named "Zarya," was launched from the Baikonur Cosmodrome in Kazakhstan on Nov. 20, 1998. Two weeks later, on Dec. 4, 1998, the space shuttle Endeavour lifted off from Kennedy on STS-88 with node 1, called "Unity." In addition to Cabana, Curie and Ross, the crew also included pilot Rick Sturckow, along with mission specialists Jim Newman and Sergei Krikalev, a Russian cosmonaut. For more information, visit: http://www.nasa.gov/mission_pages/station/main/index.html Photo credit: NASA/Jim Grossman
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Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy
Cullup, Thomas; Kho, Ay L.; Dionisi-Vici, Carlo; Brandmeier, Birgit; Smith, Frances; Urry, Zoe; Simpson, Michael A.; Yau, Shu; Bertini, Enrico; McClelland, Verity; Al-Owain, Mohammed; Koelker, Stefan; Koerner, Christian; Hoffmann, Georg F.; Wijburg, Frits A.; Hoedt, Amber E. ten; Rogers, Curtis; Manchester, David; Miyata, Rie; Hayashi, Masaharu; Said, Elizabeth; Soler, Doriette; Kroisel, Peter M.; Windpassinger, Christian; Filloux, Francis M.; Al-Kaabi, Salwa; Hertecant, Jozef; Del Campo, Miguel; Buk, Stefan; Bodi, Istvan; Goebel, Hans-Hilmar; Sewry, Caroline A.; Abbs, Stephen; Mohammed, Shehla; Josifova, Dragana; Gautel, Mathias; Jungbluth, Heinz
2012-01-01
Vici syndrome is a recessively inherited multisystem disorder characterized by callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and hypopigmentation. To investigate the molecular basis of Vici syndrome, we carried out exome and Sanger sequence analysis in a cohort of 18 patients. We identified recessive mutations in EPG5 (previously KIAA1632), indicating a causative role in Vici syndrome. EPG5 is the human homologue of the metazoan-specific autophagy gene epg-5, encoding a key autophagy regulator (ectopic P-granules autophagy protein 5) implicated in the formation of autolysosomes. Further studies demonstrated a severe block of autophagosomal clearance in muscle and fibroblasts from EPG5 mutant patients, resulting in autophagic cargo accumulation in autophagosomes. These findings indicate Vici syndrome as a paradigm of a human multisystem disorder associated with defective autophagy, and suggest a fundamental role of the autophagy pathway in the anatomical and functional formation of organs such as the brain, the heart and the immune system. PMID:23222957
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Mechanized azobenzene-functionalized zirconium metal-organic framework for on-command cargo release.
Meng, Xiangshi; Gui, Bo; Yuan, Daqiang; Zeller, Matthias; Wang, Cheng
2016-08-01
Stimuli-responsive metal-organic frameworks (MOFs) have gained increasing attention recently for their potential applications in many areas. We report the design and synthesis of a water-stable zirconium MOF (Zr-MOF) that bears photoresponsive azobenzene groups. This particular MOF can be used as a reservoir for storage of cargo in water, and the cargo-loaded MOF can be further capped to construct a mechanized MOF through the binding of β-cyclodextrin with the azobenzene stalks on the MOF surface. The resulting mechanized MOF has shown on-command cargo release triggered by ultraviolet irradiation or addition of competitive agents without premature release. This study represents a simple approach to the construction of stimuli-responsive mechanized MOFs, and considering mechanized UiO-68-azo made from biocompatible components, this smart system may provide a unique MOF platform for on-command drug delivery in the future.
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Uterosomes: Exosomal cargo during the estrus cycle and interaction with sperm.
Martin-DeLeon, Patricia Anastasia
2016-01-01
The term "uterosomes" was first used to classify extracellular membrane vesicles released into the uterine luminal fluid. These extracellular vesicles (EVs), varying in sizes, fit the classification of exosomes and microvesicles on the basis of size, the presence of the CD9 biochemical marker, and lateral orientation of the membrane. Uterosomes appear to be formed by the apocrine pathway, similar to other reproductive EVs. In the murine system, the protein cargo carried by uterosomes includes glycosyl phosphatidylinositol (GPI)-linked and transmembrane proteins and these are hormonally regulated, appearing at high levels during proestrus/estrus and only marginally present at diestrus /metestrus. Uterosomes have been shown to deliver proteins in their cargo to sperm, with a functional impact, and are thought to participate in promoting sperm capacitation. Further studies are warranted, particularly those aimed at identifying the contents of their cargo during the estrus and menstrual cycle and the role they play n sperm maturation.
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Mechanized azobenzene-functionalized zirconium metal-organic framework for on-command cargo release
Meng, Xiangshi; Gui, Bo; Yuan, Daqiang; Zeller, Matthias; Wang, Cheng
2016-01-01
Stimuli-responsive metal-organic frameworks (MOFs) have gained increasing attention recently for their potential applications in many areas. We report the design and synthesis of a water-stable zirconium MOF (Zr-MOF) that bears photoresponsive azobenzene groups. This particular MOF can be used as a reservoir for storage of cargo in water, and the cargo-loaded MOF can be further capped to construct a mechanized MOF through the binding of β-cyclodextrin with the azobenzene stalks on the MOF surface. The resulting mechanized MOF has shown on-command cargo release triggered by ultraviolet irradiation or addition of competitive agents without premature release. This study represents a simple approach to the construction of stimuli-responsive mechanized MOFs, and considering mechanized UiO-68-azo made from biocompatible components, this smart system may provide a unique MOF platform for on-command drug delivery in the future. PMID:27493996
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Mechanisms of Size Control and Polymorphism in Viral Capsid Assembly
Elrad, Oren M.; Hagan, Michael F.
2009-01-01
We simulate the assembly dynamics of icosahedral capsids from subunits that interconvert between different conformations (or quasi-equivalent states). The simulations identify mechanisms by which subunits form empty capsids with only one morphology, but adaptively assemble into different icosahedral morphologies around nanoparticle cargoes with varying sizes, as seen in recent experiments with brome mosaic virus (BMV) capsid proteins. Adaptive cargo encapsidation requires moderate cargo-subunit interaction strengths; stronger interactions frustrate assembly by stabilizing intermediates with incommensurate curvature. We compare simulation results to experiments with cowpea chlorotic mottle virus empty capsids and BMV capsids assembled on functionalized nanoparticles, and suggest new cargo encapsidation experiments. Finally, we find that both empty and templated capsids maintain the precise spatial ordering of subunit conformations seen in the crystal structure even if interactions that preserve this arrangement are favored by as little as the thermal energy, consistent with experimental observations that different subunit conformations are highly similar. PMID:18950240
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The secretion and biological function of tumor suppressor maspin as an exosome cargo protein.
Dean, Ivory; Dzinic, Sijana H; Bernardo, M Margarida; Zou, Yi; Kimler, Vickie; Li, Xiaohua; Kaplun, Alexander; Granneman, James; Mao, Guangzhao; Sheng, Shijie
2017-01-31
Maspin is an epithelial-specific tumor suppressor shown to exert its biological effects as an intracellular, cell membrane-associated, and secreted free molecule. A recent study suggests that upon DNA-damaging g-irradiation, tumor cells can secrete maspin as an exosome-associated protein. To date, the biological significance of exosomal secretion of maspin is unknown. The current study aims at addressing whether maspin is spontaneously secreted as an exosomal protein to regulate tumor/stromal interactions. We prepared exosomes along with cell extracts and vesicle-depleted conditioned media (VDCM) from normal epithelial (CRL2221, MCF-10A and BEAS-2B) and cancer (LNCaP, PC3 and SUM149) cell lines. Atomic force microscopy and dynamic light scattering analysis revealed similar size distribution patterns and surface zeta potentials between the normal cells-derived and tumor cells-derived exosomes. Electron microscopy revealed that maspin was encapsulated by the exosomal membrane as a cargo protein. While western blotting revealed that the level of exosomal maspin from tumor cell lines was disproportionally lower relative to the levels of corresponding intracellular and VDCM maspin, as compared to that from normal cell lines, maspin knockdown in MCF-10A cells led to maspin-devoid exosomes, which exhibited significantly reduced suppressive effects on the chemotaxis activity of recipient NIH3T3 fibroblast cells. These data are the first to demonstrate the potential of maspin delivered by exosomes to block tumor-induced stromal response, and support the clinical application of exosomal maspin in cancer diagnosis and treatment.
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Navigating the plant cell: intracellular transport logistics in the green kingdom
Geitmann, Anja; Nebenführ, Andreas
2015-01-01
Intracellular transport in plant cells occurs on microtubular and actin arrays. Cytoplasmic streaming, the rapid motion of plant cell organelles, is mostly driven by an actin–myosin mechanism, whereas specialized functions, such as the transport of large cargo or the assembly of a new cell wall during cell division, are performed by the microtubules. Different modes of transport are used, fast and slow, to either haul cargo over long distances or ascertain high-precision targeting, respectively. Various forms of the actin-specific motor protein myosin XI exist in plant cells and might be involved in different cellular functions. PMID:26416952
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STS-102 Onboard Photograph Inside Multipurpose Logistics Module, Leonardo
NASA Technical Reports Server (NTRS)
2001-01-01
Pilot James M. Kelly (left) and Commander James D. Wetherbee for the STS-102 mission, participate in the movement of supplies inside Leonardo, the Italian Space Agency built Multipurpose Logistics Module (MPLM). In this particular photograph, the two are handling a film magazine for the IMAX cargo bay camera. The primary cargo of the STS-102 mission, the Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth station assembly flight, the STS-102 mission also served as a crew rotation flight. It delivered the Expedition Two crew to the Station and returned the Expedition One crew back to Earth.
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International Space Station (ISS)
2001-03-01
Pilot James M. Kelly (left) and Commander James D. Wetherbee for the STS-102 mission, participate in the movement of supplies inside Leonardo, the Italian Space Agency built Multipurpose Logistics Module (MPLM). In this particular photograph, the two are handling a film magazine for the IMAX cargo bay camera. The primary cargo of the STS-102 mission, the Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth station assembly flight, the STS-102 mission also served as a crew rotation flight. It delivered the Expedition Two crew to the Station and returned the Expedition One crew back to Earth.
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Llopis-Lorente, Antoni; Díez, Paula; de la Torre, Cristina; Sánchez, Alfredo; Sancenón, Félix; Aznar, Elena; Marcos, María D; Martínez-Ruíz, Paloma; Martínez-Máñez, Ramón; Villalonga, Reynaldo
2017-03-28
This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular β-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Bouzat, Sebastián
2016-01-01
One-dimensional models coupling a Langevin equation for the cargo position to stochastic stepping dynamics for the motors constitute a relevant framework for analyzing multiple-motor microtubule transport. In this work we explore the consistence of these models focusing on the effects of the thermal noise. We study how to define consistent stepping and detachment rates for the motors as functions of the local forces acting on them in such a way that the cargo velocity and run-time match previously specified functions of the external load, which are set on the base of experimental results. We show that due to the influence of the thermal fluctuations this is not a trivial problem, even for the single-motor case. As a solution, we propose a motor stepping dynamics which considers memory on the motor force. This model leads to better results for single-motor transport than the approaches previously considered in the literature. Moreover, it gives a much better prediction for the stall force of the two-motor case, highly compatible with the experimental findings. We also analyze the fast fluctuations of the cargo position and the influence of the viscosity, comparing the proposed model to the standard one, and we show how the differences on the single-motor dynamics propagate to the multiple motor situations. Finally, we find that the one-dimensional character of the models impede an appropriate description of the fast fluctuations of the cargo position at small loads. We show how this problem can be solved by considering two-dimensional models.
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van Niel, Guillaume; Charrin, Stéphanie; Simoes, Sabrina; Romao, Maryse; Rochin, Leila; Saftig, Paul; Marks, Michael S.; Rubinstein, Eric; Raposo, Graça
2011-01-01
Summary Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for numerous physiological processes including lysosome-related organelle (LRO) biogenesis. PMEL – a component of melanocyte LROs (melanosomes) – is sorted to ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting, the disposal of the remaining PMEL transmembrane fragment requires functional ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a tight interplay regulated by CD63 between two distinct endosomal ILV sorting processes for a single cargo during LRO biogenesis. PMID:21962903
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BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery
Dennis, Megan K.; Mantegazza, Adriana R.; Snir, Olivia L.; Tenza, Danièle; Acosta-Ruiz, Amanda; Delevoye, Cédric; Zorger, Richard; Sitaram, Anand; de Jesus-Rojas, Wilfredo; Ravichandran, Keerthana; Rux, John; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Setty, Subba Rao Gangi
2015-01-01
Hermansky–Pudlak syndrome (HPS) is a group of disorders characterized by the malformation of lysosome-related organelles, such as pigment cell melanosomes. Three of nine characterized HPS subtypes result from mutations in subunits of BLOC-2, a protein complex with no known molecular function. In this paper, we exploit melanocytes from mouse HPS models to place BLOC-2 within a cargo transport pathway from recycling endosomal domains to maturing melanosomes. In BLOC-2–deficient melanocytes, the melanosomal protein TYRP1 was largely depleted from pigment granules and underwent accelerated recycling from endosomes to the plasma membrane and to the Golgi. By live-cell imaging, recycling endosomal tubules of wild-type melanocytes made frequent and prolonged contacts with maturing melanosomes; in contrast, tubules from BLOC-2–deficient cells were shorter in length and made fewer, more transient contacts with melanosomes. These results support a model in which BLOC-2 functions to direct recycling endosomal tubular transport intermediates to maturing melanosomes and thereby promote cargo delivery and optimal pigmentation. PMID:26008744
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The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond
Cavazza, Tommaso; Vernos, Isabelle
2016-01-01
The small GTPase Ran regulates the interaction of transport receptors with a number of cellular cargo proteins. The high affinity binding of the GTP-bound form of Ran to import receptors promotes cargo release, whereas its binding to export receptors stabilizes their interaction with the cargo. This basic mechanism linked to the asymmetric distribution of the two nucleotide-bound forms of Ran between the nucleus and the cytoplasm generates a switch like mechanism controlling nucleo-cytoplasmic transport. Since 1999, we have known that after nuclear envelope breakdown (NEBD) Ran and the above transport receptors also provide a local control over the activity of factors driving spindle assembly and regulating other aspects of cell division. The identification and functional characterization of RanGTP mitotic targets is providing novel insights into mechanisms essential for cell division. Here we review our current knowledge on the RanGTP system and its regulation and we focus on the recent advances made through the characterization of its mitotic targets. We then briefly review the novel functions of the pathway that were recently described. Altogether, the RanGTP system has moonlighting functions exerting a spatial control over protein interactions that drive specific functions depending on the cellular context. PMID:26793706
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Ho, Vincent K.; Angelotti, Timothy
2013-01-01
Receptor expression enhancing proteins (REEPs) were identified by their ability to enhance cell surface expression of a subset of G protein-coupled receptors (GPCRs), specifically GPCRs that have proven difficult to express in heterologous cell systems. Further analysis revealed that they belong to the Yip (Ypt-interacting protein) family and that some REEP subtypes affect ER structure. Yip family comparisons have established other potential roles for REEPs, including regulation of ER-Golgi transport and processing/neuronal localization of cargo proteins. However, these other potential REEP functions and the mechanism by which they selectively enhance GPCR cell surface expression have not been clarified. By utilizing several REEP family members (REEP1, REEP2, and REEP6) and model GPCRs (α2A and α2C adrenergic receptors), we examined REEP regulation of GPCR plasma membrane expression, intracellular processing, and trafficking. Using a combination of immunolocalization and biochemical methods, we demonstrated that this REEP subset is localized primarily to ER, but not plasma membranes. Single cell analysis demonstrated that these REEPs do not specifically enhance surface expression of all GPCRs, but affect ER cargo capacity of specific GPCRs and thus their surface expression. REEP co-expression with α2 adrenergic receptors (ARs) revealed that this REEP subset interacts with and alter glycosidic processing of α2C, but not α2A ARs, demonstrating selective interaction with cargo proteins. Specifically, these REEPs enhanced expression of and interacted with minimally/non-glycosylated forms of α2C ARs. Most importantly, expression of a mutant REEP1 allele (hereditary spastic paraplegia SPG31) lacking the carboxyl terminus led to loss of this interaction. Thus specific REEP isoforms have additional intracellular functions besides altering ER structure, such as enhancing ER cargo capacity, regulating ER-Golgi processing, and interacting with select cargo proteins. Therefore, some REEPs can be further described as ER membrane shaping adapter proteins. PMID:24098485
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Goldman, Stephen D. B.; Krise, Jeffrey P.
2010-01-01
The rare neurodegenerative disease Niemann-Pick Type C (NPC) results from mutations in either NPC1 or NPC2, which are membrane-bound and soluble lysosomal proteins, respectively. Previous studies have shown that mutations in either protein result in biochemically indistinguishable phenotypes, most notably the hyper-accumulation of cholesterol and other cargo in lysosomes. We comparatively evaluated the kinetics of [3H]dextran release from lysosomes of wild type, NPC1, NPC2, and NPC1/NPC2 pseudo-double mutant cells and found significant differences between all cell types examined. Specifically, NPC1 or NPC2 mutant fibroblasts treated with NPC1 or NPC2 siRNA (to create NPC1/NPC2 pseudo-double mutants) secreted dextran less efficiently than did either NPC1 or NPC2 single mutant cell lines, suggesting that the two proteins may work independently of one another in the egress of membrane-impermeable lysosomal cargo. To investigate the basis for these differences, we examined the role of NPC1 and NPC2 in the retrograde fusion of lysosomes with late endosomes to create so-called hybrid organelles, which is believed to be the initial step in the egress of cargo from lysosomes. We show here that cells with mutated NPC1 have significantly reduced rates of late endosome/lysosome fusion relative to wild type cells, whereas cells with mutations in NPC2 have rates that are similar to those observed in wild type cells. Instead of being involved in hybrid organelle formation, we show that NPC2 is required for efficient membrane fission events from nascent hybrid organelles, which is thought to be required for the reformation of lysosomes and the release of lysosomal cargo-containing membrane vesicles. Collectively, these results suggest that NPC1 and NPC2 can function independently of one another in the egress of certain membrane-impermeable lysosomal cargo. PMID:20007703
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NASA Astrophysics Data System (ADS)
Honarbakhsh, Sara
A biodegradable and controlled drug delivery system has been developed herein composed of electrospun polymeric nanofibers impregnated with cargo loaded Red clover necrotic mosaic virus (RCNMV)---a robust plant virus---as the drug carrier nanoparticle. In this system, controlled drug release is achieved by altering the porosity of the biodegradable matrix as well as controlling the position and distribution of the cargo loaded nanocarriers in the matrix. Solution electrospinning as well as dipping method are used to create and to impregnate the matrix (the fibers of which possess uniformly distributed nano-size surface pores) with cargo loaded nanocarriers. Prior to the impregnation stage of cargo loaded nanocarriers into the matrix, compatibility of a group of candidate cargos (Ampicillin, Novanthrone, Doxorubicin and Ethidium Bromide) and RCNMV functionality with potential electrospinning solvents were investigated and a solvent with the least degradative effect was selected. In order to achieve both sustained and immediate drug release profiles, cargo loaded nanocarriers were embedded into the matrix---through co-spinning process---as well as on the surface of matrix fibers---through dipping method. SEM, TEM and Fluorescent Light Microscopy images of the medicated structures suggested that the nanocarriers were incorporated into/on the matrix. In vitro release assays were also carried out the results of which confirmed having obtained sustained release in the co-spun medicated structures where as dipped samples showed an immediate release profile.
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Monitoring Extracellular Vesicle Cargo Active Uptake by Imaging Flow Cytometry.
Ofir-Birin, Yifat; Abou Karam, Paula; Rudik, Ariel; Giladi, Tal; Porat, Ziv; Regev-Rudzki, Neta
2018-01-01
Extracellular vesicles are essential for long distance cell-cell communication. They function as carriers of different compounds, including proteins, lipids and nucleic acids. Pathogens, like malaria parasites ( Plasmodium falciparum, Pf ), excel in employing vesicle release to mediate cell communication in diverse processes, particularly in manipulating the host response. Establishing research tools to study the interface between pathogen-derived vesicles and their host recipient cells will greatly benefit the scientific community. Here, we present an imaging flow cytometry (IFC) method for monitoring the uptake of malaria-derived vesicles by host immune cells. By staining different cargo components, we were able to directly track the cargo's internalization over time and measure the kinetics of its delivery. Impressively, we demonstrate that this method can be used to specifically monitor the translocation of a specific protein within the cellular milieu upon internalization of parasitic cargo; namely, we were able to visually observe how uptaken parasitic Pf -DNA cargo leads to translocation of transcription factor IRF3 from the cytosol to the nucleus within the recipient immune cell. Our findings demonstrate that our method can be used to study cellular dynamics upon vesicle uptake in different host-pathogen and pathogen-pathogen systems.
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García, Iris A; Torres Demichelis, Vanina; Viale, Diego L; Di Giusto, Pablo; Ezhova, Yulia; Polishchuk, Roman S; Sampieri, Luciana; Martinez, Hernán; Sztul, Elizabeth; Alvarez, Cecilia
2017-12-15
Many secretory cells increase the synthesis and secretion of cargo proteins in response to specific stimuli. How cells couple increased cargo load with a coordinate rise in secretory capacity to ensure efficient transport is not well understood. We used thyroid cells stimulated with thyrotropin (TSH) to demonstrate a coordinate increase in the production of thyroid-specific cargo proteins and ER-Golgi transport factors, and a parallel expansion of the Golgi complex. TSH also increased expression of the CREB3L1 transcription factor, which alone caused amplified transport factor levels and Golgi enlargement. Furthermore, CREB3L1 potentiated the TSH-induced increase in Golgi volume. A dominant-negative CREB3L1 construct hampered the ability of TSH to induce Golgi expansion, implying that this transcription factor contributes to Golgi expansion. Our findings support a model in which CREB3L1 acts as a downstream effector of TSH to regulate the expression of cargo proteins, and simultaneously increases the synthesis of transport factors and the expansion of the Golgi to synchronize the rise in cargo load with the amplified capacity of the secretory pathway. © 2017. Published by The Company of Biologists Ltd.
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Rosas-Santiago, Paul; Lagunas-Gómez, Daniel; Barkla, Bronwyn J.; Vera-Estrella, Rosario; Lalonde, Sylvie; Jones, Alexander; Frommer, Wolf B.; Zimmermannova, Olga; Sychrová, Hana; Pantoja, Omar
2015-01-01
Membrane proteins are synthesized and folded in the endoplasmic reticulum (ER), and continue their path to their site of residence along the secretory pathway. The COPII system has been identified as a key player for selecting and directing the fate of membrane and secretory cargo proteins. Selection of cargo proteins within the COPII vesicles is achieved by cargo receptors. The cornichon cargo receptor belongs to a conserved protein family found in eukaryotes that has been demonstrated to participate in the selection of integral membrane proteins as cargo for their correct targeting. Here it is demonstrated at the cellular level that rice cornichon OsCNIH1 interacts with OsHKT1;3 and, in yeast cells, enables the expression of the sodium transporter to the Golgi apparatus. Physical and functional HKT–cornichon interactions are confirmed by the mating-based split ubiquitin system, bimolecular fluorescence complementation, and Xenopus oocyte and yeast expression systems. The interaction between the two proteins occurs in the ER of plant cells and their co-expression in oocytes leads to the sequestration of the transporter in the ER. In the yeast cornichon mutant erv14, OsHKT1;3 is mistargeted, preventing the toxic effects of sodium transport in the cell observed in wild-type cells or in the erv14 mutant that co-expressed OsHKT1;3 with either OsCNIH1 or Erv14p. Identification and characterization of rice cornichon as a possible cargo receptor opens up the opportunity to improve our knowledge on membrane protein targeting in plant cells. PMID:25750424
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Xu, Weinan; Ledin, Petr A; Iatridi, Zacharoula; Tsitsilianis, Constantinos; Tsukruk, Vladimir V
2016-04-11
Multicompartmental responsive microstructures with the capability for the pre-programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N-isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2-vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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NASA Technical Reports Server (NTRS)
Stone, Ralph W., Jr.; Hultz, Burton E.
1949-01-01
The characteristics of a cargo-dropping device having extensible rotating blades as load-carrying surfaces have been studied in simulated vertical descent in the Langley 20-foot free-spinning tunnel. The investigation included tests to determine the variation in vertical sinking speed with load. A study of the blade characteristics and of the test results indicated a method of dynamically balancing the blades to permit proper functioning of the device.
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Rosas-Santiago, Paul; Lagunas-Gómez, Daniel; Barkla, Bronwyn J; Vera-Estrella, Rosario; Lalonde, Sylvie; Jones, Alexander; Frommer, Wolf B; Zimmermannova, Olga; Sychrová, Hana; Pantoja, Omar
2015-05-01
Membrane proteins are synthesized and folded in the endoplasmic reticulum (ER), and continue their path to their site of residence along the secretory pathway. The COPII system has been identified as a key player for selecting and directing the fate of membrane and secretory cargo proteins. Selection of cargo proteins within the COPII vesicles is achieved by cargo receptors. The cornichon cargo receptor belongs to a conserved protein family found in eukaryotes that has been demonstrated to participate in the selection of integral membrane proteins as cargo for their correct targeting. Here it is demonstrated at the cellular level that rice cornichon OsCNIH1 interacts with OsHKT1;3 and, in yeast cells, enables the expression of the sodium transporter to the Golgi apparatus. Physical and functional HKT-cornichon interactions are confirmed by the mating-based split ubiquitin system, bimolecular fluorescence complementation, and Xenopus oocyte and yeast expression systems. The interaction between the two proteins occurs in the ER of plant cells and their co-expression in oocytes leads to the sequestration of the transporter in the ER. In the yeast cornichon mutant erv14, OsHKT1;3 is mistargeted, preventing the toxic effects of sodium transport in the cell observed in wild-type cells or in the erv14 mutant that co-expressed OsHKT1;3 with either OsCNIH1 or Erv14p. Identification and characterization of rice cornichon as a possible cargo receptor opens up the opportunity to improve our knowledge on membrane protein targeting in plant cells. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.
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Zhang, Xuan; Wang, Youpeng; Li, Guo; Liu, Zhaotie; Liu, Zhongwen; Jiang, Jinqiang
2017-01-01
An amphiphilic block copolymer of poly(ethylene oxide)-b-poly((N-methacryloxy phthalimide)-co-(7-(4-vinyl-benzyloxyl)-4-methylcoumarin)) (PEO 45 -b-P(MAPI 36 -co-VBC 4 )) is designed to improve the micellar stability during the photo-triggered release of hydrophobic cargoes. Analysis of absorption and emission spectra, solution transmittance, dynamic light scattering, and transmission electron microscopy supports that polymer micelles of PEO 45 -b-P(MAPI 36 -co-VBC 4 ) upon the combinational irradiation of 365 and 254 nm light can be solubilized through the photolysis of phthalimide esters and simultaneously crosslinked via the partially reversible photo-dimerization of coumarins. The photo-triggered release experiment shows that the leakage of doxorubicin molecules from crosslinked micelles can be predictably regulated by controlling the irradiation time of 365 and 254 nm light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Cyrus, Bita F.; Muller, William A.
2017-01-01
A reservoir of parajunctional membrane in endothelial cells, the lateral border recycling compartment (LBRC), is critical for transendothelial migration (TEM). We have previously shown that targeted recycling of the LBRC to the site of TEM requires microtubules and a kinesin molecular motor. However, the identity of the kinesin and mechanism of cargo binding were not known. We show that microinjection of endothelial cells with a monoclonal antibody specific for kinesin-1 significantly blocked LBRC-targeted recycling and TEM. In complementary experiments, knocking down KIF5B, a ubiquitous kinesin-1 isoform, in endothelial cells significantly decreased targeted recycling of the LBRC and leukocyte TEM. Kinesin heavy chains move cargo along microtubules by one of many kinesin light chains (KLCs), which directly bind the cargo. Knocking down KLC 1 isoform variant 1 (KLC1C) significantly decreased LBRC-targeted recycling and TEM, whereas knocking down other isoforms of KLC1 had no effect. Re-expression of KLC1C resistant to the knockdown shRNA restored targeted recycling and TEM. Thus kinesin-1 and KLC1C are specifically required for targeted recycling and TEM. These data suggest that of the many potential combinations of the 45 kinesin family members and multiple associated light chains, KLC1C links the LBRC to kinesin-1 (KIF5B) during targeted recycling and TEM. Thus, KLC1C can potentially be used as a target for anti-inflammatory therapy. PMID:26994343
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NASA Astrophysics Data System (ADS)
Lucon, Janice; Qazi, Shefah; Uchida, Masaki; Bedwell, Gregory J.; Lafrance, Ben; Prevelige, Peter E.; Douglas, Trevor
2012-10-01
Virus-like particles (VLPs) have emerged as important and versatile architectures for chemical manipulation in the development of functional hybrid nanostructures. Here we demonstrate a successful site-selective initiation of atom-transfer radical polymerization reactions to form an addressable polymer constrained within the interior cavity of a VLP. Potentially, this protein-polymer hybrid of P22 and cross-linked poly(2-aminoethyl methacrylate) could be useful as a new high-density delivery vehicle for the encapsulation and delivery of small-molecule cargos. In particular, the encapsulated polymer can act as a scaffold for the attachment of small functional molecules, such as fluorescein dye or the magnetic resonance imaging (MRI) contrast agent Gd-diethylenetriaminepentacetate, through reactions with its pendant primary amine groups. Using this approach, a significant increase in the labelling density of the VLP, compared to that of previous modifications of VLPs, can be achieved. These results highlight the use of multimeric protein-polymer conjugates for their potential utility in the development of VLP-based MRI contrast agents with the possibility of loading other cargos.
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Multipurpose Logistics Module, Leonardo, Rests in Discovery's Payload Bay
NASA Technical Reports Server (NTRS)
2001-01-01
This in-orbit close up shows the Italian Space Agency-built multipurpose Logistics Module (MPLM), Leonardo, the primary cargo of the STS-102 mission, resting in the payload bay of the Space Shuttle Orbiter Discovery. The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth station assembly flight and NASA's 103rd overall flight, STS-102 launched March 8, 2001 for an almost 13 day mission.
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International Space Station (ISS)
2001-03-10
This in-orbit close up shows the Italian Space Agency-built multipurpose Logistics Module (MPLM), Leonardo, the primary cargo of the STS-102 mission, resting in the payload bay of the Space Shuttle Orbiter Discovery. The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth station assembly flight and NASA's 103rd overall flight, STS-102 launched March 8, 2001 for an almost 13 day mission.
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Lissencephaly-1 is a context-dependent regulator of the human dynein complex
Baumbach, Janina; Murthy, Andal; McClintock, Mark A; Dix, Carly I; Zalyte, Ruta; Hoang, Ha Thi; Bullock, Simon L
2017-01-01
The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends. LIS1 also increases the frequency and velocity of processive dynein movements that are activated by complex formation with dynactin and a cargo adaptor. This stimulatory effect of LIS1 contrasts sharply with its documented ability to inhibit the activity of isolated dyneins. Collectively, our findings shed light on how mammalian dynein complexes associate with dynamic microtubules and help clarify how LIS1 promotes the plus-end localisation and cargo transport functions of dynein in vivo. DOI: http://dx.doi.org/10.7554/eLife.21768.001 PMID:28406398
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Zhang, Li; Petit, Tristan; Lu, Yang; Kratochvil, Bradley E; Peyer, Kathrin E; Pei, Ryan; Lou, Jun; Nelson, Bradley J
2010-10-26
We show that rotating Ni nanowires are capable of propulsion and transport of colloidal cargo near a complex surface. When dissimilar boundary conditions exist at the two ends of a nanowire, such as when a nanowire is near a wall, tumbling motion can be generated that leads to propulsion of the nanowire. The motion of the nanowire can be precisely controlled using a uniform rotating magnetic field. We investigate the propulsion mechanism and the trajectory of the nanowire during the tumbling motion and demonstrate cargo transport of a polystyrene microbead by the nanowire over a flat surface or across an open microchannel. The results imply that functionalized, ferromagnetic one-dimensional, tumbling nanostructures can be used for cell manipulation and targeted drug delivery in a low Reynolds number aqueous environment.
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A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling.
Bai, Zhiyong; Grant, Barth D
2015-03-24
Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.
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A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling
Bai, Zhiyong; Grant, Barth D.
2015-01-01
Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1–positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42–associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling. PMID:25775511
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The Complete Exosome Workflow Solution: From Isolation to Characterization of RNA Cargo
Schageman, Jeoffrey; Li, Mu; Barta, Tim; Lea, Kristi; Gu, Jian; Magdaleno, Susan; Setterquist, Robert; Vlassov, Alexander V.
2013-01-01
Exosomes are small (30–150 nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. At the moment, the mechanism of exosome formation, the makeup of the cargo, biological pathways, and resulting functions are incompletely understood. One of their most intriguing roles is intercellular communication—exosomes function as the messengers, delivering various effector or signaling macromolecules between specific cells. There is an exponentially growing need to dissect structure and the function of exosomes and utilize them for development of minimally invasive diagnostics and therapeutics. Critical to further our understanding of exosomes is the development of reagents, tools, and protocols for their isolation, characterization, and analysis of their RNA and protein contents. Here we describe a complete exosome workflow solution, starting from fast and efficient extraction of exosomes from cell culture media and serum to isolation of RNA followed by characterization of exosomal RNA content using qRT-PCR and next-generation sequencing techniques. Effectiveness of this workflow is exemplified by analysis of the RNA content of exosomes derived from HeLa cell culture media and human serum, using Ion Torrent PGM as a sequencing platform. PMID:24205503
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Experimental Test Concept for a Cargo Data Interchange System (CARDIS) : Volume 1. Text.
DOT National Transportation Integrated Search
1976-05-01
This report includes the recommended CARDIS experimental test system functional capabilities. It identifies the CARDIS functions that are inherent to an information exchange capability and optional systems which are required by the transportation rel...
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Experimental Test Concept for a Cargo Data Interchange System (CARDIS) : Volume 2. Appendixes.
DOT National Transportation Integrated Search
1976-05-01
This report includes the recommended CARDIS experimental test system functional capabilities. It identifies the CARDIS functions that are inherent to an information exchange capability and optional systems which are required by the transportation rel...
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Cosmonaut Dezhurov Talks With Flight Controllers
NASA Technical Reports Server (NTRS)
2001-01-01
Aboard the International Space Station (ISS), Cosmonaut and Expedition Three flight engineer Vladimir N. Dezhurov, representing Rosaviakosmos, talks with flight controllers from the Zvezda Service Module. Russian-built Zvezda is linked to the Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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International Space Station (ISS)
2001-09-16
Aboard the International Space Station (ISS), Cosmonaut and Expedition Three flight engineer Vladimir N. Dezhurov, representing Rosaviakosmos, talks with flight controllers from the Zvezda Service Module. Russian-built Zvezda is linked to the Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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International Space Station (ISS)
2001-12-12
Astronauts Frank L. Culbertson, Jr. (left), Expedition Three mission commander, and Daniel W. Bursch, Expedition Four flight engineer, work in the Russian Zvezda Service Module on the International Space Station (ISS). Zvezda is linked to the Russian built Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the Station, providing living quarters, a life support system, electrical power distribution, a data processing system, a flight control system, and a propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000 pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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International Space Station (ISS)
2001-03-30
Astronaut James S. Voss, Expedition Two flight engineer, performs an electronics task in the Russian Zvezda Service Module on the International Space Station (ISS). Zvezda is linked to the Russian-built Functional Cargo Block (FGB), or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity, the first U.S.-built component to the ISS. Zvezda (Russian word for star), the third component of the ISS and the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the station, providing living quarters, a life support system, electrical power distribution, a data processing system, a flight control system, and a propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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International Space Station (ISS)
2002-03-25
Cosmonaut Yury I. Onufrienko, Expedition Four mission commander, uses a communication system in the Russian Zvezda Service Module on the International Space Station (ISS). The Zvezda is linked to the Russian-built Functional Cargo Block (FGB) or Zarya, the first component of the ISS. Zarya was launched on a Russian Proton rocket prior to the launch of Unity. The third component of the ISS, Zvezda (Russian word for star), the primary Russian contribution to the ISS, was launched by a three-stage Proton rocket on July 12, 2000. Zvezda serves as the cornerstone for early human habitation of the station, providing living quarters, a life support system, electrical power distribution, a data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein.
Klinman, Eva; Holzbaur, Erika L F
2015-07-21
Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5) activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
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International Space Station (ISS)
1997-10-01
The Zvezda Service Module, the first Russian contribution and third element to the International Space Station (ISS), is shown under construction in the Krunichev State Research and Production Facility (KhSC) in Moscow. Russian technicians work on the module shortly after it completed a pressurization test. In the foreground is the forward portion of the module, including the spherical transfer compartment and its three docking ports. The forward port docked with the cornected Functional Cargo Block, followed by Node 1. Launched via a three-stage Proton rocket on July 12, 2000, the Zvezda Service Module serves as the cornerstone for early human habitation of the Station, providing living quarters, life support system, electrical power distribution, data processing system, flight control system, and propulsion system. It also provides a communications system that includes remote command capabilities from ground flight controllers. The 42,000-pound module measures 43 feet in length and has a wing span of 98 feet. Similar in layout to the core module of Russia's Mir space station, it contains 3 pressurized compartments and 13 windows that allow ultimate viewing of Earth and space.
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Unity with PMA-2 attached awaits further processing in the SSPF
NASA Technical Reports Server (NTRS)
1998-01-01
The International Space Station's (ISS) Unity node, with Pressurized Mating Adapter (PMA)-2 attached, awaits further processing by Boeing technicians in its workstand in the Space Station Processing Facility (SSPF). The Unity node is the first element of the ISS to be manufactured in the United States and is currently scheduled to lift off aboard the Space Shuttle Endeavour on STS-88 later this year. Unity has two PMAs attached to it now that this mate is completed. PMAs are conical docking adapters which will allow the docking systems used by the Space Shuttle and by Russian modules to attach to the node's hatches and berthing mechanisms. Once in orbit, Unity, which has six hatches, will be mated with the already orbiting Control Module and will eventually provide attachment points for the U.S. laboratory module; Node 3; an early exterior framework or truss for the station; an airlock; and a multi-windowed cupola. The Control Module, or Functional Cargo Block, is a U.S.-funded and Russian-built component that will be launched aboard a Russian rocket from Kazakstan.
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Unity with PMA-2 attached awaits further processing in the SSPF
NASA Technical Reports Server (NTRS)
1998-01-01
The International Space Station's (ISS) Unity node, with Pressurized Mating Adapter (PMA)-2 attached, awaits further processing in the Space Station Processing Facility (SSPF). The Unity node is the first element of the ISS to be manufactured in the United States and is currently scheduled to lift off aboard the Space Shuttle Endeavour on STS-88 later this year. Unity has two PMAs attached to it now that this mate is completed. PMAs are conical docking adapters which will allow the docking systems used by the Space Shuttle and by Russian modules to attach to the node's hatches and berthing mechanisms. Once in orbit, Unity, which has six hatches, will be mated with the already orbiting Control Module and will eventually provide attachment points for the U.S. laboratory module; Node 3; an early exterior framework or truss for the station; an airlock; and a multi-windowed cupola. The Control Module, or Functional Cargo Block, is a U.S.- funded and Russian-built component that will be launched aboard a Russian rocket from Kazakstan.
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1998-05-22
KENNEDY SPACE CENTER, FLA. -- The International Space Station's (ISS) Unity node, with Pressurized Mating Adapter (PMA)-2 attached, awaits further processing by Boeing technicians in its workstand in the Space Station Processing Facility (SSPF). The Unity node is the first element of the ISS to be manufactured in the United States and is currently scheduled to lift off aboard the Space Shuttle Endeavour on STS-88 later this year. Unity has two PMAs attached to it now that this mate is completed. PMAs are conical docking adapters which will allow the docking systems used by the Space Shuttle and by Russian modules to attach to the node's hatches and berthing mechanisms. Once in orbit, Unity, which has six hatches, will be mated with the already orbiting Control Module and will eventually provide attachment points for the U.S. laboratory module; Node 3; an early exterior framework or truss for the station; an airlock; and a multi-windowed cupola. The Control Module, or Functional Cargo Block, is a U.S.-funded and Russian-built component that will be launched aboard a Russian rocket from Kazakstan
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Adamowski, Maciek; Kania, Urszula
2018-01-01
Clathrin-mediated endocytosis (CME) is a cellular trafficking process in which cargoes and lipids are internalized from the plasma membrane into vesicles coated with clathrin and adaptor proteins. CME is essential for many developmental and physiological processes in plants, but its underlying mechanism is not well characterized compared with that in yeast and animal systems. Here, we searched for new factors involved in CME in Arabidopsis thaliana by performing tandem affinity purification of proteins that interact with clathrin light chain, a principal component of the clathrin coat. Among the confirmed interactors, we found two putative homologs of the clathrin-coat uncoating factor auxilin previously described in non-plant systems. Overexpression of AUXILIN-LIKE1 and AUXILIN-LIKE2 in Arabidopsis caused an arrest of seedling growth and development. This was concomitant with inhibited endocytosis due to blocking of clathrin recruitment after the initial step of adaptor protein binding to the plasma membrane. By contrast, auxilin-like1/2 loss-of-function lines did not present endocytosis-related developmental or cellular phenotypes under normal growth conditions. This work contributes to the ongoing characterization of the endocytotic machinery in plants and provides a robust tool for conditionally and specifically interfering with CME in Arabidopsis. PMID:29511054
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Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata
2016-01-01
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407
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Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata
2016-02-16
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.
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Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; ...
2016-02-02
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.
A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less
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46 CFR 154.315 - Cargo pump and cargo compressor rooms.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pump and cargo compressor rooms. 154.315 Section... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Ship Arrangements § 154.315 Cargo pump and cargo compressor rooms. (a) Cargo pump rooms and cargo...
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Cooper, Colin A; Zhang, Kun; Andres, Sara N; Fang, Yuan; Kaniuk, Natalia A; Hannemann, Mandy; Brumell, John H; Foster, Leonard J; Junop, Murray S; Coombes, Brian K
2010-02-05
Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for effector translocation into host cells. In Salmonella enterica serovar Typhimurium, a T3SS encoded in a large genomic island (SPI-2) is required for intracellular infection, but the chaperone complement required for effector translocation by this system is not known. Using a reverse genetics approach, we identified a multi-cargo secretion chaperone that is functionally integrated with the SPI-2-encoded T3SS and required for systemic infection in mice. Crystallographic analysis of SrcA at a resolution of 2.5 A revealed a dimer similar to the CesT chaperone from enteropathogenic E. coli but lacking a 17-amino acid extension at the carboxyl terminus. Further biochemical and quantitative proteomics data revealed three protein interactions with SrcA, including two effector cargos (SseL and PipB2) and the type III-associated ATPase, SsaN, that increases the efficiency of effector translocation. Using competitive infections in mice we show that SrcA increases bacterial fitness during host infection, highlighting the in vivo importance of effector chaperones for the SPI-2 T3SS.
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Matsuura, Yoshiyuki
2016-05-22
Understanding how macromolecules are rapidly exchanged between the nucleus and the cytoplasm through nuclear pore complexes is a fundamental problem in biology. Exportins are Ran-GTPase-dependent nuclear transport factors that belong to the karyopherin-β family and mediate nuclear export of a plethora of proteins and RNAs, except for bulk mRNA nuclear export. Exportins bind cargo macromolecules in a Ran-GTP-dependent manner in the nucleus, forming exportin-cargo-Ran-GTP complexes (nuclear export complexes). Transient weak interactions between exportins and nucleoporins containing characteristic FG (phenylalanine-glycine) repeat motifs facilitate nuclear pore complex passage of nuclear export complexes. In the cytoplasm, nuclear export complexes are disassembled, thereby releasing the cargo. GTP hydrolysis by Ran promoted in the cytoplasm makes the disassembly reaction virtually irreversible and provides thermodynamic driving force for the overall export reaction. In the past decade, X-ray crystallography of some of the exportins in various functional states coupled with functional analyses, single-particle electron microscopy, molecular dynamics simulations, and small-angle solution X-ray scattering has provided rich insights into the mechanism of cargo binding and release and also begins to elucidate how exportins interact with the FG repeat motifs. The knowledge gained from structural analyses of nuclear export is being translated into development of clinically useful inhibitors of nuclear export to treat human diseases such as cancer and influenza. Copyright © 2015 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
de Pablo, Pedro J.
The basic architecture of a virus consists of the capsid, a shell made up of repeating protein subunits, which packs, shuttles and delivers their genome at the right place and moment. Viral particles are endorsed with specific physicochemical properties which confer to their structures certain meta-stability whose modulation permits fulfilling each task of the viral cycle. These natural designed capabilities have impelled using viral capsids as protein containers of artificial cargoes (drugs, polymers, enzymes, minerals) with applications in biomedical and materials sciences. Both natural and artificial protein cages have to protect their cargo against a variety of physicochemical aggressive environments, including molecular impacts of highly crowded media, thermal and chemical stresses, and osmotic shocks. Viral cages stability under these ambiences depend not only on the ultimate structure of the external capsid, which rely on the interactions between protein subunits, but also on the nature of the cargo. During the last decade our lab has focused on the study of protein cages with Atomic Force Microscopy (AFM) (figure 1). We are interested in stablishing links of their mechanical properties with their structure and function. In particular, mechanics provide information about the cargo storage strategies of both natural and virus-derived protein cages. Mechanical fatigue has revealed as a nanosurgery tool to unveil the strength of the capisd subunit bonds. We also interrogated the electrostatics of individual protein shells. Our AFM-fluorescence combination provided information about DNA diffusing out cracked-open protein cages in real time.
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Ran-dependent nuclear export mediators: a structural perspective
Güttler, Thomas; Görlich, Dirk
2011-01-01
Nuclear export is an essential eukaryotic activity. It proceeds through nuclear pore complexes (NPCs) and is mediated by soluble receptors that shuttle between nucleus and cytoplasm. RanGTPase-dependent export mediators (exportins) constitute the largest class of these carriers and are functionally highly versatile. All of these exportins load their substrates in response to RanGTP binding in the nucleus and traverse NPCs as ternary RanGTP–exportin–cargo complexes to the cytoplasm, where GTP hydrolysis leads to export complex disassembly. The different exportins vary greatly in their substrate range. Recent structural studies of both protein- and RNA-specific exporters have illuminated how exportins bind their cargoes, how Ran triggers cargo loading and how export complexes are disassembled in the cytoplasm. Here, we review the current state of knowledge and highlight emerging principles as well as prevailing questions. PMID:21878989
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GFP-complementation assay to detect functional CPP and protein delivery into living cells
Milech, Nadia; Longville, Brooke AC; Cunningham, Paula T; Scobie, Marie N; Bogdawa, Heique M; Winslow, Scott; Anastasas, Mark; Connor, Theresa; Ong, Ferrer; Stone, Shane R; Kerfoot, Maria; Heinrich, Tatjana; Kroeger, Karen M; Tan, Yew-Foon; Hoffmann, Katrin; Thomas, Wayne R; Watt, Paul M; Hopkins, Richard M
2015-01-01
Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID:26671759
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46 CFR 154.534 - Cargo pumps and cargo compressors.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pumps and cargo compressors. 154.534 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.534 Cargo pumps and cargo compressors. Cargo pumps and...
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Federal Register 2010, 2011, 2012, 2013, 2014
2013-11-04
... Customs Automation Program Test Concerning Automated Commercial Environment (ACE) Cargo Release (Formerly... Simplified Entry functionality in the Automated Commercial Environment (ACE). Originally, the test was known...) test concerning Automated Commercial Environment (ACE) Simplified Entry (SE test) functionality is...
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Mesa-Torres, Noel; Tomic, Nenad; Albert, Armando; Salido, Eduardo; Pey, Angel L
2015-02-13
Peroxisomal biogenesis and function critically depends on the import of cytosolic proteins carrying a PTS1 sequence into this organelle upon interaction with the peroxin Pex5p. Recent structural studies have provided important insights into the molecular recognition of cargo proteins by Pex5p. Peroxisomal import is a key feature in the pathogenesis of primary hyperoxaluria type 1 (PH1), where alanine:glyoxylate aminotransferase (AGT) undergoes mitochondrial mistargeting in about a third of patients. Here, we study the molecular recognition of PTS1 cargo proteins by Pex5p using oligopeptides and AGT variants bearing different natural PTS1 sequences, and employing an array of biophysical, computational and cell biology techniques. Changes in affinity for Pex5p (spanning over 3-4 orders of magnitude) reflect different thermodynamic signatures, but overall bury similar amounts of molecular surface. Structure/energetic analyses provide information on the contribution of ancillary regions and the conformational changes induced in Pex5p and the PTS1 cargo upon complex formation. Pex5p stability in vitro is enhanced upon cargo binding according to their binding affinities. Moreover, we provide evidence that the rational modulation of the AGT: Pex5p binding affinity might be useful tools to investigate mistargeting and misfolding in PH1 by pulling the folding equilibria towards the native and peroxisomal import competent state.
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Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M.
2014-01-01
Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the primary nuclear export molecule involved in these processes being chromosome region maintenance 1 (CRM1, exportin 1 or XPO1). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM1 protein. CRM1 inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM1 inhibitor, CRM1 binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM1 inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM1 inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors are being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM1 inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM1 inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM1 inhibitors and the addition of alkylating agents (melphalan), anthracyclines (doxorubicin and daunomycin), BRAF inhibitors, platinum drugs (cisplatin and oxaliplatin), proteosome inhibitors (bortezomib and carfilzomib), or tyrosine-kinase inhibitors (imatinib). Also, the sequence of treatment may be important for combination therapy. We found that the most effective treatment regimen involved first priming the cancer cells with the CRM1 inhibitor followed by doxorubicin, bortezomib, carfilzomib, or melphalan. This order sensitized both de novo and acquired drug-resistant cancer cell lines. PMID:24631834
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Definition of avionics concepts for a heavy lift cargo vehicle. Volume 1: Executive summary
NASA Technical Reports Server (NTRS)
1989-01-01
A cost effective, multiuser simulation, test, and demonstration facility to support the development of avionics systems for future space vehicles is examined. The technology needs and requirements of future Heavy Lift Cargo Vehicles (HLCVs) are analyzed and serve as the basis for sizing of the avionics facility, although the lab is not limited in use to support of HLCVs. Volume 1 provides a summary of the vehicle avionics trade studies, the avionics lab objectives, a summary of the lab's functional requirements and design, physical facility considerations, and cost estimates.
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deRonde, Brittany M; Posey, Nicholas D; Otter, Ronja; Caffrey, Leah M; Minter, Lisa M; Tew, Gregory N
2016-06-13
Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siRNA internalization. To explore the hydrophobic block length, two different series of diblock copolymers were synthesized: one series with symmetric block lengths and one with asymmetric block lengths. At similar cationic block lengths, asymmetric and symmetric PTDMs promoted siRNA internalization in the same percentages of the cell population regardless of the hydrophobic block length; however, with 20 repeat units of cationic charge, the asymmetric block length had greater siRNA internalization, highlighting the nontrivial relationships between hydrophobicity and overall cationic charge. To further probe how the hydrophobic side chains impacted siRNA internalization, an additional series of asymmetric PTDMs was synthesized that featured a fixed hydrophobic block length of five repeat units that contained either dimethyl (dMe), methyl phenyl (MePh), or diphenyl (dPh) side chains and varied cationic block lengths. This series was further expanded to incorporate hydrophobic blocks consisting of diethyl (dEt), diisobutyl (diBu), and dicyclohexyl (dCy) based repeat units to better define the hydrophobic window for which our PTDMs had optimal activity. High-performance liquid chromatography retention times quantified the relative hydrophobicities of the noncationic building blocks. PTDMs containing the MePh, diBu, and dPh hydrophobic blocks were shown to have superior siRNA internalization capabilities compared to their more and less hydrophobic counterparts, demonstrating a critical window of relative hydrophobicity for optimal internalization. This better understanding of how hydrophobicity impacts PTDM-induced internalization efficiencies will help guide the development of future delivery reagents.
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NASA Astrophysics Data System (ADS)
Seamster, Pamela E.; Loewenberg, Michael; Pascal, Jennifer; Chauviere, Arnaud; Gonzales, Aaron; Cristini, Vittorio; Bearer, Elaine L.
2012-10-01
The kinesins have long been known to drive microtubule-based transport of sub-cellular components, yet the mechanisms of their attachment to cargo remain a mystery. Several different cargo-receptors have been proposed based on their in vitro binding affinities to kinesin-1. Only two of these—phosphatidyl inositol, a negatively charged lipid, and the carboxyl terminus of the amyloid precursor protein (APP-C), a trans-membrane protein—have been reported to mediate motility in living systems. A major question is how these many different cargo, receptors and motors interact to produce the complex choreography of vesicular transport within living cells. Here we describe an experimental assay that identifies cargo-motor receptors by their ability to recruit active motors and drive transport of exogenous cargo towards the synapse in living axons. Cargo is engineered by derivatizing the surface of polystyrene fluorescent nanospheres (100 nm diameter) with charged residues or with synthetic peptides derived from candidate motor receptor proteins, all designed to display a terminal COOH group. After injection into the squid giant axon, particle movements are imaged by laser-scanning confocal time-lapse microscopy. In this report we compare the motility of negatively charged beads with APP-C beads in the presence of glycine-conjugated non-motile beads using new strategies to measure bead movements. The ensuing quantitative analysis of time-lapse digital sequences reveals detailed information about bead movements: instantaneous and maximum velocities, run lengths, pause frequencies and pause durations. These measurements provide parameters for a mathematical model that predicts the spatiotemporal evolution of distribution of the two different types of bead cargo in the axon. The results reveal that negatively charged beads differ from APP-C beads in velocity and dispersion, and predict that at long time points APP-C will achieve greater progress towards the presynaptic terminal. The significance of this data and accompanying model pertains to the role transport plays in neuronal function, connectivity, and survival, and has implications in the pathogenesis of neurological disorders, such as Alzheimer’s, Huntington and Parkinson's diseases.
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Liu, Betty R; Huang, Yue-Wern; Korivi, Mallikarjuna; Lo, Shih-Yen; Aronstam, Robert S; Lee, Han-Jung
2017-01-01
Development of effective drug delivery systems (DDS) is a critical issue in health care and medicine. Advances in molecular biology and nanotechnology have allowed the introduction of nanomaterial-based drug delivery systems. Cell-penetrating peptides (CPPs) can form the basis of drug delivery systems by virtue of their ability to support the transport of cargoes into the cell. Potential cargoes include proteins, DNA, RNA, liposomes, and nanomaterials. These cargoes generally retain their bioactivities upon entering cells. In the present study, the smallest, fully-active lactoferricin-derived CPP, L5a is used to demonstrate the primary contributor of cellular internalization. The secondary helical structure of L5a encompasses symmetrical positive charges around the periphery. The contributions of cell-specificity, peptide length, concentration, zeta potential, particle size, and spatial structure of the peptides were examined, but only zeta potential and spatial structure affected protein transduction efficiency. FITC-labeled L5a appeared to enter cells via direct membrane translocation insofar as endocytic modulators did not block FITC-L5a entry. This is the same mechanism of protein transduction active in Cy5 labeled DNA delivery mediated by FITC-L5a. A significant reduction of transduction efficiency was observed with structurally incomplete FITC-L5a formed by tryptic destruction, in which case the mechanism of internalization switched to a classical energydependent endocytosis pathway. These results support the continued development of the non-cytotoxic L5a as an efficient tool for drug delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Code of Federal Regulations, 2014 CFR
2014-10-01
... pierced by fixed lights, drive shafts, and pump-engine control rods, provided that the shafts and rods are... 46 Shipping 4 2014-10-01 2014-10-01 false Cargo handling devices or cargo pump rooms handling... OSVs § 111.106-13 Cargo handling devices or cargo pump rooms handling flammable or combustible cargoes...
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STS-102 Onboard Photograph-Multi-Purpose Logistics Module, Leonardo
NASA Technical Reports Server (NTRS)
2001-01-01
A crewmember of Expedition One, cosmonaut Yuri P. Gidzenko, is dwarfed by transient hardware aboard Leonardo, the Italian Space Agency-built Multi-Purpose Logistics Module (MPLM), a primary cargo of the STS-102 mission. The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS's) moving vans, carrying laboratory racks filled with equipment, experiments and supplies to and from the Space Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo into 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth Shuttle mission to visit the ISS, the STS-102 mission served as a crew rotation flight. It delivered the Expedition Two crew to the Station and returned the Expedition One crew back to Earth.
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A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome
Dodding, Mark P; Mitter, Richard; Humphries, Ashley C; Way, Michael
2011-01-01
Transport of cargoes by kinesin-1 is essential for many cellular processes. Nevertheless, the number of proteins known to recruit kinesin-1 via its cargo binding light chain (KLC) is still quite small. We also know relatively little about the molecular features that define kinesin-1 binding. We now show that a bipartite tryptophan-based kinesin-1 binding motif, originally identified in Calsyntenin is present in A36, a vaccinia integral membrane protein. This bipartite motif in A36 is required for kinesin-1-dependent transport of the virus to the cell periphery. Bioinformatic analysis reveals that related bipartite tryptophan-based motifs are present in over 450 human proteins. Using vaccinia as a surrogate cargo, we show that regions of proteins containing this motif can function to recruit KLC and promote virus transport in the absence of A36. These proteins interact with the kinesin light chain outside the context of infection and have distinct preferences for KLC1 and KLC2. Our observations demonstrate that KLC binding can be conferred by a common set of features that are found in a wide range of proteins associated with diverse cellular functions and human diseases. PMID:21915095
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International Space Station (ISS)
2001-03-01
A crewmember of Expedition One, cosmonaut Yuri P. Gidzenko, is dwarfed by transient hardware aboard Leonardo, the Italian Space Agency-built Multi-Purpose Logistics Module (MPLM), a primary cargo of the STS-102 mission. The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS's) moving vans, carrying laboratory racks filled with equipment, experiments and supplies to and from the Space Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo into 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. The eighth Shuttle mission to visit the ISS, the STS-102 mission served as a crew rotation flight. It delivered the Expedition Two crew to the Station and returned the Expedition One crew back to Earth.
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Gallon, Matthew; Clairfeuille, Thomas; Steinberg, Florian; Mas, Caroline; Ghai, Rajesh; Sessions, Richard B; Teasdale, Rohan D; Collins, Brett M; Cullen, Peter J
2014-09-02
The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo-1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. With disruption of SNX27 and retromer function linked to synaptic dysfunction and neurodegenerative disease, our work provides the first step, to our knowledge, in the molecular description of this important sorting complex, and more broadly describes a unique interaction between a PDZ domain and an arrestin-like fold.
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Risk Mitigation Approach to Commercial Resupply to the International Space Station
NASA Technical Reports Server (NTRS)
Koons, Diane S.; Schreiber, Craig
2010-01-01
In August 2006, NASA awarded Space Act Agreements (SAAs) for Commercial Orbital Transportation Services (COTS) under the Commercial Crew and Cargo Project Office at Johnson Space Center. One of the goals of the SAAs is to facilitate U.S. private industry demonstration of cargo transportation capabilities, ultimately achieving reliable, cost effective access to low-Earth orbit (LEO). Each COTS provider is required to complete International Space Stations (ISS) Integration activities, which includes meeting the physical and functional interfaces and interface requirements between the ISS and COTS vehicles. These requirements focus on the areas of risk to the ISS during rendezvous and proximity operations, as well as the integration operations while the COTS vehicle is berthed to the ISS. On December 23, 2008, NASA awarded Commercial Resupply Service (CRS) contracts to provide resupply services to the ISS, following the Shuttle retirement. In addition to performing any ISS Integration activities, NASA will be performing independent assessments of the launch vehicle and orbital vehicle to evaluate the readiness of the contractor to deliver NASA cargo safely to the ISS. This paper will address the activities NASA Centers, both JSC and KSC, in the oversight and insight function over commercial visiting vehicles to the ISS.
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Monte Carlo analysis of tagged neutron beams for cargo container inspection.
Pesente, S; Lunardon, M; Nebbia, G; Viesti, G; Sudac, D; Valkovic, V
2007-12-01
Fast neutrons produced via D+T reactions and tagged by the associated particle technique have been recently proposed to inspect cargo containers. The general characteristics of this technique are studied with Monte Carlo simulations by determining the properties of the tagged neutron beams as a function of the relevant design parameters (energy and size of the deuteron beam, geometry of the charged particle detector). Results from simulations, validated by experiments, show that the broadening of the correlation between the alpha-particle and the neutron, induced by kinematical as well as geometrical (beam and detector size) effects, is important and limits the dimension of the minimum voxel to be inspected. Moreover, the effect of the container filling is explored. The material filling produces a sizeable loss of correlation between alpha-particles and neutrons due to scattering and absorption. Conditions in inspecting cargo containers are discussed.
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Peroxisome protein import: a complex journey.
Baker, Alison; Lanyon-Hogg, Thomas; Warriner, Stuart L
2016-06-15
The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor-cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes. © 2016 The Author(s).
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Ubiquitin-dependent sorting of integral membrane proteins for degradation in lysosomes
Piper, Robert C.
2007-01-01
Summary The pathways that deliver newly synthesized proteins that reside in lysosomes are well understood by comparison with our knowledge of how integral membrane proteins are sorted and delivered to the lysosome for degradation. Many membrane proteins are sorted to lysosomes following ubiquitination, which provides a sorting signal that can operate for sorting at the TGN (trans-Golgi network), at the plasma membrane or at the endosome for delivery into lumenal vesicles. Candidate multicomponent machines that can potentially move ubiquitinated integral membrane cargo proteins have been identified, but much work is still required to ascertain which of these candidates directly recognizes ubiquitinated cargo and what they do with cargo after recognition. In the case of the machinery required for sorting into the lumenal vesicles of endosomes, other functions have also been determined including a link between sorting and movement of endosomes along microtubules. PMID:17689064
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Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions
Breakefield, Xandra O.; Leonard, Joshua N.
2015-01-01
This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury. PMID:25292428
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Code of Federal Regulations, 2011 CFR
2011-10-01
.... For purposes of this part only: (a) Commercial cargo means cargo other than military cargo and civilian preference cargo. (b) Military cargo means that cargo required to be carried on a U.S.-flag vessel... by law to be carried on a U.S.-flag vessel, including, but not limited to, cargo required to be...
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Compressed Sensing Techniques Applied to Ultrasonic Imaging of Cargo Containers.
López, Yuri Álvarez; Lorenzo, José Ángel Martínez
2017-01-15
One of the key issues in the fight against the smuggling of goods has been the development of scanners for cargo inspection. X-ray-based radiographic system scanners are the most developed sensing modality. However, they are costly and use bulky sources that emit hazardous, ionizing radiation. Aiming to improve the probability of threat detection, an ultrasonic-based technique, capable of detecting the footprint of metallic containers or compartments concealed within the metallic structure of the inspected cargo, has been proposed. The system consists of an array of acoustic transceivers that is attached to the metallic structure-under-inspection, creating a guided acoustic Lamb wave. Reflections due to discontinuities are detected in the images, provided by an imaging algorithm. Taking into consideration that the majority of those images are sparse, this contribution analyzes the application of Compressed Sensing (CS) techniques in order to reduce the amount of measurements needed, thus achieving faster scanning, without compromising the detection capabilities of the system. A parametric study of the image quality, as a function of the samples needed in spatial and frequency domains, is presented, as well as the dependence on the sampling pattern. For this purpose, realistic cargo inspection scenarios have been simulated.
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Compressed Sensing Techniques Applied to Ultrasonic Imaging of Cargo Containers
Álvarez López, Yuri; Martínez Lorenzo, José Ángel
2017-01-01
One of the key issues in the fight against the smuggling of goods has been the development of scanners for cargo inspection. X-ray-based radiographic system scanners are the most developed sensing modality. However, they are costly and use bulky sources that emit hazardous, ionizing radiation. Aiming to improve the probability of threat detection, an ultrasonic-based technique, capable of detecting the footprint of metallic containers or compartments concealed within the metallic structure of the inspected cargo, has been proposed. The system consists of an array of acoustic transceivers that is attached to the metallic structure-under-inspection, creating a guided acoustic Lamb wave. Reflections due to discontinuities are detected in the images, provided by an imaging algorithm. Taking into consideration that the majority of those images are sparse, this contribution analyzes the application of Compressed Sensing (CS) techniques in order to reduce the amount of measurements needed, thus achieving faster scanning, without compromising the detection capabilities of the system. A parametric study of the image quality, as a function of the samples needed in spatial and frequency domains, is presented, as well as the dependence on the sampling pattern. For this purpose, realistic cargo inspection scenarios have been simulated. PMID:28098841
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Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles.
Zhan, Xi; Tran, Kenny K; Wang, Liguo; Shen, Hong
2015-07-01
A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.
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Controlled endolysosomal release of agents by pH-responsive polymer blend particles
Zhan, Xi; Tran, Kenny K.; Wang, Liguo; Shen, Hong
2015-01-01
Purpose A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly (lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer. Methods We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space. Results We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes. Conclusions This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity. PMID:25592550
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Systematic analysis of barrier-forming FG hydrogels from Xenopus nuclear pore complexes
Labokha, Aksana A; Gradmann, Sabine; Frey, Steffen; Hülsmann, Bastian B; Urlaub, Henning; Baldus, Marc; Görlich, Dirk
2013-01-01
Nuclear pore complexes (NPCs) control the traffic between cell nucleus and cytoplasm. While facilitating translocation of nuclear transport receptors (NTRs) and NTR·cargo complexes, they suppress passive passage of macromolecules ⩾30 kDa. Previously, we reconstituted the NPC barrier as hydrogels comprising S. cerevisiae FG domains. We now studied FG domains from 10 Xenopus nucleoporins and found that all of them form hydrogels. Related domains with low FG motif density also substantially contribute to the NPC's hydrogel mass. We characterized all these hydrogels and observed the strictest sieving effect for the Nup98-derived hydrogel. It fully blocks entry of GFP-sized inert objects, permits facilitated entry of the small NTR NTF2, but arrests importin β-type NTRs at its surface. O-GlcNAc modification of the Nup98 FG domain prevented this arrest and allowed also large NTR·cargo complexes to enter. Solid-state NMR spectroscopy revealed that the O-GlcNAc-modified Nup98 gel lacks amyloid-like β-structures that dominate the rigid regions in the S. cerevisiae Nsp1 FG hydrogel. This suggests that FG hydrogels can assemble through different structural principles and yet acquire the same NPC-like permeability. PMID:23202855
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The Broken Belt: Meteorite Concentrations on Stranded Ice
NASA Technical Reports Server (NTRS)
Harvey, R. P.
2003-01-01
Since the first Antarctic meteorite concentrations were discovered more than 25 years ago, many theories regarding the role of iceflow in the production of meteorite concentrations have been put forward, and most agree on the basic principles. These models suggest that as the East Antarctic icesheet flows toward the margins of the continent, meteorites randomly located within the volume of ice are transported toward the icesheet margin. Where mountains or subsurface obstructions block glacial flow, diversion of ice around or over an obstruction reduces horizontal ice movement rates adjacent to the barriers and creates a vertical (upward) component of movement. If local mechanisms for ice loss (ablation) exist at such sites, an equilibrium surface will develop according to the balance between ice supply and loss, and the cargo of meteorites is exhumed on a blue ice surface. The result is a conceptual conveyor belt bringing meteorite-bearing volumes of ice from the interior of the continent to stagnant or slowmoving surfaces where ice is then lost and a precious cargo is left as a lag deposit. Cassidy et al. provides an excellent overview of how this model has been adapted to several Antarctic stranding surfaces.
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46 CFR 150.130 - Loading a cargo on vessels carrying cargoes with which it is incompatible.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Loading a cargo on vessels carrying cargoes with which it is incompatible. 150.130 Section 150.130 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.130 Loading a cargo on vessels...
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46 CFR 150.130 - Loading a cargo on vessels carrying cargoes with which it is incompatible.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Loading a cargo on vessels carrying cargoes with which it is incompatible. 150.130 Section 150.130 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.130 Loading a cargo on vessels...
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46 CFR 150.130 - Loading a cargo on vessels carrying cargoes with which it is incompatible.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Loading a cargo on vessels carrying cargoes with which it is incompatible. 150.130 Section 150.130 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.130 Loading a cargo on vessels...
-
46 CFR 150.130 - Loading a cargo on vessels carrying cargoes with which it is incompatible.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Loading a cargo on vessels carrying cargoes with which it is incompatible. 150.130 Section 150.130 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.130 Loading a cargo on vessels...
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46 CFR 97.12-1 - Bulk ores and similar cargoes.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 4 2010-10-01 2010-10-01 false Bulk ores and similar cargoes. 97.12-1 Section 97.12-1... OPERATIONS Cargo Stowage § 97.12-1 Bulk ores and similar cargoes. (a) The owners or operators of general cargo vessels which carry bulk cargoes such as ore, ore concentrates, and similar cargoes shall furnish...
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Code of Federal Regulations, 2012 CFR
2012-10-01
... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2012-10-01 2012-10-01 false Access to cargo and cargo screening: Security...
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Code of Federal Regulations, 2014 CFR
2014-10-01
... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2014-10-01 2014-10-01 false Access to cargo and cargo screening: Security...
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Code of Federal Regulations, 2013 CFR
2013-10-01
... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2013-10-01 2013-10-01 false Access to cargo and cargo screening: Security...
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Code of Federal Regulations, 2011 CFR
2011-10-01
... cargo enters an airport Security Identification Display Area or is transferred to another TSA-regulated... program accepts the cargo until the cargo— (A) Enters an airport Security Identification Display Area; (B... 49 Transportation 9 2011-10-01 2011-10-01 false Access to cargo and cargo screening: Security...
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ROSA Transfer (for SpaceX CRS-11)
2017-04-12
Inside the Space Station Processing Facility high bay at NASA's Kennedy Space Center in Florida, the Roll-Out Solar Array, or ROSA, is being prepared for transfer out of the high bay. ROSA will be delivered to the International Space Station aboard the SpaceX Dragon cargo carrier on the company’s 11th commercial resupply services mission to the space station. ROSA is a new type of solar panel that rolls open in space and is more compact than current rigid panel designs. The ROSA investigation will test deployment and retraction, shape changes when the Earth blocks the sun, and other physical challenges to determine the array's strength and durability.
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1976-07-30
Interface Requirements 4 3.1.1.1 Interface Block Diagram 4 3.1.1.2 Detailed Interface Definition 7 3.1.1.2.1 Subsystems 7 3.1.1.2.2 Controls & Displays 11 r...116 3.2.3.2 Navigation Brute Force 121 3.2.3.3 Cargo Brute Force 125 3.2.3.4 Sensor Brute Force 129 3.2.3.5 Controls /Displays Brute Force 135 3.2.3.6...STD-T553 Multiplex Data Bus, with the avionic subsystems, flight * control system, the controls /displays, engine sensors, and airframe sensors. 3.1
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Steinman, Jonathan B; Santarossa, Cristina C; Miller, Rand M; Yu, Lola S; Serpinskaya, Anna S; Furukawa, Hideki; Morimoto, Sachie; Tanaka, Yuta; Nishitani, Mitsuyoshi; Asano, Moriteru; Zalyte, Ruta; Ondrus, Alison E; Johnson, Alex G; Ye, Fan; Nachury, Maxence V; Fukase, Yoshiyuki; Aso, Kazuyoshi; Foley, Michael A; Gelfand, Vladimir I; Chen, James K; Carter, Andrew P; Kapoor, Tarun M
2017-01-01
Cytoplasmic dyneins are motor proteins in the AAA+ superfamily that transport cellular cargos toward microtubule minus-ends. Recently, ciliobrevins were reported as selective cell-permeable inhibitors of cytoplasmic dyneins. As is often true for first-in-class inhibitors, the use of ciliobrevins has in part been limited by low potency. Moreover, suboptimal chemical properties, such as the potential to isomerize, have hindered efforts to improve ciliobrevins. Here, we characterized the structure of ciliobrevins and designed conformationally constrained isosteres. These studies identified dynapyrazoles, inhibitors more potent than ciliobrevins. At single-digit micromolar concentrations dynapyrazoles block intraflagellar transport in the cilium and lysosome motility in the cytoplasm, processes that depend on cytoplasmic dyneins. Further, we find that while ciliobrevins inhibit both dynein's microtubule-stimulated and basal ATPase activity, dynapyrazoles strongly block only microtubule-stimulated activity. Together, our studies suggest that chemical-structure-based analyses can lead to inhibitors with improved properties and distinct modes of inhibition. DOI: http://dx.doi.org/10.7554/eLife.25174.001 PMID:28524820
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Ligand-targeted theranostic nanomedicines against cancer
Yao, Virginia J.; D'Angelo, Sara; Butler, Kimberly S.; ...
2016-01-06
Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentiallymore » overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. As a result, the modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.« less
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Ligand-targeted theranostic nanomedicines against cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yao, Virginia J.; D'Angelo, Sara; Butler, Kimberly S.
Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conventional, systemic chemotherapy. In the past 20 years, we have identified specific receptors expressed on the surfaces of tumor endothelial and perivascular cells, tumor cells, the extracellular matrix and stromal cells using combinatorial peptide libraries displayed on bacteriophage. These studies corroborate the notion that unique receptor proteins such as IL-11Rα, GRP78, EphA5, among others, are differentiallymore » overexpressed in tumors and present opportunities to deliver tumor-specific therapeutic drugs. By using peptides that bind to tumor-specific cell-surface receptors, therapeutic agents such as apoptotic peptides, suicide genes, imaging dyes or chemotherapeutics can be precisely and systemically delivered to reduce tumor growth in vivo, without harming healthy cells. Given the clinical applicability of peptide-based therapeutics, targeted delivery of nanocarriers loaded with therapeutic cargos seems plausible. We propose a modular design of a functionalized protocell in which a tumor-targeting moiety, such as a peptide or recombinant human antibody single chain variable fragment (scFv), is conjugated to a lipid bilayer surrounding a silica-based nanocarrier core containing a protected therapeutic cargo. The functionalized protocell can be tailored to a specific cancer subtype and treatment regimen by exchanging the tumor-targeting moiety and/or therapeutic cargo or used in combination to create unique, theranostic agents. In this review, we summarize the identification of tumor-specific receptors through combinatorial phage display technology and the use of antibody display selection to identify recombinant human scFvs against these tumor-specific receptors. We compare the characteristics of different types of simple and complex nanocarriers, and discuss potential types of therapeutic cargos and conjugation strategies. As a result, the modular design of functionalized protocells may improve the efficacy and safety of nanomedicines for future cancer therapy.« less
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Moua, Pachai S; Gonzalez, Alfonso; Oshiro, Kristin T; Tam, Vivian; Li, Zhiguo Harry; Chang, Jennifer; Leung, Wilson; Yon, Amy; Thor, Der; Venkatram, Sri; Franz, Andreas H; Risser, Douglas D; Lin-Cereghino, Joan; Lin-Cereghino, Geoff P
2016-08-01
The Escherichia coli maltose binding protein (MBP) is an N-terminal fusion partner that was shown to enhance the secretion of some heterologous proteins from the yeast Pichia pastoris, a popular host for recombinant protein expression. The amount of increase in secretion was dependent on the identity of the cargo protein, and the fusions were proteolyzed prior to secretion, limiting its use as a purification tag. In order to overcome these obstacles, we used the MBP as C-terminal partner for several cargo peptides. While the Cargo-MBP proteins were no longer proteolyzed in between these two moieties when the MBP was in this relative position, the secretion efficiency of several fusions was lower than when MBP was located at the opposite end of the cargo protein (MBP-Cargo). Furthermore, fluorescence analysis suggested that the MBP-EGFP and EGFP-MBP proteins followed different routes within the cell. The effect of several Pichia pastoris beta-galactosidase supersecretion (bgs) strains, mutants showing enhanced secretion of select reporters, was also investigated on both MBP-EGFP and EGFP-MBP. While the secretion efficiency, proteolysis and localization of the MBP-EGFP was influenced by the modified function of Bgs13, EGFP-MBP behavior was not affected in the bgs strain. Taken together, these results indicate that the location of the MBP in a fusion affects the pathway and trans-acting factors regulating secretion in P. pastoris. Copyright © 2016 Elsevier Inc. All rights reserved.
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Vogel, Georg F; van Rijn, Jorik M; Krainer, Iris M; Janecke, Andreas R; Posovszky, Carsten; Cohen, Marta; Searle, Claire; Jantchou, Prevost; Escher, Johanna C; Patey, Natalie; Cutz, Ernest; Müller, Thomas; Middendorp, Sabine; Hess, Michael W; Huber, Lukas A
2017-07-20
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied. Morphology of duodenal sections was analyzed by electron and fluorescence microscopy. Small intestinal enterocytes and organoid-derived monolayers displayed the subcellular characteristics of MVID. For the analyses of Munc18-2-dependent SNARE-protein interactions, a Munc18-2 CaCo2-KO model cell line was generated by applying CRISPR/Cas9 technology. Munc18-2 is required for Slp4a/Stx3 interaction in fusion of cargo vesicles with the apical plasma membrane. Cargo trafficking was investigated in patient biopsies, patient-derived organoids, and the genome-edited model cell line. Loss of Munc18-2 selectively disrupts trafficking of certain apical brush-border proteins (NHE3 and GLUT5), while transport of DPPIV remained unaffected. Here, we describe the molecular mechanism how the loss of function of Munc18-2 leads to cargo-selective mislocalization of brush-border components and a subapical accumulation of cargo vesicles, as it is known from the loss of polarity phenotype in MVID.
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33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.
Code of Federal Regulations, 2014 CFR
2014-07-01
... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...
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33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.
Code of Federal Regulations, 2012 CFR
2012-07-01
... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...
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33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.
Code of Federal Regulations, 2013 CFR
2013-07-01
... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...
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33 CFR 155.1045 - Response plan requirements for vessels carrying oil as a secondary cargo.
Code of Federal Regulations, 2011 CFR
2011-07-01
... must include the following functional areas and must further include information for key components within each functional area: (i) Command and control; (ii) Public information; (iii) Safety; (iv) Liaison with government agencies; (v) Spill response operations; (vi) Planning; (vii) Logistics support; and...
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NASA Astrophysics Data System (ADS)
Llauró, Aida; Luque, Daniel; Edwards, Ethan; Trus, Benes L.; Avera, John; Reguera, David; Douglas, Trevor; Pablo, Pedro J. De; Castón, José R.
2016-04-01
Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers.Nucleic acids are the natural cargo of viruses and key determinants that affect viral shell stability. In some cases the genome structurally reinforces the shell, whereas in others genome packaging causes internal pressure that can induce destabilization. Although it is possible to pack heterologous cargoes inside virus-derived shells, little is known about the physical determinants of these artificial nanocontainers' stability. Atomic force and three-dimensional cryo-electron microscopy provided mechanical and structural information about the physical mechanisms of viral cage stabilization beyond the mere presence/absence of cargos. We analyzed the effects of cargo-shell and cargo-cargo interactions on shell stability after encapsulating two types of proteinaceous payloads. While bound cargo to the inner capsid surface mechanically reinforced the capsid in a structural manner, unbound cargo diffusing freely within the shell cavity pressurized the cages up to ~30 atm due to steric effects. Strong cargo-cargo coupling reduces the resilience of these nanocompartments in ~20% when bound to the shell. Understanding the stability of artificially loaded nanocages will help to design more robust and durable molecular nanocontainers. Electronic supplementary information (ESI) available: 6 figures, 3 tables and theory. See DOI: 10.1039/c6nr01007e
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Mechanisms to deploy the two-stage IUS from the shuttle cargo bay
NASA Technical Reports Server (NTRS)
Haynie, H. T.
1980-01-01
The Inertial Upper Stage (IUS) is a two-stage or three-stage booster used to transport spacecraft from the space shuttle orbit to synchronous orbit or on an interplanetary trajectory. The mechanisms which were designed specifically to perform the two-stage IUS required functions while contained within the cargo bay of the space shuttle during the boost phase and while in a low Earth orbit are discussed. The requirements, configuration, and operation of the mechanisms are described, with particular emphasis on the tilt actuator and the mechanism for decoupling the actuators during boost to eliminate redundant load paths.
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Definition of avionics concepts for a heavy lift cargo vehicle, volume 2
NASA Technical Reports Server (NTRS)
1989-01-01
A cost effective, multiuser simulation, test, and demonstration facility to support the development of avionics systems for future space vehicles is defined. The technology needs and requirements of future Heavy Lift Cargo Vehicles (HLCVs) are analyzed and serve as the basis for sizing of the avionics facility although the lab is not limited in use to support of HLCVs. Volume 2 is the technical volume and provides the results of the vehicle avionics trade studies, the avionics lab objectives, the lab's functional requirements and design, physical facility considerations, and a summary cost estimate.
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Molecular Structure, Function, and Dynamics of Clathrin-Mediated Membrane Traffic
Kirchhausen, Tom; Owen, David; Harrison, Stephen C.
2014-01-01
Clathrin is a molecular scaffold for vesicular uptake of cargo at the plasma membrane, where its assembly into cage-like lattices underlies the clathrin-coated pits of classical endocytosis. This review describes the structures of clathrin, major cargo adaptors, and other proteins that participate in forming a clathrin-coated pit, loading its contents, pinching off the membrane as a lattice-enclosed vesicle, and recycling the components. It integrates as much of the structural information as possible at the time of writing into a sketch of the principal steps in coated-pit and coated-vesicle formation. PMID:24789820
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Sorting by COP I-coated vesicles under interphase and mitotic conditions
1996-01-01
COP I-coated vesicles were analyzed for their content of resident Golgi enzymes (N-acetylgalactosaminyltransferase; N- acetylglucosaminyltransferase I; mannosidase II; galactosyltransferase), cargo (rat serum albumin; polyimmunoglobulin receptor), and recycling proteins (-KDEL receptor; ERGIC-53/p58) using biochemical and morphological techniques. The levels of these proteins were similar when the vesicles were prepared under interphase or mitotic conditions showing that sorting was unaffected. The average density relative to starting membranes for resident enzymes (14-30%), cargo (16-23%), and recycling proteins (81-125%) provides clues to the function of COP I vesicles in transport through the Golgi apparatus. PMID:8830771
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Code of Federal Regulations, 2010 CFR
2010-10-01
... HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-1 General. This subpart prescribes the requirements for cargo segregation for cargo tanks. These requirements are based on considerations of cargo...
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Code of Federal Regulations, 2011 CFR
2011-10-01
... HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-1 General. This subpart prescribes the requirements for cargo segregation for cargo tanks. These requirements are based on considerations of cargo...
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NASA Technical Reports Server (NTRS)
Hart, Angela
2006-01-01
A description of internal cargo integration is presented. The topics include: 1) Typical Cargo for Launch/Disposal; 2) Cargo Delivery Requirements; 3) Cargo Return Requirements; and 4) Vehicle On-Orbit Stay Time.
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46 CFR 150.120 - Definition of incompatible cargoes.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Definition of incompatible cargoes. 150.120 Section 150.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.120 Definition of incompatible cargoes. Except as described in § 150.150, a cargo...
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46 CFR 150.120 - Definition of incompatible cargoes.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Definition of incompatible cargoes. 150.120 Section 150.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.120 Definition of incompatible cargoes. Except as described in § 150.150, a cargo...
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46 CFR 150.120 - Definition of incompatible cargoes.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Definition of incompatible cargoes. 150.120 Section 150.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.120 Definition of incompatible cargoes. Except as described in § 150.150, a cargo...
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46 CFR 150.120 - Definition of incompatible cargoes.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Definition of incompatible cargoes. 150.120 Section 150.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.120 Definition of incompatible cargoes. Except as described in § 150.150, a cargo...
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46 CFR 150.120 - Definition of incompatible cargoes.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Definition of incompatible cargoes. 150.120 Section 150.120 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.120 Definition of incompatible cargoes. Except as described in § 150.150, a cargo...
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46 CFR 151.13-5 - Cargo segregation-tanks.
Code of Federal Regulations, 2014 CFR
2014-10-01
... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... through design. (2) Segregation of cargo space from machinery spaces and other spaces which have or could... Grade E Liquid (if compatible with cargo) is satisfactory. (b) [Reserved] (c) If a cofferdam is required...
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46 CFR 151.13-5 - Cargo segregation-tanks.
Code of Federal Regulations, 2013 CFR
2013-10-01
... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... through design. (2) Segregation of cargo space from machinery spaces and other spaces which have or could... Grade E Liquid (if compatible with cargo) is satisfactory. (b) [Reserved] (c) If a cofferdam is required...
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49 CFR 392.9 - Inspection of cargo, cargo securement devices and systems.
Code of Federal Regulations, 2010 CFR
2010-10-01
...) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES General § 392.9 Inspection of cargo, cargo securement devices... drives that commercial motor vehicle; (2) Inspect the cargo and the devices used to secure the cargo...
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33 CFR 105.265 - Security measures for handling cargo.
Code of Federal Regulations, 2011 CFR
2011-07-01
..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo..., containers or other cargo transport units, and cargo storage areas within the facility for evidence of... cargo. 105.265 Section 105.265 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...
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33 CFR 105.265 - Security measures for handling cargo.
Code of Federal Regulations, 2010 CFR
2010-07-01
..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo..., containers or other cargo transport units, and cargo storage areas within the facility for evidence of... cargo. 105.265 Section 105.265 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...
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33 CFR 105.265 - Security measures for handling cargo.
Code of Federal Regulations, 2014 CFR
2014-07-01
..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo..., containers or other cargo transport units, and cargo storage areas within the facility for evidence of... cargo. 105.265 Section 105.265 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...
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33 CFR 105.265 - Security measures for handling cargo.
Code of Federal Regulations, 2012 CFR
2012-07-01
..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo..., containers or other cargo transport units, and cargo storage areas within the facility for evidence of... cargo. 105.265 Section 105.265 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...
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33 CFR 105.265 - Security measures for handling cargo.
Code of Federal Regulations, 2013 CFR
2013-07-01
..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo..., containers or other cargo transport units, and cargo storage areas within the facility for evidence of... cargo. 105.265 Section 105.265 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...
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46 CFR 154.235 - Cargo tank location.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo tank location. 154.235 Section 154.235 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo...
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46 CFR 154.476 - Cargo transfer devices and means.
Code of Federal Regulations, 2010 CFR
2010-10-01
... of cargo transfer, such as another pump or gas pressurization. (b) If cargo is transferred by gas... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Support System § 154.476 Cargo transfer devices and means. (a) If a cargo pump in a cargo tank is...
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Code of Federal Regulations, 2010 CFR
2010-10-01
... threat assessments for cargo personnel in the United States. 1544.228 Section 1544.228 Transportation... COMMERCIAL OPERATORS Operations § 1544.228 Access to cargo and cargo screening: Security threat assessments... paragraph (b) of this section— (1) Each individual must successfully complete a security threat assessment...
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46 CFR 154.1200 - Mechanical ventilation system: General.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) Each cargo compressor room, pump room, gas-dangerous cargo control station, and space that contains... motors for cargo handling equipment. (2) Each gas-safe cargo control station in the cargo area. (3) Each...
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46 CFR 154.1200 - Mechanical ventilation system: General.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) Each cargo compressor room, pump room, gas-dangerous cargo control station, and space that contains... motors for cargo handling equipment. (2) Each gas-safe cargo control station in the cargo area. (3) Each...
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46 CFR 154.1200 - Mechanical ventilation system: General.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) Each cargo compressor room, pump room, gas-dangerous cargo control station, and space that contains... motors for cargo handling equipment. (2) Each gas-safe cargo control station in the cargo area. (3) Each...
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Fast Track Lunar NTR Systems Assessment for NASA's First Lunar Outpost and Its Evolvability to Mars
NASA Technical Reports Server (NTRS)
Borowski, Stanley K.; Alexander, Stephen W.
1995-01-01
Integrated systems and missions studies are presented for an evolutionary lunar-to-Mars space transportation system (STS) based on nuclear thermal rocket (NTR) technology. A 'standardized' set of engine and stage components are identified and used in a 'building block' fashion to configure a variety of piloted and cargo, lunar and Mars vehicles. The reference NTR characteristics include a thrust of 50 thousand pounds force (klbf), specific impulse (I(sub sp)) of 900 seconds, and an engine thrust-to-weight ratio of 4. 3. For the National Aeronautics and Space Administrations (NASA) First Lunar Outpost (FLO) mission, and expendable NTR stage powered by two such engines can deliver approximately 96 metric tonnes (t) to trans-lunar injection (TLI) conditions for an initial mass in low Earth orbit (IMLEO) of approximately 198 t compared to 250 t for a cryogenic chemical system. The stage liquid hydrogen (LH2) tank has a diameter, length, and capacity of 10 m, 14.5 m and 66 t, respectively. By extending the stage length and LH2 capacity to approximately 20 m and 96 t, a single launch Mars cargo vehicle could deliver to an elliptical Mars parking orbit a 63 t Mars excursion vehicle (MEV) with a 45 t surface payload. Three 50 klbf engines and the two standardized LH2 tanks developed for the lunar and Mars cargo vehicles are used to configure the vehicles supporting piloted Mars missions as early as 2010. The 'modular' NTR vehicle approach forms the basis for an efficient STS able to handle the needs of a wide spectrum of lunar and Mars missions.
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Insulin-mediated translocation of GLUT-4-containing vesicles is preserved in denervated muscles.
Zhou, M; Vallega, G; Kandror, K V; Pilch, P F
2000-06-01
Skeletal muscle denervation decreases insulin-sensitive glucose uptake into this tissue as a result of marked GLUT-4 protein downregulation ( approximately 20% of controls). The process of insulin-stimulated glucose transport in muscle requires the movement or translocation of intracellular GLUT-4-rich vesicles to the cell surface, and it is accompanied by the translocation of several additional vesicular cargo proteins. Thus examining GLUT-4 translocation in muscles from denervated animals allows us to determine whether the loss of a major cargo protein, GLUT-4, affects the insulin-dependent behavior of the remaining cargo proteins. We find no difference, control vs. denervated, in the insulin-dependent translocation of the insulin-responsive aminopeptidase (IRAP) and the receptors for transferrin and insulin-like growth factor II/mannose 6-phosphate, proteins that completely (IRAP) or partially co-localize with GLUT-4. We conclude that 1) denervation of skeletal muscle does not block the specific branch of insulin signaling pathway that connects receptor proximal events to intracellular GLUT-4-vesicles, and 2) normal levels of GLUT-4 protein are not necessary for the structural organization and insulin-sensitive translocation of its cognate intracellular compartment. Muscle denervation also causes a twofold increase in GLUT-1. In normal muscle, all GLUT-1 is present at the cell surface, but in denervated muscle a significant fraction (25.1 +/- 6.1%) of this transporter is found in intracellular vesicles that have the same sedimentation coefficient as GLUT-4-containing vesicles but can be separated from the latter by immunoadsorption. These GLUT-1-containing vesicles respond to insulin and translocate to the cell surface. Thus the formation of insulin-sensitive GLUT-1-containing vesicles in denervated muscle may be a compensatory mechanism for the decreased level of GLUT-4.
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Microtubule defects influence kinesin-based transport in vitro.
NASA Astrophysics Data System (ADS)
Xu, Jing
Microtubules are protein polymers that form ``molecular highways'' for long-range transport within living cells. Molecular motors actively step along microtubules to shuttle cellular materials between the nucleus and the cell periphery; this transport is critical for the survival and health of all eukaryotic cells. Structural defects in microtubules exist, but whether these defects impact molecular motor-based transport remains unknown. Here, we report a new, to our knowledge, approach that allowed us to directly investigate the impact of such defects. Using a modified optical-trapping method, we examined the group function of a major molecular motor, conventional kinesin, when transporting cargos along individual microtubules. We found that microtubule defects influence kinesin-based transport in vitro. The effects depend on motor number: cargos driven by a few motors tended to unbind prematurely from the microtubule, whereas cargos driven by more motors tended to pause. To our knowledge, our study provides the first direct link between microtubule defects and kinesin function. The effects uncovered in our study may have physiological relevance in vivo. Supported by the UC Merced (to J.X.), NIH (NS048501 to S.J.K.), NSF (EF-1038697 to A.G.), and the James S. McDonnell Foundation (to A.G.). Work carried out at the Aspen Center for Physics was supported by NSF Grant PHY-1066293.
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International Space Station (ISS)
2003-03-08
The Space Shuttle Discovery, STS-102 mission, clears launch pad 39B at the Kennedy Space Center as the sun peers over the Atlantic Ocean on March 8, 2001. STS-102's primary cargo was the Leonardo, the Italian Space Agency built Multipurpose Logistics Module (MPLM). The Leonardo MPLM is the first of three such pressurized modules that will serve as the International Space Station's (ISS') moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. NASA's 103rd overall flight and the eighth assembly flight, STS-102 was also the first flight involved with Expedition Crew rotation. The Expedition Two crew was delivered to the station while Expedition One was returned home to Earth.
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International Space Station (ISS)
2001-03-08
STS-102 astronaut and mission specialist, Andrew S.W. Thomas, gazes through an aft window of the Space Shuttle Orbiter Discovery as it approaches the docking bay of the International Space Station (ISS). Launched March 8, 2001, STS-102's primary cargo was the Leonardo, the Italian Space Agency-built Multipurpose Logistics Module (MPLM). The Leonardo MPLM is the first of three such pressurized modules that will serve as the ISS's moving vans, carrying laboratory racks filled with equipment, experiments, and supplies to and from the Station aboard the Space Shuttle. The cylindrical module is approximately 21-feet long and 15- feet in diameter, weighing almost 4.5 tons. It can carry up to 10 tons of cargo in 16 standard Space Station equipment racks. Of the 16 racks the module can carry, 5 can be furnished with power, data, and fluid to support refrigerators or freezers. In order to function as an attached station module as well as a cargo transport, the logistics module also includes components that provide life support, fire detection and suppression, electrical distribution, and computer functions. NASA's 103rd overall mission and the 8th Space Station Assembly Flight, STS-102 mission also served as a crew rotation flight. It delivered the Expedition Two crew to the Station and returned the Expedition One crew back to Earth.
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Mahogunin regulates fusion between amphisomes/MVBs and lysosomes via ubiquitination of TSG101
Majumder, P; Chakrabarti, O
2015-01-01
Aberrant metabolic forms of the prion protein (PrP), membrane-associated CtmPrP and cytosolic (cyPrP) interact with the cytosolic ubiquitin E3 ligase, Mahogunin Ring Finger-1 (MGRN1) and affect lysosomes. MGRN1 also interacts with and ubiquitinates TSG101, an ESCRT-I protein, involved in endocytosis. We report that MGRN1 modulates macroautophagy. In cultured cells, functional depletion of MGRN1 or overexpression of CtmPrP and cyPrP blocks autophagosome–lysosome fusion, alleviates the autophagic flux and its degradative competence. Concurrently, the degradation of cargo from the endo-lysosomal pathway is also affected. This is significant because catalytic inactivation of MGRN1 alleviates fusion of lysosomes with either autophagosomes (via amphisomes) or late endosomes (either direct or mediated through amphisomes), without drastically perturbing maturation of late endosomes, generation of amphisomes or lysosomal proteolytic activity. The compromised lysosomal fusion events are rescued by overexpression of TSG101 and/or its monoubiquitination in the presence of MGRN1. Thus, for the first time we elucidate that MGRN1 simultaneously modulates both autophagy and heterophagy via ubiquitin-mediated post-translational modification of TSG101. PMID:26539917
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Cosmonaut Gidzenko Near Hatch Between Unity and Destiny
NASA Technical Reports Server (NTRS)
2001-01-01
Cosmonaut Yuri P. Gidzenko, Expedition One Soyuz commander, stands near the hatch leading from the Unity node into the newly-attached Destiny laboratory aboard the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules. The U.S.-built Unity module was launched aboard the Orbiter Endeavour (STS-88 mission) on December 4, 1998, and connected to Zarya, the Russian-built Functional Cargo Block (FGB). The U.S. Laboratory (Destiny) module is the centerpiece of the ISS, where science experiments will be performed in the near-zero gravity in space. The Destiny Module was launched aboard the Space Shuttle Orbiter Atlantis (STS-98 mission) on February 7, 2001. The aluminum module is 8.5 meters (28 feet) long and 4.3 meters (14 feet) in diameter. The laboratory consists of three cylindrical sections and two endcones with hatches that will be mated to other station components. A 50.9-centimeter- (20-inch-) diameter window is located on one side of the center module segment. This pressurized module is designed to accommodate pressurized payloads. It has a capacity of 24 rack locations, and payload racks will occupy 13 locations especially designed to support experiments.
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Molecular gated nanoporous anodic alumina for the detection of cocaine
NASA Astrophysics Data System (ADS)
Ribes, Àngela; Xifré-Pérez, Elisabet; Aznar, Elena; Sancenón, Félix; Pardo, Teresa; Marsal, Lluís F.; Martínez-Máñez, Ramόn
2016-12-01
We present herein the use of nanoporous anodic alumina (NAA) as a suitable support to implement “molecular gates” for sensing applications. In our design, a NAA support is loaded with a fluorescent reporter (rhodamine B) and functionalized with a short single-stranded DNA. Then pores are blocked by the subsequent hybridisation of a specific cocaine aptamer. The response of the gated material was studied in aqueous solution. In a typical experiment, the support was immersed in hybridisation buffer solution in the absence or presence of cocaine. At certain times, the release of rhodamine B from pore voids was measured by fluorescence spectroscopy. The capped NAA support showed poor cargo delivery, but presence of cocaine in the solution selectively induced rhodamine B release. By this simple procedure a limit of detection as low as 5 × 10-7 M was calculated for cocaine. The gated NAA was successfully applied to detect cocaine in saliva samples and the possible re-use of the nanostructures was assessed. Based on these results, we believe that NAA could be a suitable support to prepare optical gated probes with a synergic combination of the favourable features of selected gated sensing systems and NAA.
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International Space Station (ISS)
2001-02-10
Cosmonaut Yuri P. Gidzenko, Expedition One Soyuz commander, stands near the hatch leading from the Unity node into the newly-attached Destiny laboratory aboard the International Space Station (ISS). The Node 1, or Unity, serves as a cornecting passageway to Space Station modules. The U.S.-built Unity module was launched aboard the Orbiter Endeavour (STS-88 mission) on December 4, 1998, and connected to Zarya, the Russian-built Functional Cargo Block (FGB). The U.S. Laboratory (Destiny) module is the centerpiece of the ISS, where science experiments will be performed in the near-zero gravity in space. The Destiny Module was launched aboard the Space Shuttle Orbiter Atlantis (STS-98 mission) on February 7, 2001. The aluminum module is 8.5 meters (28 feet) long and 4.3 meters (14 feet) in diameter. The laboratory consists of three cylindrical sections and two endcones with hatches that will be mated to other station components. A 50.9-centimeter- (20-inch-) diameter window is located on one side of the center module segment. This pressurized module is designed to accommodate pressurized payloads. It has a capacity of 24 rack locations, and payload racks will occupy 13 locations especially designed to support experiments.
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Molecular gated nanoporous anodic alumina for the detection of cocaine.
Ribes, Àngela; Xifré-Pérez, Elisabet; Aznar, Elena; Sancenón, Félix; Pardo, Teresa; Marsal, Lluís F; Martínez-Máñez, Ramόn
2016-12-07
We present herein the use of nanoporous anodic alumina (NAA) as a suitable support to implement "molecular gates" for sensing applications. In our design, a NAA support is loaded with a fluorescent reporter (rhodamine B) and functionalized with a short single-stranded DNA. Then pores are blocked by the subsequent hybridisation of a specific cocaine aptamer. The response of the gated material was studied in aqueous solution. In a typical experiment, the support was immersed in hybridisation buffer solution in the absence or presence of cocaine. At certain times, the release of rhodamine B from pore voids was measured by fluorescence spectroscopy. The capped NAA support showed poor cargo delivery, but presence of cocaine in the solution selectively induced rhodamine B release. By this simple procedure a limit of detection as low as 5 × 10 -7 M was calculated for cocaine. The gated NAA was successfully applied to detect cocaine in saliva samples and the possible re-use of the nanostructures was assessed. Based on these results, we believe that NAA could be a suitable support to prepare optical gated probes with a synergic combination of the favourable features of selected gated sensing systems and NAA.
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Molecular gated nanoporous anodic alumina for the detection of cocaine
Ribes, Àngela; Xifré -Pérez, Elisabet; Aznar, Elena; Sancenón, Félix; Pardo, Teresa; Marsal, Lluís F.; Martínez-Máñez, Ramόn
2016-01-01
We present herein the use of nanoporous anodic alumina (NAA) as a suitable support to implement “molecular gates” for sensing applications. In our design, a NAA support is loaded with a fluorescent reporter (rhodamine B) and functionalized with a short single-stranded DNA. Then pores are blocked by the subsequent hybridisation of a specific cocaine aptamer. The response of the gated material was studied in aqueous solution. In a typical experiment, the support was immersed in hybridisation buffer solution in the absence or presence of cocaine. At certain times, the release of rhodamine B from pore voids was measured by fluorescence spectroscopy. The capped NAA support showed poor cargo delivery, but presence of cocaine in the solution selectively induced rhodamine B release. By this simple procedure a limit of detection as low as 5 × 10−7 M was calculated for cocaine. The gated NAA was successfully applied to detect cocaine in saliva samples and the possible re-use of the nanostructures was assessed. Based on these results, we believe that NAA could be a suitable support to prepare optical gated probes with a synergic combination of the favourable features of selected gated sensing systems and NAA. PMID:27924950
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Soluble TNF receptor 1-secreting ex vivo-derived dendritic cells reduce injury after stroke.
Works, Melissa G; Koenig, Jenny B; Sapolsky, Robert M
2013-09-01
Inflammation is a major factor in the progression of damage after stroke and in the clinic, current therapies treat the clot, not the resulting damage. We have developed a novel method of protein delivery that exploits the migration ability of leukocytes after ischemic stroke (transient middle cerebral artery occlusion; tMCAO). In our studies, ex vivo-derived dendritic cells (exDCs) migrate to the inflamed rat brain soon after tMCAO onset and the number of cells that remain in the brain after injection is significantly correlated with the amount of local inflammation at the injury site. In addition, exDCs transduced to overexpress soluble tumor necrosis factor (TNF) receptor1 (sTNFR1) produce functional cargo that is secreted and that blocks TNF-α bioavailability in vitro. When delivered at 6 hours post-tMCAO reperfusion, sTNFR1-exDC-treated rats show significantly smaller infarct size and decreased inflammation compared with animals treated with exDCs transduced with GFP lentivirus. These studies indicate that cell-mediated delivery of proteins may be a promising new approach to reduce brain damage after acute neurologic insult.
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δ-COP contains a helix C-terminal to its longin domain key to COPI dynamics and function
Arakel, Eric C.; Richter, Kora P.; Clancy, Anne; Schwappach, Blanche
2016-01-01
Membrane recruitment of coatomer and formation of coat protein I (COPI)-coated vesicles is crucial to homeostasis in the early secretory pathway. The conformational dynamics of COPI during cargo capture and vesicle formation is incompletely understood. By scanning the length of δ-COP via functional complementation in yeast, we dissect the domains of the δ-COP subunit. We show that the μ-homology domain is dispensable for COPI function in the early secretory pathway, whereas the N-terminal longin domain is essential. We map a previously uncharacterized helix, C-terminal to the longin domain, that is specifically required for the retrieval of HDEL-bearing endoplasmic reticulum-luminal residents. It is positionally analogous to an unstructured linker that becomes helical and membrane-facing in the open form of the AP2 clathrin adaptor complex. Based on the amphipathic nature of the critical helix it may probe the membrane for lipid packing defects or mediate interaction with cargo and thus contribute to stabilizing membrane-associated coatomer. PMID:27298352
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46 CFR 151.20-15 - Cargo hose if carried on the barge.
Code of Federal Regulations, 2012 CFR
2012-10-01
... CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-15 Cargo hose if carried on the barge. (a) Liquid and vapor line hose used for cargo transfer shall be of suitable material... subjected and shall be acceptable to the Commandant. (b) Hose subject to tank pressure, or the discharge...
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46 CFR 151.20-15 - Cargo hose if carried on the barge.
Code of Federal Regulations, 2013 CFR
2013-10-01
... CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-15 Cargo hose if carried on the barge. (a) Liquid and vapor line hose used for cargo transfer shall be of suitable material... subjected and shall be acceptable to the Commandant. (b) Hose subject to tank pressure, or the discharge...
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46 CFR 151.20-15 - Cargo hose if carried on the barge.
Code of Federal Regulations, 2011 CFR
2011-10-01
... CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-15 Cargo hose if carried on the barge. (a) Liquid and vapor line hose used for cargo transfer shall be of suitable material... subjected and shall be acceptable to the Commandant. (b) Hose subject to tank pressure, or the discharge...
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46 CFR 151.20-15 - Cargo hose if carried on the barge.
Code of Federal Regulations, 2014 CFR
2014-10-01
... CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-15 Cargo hose if carried on the barge. (a) Liquid and vapor line hose used for cargo transfer shall be of suitable material... subjected and shall be acceptable to the Commandant. (b) Hose subject to tank pressure, or the discharge...
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Code of Federal Regulations, 2014 CFR
2014-10-01
... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or butyl...
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Code of Federal Regulations, 2010 CFR
2010-10-01
... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or butyl...
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Code of Federal Regulations, 2012 CFR
2012-10-01
... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or butyl...
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Code of Federal Regulations, 2013 CFR
2013-10-01
... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or butyl...
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Code of Federal Regulations, 2011 CFR
2011-10-01
... benzene and benzene containing cargoes, or butyl acrylate cargoes. 151.05-2 Section 151.05-2 Shipping... Compliance with requirements for tank barges carrying benzene and benzene containing cargoes, or butyl acrylate cargoes. A tank barge certificated to carry benzene and benzene containing cargoes or butyl...
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Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo viscosity and melting point information; measuring... Cargo viscosity and melting point information; measuring cargo temperature during discharge: Categories... lading, a written statement of the following: (1) For Category A or B NLS, the cargo's viscosity at 20 °C...
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Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo viscosity and melting point information; measuring... Cargo viscosity and melting point information; measuring cargo temperature during discharge: Categories... lading, a written statement of the following: (1) For Category A or B NLS, the cargo's viscosity at 20 °C...
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Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo viscosity and melting point information; measuring... Cargo viscosity and melting point information; measuring cargo temperature during discharge: Categories... lading, a written statement of the following: (1) For Category A or B NLS, the cargo's viscosity at 20 °C...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... confidential cargo; (v) The preservation of fragile or perishable cargo; (vi) Experiments on, or testing of, cargo containers or cargo handling devices; (vii) The operation of special equipment for loading or unloading cargo; and (viii) The loading or unloading of outsize cargo. (5) A person described in paragraph...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... confidential cargo; (v) The preservation of fragile or perishable cargo; (vi) Experiments on, or testing of, cargo containers or cargo handling devices; (vii) The operation of special equipment for loading or unloading cargo; and (viii) The loading or unloading of outsize cargo. (5) A person described in paragraph...
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Code of Federal Regulations, 2013 CFR
2013-07-01
... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...
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Code of Federal Regulations, 2011 CFR
2011-07-01
... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...
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33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.
Code of Federal Regulations, 2014 CFR
2014-07-01
... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...
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Code of Federal Regulations, 2012 CFR
2012-07-01
... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...
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33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.
Code of Federal Regulations, 2013 CFR
2013-07-01
... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...
-
Code of Federal Regulations, 2014 CFR
2014-07-01
... the towing vessel crew and facility or fleeting area personnel, if any, to initiate a response and... functional areas and must further include information for key components within each functional area: (i...) Spill response operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The...
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33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.
Code of Federal Regulations, 2011 CFR
2011-07-01
... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...
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33 CFR 155.1035 - Response plan requirements for manned vessels carrying oil as a primary cargo.
Code of Federal Regulations, 2012 CFR
2012-07-01
... be used to manage the response actions. This structure must include the following functional areas and must further include information for key components within each functional area: (i) Command and... operations; (vi) Planning; (vii) Logistics support; and (viii) Finance. (5) The responsibilities of, duties...
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Fission yeast tropomyosin specifies directed transport of myosin-V along actin cables
Clayton, Joseph E.; Pollard, Luther W.; Sckolnick, Maria; Bookwalter, Carol S.; Hodges, Alex R.; Trybus, Kathleen M.; Lord, Matthew
2014-01-01
A hallmark of class-V myosins is their processivity—the ability to take multiple steps along actin filaments without dissociating. Our previous work suggested, however, that the fission yeast myosin-V (Myo52p) is a nonprocessive motor whose activity is enhanced by tropomyosin (Cdc8p). Here we investigate the molecular mechanism and physiological relevance of tropomyosin-mediated regulation of Myo52p transport, using a combination of in vitro and in vivo approaches. Single molecules of Myo52p, visualized by total internal reflection fluorescence microscopy, moved processively only when Cdc8p was present on actin filaments. Small ensembles of Myo52p bound to a quantum dot, mimicking the number of motors bound to physiological cargo, also required Cdc8p for continuous motion. Although a truncated form of Myo52p that lacked a cargo-binding domain failed to support function in vivo, it still underwent actin-dependent movement to polarized growth sites. This result suggests that truncated Myo52p lacking cargo, or single molecules of wild-type Myo52p with small cargoes, can undergo processive movement along actin-Cdc8p cables in vivo. Our findings outline a mechanism by which tropomyosin facilitates sorting of transport to specific actin tracks within the cell by switching on myosin processivity. PMID:24196839
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2012-04-20
CAPE CANAVERAL, Fla. – The van transporting the cargo bag packed with NanoRacks-CubeLabs Module-9 experiments, arrives at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida for cold stowage. The bag will be loaded into the Space Exploration Technologies Dragon capsule in preparation for its scheduled April 30 liftoff aboard a Falcon 9 rocket. NanoRacks-CubeLabs Module-9 uses a two-cube unit box for student competition investigations using 15 liquid mixing tube assemblies that function similar to commercial glow sticks. The investigations range from microbial growth to water purification in microgravity. Known as SpaceX, the launch will be the company's second demonstration test flight for NASA's Commercial Orbital Transportation Services program, or COTS. During the flight, the capsule will conduct a series of check-out procedures to test and prove its systems, including rendezvous and berthing with the International Space Station. If the capsule performs as planned, the module and other cargo will be transferred to the station. The cargo includes food, water and provisions for the station’s Expedition crews, such as clothing, batteries and computer equipment. Under COTS, NASA has partnered with two private companies to launch cargo safely to the station. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann
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Elastic Network Model of a Nuclear Transport Complex
NASA Astrophysics Data System (ADS)
Ryan, Patrick; Liu, Wing K.; Lee, Dockjin; Seo, Sangjae; Kim, Young-Jin; Kim, Moon K.
2010-05-01
The structure of Kap95p was obtained from the Protein Data Bank (www.pdb.org) and analyzed RanGTP plays an important role in both nuclear protein import and export cycles. In the nucleus, RanGTP releases macromolecular cargoes from importins and conversely facilitates cargo binding to exportins. Although the crystal structure of the nuclear import complex formed by importin Kap95p and RanGTP was recently identified, its molecular mechanism still remains unclear. To understand the relationship between structure and function of a nuclear transport complex, a structure-based mechanical model of Kap95p:RanGTP complex is introduced. In this model, a protein structure is simply modeled as an elastic network in which a set of coarse-grained point masses are connected by linear springs representing biochemical interactions at atomic level. Harmonic normal mode analysis (NMA) and anharmonic elastic network interpolation (ENI) are performed to predict the modes of vibrations and a feasible pathway between locked and unlocked conformations of Kap95p, respectively. Simulation results imply that the binding of RanGTP to Kap95p induces the release of the cargo in the nucleus as well as prevents any new cargo from attaching to the Kap95p:RanGTP complex.
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46 CFR 232.5 - Income Statement Accounts.
Code of Federal Regulations, 2012 CFR
2012-10-01
... as terminal operations, cargo equipment, fleet operations, cargo pooling agreements, container... revenue from pooling agreements, terminal services provided to others, and cargo handling services performed for others; cargo equipment rentals, and repairs to cargo equipment belonging to others; agency...
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46 CFR 232.5 - Income Statement Accounts.
Code of Federal Regulations, 2011 CFR
2011-10-01
... as terminal operations, cargo equipment, fleet operations, cargo pooling agreements, container... revenue from pooling agreements, terminal services provided to others, and cargo handling services performed for others; cargo equipment rentals, and repairs to cargo equipment belonging to others; agency...
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46 CFR 232.5 - Income Statement Accounts.
Code of Federal Regulations, 2014 CFR
2014-10-01
... as terminal operations, cargo equipment, fleet operations, cargo pooling agreements, container... revenue from pooling agreements, terminal services provided to others, and cargo handling services performed for others; cargo equipment rentals, and repairs to cargo equipment belonging to others; agency...
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46 CFR 232.5 - Income Statement Accounts.
Code of Federal Regulations, 2013 CFR
2013-10-01
... as terminal operations, cargo equipment, fleet operations, cargo pooling agreements, container... revenue from pooling agreements, terminal services provided to others, and cargo handling services performed for others; cargo equipment rentals, and repairs to cargo equipment belonging to others; agency...
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46 CFR 150.140 - Cargoes not listed in Table I or II.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargoes not listed in Table I or II. 150.140 Section 150.140 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.140 Cargoes not listed in Table I or II. A cargo of hazardous material not listed...
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46 CFR 150.140 - Cargoes not listed in Table I or II.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Cargoes not listed in Table I or II. 150.140 Section 150.140 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.140 Cargoes not listed in Table I or II. A cargo of hazardous material not listed...
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46 CFR 150.140 - Cargoes not listed in Table I or II.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Cargoes not listed in Table I or II. 150.140 Section 150.140 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.140 Cargoes not listed in Table I or II. A cargo of hazardous material not listed...
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46 CFR 150.140 - Cargoes not listed in Table I or II.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Cargoes not listed in Table I or II. 150.140 Section 150.140 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.140 Cargoes not listed in Table I or II. A cargo of hazardous material not listed...
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46 CFR 150.140 - Cargoes not listed in Table I or II.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Cargoes not listed in Table I or II. 150.140 Section 150.140 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES § 150.140 Cargoes not listed in Table I or II. A cargo of hazardous material not listed...
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Aviation System Analysis Capability Air Carrier Investment Model-Cargo
NASA Technical Reports Server (NTRS)
Johnson, Jesse; Santmire, Tara
1999-01-01
The purpose of the Aviation System Analysis Capability (ASAC) Air Cargo Investment Model-Cargo (ACIMC), is to examine the economic effects of technology investment on the air cargo market, particularly the market for new cargo aircraft. To do so, we have built an econometrically based model designed to operate like the ACIM. Two main drivers account for virtually all of the demand: the growth rate of the Gross Domestic Product (GDP) and changes in the fare yield (which is a proxy of the price charged or fare). These differences arise from a combination of the nature of air cargo demand and the peculiarities of the air cargo market. The net effect of these two factors are that sales of new cargo aircraft are much less sensitive to either increases in GDP or changes in the costs of labor, capital, fuel, materials, and energy associated with the production of new cargo aircraft than the sales of new passenger aircraft. This in conjunction with the relatively small size of the cargo aircraft market means technology improvements to the cargo aircraft will do relatively very little to spur increased sales of new cargo aircraft.
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System Concept Study for a Cargo Data Interchange System (CARDIS)
DOT National Transportation Integrated Search
1975-04-01
The report presents the analysis of functional and operational requirements of CARDIS. From these requirements, system sizing estimates are derived. Three potential CARDIS concepts are introduced for consideration in subsequent analysis. Their charac...
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Zhang, Shanshan; Anderson, Mark A.; Ao, Yan; Khakh, Baljit S.; Fan, Jessica; Deming, Timothy J.; Sofroniew, Michael V.
2014-01-01
Many hydrophobic small molecules are available to regulate gene expression and other cellular functions. Locally restricted application of such molecules in the central nervous system (CNS) would be desirable in many experimental and therapeutic settings, but is limited by a lack of innocuous vehicles able to load and easily deliver hydrophobic cargo. Here, we tested the potential for diblock copolypeptide hydrogels (DCH) to serve as such vehicles. In vitro tests on loading and release were conducted with cholesterol and the anti-cancer agent, temozolomide (TMZ). Loading of hydrophobic cargo modified DCH physical properties such as stiffness and viscosity, but these could readily be tuned to desired ranges by modifying DCH concentration, amino acid composition or chain lengths. Different DCH formulations exhibited different loading capacities and different rates of release. For example, comparison of different DCH with increasing alanine contents showed corresponding increases in both cargo loading capacity and time for cargo release. In vivo tests were conducted with tamoxifen, a small synthetic hydrophobic molecule widely used to regulate transgene expression. Tamoxifen released from DCH depots injected into healthy or injured CNS efficiently activated reporter gene expression in a locally restricted manner in transgenic mice. These findings demonstrate the facile and predictable tunability of DCH to achieve a wide range of loading capacities and release profiles of hydrophobic cargos while retaining CNS compatible physical properties. In addition, the findings show that DCH depots injected into the CNS can efficiently deliver small hydrophobic molecules that regulate gene expression in local cells. PMID:24314556
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Lai, Charles P.; Kim, Edward Y.; Badr, Christian E.; Weissleder, Ralph; Mempel, Thorsten R.; Tannous, Bakhos A.; Breakefield, Xandra O.
2015-01-01
Accurate spatiotemporal assessment of extracellular vesicle (EV) delivery and cargo RNA translation requires specific and robust live-cell imaging technologies. Here we engineer optical reporters to label multiple EV populations for visualization and tracking of tumour EV release, uptake and exchange between cell populations both in culture and in vivo. Enhanced green fluorescence protein (EGFP) and tandem dimer Tomato (tdTomato) were fused at NH2-termini with a palmitoylation signal (PalmGFP, PalmtdTomato) for EV membrane labelling. To monitor EV-RNA cargo, transcripts encoding PalmtdTomato were tagged with MS2 RNA binding sequences and detected by co-expression of bacteriophage MS2 coat protein fused with EGFP. By multiplexing fluorescent and bioluminescent EV membrane reporters, we reveal the rapid dynamics of both EV uptake and translation of EV-delivered cargo mRNAs in cancer cells that occurred within 1-hour post-horizontal transfer between cells. These studies confirm that EV-mediated communication is dynamic and multidirectional between cells with delivery of functional mRNA. PMID:25967391
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Retriever, a multiprotein complex for retromer-independent endosomal cargo recycling
McNally, Kerrie E.; Faulkner, Rebecca; Steinberg, Florian; Gallon, Matthew; Ghai, Rajesh; Pim, David; Langton, Paul; Pearson, Neil; Danson, Chris M.; Nägele, Heike; Morris, Lindsey M; Singla, Arnika; Overlee, Brittany L; Heesom, Kate J.; Sessions, Richard; Banks, Lawrence; Collins, Brett M; Berger, Imre; Billadeau, Daniel D.; Burstein, Ezra; Cullen, Peter J.
2018-01-01
Following endocytosis and entry into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are alternatively retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multi-protein complex which orchestrates cargo retrieval and recycling and importantly, is biochemically and functionally distinct to the established retromer pathway. Composed of a heterotrimer of DSCR3, C16orf62 and VPS29, and bearing striking similarity with retromer, we have called this complex ‘retriever’. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to the CCC and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1-integrin. Through quantitative proteomic analysis we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, which require SNX17-retriever to maintain their surface levels. Our identification of retriever establishes a major new endosomal retrieval and recycling pathway. PMID:28892079
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Utilizing ORACLE tools within Unix
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ferguson, R.
1995-07-01
Large databases, by their very nature, often serve as repositories of data which may be needed by other systems. The transmission of this data to other systems has in the past involved several layers of human intervention. The Integrated Cargo Data Base (ICDB) developed by Martin Marietta Energy Systems for the Military Traffic Management Command as part of the Worldwide Port System provides data integration and worldwide tracking of cargo that passes through common-user ocean cargo ports. One of the key functions of ICDB is data distribution of a variety of data files to a number of other systems. Developmentmore » of automated data distribution procedures had to deal with the following constraints: (1) variable generation time for data files, (2) use of only current data for data files, (3) use of a minimum number of select statements, (4) creation of unique data files for multiple recipients, (5) automatic transmission of data files to recipients, and (6) avoidance of extensive and long-term data storage.« less
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Maritime industry : cargo preference laws--estimated costs and effects
DOT National Transportation Integrated Search
1994-11-30
Cargo preference laws require that certain government-owned or government-financed cargo shipped internationally (between a U.S. port and a foreign port) be carried on U.S.-flag vessels. Cargo subject to these laws is known as preference cargo. This ...
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Characterizing Complexity of Containerized Cargo X-ray Images
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Guangxing; Martz, Harry; Glenn, Steven
X-ray imaging can be used to inspect cargos imported into the United States. In order to better understand the performance of X-ray inspection systems, the X-ray characteristics (density, complexity) of cargo need to be quantified. In this project, an image complexity measure called integrated power spectral density (IPSD) was studied using both DNDO engineered cargos and stream-of-commerce (SOC) cargos. A joint distribution of cargo density and complexity was obtained. A support vector machine was used to classify the SOC cargos into four categories to estimate the relative fractions.
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MCNP calculations for container inspection with tagged neutrons
NASA Astrophysics Data System (ADS)
Boghen, G.; Donzella, A.; Filippini, V.; Fontana, A.; Lunardon, M.; Moretto, S.; Pesente, S.; Zenoni, A.
2005-12-01
We are developing an innovative tagged neutrons inspection system (TNIS) for cargo containers: the system will allow us to assay the chemical composition of suspect objects, previously identified by a standard X-ray radiography. The operation of the system is extensively being simulated by using the MCNP Monte Carlo code to study different inspection geometries, cargo loads and hidden threat materials. Preliminary simulations evaluating the signal and the signal over background ratio expected as a function of the system parameters are presented. The results for a selection of cases are briefly discussed and demonstrate that the system can operate successfully in different filling conditions.
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Progress in tagged neutron beams for cargo inspections
NASA Astrophysics Data System (ADS)
Pesente, S.; Nebbia, G.; Viesti, G.; Daniele, F.; Fabris, D.; Lunardon, M.; Moretto, S.; Nad, K.; Sudac, D.; Valkovic, V.
2007-08-01
The use of neutron beams produced via the D + T reaction and tagged by the associated particle technique has been recently applied to cargo container inspections. In the EURITRACK project, a portable sealed-tube neutron generator has been designed and built to deliver 14 MeV neutron beams tagged by a matrix of 64 YAP:Ce alpha-particle detectors read by a multi-anode HAMAMATSU H8500 Photomultiplier Tube. The performances of this alpha-particle detector have been determined as a function of the count rate at the Rudjer Boskovic Institute, Zagreb (Croatia). Moreover, tests of the final detector operated inside the sealed-tube neutron generator are fully satisfactory.
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ROSA Transfer (for SpaceX CRS-11)
2017-04-12
Outside the Space Station Processing Facility high bay at NASA's Kennedy Space Center in Florida, a technician uses a Hyster forklift to carry the Roll-Out Solar Array, or ROSA, to the loading dock. ROSA will be delivered to the International Space Station aboard the SpaceX Dragon cargo carrier on the company’s 11th commercial resupply services mission to the space station. ROSA is a new type of solar panel that rolls open in space and is more compact than current rigid panel designs. The ROSA investigation will test deployment and retraction, shape changes when the Earth blocks the sun, and other physical challenges to determine the array's strength and durability.
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ROSA Transfer (for SpaceX CRS-11)
2017-04-12
At the loading dock outside the Space Station Processing Facility high bay at NASA's Kennedy Space Center in Florida, a technician uses a Hyster forklift to load the Roll-Out Solar Array, or ROSA, into a truck. ROSA will be delivered to the International Space Station aboard the SpaceX Dragon cargo carrier on the company’s 11th commercial resupply services mission to the space station. ROSA is a new type of solar panel that rolls open in space and is more compact than current rigid panel designs. The ROSA investigation will test deployment and retraction, shape changes when the Earth blocks the sun, and other physical challenges to determine the array's strength and durability.
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Reconstituting the motility of isolated intracellular cargoes.
Hendricks, Adam G; Goldman, Yale E; Holzbaur, Erika L F
2014-01-01
Kinesin, dynein, and myosin transport intracellular cargoes including organelles, membrane-bound vesicles, and mRNA along the cytoskeleton. These motor proteins work collectively in teams to transport cargoes over long distances and navigate around obstacles in the cell. In addition, several types of motors often interact on the same cargo to allow bidirectional transport and switching between the actin and microtubule networks. To examine transport of native cargoes in a simplified in vitro system, techniques have been developed to isolate endogenous cargoes and reconstitute their motility. Isolated cargoes can be tracked and manipulated with high precision using total internal reflection fluorescence microscopy and optical trapping. Through use of native cargoes, we can examine vesicular transport in a minimal system while retaining endogenous motor stoichiometry and the biochemical and mechanical characteristics of both motor and cargo. © 2014 Elsevier Inc. All rights reserved.
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Optimization of Blocked Designs in fMRI Studies
ERIC Educational Resources Information Center
Maus, Barbel; van Breukelen, Gerard J. P.; Goebel, Rainer; Berger, Martijn P. F.
2010-01-01
Blocked designs in functional magnetic resonance imaging (fMRI) are useful to localize functional brain areas. A blocked design consists of different blocks of trials of the same stimulus type and is characterized by three factors: the length of blocks, i.e., number of trials per blocks, the ordering of task and rest blocks, and the time between…
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33 CFR 126.17 - Permits required for handling designated dangerous cargo.
Code of Federal Regulations, 2013 CFR
2013-07-01
... designated dangerous cargo. 126.17 Section 126.17 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) WATERFRONT FACILITIES HANDLING OF DANGEROUS CARGO AT WATERFRONT FACILITIES § 126.17 Permits required for handling designated dangerous cargo. Designated dangerous cargo may be...
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46 CFR 148.72 - Dangerous cargo manifest; exceptions.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...
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33 CFR 126.17 - Permits required for handling designated dangerous cargo.
Code of Federal Regulations, 2014 CFR
2014-07-01
... designated dangerous cargo. 126.17 Section 126.17 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) WATERFRONT FACILITIES HANDLING OF DANGEROUS CARGO AT WATERFRONT FACILITIES § 126.17 Permits required for handling designated dangerous cargo. Designated dangerous cargo may be...
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46 CFR 148.72 - Dangerous cargo manifest; exceptions.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...
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46 CFR 148.72 - Dangerous cargo manifest; exceptions.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...
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33 CFR 126.17 - Permits required for handling designated dangerous cargo.
Code of Federal Regulations, 2012 CFR
2012-07-01
... designated dangerous cargo. 126.17 Section 126.17 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) WATERFRONT FACILITIES HANDLING OF DANGEROUS CARGO AT WATERFRONT FACILITIES § 126.17 Permits required for handling designated dangerous cargo. Designated dangerous cargo may be...
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33 CFR 126.17 - Permits required for handling designated dangerous cargo.
Code of Federal Regulations, 2010 CFR
2010-07-01
... designated dangerous cargo. 126.17 Section 126.17 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) WATERFRONT FACILITIES HANDLING OF DANGEROUS CARGO AT WATERFRONT FACILITIES § 126.17 Permits required for handling designated dangerous cargo. Designated dangerous cargo may be...
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46 CFR 148.72 - Dangerous cargo manifest; exceptions.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Dangerous cargo manifest; exceptions. 148.72 Section 148.72 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES CARRIAGE OF... Dangerous cargo manifest; exceptions. (a) No dangerous cargo manifest is required for— (1) Shipments by...
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33 CFR 126.17 - Permits required for handling designated dangerous cargo.
Code of Federal Regulations, 2011 CFR
2011-07-01
... designated dangerous cargo. 126.17 Section 126.17 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) WATERFRONT FACILITIES HANDLING OF DANGEROUS CARGO AT WATERFRONT FACILITIES § 126.17 Permits required for handling designated dangerous cargo. Designated dangerous cargo may be...
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46 CFR 153.235 - Exceptions to cargo piping location restrictions.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Exceptions to cargo piping location restrictions. 153... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.235 Exceptions to cargo piping location restrictions...
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46 CFR 153.235 - Exceptions to cargo piping location restrictions.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Exceptions to cargo piping location restrictions. 153... DANGEROUS CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Containment Systems § 153.235 Exceptions to cargo piping location restrictions...
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The Origin and Functions of Exosomes in Cancer
Rajagopal, Chitra; Harikumar, K. B.
2018-01-01
Exosomes are nanovesicles having a maximum size of 150 nm and is a newly emerging focus in various fields of research. Its role in cargo trafficking along with its differential expression is associated with the disrupted homeostasis and provides an opportunity to defend against different diseases like cancer. Furthermore, exosomes are rich in cargos, which contain proteins and nucleic acids that directly reflect the metabolic state of the cells from which it originates. This review summarizes recent studies on tumor-derived exosomes with an overview about biogenesis, their functions and potential of using as diagnostic and prognostic markers. We also discussed the current challenges and microfluidic-based detection approaches that might improve the detection of exosomes in different settings. More intricate studies of the molecular mechanisms in angiogenesis, pre-metastatic niche formation, and metastasis can give more promising insights and novel strategies in oncotherapeutics. PMID:29616188
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Navigating the plant cell: intracellular transport logistics in the green kingdom.
Geitmann, Anja; Nebenführ, Andreas
2015-10-01
Intracellular transport in plant cells occurs on microtubular and actin arrays. Cytoplasmic streaming, the rapid motion of plant cell organelles, is mostly driven by an actin-myosin mechanism, whereas specialized functions, such as the transport of large cargo or the assembly of a new cell wall during cell division, are performed by the microtubules. Different modes of transport are used, fast and slow, to either haul cargo over long distances or ascertain high-precision targeting, respectively. Various forms of the actin-specific motor protein myosin XI exist in plant cells and might be involved in different cellular functions. © 2015 Geitmann and Nebenführ. 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).
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46 CFR 151.01-15 - Dangerous cargoes not specifically named.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Dangerous cargoes not specifically named. 151.01-15 Section 151.01-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-15 Dangerous cargoes not...
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46 CFR 151.01-15 - Dangerous cargoes not specifically named.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Dangerous cargoes not specifically named. 151.01-15 Section 151.01-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-15 Dangerous cargoes not...
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46 CFR 151.01-15 - Dangerous cargoes not specifically named.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Dangerous cargoes not specifically named. 151.01-15 Section 151.01-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-15 Dangerous cargoes not...
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46 CFR 151.01-15 - Dangerous cargoes not specifically named.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Dangerous cargoes not specifically named. 151.01-15 Section 151.01-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-15 Dangerous cargoes not...
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46 CFR 151.01-15 - Dangerous cargoes not specifically named.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Dangerous cargoes not specifically named. 151.01-15 Section 151.01-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES General § 151.01-15 Dangerous cargoes not...
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46 CFR 105.20-3 - Cargo tanks.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 4 2013-10-01 2013-10-01 false Cargo tanks. 105.20-3 Section 105.20-3 Shipping COAST... VESSELS DISPENSING PETROLEUM PRODUCTS Specific Requirements-Cargo Tanks § 105.20-3 Cargo tanks. (a) Construction and Materials. (1) The cargo tanks must be constructed of iron, steel, copper, nickel alloy...
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46 CFR 105.20-3 - Cargo tanks.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 4 2014-10-01 2014-10-01 false Cargo tanks. 105.20-3 Section 105.20-3 Shipping COAST... VESSELS DISPENSING PETROLEUM PRODUCTS Specific Requirements-Cargo Tanks § 105.20-3 Cargo tanks. (a) Construction and Materials. (1) The cargo tanks must be constructed of iron, steel, copper, nickel alloy...
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46 CFR 105.20-3 - Cargo tanks.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 4 2011-10-01 2011-10-01 false Cargo tanks. 105.20-3 Section 105.20-3 Shipping COAST... VESSELS DISPENSING PETROLEUM PRODUCTS Specific Requirements-Cargo Tanks § 105.20-3 Cargo tanks. (a) Construction and Materials. (1) The cargo tanks must be constructed of iron, steel, copper, nickel alloy...
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46 CFR 105.20-3 - Cargo tanks.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 4 2012-10-01 2012-10-01 false Cargo tanks. 105.20-3 Section 105.20-3 Shipping COAST... VESSELS DISPENSING PETROLEUM PRODUCTS Specific Requirements-Cargo Tanks § 105.20-3 Cargo tanks. (a) Construction and Materials. (1) The cargo tanks must be constructed of iron, steel, copper, nickel alloy...
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46 CFR 153.285 - Valving for cargo pump manifolds.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo...
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46 CFR 153.438 - Cargo pressure or temperature alarms required.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo pressure or temperature alarms required. 153.438... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.438 Cargo pressure or temperature alarms required. (a...
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46 CFR 153.438 - Cargo pressure or temperature alarms required.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo pressure or temperature alarms required. 153.438... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.438 Cargo pressure or temperature alarms required. (a...
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46 CFR 153.438 - Cargo pressure or temperature alarms required.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo pressure or temperature alarms required. 153.438... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.438 Cargo pressure or temperature alarms required. (a...
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46 CFR 153.438 - Cargo pressure or temperature alarms required.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pressure or temperature alarms required. 153.438... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.438 Cargo pressure or temperature alarms required. (a...
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46 CFR 153.438 - Cargo pressure or temperature alarms required.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo pressure or temperature alarms required. 153.438... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Temperature Control Systems § 153.438 Cargo pressure or temperature alarms required. (a...
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29 CFR 1918.87 - Ship's cargo elevators.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 29 Labor 7 2011-07-01 2011-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe working loads of ship's cargo elevators shall be determined and followed...
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46 CFR 153.977 - Supervision of cargo transfer.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...
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46 CFR 153.977 - Supervision of cargo transfer.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...
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46 CFR 153.977 - Supervision of cargo transfer.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...
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46 CFR 153.977 - Supervision of cargo transfer.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...
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46 CFR 153.977 - Supervision of cargo transfer.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Supervision of cargo transfer. 153.977 Section 153.977 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.977 Supervision of cargo transfer. The person in charge of cargo transfer shall: (a...
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29 CFR 1918.87 - Ship's cargo elevators.
Code of Federal Regulations, 2014 CFR
2014-07-01
... 29 Labor 7 2014-07-01 2014-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe working loads of ship's cargo elevators shall be determined and followed...
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29 CFR 1918.87 - Ship's cargo elevators.
Code of Federal Regulations, 2012 CFR
2012-07-01
... 29 Labor 7 2012-07-01 2012-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe working loads of ship's cargo elevators shall be determined and followed...
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29 CFR 1918.87 - Ship's cargo elevators.
Code of Federal Regulations, 2013 CFR
2013-07-01
... 29 Labor 7 2013-07-01 2013-07-01 false Ship's cargo elevators. 1918.87 Section 1918.87 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.87 Ship's cargo elevators. (a) Safe working load. The safe working loads of ship's cargo elevators shall be determined and followed...
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46 CFR 154.235 - Cargo tank location.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo tank location. 154.235 Section 154.235 Shipping... FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Ship Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo...
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46 CFR 154.235 - Cargo tank location.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo tank location. 154.235 Section 154.235 Shipping... FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Ship Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo...
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46 CFR 154.235 - Cargo tank location.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo tank location. 154.235 Section 154.235 Shipping... FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Ship Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo...
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46 CFR 151.13-5 - Cargo segregation-tanks.
Code of Federal Regulations, 2010 CFR
2010-10-01
... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... design. (2) Segregation of cargo space from machinery spaces and other spaces which have or could have a... separating medium. ii=Double bulkhead, required. Cofferdam, empty tank, pumproom, tank with Grade E Liquid...
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46 CFR 151.13-5 - Cargo segregation-tanks.
Code of Federal Regulations, 2011 CFR
2011-10-01
... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... design. (2) Segregation of cargo space from machinery spaces and other spaces which have or could have a... separating medium. ii=Double bulkhead, required. Cofferdam, empty tank, pumproom, tank with Grade E Liquid...
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46 CFR 151.13-5 - Cargo segregation-tanks.
Code of Federal Regulations, 2012 CFR
2012-10-01
... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... design. (2) Segregation of cargo space from machinery spaces and other spaces which have or could have a... separating medium. ii=Double bulkhead, required. Cofferdam, empty tank, pumproom, tank with Grade E Liquid...
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46 CFR 154.701 - Cargo pressure and temperature control: General.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo pressure and temperature control: General. 154.701... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Pressure and Temperature Control § 154.701 Cargo pressure and temperature control: General...
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46 CFR 154.701 - Cargo pressure and temperature control: General.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo pressure and temperature control: General. 154.701... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Pressure and Temperature Control § 154.701 Cargo pressure and temperature control: General...
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46 CFR 154.701 - Cargo pressure and temperature control: General.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo pressure and temperature control: General. 154.701... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Pressure and Temperature Control § 154.701 Cargo pressure and temperature control: General...
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46 CFR 154.701 - Cargo pressure and temperature control: General.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pressure and temperature control: General. 154.701... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Pressure and Temperature Control § 154.701 Cargo pressure and temperature control: General...
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46 CFR 154.701 - Cargo pressure and temperature control: General.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo pressure and temperature control: General. 154.701... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Pressure and Temperature Control § 154.701 Cargo pressure and temperature control: General...
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46 CFR 308.545 - Facultative cargo policy, Form MA-316.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 308.545 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.545 Facultative cargo policy, Form MA-316. The standard form of War Risk Facultative Cargo Policy, Form MA-316, may be obtained...
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46 CFR 308.545 - Facultative cargo policy, Form MA-316.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 308.545 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Iii-Facultative War Risk Cargo Insurance § 308.545 Facultative cargo policy, Form MA-316. The standard form of War Risk Facultative Cargo Policy, Form MA-316, may be obtained...
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46 CFR 308.511 - Cancellation of Open Cargo Policy.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 46 Shipping 8 2014-10-01 2014-10-01 false Cancellation of Open Cargo Policy. 308.511 Section 308.511 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Open Policy War Risk Cargo Insurance § 308.511 Cancellation of Open Cargo...