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Sample records for cargo delivery kinetics

  1. Cargo-Delivery Platforms for Targeted Delivery of Inhibitor Cargos Against Botulism

    PubMed Central

    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

  2. Kinesin regulation dynamics through cargo delivery, a single molecule investigation

    NASA Astrophysics Data System (ADS)

    Kovacs, Anthony; Kessler, Jonathan; Lin, Huawen; Dutcher, Susan; Wang, Yan Mei

    2015-03-01

    Kinesins are microtubule-based motors that deliver cargo to their destinations in a highly regulated manner. Although in recent years numerous regulators of cargo delivery have been identified, the regulation mechanism of kinesin through the cargo delivery and recycling process is not known. By performing single molecule fluorescence imaging measurements in Chlamydomonas flagella, which are 200 nm in diameter, 10 microns in length, and contain 9 sets of microtubule doublets, we tracked the intraflagellar transport (IFT) trains, BBSome cargo, and kinesin-2 motors through the cargo delivery process and determined the aforementioned dynamics. Upon arrival at the microtubule plus end at the flagellar tip, (1) IFT trains and BBSome cargo remain intact, dissociate together from kinesins and microtubules, and diffuse along flagellar membrane for a mean of 2.3 sec before commencing retrograde travel. (2) Kinesin motors remain bound to and diffuse along microtubules for 1.3 sec before dissociating into the flagellar lumen for recycling.

  3. Materials innovation for co-delivery of diverse therapeutic cargos

    PubMed Central

    Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

    2014-01-01

    Co-delivery is a rapidly growing sector of drug delivery that aspires to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes with synergistic activities. It requires the design of carriers capable of simultaneously transporting to and releasing multiple therapeutics at a disease site. Co-delivery has arisen from the emerging trend of combination therapy, where treatment with two or more therapeutics at the same time can succeed where single therapeutics fail. However, conventional combination therapy offers little control over achieving an optimized therapeutic ratio at the target site. Co-delivery via inclusion of multiple therapeutic cargos within the same carrier addresses this issue by not only ensuring delivery of both therapeutics to the same cell, but also offering a platform for control of the delivery process, from loading to release. Co-delivery systems have been formulated using a number of carriers previously developed for single-therapeutic delivery. Liposomes, polymeric micelles, PLGA nanoparticles, and dendrimers have all been adapted for co-delivery. Much of the effort focuses on dealing with drugs having dissimilar properties, increasing loading efficiencies, and controlling loading and release ratios. In this review, we highlight the innovations in carrier designs and formulations to deliver combination cargoes of drug/drug, drug/siRNA, and drug/pDNA toward disease therapy. With rapid advances in mechanistic understanding of interrelating molecular pathways and development of molecular medicine, the future of co-delivery will become increasingly promising and prominent. PMID:24818000

  4. Catalytic Mesoporous Janus Nanomotors for Active Cargo Delivery

    PubMed Central

    2015-01-01

    We report on the synergy between catalytic propulsion and mesoporous silica nanoparticles (MSNPs) for the design of Janus nanomotors as active cargo delivery systems with sizes <100 nm (40, 65, and 90 nm). The Janus asymmetry of the nanomotors is given by electron beam (e-beam) deposition of a very thin platinum (2 nm) layer on MSNPs. The chemically powered Janus nanomotors present active diffusion at low H2O2 fuel concentration (i.e., <3 wt %). Their apparent diffusion coefficient is enhanced up to 100% compared to their Brownian motion. Due to their mesoporous architecture and small dimensions, they can load cargo molecules in large quantity and serve as active nanocarriers for directed cargo delivery on a chip. PMID:25844893

  5. Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery.

    PubMed

    Prevo, Bram; Scholey, Jonathan M; Peterman, Erwin J G

    2017-03-25

    Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium. Following its discovery in Chlamydomonas, IFT has emerged as a powerful model system for studying general principles of motor-dependent cargo transport and we now appreciate the diversity that exists in the mechanism of IFT within cilia of different cell types. The absence of heterotrimeric kinesin-2 function, for example, causes a complete loss of both IFT and cilia in Chlamydomonas, but following its loss in Caenorhabditis elegans, where its primary function is loading the IFT machinery into cilia, homodimeric kinesin-2-driven IFT persists and assembles a full-length cilium. Generally, heterotrimeric kinesin-2 and IFT dynein motors are thought to play widespread roles as core IFT motors, whereas homodimeric kinesin-2 motors are accessory motors that mediate different functions in a broad range of cilia, in some cases contributing to axoneme assembly or the delivery of signaling molecules but in many other cases their ciliary functions, if any, remain unknown. In this review, we focus on mechanisms of motor action, motor cooperation, and motor-dependent cargo delivery during IFT. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  6. The development of a parachute system for aerial delivery from high speed cargo aircraft

    SciTech Connect

    Behr, V.L.

    1992-01-01

    Supply of military personnel on the ground with cargo has long been accomplished with parachute delivery systems from aircraft. Structural limits of aircraft have typically limited these operations to no more than 150 KCAS. A desire for increased survivability of cargo delivery aircraft has led to the development and fielding of aircraft capable of delivering cargo at substantially higher speeds. This paper describes efforts undertaken to design develop and test a cargo delivery system for use at speeds compatible with those high speed cargo aircraft.

  7. The development of a parachute system for aerial delivery from high speed cargo aircraft

    SciTech Connect

    Behr, V.L.

    1992-12-31

    Supply of military personnel on the ground with cargo has long been accomplished with parachute delivery systems from aircraft. Structural limits of aircraft have typically limited these operations to no more than 150 KCAS. A desire for increased survivability of cargo delivery aircraft has led to the development and fielding of aircraft capable of delivering cargo at substantially higher speeds. This paper describes efforts undertaken to design develop and test a cargo delivery system for use at speeds compatible with those high speed cargo aircraft.

  8. Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord

    PubMed Central

    Dengler, Ellen C.; Liu, Juewen; Kerwin, Audra; Torres, Sergio; Olcott, Clara M.; Bowman, Brandi N.; Armijo, Leisha; Gentry, Katherine; Wilkerson, Jenny; Wallace, James; Jiang, Xingmao; Carnes, Eric C.; Brinker, C. Jeffrey; Milligan, Erin D.

    2013-01-01

    Amorphous mesoporous silica nanoparticles (‘protocells’) that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) -cholesterol (DOTAP:Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection. Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space has yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system. Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent. We report here that i.t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP:Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods. This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery. PMID:23517784

  9. Mesoporous Silica Nanoparticles and Films for Cargo Delivery

    NASA Astrophysics Data System (ADS)

    Guardado Alvarez, Tania Maria

    Mesoporous silica materials are well known materials that can range from films to nanoparticles. Mesoporous silica nanoparticles (MSNs) and mesoporous silica films have been of increasing interest among the scientific community for its use in cargo delivery. Silica provides ease of functionalization, a robust support and biocompatibility. Several methods have been used in order to give the mesoporous silica nanomaterials different qualities that render them a useful material with different characteristics. Among these methods is surface modification by taking advantage of the OH groups on the surface. When a molecule attached to the surface can act as a molecular machine it transforms the nanomaterial to act as delivery system that can be activated upon command. The work covered in this thesis focuses on the development and synthesis of different mesoporous silica materials for the purpose of trapping and releasing cargo molecules. Chapter 2 focuses in the photoactivation of "snap-top" stoppers over the pore openings of mesoporous silica nanoparticles that releases intact cargo molecules from the pores. The on-command release can be stimulated by either one UV photon or two coherent near-IR photons. Two-photon activation is particularly desirable for use in biological systems because it enables good tissue penetration and precise spatial control. Chapter 3 focuses on the design and synthesis of a nano-container consisting of mesoporous silica nanoparticles with the pore openings covered by "snap-top" caps that are opened by near-IR light. A photo transducer molecule that is a reducing agent in an excited electronic state is covalently attached to the system. Near IR two-photon excitation causes intermolecular electron transfer that reduces a disulfide bond holding the cap in place, thus allowing the cargo molecules to escape. The operation of the "snap-top" release mechanism by both one- and two photon is described. This system presents a proof of concept of a near

  10. Extracellular Vesicles Exploit Viral Entry Routes for Cargo Delivery

    PubMed Central

    van Dongen, Helena M.; Masoumi, Niala

    2016-01-01

    SUMMARY Extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, being involved in a wide array of key biological processes. Eukaryotic cells, and also bacteria, actively release heterogeneous subtypes of EVs into the extracellular space, where their contents reflect their (sub)cellular origin and the physiologic state of the parent cell. Within the past 20 years, presumed subtypes of EVs have been given a rather confusing diversity of names, including exosomes, microvesicles, ectosomes, microparticles, virosomes, virus-like particles, and oncosomes, and these names are variously defined by biogenesis, physical characteristics, or function. The latter category, functions, in particular the transmission of biological signals between cells in vivo and how EVs control biological processes, has garnered much interest. EVs have pathophysiological properties in cancer, neurodegenerative disorders, infectious disease, and cardiovascular disease, highlighting possibilities not only for minimally invasive diagnostic applications but also for therapeutic interventions, like macromolecular drug delivery. Yet, in order to pursue therapies involving EVs and delivering their cargo, a better grasp of EV targeting is needed. Here, we review recent progress in understanding the molecular mechanisms underpinning EV uptake by receptor-ligand interactions with recipient cells, highlighting once again the overlap of EVs and viruses. Despite their highly heterogeneous nature, EVs require common viral entry pathways, and an unanticipated specificity for cargo delivery is being revealed. We discuss the challenges ahead in delineating specific roles for EV-associated ligands and cellular receptors. PMID:26935137

  11. A self-powered kinesin-microtubule system for smart cargo delivery

    NASA Astrophysics Data System (ADS)

    Jia, Yi; Dong, Weiguang; Feng, Xiyun; Li, Jieling; Li, Junbai

    2014-11-01

    A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time.A smart self-powered cargo delivery system that is composed of creatine phosphate kinase (CPK) microspheres, kinesins and microtubules is demonstrated. The CPK microsphere not only acts as an ATP generation and buffering system, but also as a carrier for cargo transport, thus realizing the easy loading and self-powered delivery of cargos at the same time. Electronic supplementary information (ESI) available: Experimental details, Fig. S1-S4, and Mov. S1-S6. See DOI: 10.1039/c4nr04454a

  12. Logistics: Delivery and Receipt of DoD Cargo Inbound to the Republic of Korea

    DTIC Science & Technology

    2002-04-05

    distribution system. Customer Wait Time measures delivery time for cargo from the time it is ordered until delivered to the end user. See...cargo to an overseas theater, UMMIPS allows .5 days for ports of debarkation (POD)1 processing and 1 day of delivery time to the consignee,2 for a...total delivery time of 1.5 days. However, for commercial express deliveries (Transportation Priority 1) to an overseas theater, UMMIPS does not

  13. Oviductosome-Sperm Membrane Interaction in Cargo Delivery

    PubMed Central

    Al-Dossary, Amal A.; Bathala, Pradeepthi; Caplan, Jeffrey L.; Martin-DeLeon, Patricia A.

    2015-01-01

    Oviductosomes ((OVS), exosomes/microvesicles), which deliver the Ca2+ efflux pump, plasma membrane Ca2+ATPase 4 (PMCA4), to sperm are likely to play an important role in sperm fertilizing ability (Al-Dossary, A. A., Strehler, E. E., and Martin-DeLeon, P. A. (2013) PloS one 8, e80181). It is unknown how exosomes/microvesicles deliver transmembrane proteins such as PMCA4 to sperm. Here we define a novel experimental approach for the assessment of the interaction of OVS with sperm at a nanoscale level, using a lipophilic dye (FM4–64FX) and three-dimensional SR/SIM, which has an 8-fold increase in volumetric resolution, compared with conventional confocal microscopy. Coincubation assays detected fusion of prelabeled OVS with sperm, primarily over the head and midpiece. Immunofluorescence revealed oviductosomal delivery of PMCA4a to WT and Pmca4 KO sperm, and also endogenous PMCA4a on the inner acrosomal membrane. Fusion was confirmed by transmission immunoelectron microscopy, showing immunogold particles in OVS, and fusion stalks on sperm membrane. Immunofluorescence colocalized OVS with the αv integrin subunit which, along with CD9, resides primarily on the sperm head and midpiece. In capacitated and acrosome reacted sperm, fusion was significantly (p < 0.001) inhibited by blocking integrin/ligand interactions via antibodies, exogenous ligands (vitronectin and fibronectin), and their RGD recognition motif. Our results provide evidence that receptor/ligand interactions, involving αvβ3 and α5β1integrins on sperm and OVS, facilitate fusion of OVS in the delivery of transmembrane proteins to sperm. The mechanism uncovered is likely to be also involved in cargo delivery of prostasomes, epididymosomes, and uterosomes. PMID:26023236

  14. Airlift Cargo Hub Port Hold Times: Controlling Variations in Defense Supply Chain Delivery

    DTIC Science & Technology

    2010-06-01

    Pagh, 1997). Finally, SCM seeks to establish a flow of goods and information across the chain in order to generate system efficiencies. By...efficiently as possible. High system demand, limited cargo capacity, and desired cost efficiencies drive significant portions of even the highest...priority wartime cargo into a hub and spoke delivery system . However, additional efficiencies afforded through hub and spoke delivery come at the

  15. A platform for actively loading cargo RNA to elucidate limiting steps in EV-mediated delivery

    PubMed Central

    Hung, Michelle E.; Leonard, Joshua N.

    2016-01-01

    Extracellular vesicles (EVs) mediate intercellular communication through transfer of RNA and protein between cells. Thus, understanding how cargo molecules are loaded and delivered by EVs is of central importance for elucidating the biological roles of EVs and developing EV-based therapeutics. While some motifs modulating the loading of biomolecular cargo into EVs have been elucidated, the general rules governing cargo loading and delivery remain poorly understood. To investigate how general biophysical properties impact loading and delivery of RNA by EVs, we developed a platform for actively loading engineered cargo RNAs into EVs. In our system, the MS2 bacteriophage coat protein was fused to EV-associated proteins, and the cognate MS2 stem loop was engineered into cargo RNAs. Using this Targeted and Modular EV Loading (TAMEL) approach, we identified a configuration that substantially enhanced cargo RNA loading (up to 6-fold) into EVs. When applied to vesicles expressing the vesicular stomatitis virus glycoprotein (VSVG) – gesicles – we observed a 40-fold enrichment in cargo RNA loading. While active loading of mRNA-length (>1.5 kb) cargo molecules was possible, active loading was much more efficient for smaller (~0.5 kb) RNA molecules. We next leveraged the TAMEL platform to elucidate the limiting steps in EV-mediated delivery of mRNA and protein to prostate cancer cells, as a model system. Overall, most cargo was rapidly degraded in recipient cells, despite high EV-loading efficiencies and substantial EV uptake by recipient cells. While gesicles were efficiently internalized via a VSVG-mediated mechanism, most cargo molecules were rapidly degraded. Thus, in this model system, inefficient endosomal fusion or escape likely represents a limiting barrier to EV-mediated transfer. Altogether, the TAMEL platform enabled a comparative analysis elucidating a key opportunity for enhancing EV-mediated delivery to prostate cancer cells, and this technology should be of

  16. Reevaluating the nicotine delivery kinetics hypothesis.

    PubMed

    Dar, Reuven; Frenk, Hanan

    2007-05-01

    The view of smoking as an addiction to nicotine implies that nicotine is an addictive drug and a primary reinforcer. However, nicotine other than in tobacco does not appear to be very rewarding for smokers. This potential anomaly to the nicotine addiction thesis is resolved by the proposition that the reward associated with smoking depends on "high-nicotine boli." According to the nicotine delivery kinetics hypothesis, smoked nicotine reaches the brain in 5-10 s in high concentrations, which provide reinforcing "hits" of nicotine to the brain. Because of its essential role in the nicotine addiction thesis, this review set out to examine the current empirical basis of the nicotine delivery kinetics hypothesis. We reviewed studies that bear on two questions: First, does nicotine from cigarettes reach the brain significantly faster than from other nicotine delivery devices? Second, is there a relationship between delivery kinetics and any rewarding effects of nicotine? There is little empirical support for the nicotine delivery kinetics hypothesis. Several studies found that arterial nicotine levels associated with smoking are much lower than predicted by the nicotine delivery kinetics thesis and not higher than with other nicotine delivery devices. More importantly, comparisons of nicotine delivery devices with varying speeds of delivery do not suggest any correlation between nicotine delivery profile and subjective reward. This review indicates that the wide endorsement of the nicotine delivery kinetics hypothesis is unjustified. Critical research is required to resolve the anomalies within the nicotine addiction theory of smoking.

  17. Systems Analysis and Structural Design of an Unpressurized Cargo Delivery Vehicle

    NASA Technical Reports Server (NTRS)

    Wu, K. Chauncey; Cruz, Jonathan N.; Antol, Jeffrey; Sasamoto, Washito A.

    2007-01-01

    The International Space Station will require a continuous supply of replacement parts for ongoing maintenance and repair after the planned retirement of the Space Shuttle in 2010. These parts are existing line-replaceable items collectively called Orbital Replacement Units, and include heavy and oversized items such as Control Moment Gyroscopes and stowed radiator arrays originally intended for delivery aboard the Space Shuttle. Current resupply spacecraft have limited to no capability to deliver these external logistics. In support of NASA's Exploration Systems Architecture Study, a team at Langley Research Center designed an Unpressurized Cargo Delivery Vehicle to deliver bulk cargo to the Space Station. The Unpressurized Cargo Delivery Vehicle was required to deliver at least 13,200 lbs of cargo mounted on at least 18 Flight Releasable Attachment Mechanisms. The Crew Launch Vehicle design recommended in the Exploration Systems Architecture Study would be used to launch one annual resupply flight to the International Space Station. The baseline vehicle design developed here has a cargo capacity of 16,000 lbs mounted on up to 20 Flight Releasable Attachment Mechanisms. Major vehicle components are a 5.5m-diameter cargo module containing two detachable cargo pallets with the payload, a Service Module to provide propulsion and power, and an aerodynamic nose cone. To reduce cost and risk, the Service Module is identical to the one used for the Crew Exploration Vehicle design.

  18. Bacteria-mediated delivery of nanoparticles and cargo into cells

    NASA Astrophysics Data System (ADS)

    Akin, Demir; Sturgis, Jennifer; Ragheb, Kathy; Sherman, Debby; Burkholder, Kristin; Robinson, J. Paul.; Bhunia, Arun K.; Mohammed, Sulma; Bashir, Rashid

    2007-07-01

    Nanoparticles and bacteria can be used, independently, to deliver genes and proteins into mammalian cells for monitoring or altering gene expression and protein production. Here, we show the simultaneous use of nanoparticles and bacteria to deliver DNA-based model drug molecules in vivo and in vitro. In our approach, cargo (in this case, a fluorescent or a bioluminescent gene) is loaded onto the nanoparticles, which are carried on the bacteria surface. When incubated with cells, the cargo-carrying bacteria (`microbots') were internalized by the cells, and the genes released from the nanoparticles were expressed in the cells. Mice injected with microbots also successfully expressed the genes as seen by the luminescence in different organs. This new approach may be used to deliver different types of cargo into live animals and a variety of cells in culture without the need for complicated genetic manipulations.

  19. Regulated delivery of molecular cargo to invasive tumour-derived microvesicles.

    PubMed

    Clancy, James W; Sedgwick, Alanna; Rosse, Carine; Muralidharan-Chari, Vandhana; Raposo, Graca; Method, Michael; Chavrier, Philippe; D'Souza-Schorey, Crislyn

    2015-04-21

    Cells release multiple, distinct forms of extracellular vesicles including structures known as microvesicles, which are known to alter the extracellular environment. Despite growing understanding of microvesicle biogenesis, function and contents, mechanisms regulating cargo delivery and enrichment remain largely unknown. Here we demonstrate that in amoeboid-like invasive tumour cell lines, the v-SNARE, VAMP3, regulates delivery of microvesicle cargo such as the membrane-type 1 matrix metalloprotease (MT1-MMP) to shedding microvesicles. MT1-MMP delivery to nascent microvesicles depends on the association of VAMP3 with the tetraspanin CD9 and facilitates the maintenance of amoeboid cell invasion. VAMP3-shRNA expression depletes shed vesicles of MT1-MMP and decreases cell invasiveness when embedded in cross-linked collagen matrices. Finally, we describe functionally similar microvesicles isolated from bodily fluids of ovarian cancer patients. Together these studies demonstrate the importance of microvesicle cargo sorting in matrix degradation and disease progression.

  20. Regulated Delivery of Molecular Cargo to Invasive Tumor-derived Microvesicles

    PubMed Central

    Clancy, James W.; Sedgwick, Alanna; Rosse, Carine; Muralidharan-Chari, Vandhana; Raposo, Graca; Method, Michael; Chavrier, Philippe; D'Souza-Schorey, Crislyn

    2015-01-01

    Cells release multiple, distinct, forms of extracellular vesicles including structures known as microvesicles which are known to alter the extracellular environment. Despite growing understanding of microvesicle biogenesis, function, and contents, mechanisms regulating cargo delivery and enrichment remain largely unknown. Here we demonstrate that in amoeboid-like invasive tumor cell lines, the v-SNARE, VAMP3, regulates delivery of microvesicle cargo such as the membrane-type 1 matrix metalloprotease (MT1-MMP) to shedding microvesicles. MT1-MMP delivery to nascent microvesicles depends on the association of VAMP3 with the tetraspanin CD9 and facilitates the maintenance of amoeboid cell invasion. VAMP3-shRNA expression depletes shed vesicles of MT1-MMP and decreases cell invasiveness when embedded in cross-linked collagen matrices. Finally, we describe functionally similar microvesicles isolated from bodily fluids of ovarian cancer patients. Together these studies demonstrate the importance of microvesicle cargo sorting in matrix degradation and disease progression. PMID:25897521

  1. Photothermal nanoblade for large cargo delivery into mammalian cells

    PubMed Central

    Wu, Ting-Hsiang; Teslaa, Tara; Kalim, Sheraz; French, Christopher T.; Maghadam, Shahriar; Wall, Randolph; Miller, Jeffery F.; Witte, Owen N.; Teitell, Michael A.; Chiou, Pei-Yu

    2011-01-01

    It is difficult to achieve controlled cutting of elastic, mechanically fragile, and rapidly resealing mammalian cell membranes. Here, we report a photothermal nanoblade that utilizes a metallic nanostructure to harvest short laser pulse energy and convert it into a highly localized explosive vapor bubble, which rapidly punctures a lightly-contacting cell membrane via high-speed fluidic flows and induced transient shear stress. The cavitation bubble pattern is controlled by the metallic structure configuration and laser pulse duration and energy. Integrating the metallic nanostructure with a micropipette, the nanoblade generates a micron-sized membrane access port for delivering highly concentrated cargo (5×108 live bacteria/ml) with high efficiency (46%) and cell viability (>90%) into mammalian cells. Additional biologic and inanimate cargo over 3-orders of magnitude in size including DNA, RNA, 200 nm polystyrene beads to 2 μm bacteria have also been delivered into multiple mammalian cell types. Overall, the photothermal nanoblade is a new approach for delivering difficult to transfer cargo into mammalian cells. PMID:21247066

  2. Protocells and their use for targeted delivery of multicomponent cargos to cancer cells

    DOEpatents

    Brinker, Jeffrey C.; Ashley, Carlee Erin; Jiang, Xingmao; Liu, Juewen; Peabody, David S.; Wharton, Walker Richard; Carnes, Eric; Chackerian, Bryce; Willman, Cheryl L.

    2016-11-01

    Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

  3. Protocells and their use for targeted delivery of multicomponent cargos to cancer cells

    DOEpatents

    Brinker, C Jeffrey; Ashley, Carlee Erin; Jiang, Xingmao; Liu, Juewen; Peabody, David S; Wharton, Walker Richard; Carnes, Eric; Chackerian, Bryce; Willman, Cheryl L

    2015-03-31

    Various embodiments provide materials and methods for synthesizing protocells for use in targeted delivery of cargo components to cancer cells. In one embodiment, the lipid bilayer can be fused to the porous particle core to form a protocell. The lipid bilayer can be modified with targeting ligands or other ligands to achieve targeted delivery of cargo components that are loaded within the protocell to a target cell, e.g., a type of cancer. Shielding materials can be conjugated to the surface of the lipid bilayer to reduce undesired non-specific binding.

  4. Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the Combination Strategies

    PubMed Central

    Li, Hua; Tsui, Tung Yu; Ma, Wenxue

    2015-01-01

    Cell-penetrating peptides (CPPs) can cross cellular membranes in a non-toxic fashion, improving the intracellular delivery of various molecular cargos such as nanoparticles, small molecules and plasmid DNA. Because CPPs provide a safe, efficient, and non-invasive mode of transport for various cargos into cells, they have been developed as vectors for the delivery of genetic and biologic products in recent years. Most common CPPs are positively charged peptides. While delivering negatively charged molecules (e.g., nucleic acids) to target cells, the internalization efficiency of CPPs is reduced and inhibited because the cationic charges on the CPPs are neutralized through the covering of CPPs by cargos on the structure. Even under these circumstances, the CPPs can still be non-covalently complexed with the negatively charged molecules. To address this issue, combination strategies of CPPs with other typical carriers provide a promising and novel delivery system. This review summarizes the latest research work in using CPPs combined with molecular cargos including liposomes, polymers, cationic peptides, nanoparticles, adeno-associated virus (AAV) and calcium for the delivery of genetic products, especially for small interfering RNA (siRNA). This combination strategy remedies the reduced internalization efficiency caused by neutralization. PMID:26295227

  5. Orbital ATK Cygnus Cargo Module Ready for Delivery to International Space Station

    NASA Image and Video Library

    2017-04-13

    The Orbital ATK Cygnus pressurized cargo module is packed with science experiments, supplies and hardware for delivery to the International Space Station on CRS-7. Orbital ATK's seventh commercial resupply services mission will launch atop a United Launch Alliance Atlas V rocket from Cape Canaveral Air Force Station in Florida.

  6. Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells

    PubMed Central

    Łangowski, Łukasz; Wabnik, Krzysztof; Li, Hongjiang; Vanneste, Steffen; Naramoto, Satoshi; Tanaka, Hirokazu; Friml, Jiří

    2016-01-01

    The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells. PMID:27462465

  7. Cellular mechanisms for cargo delivery and polarity maintenance at different polar domains in plant cells.

    PubMed

    Łangowski, Łukasz; Wabnik, Krzysztof; Li, Hongjiang; Vanneste, Steffen; Naramoto, Satoshi; Tanaka, Hirokazu; Friml, Jiří

    2016-01-01

    The asymmetric localization of proteins in the plasma membrane domains of eukaryotic cells is a fundamental manifestation of cell polarity that is central to multicellular organization and developmental patterning. In plants, the mechanisms underlying the polar localization of cargo proteins are still largely unknown and appear to be fundamentally distinct from those operating in mammals. Here, we present a systematic, quantitative comparative analysis of the polar delivery and subcellular localization of proteins that characterize distinct polar plasma membrane domains in plant cells. The combination of microscopic analyses and computational modeling revealed a mechanistic framework common to diverse polar cargos and underlying the establishment and maintenance of apical, basal, and lateral polar domains in plant cells. This mechanism depends on the polar secretion, constitutive endocytic recycling, and restricted lateral diffusion of cargos within the plasma membrane. Moreover, our observations suggest that polar cargo distribution involves the individual protein potential to form clusters within the plasma membrane and interact with the extracellular matrix. Our observations provide insights into the shared cellular mechanisms of polar cargo delivery and polarity maintenance in plant cells.

  8. Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light.

    PubMed

    Karimi, Mahdi; Sahandi Zangabad, Parham; Baghaee-Ravari, Soodeh; Ghazadeh, Mehdi; Mirshekari, Hamid; Hamblin, Michael R

    2017-04-05

    Nanotechnology has begun to play a remarkable role in various fields of science and technology. In biomedical applications, nanoparticles have opened new horizons, especially for biosensing, targeted delivery of therapeutics, and so forth. Among drug delivery systems (DDSs), smart nanocarriers that respond to specific stimuli in their environment represent a growing field. Nanoplatforms that can be activated by an external application of light can be used for a wide variety of photoactivated therapies, especially light-triggered DDSs, relying on photoisomerization, photo-cross-linking/un-cross-linking, photoreduction, and so forth. In addition, light activation has potential in photodynamic therapy, photothermal therapy, radiotherapy, protected delivery of bioactive moieties, anticancer drug delivery systems, and theranostics (i.e., real-time monitoring and tracking combined with a therapeutic action to different diseases sites and organs). Combinations of these approaches can lead to enhanced and synergistic therapies, employing light as a trigger or for activation. Nonlinear light absorption mechanisms such as two-photon absorption and photon upconversion have been employed in the design of light-responsive DDSs. The integration of a light stimulus into dual/multiresponsive nanocarriers can provide spatiotemporal controlled delivery and release of therapeutic agents, targeted and controlled nanosystems, combined delivery of two or more agents, their on-demand release under specific conditions, and so forth. Overall, light-activated nanomedicines and DDSs are expected to provide more effective therapies against serious diseases such as cancers, inflammation, infections, and cardiovascular disease with reduced side effects and will open new doors toward the treatment of patients worldwide.

  9. Packaging biological cargoes in mesoporous materials: opportunities for drug delivery.

    PubMed

    Siefker, Justin; Karande, Pankaj; Coppens, Marc-Olivier

    2014-11-01

    Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants. Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments. The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.

  10. Delivery of Membrane Impermeable Cargo into CHO Cells by Peptide Nanoparticles Targeted by a Protein Corona

    PubMed Central

    Dittrich, Christian; Burckhardt, Christoph J.; Danuser, Gaudenz

    2012-01-01

    Nanocarriers can fulfill essential functions in the stabilization and delivery of drugs: they prevent solubility issues and degradation, reduce side effects and modify the pharmacokinetic profile. However, particle based pharmaceuticals are very complex and thus challenging to scale up. As formulation routines account for a large fraction of production costs, reducing complexity in the process of assembly, loading and functionalization of nanoparticles is very desirable. Unlike existing approaches with similar goals, our protocol is designed to minimize usage of material and time. Prerequisite to this elegant one-step procedure is the controlled phase-separation of a hydrophobic peptide to nanoparticles, inducing concurrent cargo-entrapment and association of a protein corona. We demonstrate the process by assembling Flutax-2 containing peptide nanoparticles functionalized with transferrin. Cellular uptake of the particles and cargo release depend on specific particle-cell interactions via transferrin receptor. These data indicate corona-mediated delivery of membrane impermeable cargo in vitro by a particulate delivery system entirely composed of amino acids. PMID:22226586

  11. STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis.

    PubMed

    Jani, Riddhi Atul; Purushothaman, Latha Kallur; Rani, Shikha; Bergam, Ptissam; Setty, Subba Rao Gangi

    2015-09-01

    Melanosomes are a class of lysosome-related organelles produced by melanocytes. Biogenesis of melanosomes requires the transport of melanin-synthesizing enzymes from tubular recycling endosomes to maturing melanosomes. The SNARE proteins involved in these transport or fusion steps have been poorly studied. We found that depletion of syntaxin 13 (STX13, also known as STX12), a recycling endosomal Qa-SNARE, inhibits pigment granule maturation in melanocytes by rerouting the melanosomal proteins such as TYR and TYRP1 to lysosomes. Furthermore, live-cell imaging and electron microscopy studies showed that STX13 co-distributed with melanosomal cargo in the tubular-vesicular endosomes that are closely associated with the maturing melanosomes. STX family proteins contain an N-terminal regulatory domain, and deletion of this domain in STX13 increases both the SNARE activity in vivo and melanosome cargo transport and pigmentation, suggesting that STX13 acts as a fusion SNARE in melanosomal trafficking pathways. In addition, STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and its silencing blocks the melanosome maturation, reflecting a defect in endosome-melanosome fusion. Moreover, we show mutual dependency between STX13 and VAMP7 in regulating their localization for efficient cargo delivery to melanosomes. © 2015. Published by The Company of Biologists Ltd.

  12. When cationic cell-penetrating peptides meet hydrocarbons to enhance in-cell cargo delivery.

    PubMed

    Di Pisa, Margherita; Chassaing, Gérard; Swiecicki, Jean-Marie

    2015-05-01

    Cell-penetrating peptides (CPPs) are short sequences often rich in cationic residues with the remarkable ability to cross cell membranes. In the past 20 years, CPPs have gained wide interest and have found numerous applications in the delivery of bioactive cargoes to the cytosol and even the nucleus of living cells. The covalent or non-covalent addition of hydrocarbon moieties to cationic CPPs alters the hydrophobicity/hydrophilicity balance in their sequence. Such perturbation dramatically influences their interaction with the cell membrane, might induce self-assembling properties and modifies their intracellular trafficking. In particular, the introduction of lipophilic moieties changes the subcellular distribution of CPPs and might result in a dramatically increase of the internalization yield of the co-transported cargoes. Herein, we offer an overview of different aspects of the recent findings concerning the properties of CPPs covalently or non-covalently associated to hydrocarbons. We will focus on the impact of the hydrocarbon moieties on the delivery of various cargoes, either covalently or non-covalently bound to the modified CPPs. We will also provide some key elements to rationalize the influence of the hydrocarbons moieties on the cellular uptake. Furthermore, the recent in vitro and in vivo successful applications of acylated CPPs will be summarized to provide a broad view of the versatility of these modified CPPs as small-molecules and oligonucleotides vectors.

  13. Structural Design and Analysis of Un-pressurized Cargo Delivery Vehicle

    NASA Technical Reports Server (NTRS)

    Martinovic, Zoran N.

    2007-01-01

    As part of the Exploration Systems Architecture Study, NASA has defined a family of vehicles to support lunar exploration and International Space Station (ISS) re-supply missions after the Shuttle s retirement. The Un-pressurized Cargo Delivery Vehicle (UCDV) has been envisioned to be an expendable logistics delivery vehicle that would be used to deliver external cargo to the ISS. It would be launched on the Crew Launch Vehicle and would replace the Crew Exploration Vehicle. The estimated cargo would be the weight of external logistics to the ISS. Determining the minimum weight design of the UCDV during conceptual design is the major issue addressed in this paper. This task was accomplished using a procedure for rapid weight estimation that was based on Finite Element Analysis and sizing of the vehicle by the use of commercially available codes. Three design concepts were analyzed and their respective weights were compared. The analytical structural weight was increased by a factor to account for structural elements that were not modeled. Significant reduction in weight of a composite design over metallic was achieved for similar panel concepts.

  14. Microfluidic Droplet-Facilitated Hierarchical Assembly for Dual Cargo Loading and Synergistic Delivery

    PubMed Central

    2016-01-01

    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. PMID:26982167

  15. Electrically controlled delivery of cargo into single human neural stem cell.

    PubMed

    Kim, Tae-Hyung; Cho, Hyeon-Yeol; Lee, Ki-Bum; Kim, Seung U; Choi, Jeong-Woo

    2014-12-10

    Nanoprobe-based techniques have emerged as an efficient tool for the manipulation and analysis of single cells. Here, we report a powerful whole-electrical single-cell manipulation tool that enables rapid and controllable delivery of cargo into single neural stem cells with precision monitoring of the cell penetration process using a conductive nanoprobe. The highly electrically sensitive nanoprobes that were fabricated and the indium tin oxide electrode-integrated cell chip were found to be very effective for monitoring the cell penetration process via current changes that appear as spike-like negative currents. Moreover, the assembly of cargoes onto the nanoprobes was controllable and could reach its maximum load in a very short period of time (<10 min) based on the same electrical system that was used for monitoring cell penetration and without the need for any complex chemical linkers or mediators. Even more remarkably, the cargo assembled on the surface of the nanoprobe was successfully released in a very short period of time (<10 s), regardless of the surrounding intracellular or extracellular environments. The monitoring of cell penetration, assembly of quantum dots (QDs), and release of QDs into the intracellular environment were all accomplished using our whole-electrical system that combined a conductive nanoprobe with cell chip technology. This is a novel technology, which can eliminate complex and time-consuming steps owing to chemical modifications, as well as reduce the time needed for the delivery of cargo into the cell cytosol/nucleus during cell penetration, which is very important for reducing cell damage.

  16. Direct Cytosolic Delivery of Polar Cargo to Cells by Spontaneous Membrane-translocating Peptides*

    PubMed Central

    He, Jing; Kauffman, W. Berkeley; Fuselier, Taylor; Naveen, Somanna K.; Voss, Thomas G.; Hristova, Kalina; Wimley, William C.

    2013-01-01

    Direct cellular entry of potentially useful polar compounds into cells is prevented by the hydrophobic barrier of the membrane. Toward circumventing this barrier, we used high throughput screening to identify a family of peptides that carry membrane-impermeant cargos across synthetic membranes. Here we characterize the plasma membrane translocation of these peptides with polar cargos under a variety of conditions. The spontaneous membrane-translocating peptides (SMTPs) delivered the zwitterionic, membrane-impermeant dye tetramethylrhodamine (TAMRA) into cells even when the conditions were not permissive for endocytosis. They also delivered the larger, anionic membrane-impermeant dye Alexa Fluor 546 but did not deliver a quantum dot nanoparticle. Under all conditions, the SMTP-cargo filled the cytoplasm with a diffuse, non-punctate fluorescence that was partially excluded from the nucleus. d-Amino acid peptides behaved identically in vitro, ruling out proteolysis as an important factor in the diffuse cellular distribution. Thus, cytosolic delivery of SMTP-cargo conjugates is dominated by direct membrane translocation. This is in sharp contrast to Arg9-TAMRA, a representative highly cationic, cell-penetrating peptide, which entered cells only when endocytosis was permitted. Arg9-TAMRA triggered large scale endocytosis and did not appreciably escape the endosomal compartments in the 1-h timescales we studied. When injected into mice, SMTP-TAMRA conjugates were found in many tissues even after 2 h. Unconjugated TAMRA was rapidly cleared and did not become systemically distributed. SMTPs are a platform that could improve delivery of many polar compounds to cells, in the laboratory or in the clinic, including those that would otherwise be rejected as drugs because they are membrane-impermeant. PMID:23983125

  17. Theranostic applications of carbon nanomaterials in cancer: Focus on imaging and cargo delivery.

    PubMed

    Chen, Daiqin; Dougherty, Casey A; Zhu, Kaicheng; Hong, Hao

    2015-07-28

    Carbon based nanomaterials have attracted significant attention over the past decades due to their unique physical properties, versatile functionalization chemistry, and biological compatibility. In this review, we will summarize the current state-of-the-art applications of carbon nanomaterials in cancer imaging and drug delivery/therapy. The carbon nanomaterials will be categorized into fullerenes, nanotubes, nanohorns, nanodiamonds, nanodots and graphene derivatives based on their morphologies. The chemical conjugation/functionalization strategies of each category will be introduced before focusing on their applications in cancer imaging (fluorescence/bioluminescence, magnetic resonance (MR), positron emission tomography (PET), single-photon emission computed tomography (SPECT), photoacoustic, Raman imaging, etc.) and cargo (chemo/gene/therapy) delivery. The advantages and limitations of each category and the potential clinical utilization of these carbon nanomaterials will be discussed. Multifunctional carbon nanoplatforms have the potential to serve as optimal candidates for image-guided delivery vectors for cancer.

  18. Rab9A is required for delivery of cargo from recycling endosomes to melanosomes

    PubMed Central

    Mahanty, Sarmistha; Ravichandran, Keerthana; Chitirala, Praneeth; Prabha, Jyothi; Jani, Riddhi Atul; Setty, Subba Rao gangi

    2016-01-01

    Melanosomes are a type of lysosome-related organelle that is commonly defective in Hermansky–Pudlak syndrome. Biogenesis of melanosomes is regulated by BLOC-1, -2, -3, or AP-1, -3 complexes, which mediate cargo transport from recycling endosomes to melanosomes. Although several Rab GTPases have been shown to regulate these trafficking steps, the precise role of Rab9A remains unknown. Here, we found that a cohort of Rab9A associates with the melanosomes and its knockdown in melanocytes results in hypopigmented melanosomes due to mistargeting of melanosomal proteins to lysosomes. In addition, the Rab9A-depletion phenotype resembles Rab38/32-inactivated or BLOC-3-deficient melanocytes, suggesting that Rab9A works in line with BLOC-3 and Rab38/32 during melanosome cargo transport. Furthermore, silencing of Rab9A, Rab38/32 or its effector VARP, or BLOC-3-deficiency in melanocytes decreased the length of STX13-positive recycling endosomal tubules and targeted the SNARE to lysosomes. This result indicates a defect in directing recycling endosomal tubules to melanosomes. Thus, Rab9A and its co-regulatory GTPases control STX13-mediated cargo delivery to maturing melanosomes. PMID:26527546

  19. Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy.

    PubMed

    Ang, Chung Yen; Tan, Si Yu; Zhao, Yanli

    2014-07-21

    Cancer is currently one of the major diseases that has gained a lot of scientific attention. Conventional cancer therapeutics involve surgical removal of tumors from patients followed by chemotherapeutic treatment. In the use of anticancer drugs during the chemotherapy process, patients often suffer from a variety of undesirable side effects including damage to normal organs. Thus, there is an urgent need for the development of novel strategies to overcome these side effect issues. Among several strategies, the utilization of nanocarriers for anticancer drug delivery has shown improved therapeutic efficiency of the drugs with minimization of the undesirable side effects. In this review, we discuss various types of nanocarriers recently reported in the literature for application in cancer therapy. We introduce some targeting ligands that have been functionalized on nanocarriers in order to impart specificity to the nanocarriers for targeted drug delivery. We also highlight some therapeutic cargoes that are commonly used and their therapeutic mechanisms in cancer treatment. Finally, we summarize some interesting stimulus strategies for controlled release of therapeutic cargoes at tumor sites. This review is expected to inspire new ideas and create novel strategies in advancing efficient cancer therapy using nanomedicine approaches.

  20. Bacteriophages and phage-inspired nanocarriers for targeted delivery of therapeutic cargos.

    PubMed

    Karimi, Mahdi; Mirshekari, Hamed; Moosavi Basri, Seyed Masoud; Bahrami, Sajad; Moghoofei, Mohsen; Hamblin, Michael R

    2016-11-15

    The main goal of drug delivery systems is to target therapeutic cargoes to desired cells and to ensure their efficient uptake. Recently a number of studies have focused on designing bio-inspired nanocarriers, such as bacteriophages, and synthetic carriers based on the bacteriophage structure. Bacteriophages are viruses that specifically recognize their bacterial hosts. They can replicate only inside their host cell and can act as natural gene carriers. Each type of phage has a particular shape, a different capacity for loading cargo, a specific production time, and their own mechanisms of supramolecular assembly, that have enabled them to act as tunable carriers. New phage-based technologies have led to the construction of different peptide libraries, and recognition abilities provided by novel targeting ligands. Phage hybridization with non-organic compounds introduces new properties to phages and could be a suitable strategy for construction of bio-inorganic carriers. In this review we try to cover the major phage species that have been used in drug and gene delivery systems, and the biological application of phages as novel targeting ligands and targeted therapeutics.

  1. Evidence of nose-to-brain delivery of nanoemulsions: cargoes but not vehicles.

    PubMed

    Ahmad, Ejaj; Feng, Yunhai; Qi, Jianping; Fan, Wufa; Ma, Yuhua; He, Haisheng; Xia, Fei; Dong, Xiaochun; Zhao, Weili; Lu, Yi; Wu, Wei

    2017-01-19

    The nose-to-brain pathway has been proven to be a shortcut for direct drug delivery to the brain. However, whether and to what extent nanoparticles can be delivered through this passage is still awaiting validation with evidence. In this study, nose-to-brain transportation of nanoparticles is tracked via fluorescence bioimaging strategies using nanoemulsions (NEs) as model carriers. Identification of NEs in biological tissues is based on the on → off signal switching of a new type of environment-responsive embedded dyes, P2 and P4, and two conventional probes, DiR and coumarin-6 (C6), are embedded to represent the cargoes. Evidence for the translocation of NEs was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Results suggest that NEs with a particle size of about 100 nm, either naked or coated with chitosan, have longer retention duration in nostrils and slower mucociliary clearance than larger ones. P2 signals, representing integral NEs, can be found in mucosa and trigeminal nerves for all size groups, whereas only weak P2 signals are detected in the olfactory bulb for chitosan-coated NEs of 100 nm. Confocal microscopy further confirms the translocation of integral 100 nm NEs in nasal mucosa and along the trigeminal nerve in decremental intensity. Weak signals of the P4 probe, also representing integral NEs, can be detected in the olfactory bulb but few in the brain. NEs as large as 900 nm cannot be transported to the olfactory bulb. However, the DiR or C6 signals that represent the cargoes can be found in significant amounts along the nose-to-brain pathway and finally reach the brain. Evidence shows that integral NEs can be delivered to the olfactory bulb, but few to the brain, whereas the cargoes can be released and permeated into the brain in greater amounts.

  2. BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery.

    PubMed

    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; Marks, Michael S; Setty, Subba Rao Gangi

    2015-05-25

    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.

  3. BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery

    PubMed Central

    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

  4. Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles.

    PubMed

    de la Torre, Cristina; Mondragón, Laura; Coll, Carmen; García-Fernández, Alba; Sancenón, Félix; Martínez-Máñez, Ramón; Amorós, Pedro; Pérez-Payá, Enrique; Orzáez, Mar

    2015-10-26

    Excessive apoptotic cell death is at the origin of several pathologies, such as degenerative disorders, stroke or ischemia-reperfusion damage. In this context, strategies to improve inhibition of apoptosis and other types of cell death are of interest and may represent a pharmacological opportunity for the treatment of cell-death-related disorders. In this scenario new peptide-containing delivery systems (solids S1 -P1 and S1 -P2 ) are described based on mesoporous silica nanoparticles (MSNs) loaded with a dye and capped with the KKGDEVDKKARDEVDK (P1 ) peptide that contains two repeats of the DEVD target sequence that are selectively hydrolyzed by caspase 3 (C3). This enzyme plays a central role in the execution-phase of apoptosis. HeLa cells electroporated with S1 -P1 are able to deliver the cargo in the presence of staurosporin (STS), which induces apoptosis with the consequent activation of the cytoplasmic C3 enzyme. Moreover, the nanoparticles S1 -P2 , containing both a cell-penetrating TAT peptide and P1 also entered in HeLa cells and delivered the cargo preferentially in cells treated with the apoptosis inducer cisplatin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers

    NASA Astrophysics Data System (ADS)

    Ashley, Carlee E.; Carnes, Eric C.; Phillips, Genevieve K.; Padilla, David; Durfee, Paul N.; Brown, Page A.; Hanna, Tracey N.; Liu, Juewen; Phillips, Brandy; Carter, Mark B.; Carroll, Nick J.; Jiang, Xingmao; Dunphy, Darren R.; Willman, Cheryl L.; Petsev, Dimiter N.; Evans, Deborah G.; Parikh, Atul N.; Chackerian, Bryce; Wharton, Walker; Peabody, David S.; Brinker, C. Jeffrey

    2011-05-01

    Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 106-fold improvement over comparable liposomes.

  6. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

    PubMed

    Ashley, Carlee E; Carnes, Eric C; Phillips, Genevieve K; Padilla, David; Durfee, Paul N; Brown, Page A; Hanna, Tracey N; Liu, Juewen; Phillips, Brandy; Carter, Mark B; Carroll, Nick J; Jiang, Xingmao; Dunphy, Darren R; Willman, Cheryl L; Petsev, Dimiter N; Evans, Deborah G; Parikh, Atul N; Chackerian, Bryce; Wharton, Walker; Peabody, David S; Brinker, C Jeffrey

    2011-05-01

    Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.

  7. Liposome-Cross-Linked Hybrid Hydrogels for Glutathione-Triggered Delivery of Multiple Cargo Molecules.

    PubMed

    Liang, Yingkai; Kiick, Kristi L

    2016-02-08

    Novel, liposome-cross-linked hybrid hydrogels cross-linked by the Michael-type addition of thiols with maleimides were prepared via the use of maleimide-functionalized liposome cross-linkers and thiolated polyethylene glycol (PEG) polymers. Gelation of the materials was confirmed by oscillatory rheology experiments. These hybrid hydrogels are rendered degradable upon exposure to thiol-containing molecules such as glutathione (GSH), via the incorporation of selected thioether succinimide cross-links between the PEG polymers and liposome nanoparticles. Dynamic light scattering (DLS) characterization confirmed that intact liposomes were released upon network degradation. Owing to the hierarchical structure of the network, multiple cargo molecules relevant for chemotherapies, namely doxorubicin (DOX) and cytochrome c, were encapsulated and simultaneously released from the hybrid hydrogels, with differential release profiles that were driven by degradation-mediated release and Fickian diffusion, respectively. This work introduces a facile approach for the development of advanced, hybrid drug delivery vehicles that exhibit novel chemical degradation.

  8. Cell-specific delivery of diverse cargos by bacteriophage MS2 virus-like particles.

    PubMed

    Ashley, Carlee E; Carnes, Eric C; Phillips, Genevieve K; Durfee, Paul N; Buley, Mekensey D; Lino, Christopher A; Padilla, David P; Phillips, Brandy; Carter, Mark B; Willman, Cheryl L; Brinker, C Jeffrey; Caldeira, Jerri do Carmo; Chackerian, Bryce; Wharton, Walker; Peabody, David S

    2011-07-26

    Virus-like particles (VLPs) of bacteriophage MS2 possess numerous features that make them well-suited for use in targeted delivery of therapeutic and imaging agents. MS2 VLPs can be rapidly produced in large quantities using in vivo or in vitro synthesis techniques. Their capsids can be modified in precise locations via genetic insertion or chemical conjugation, facilitating the multivalent display of targeting ligands. MS2 VLPs also self-assemble in the presence of nucleic acids to specifically encapsidate siRNA and RNA-modified cargos. Here we report the use of MS2 VLPs to selectively deliver nanoparticles, chemotherapeutic drugs, siRNA cocktails, and protein toxins to human hepatocellular carcinoma (HCC). MS2 VLPs modified with a peptide (SP94) that binds HCC exhibit a 10(4)-fold higher avidity for HCC than for hepatocytes, endothelial cells, monocytes, or lymphocytes and can deliver high concentrations of encapsidated cargo to the cytosol of HCC cells. SP94-targeted VLPs loaded with doxorubicin, cisplatin, and 5-fluorouracil selectively kill the HCC cell line, Hep3B, at drug concentrations <1 nM, while SP94-targeted VLPs that encapsidate a siRNA cocktail, which silences expression of cyclin family members, induce growth arrest and apoptosis of Hep3B at siRNA concentrations <150 pM. Impressively, MS2 VLPs, when loaded with ricin toxin A-chain (RTA) and modified to codisplay the SP94 targeting peptide and a histidine-rich fusogenic peptide (H5WYG) that promotes endosomal escape, kill virtually the entire population of Hep3B cells at an RTA concentration of 100 fM without affecting the viability of control cells. Our results demonstrate that MS2 VLPs, because of their tolerance of multivalent peptide display and their ability to specifically encapsidate a variety of chemically disparate cargos, induce selective cytotoxicity of cancer in vitro and represent a significant improvement in the characteristics of VLP-based delivery systems.

  9. Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles.

    PubMed

    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.

  10. Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos

    PubMed Central

    Kristensen, Mie; Birch, Ditlev; Mørck Nielsen, Hanne

    2016-01-01

    The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes. Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed. Cell-penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB). CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability-enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed. The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies. PMID:26840305

  11. New mechanisms for non-porative ultrasound stimulation of cargo delivery to cell cytosol with targeted perfluorocarbon nanoparticles

    NASA Astrophysics Data System (ADS)

    Soman, N. R.; Marsh, J. N.; Lanza, G. M.; Wickline, S. A.

    2008-05-01

    The cell membrane constitutes a major barrier for non-endocytotic intracellular delivery of therapeutic molecules from drug delivery vehicles. Existing approaches to breaching the cell membrane include cavitational ultrasound (with microbubbles), electroporation and cell-penetrating peptides. We report the use of diagnostic ultrasound for intracellular delivery of therapeutic bulky cargo with the use of molecularly targeted liquid perfluorocarbon (PFC) nanoparticles. To demonstrate the concept, we used a lipid with a surrogate polar head group, nanogold-DPPE, incorporated into the nanoparticle lipid monolayer. Melanoma cells were incubated with nanogold particles and this was followed by insonication with continuous wave ultrasound (2.25 MHz, 5 min, 0.6 MPa). Cells not exposed to ultrasound showed gold particles partitioned only in the outer bilayer of the cell membrane with no evidence of the intracellular transit of nanogold. However, the cells exposed to ultrasound exhibited numerous nanogold-DPPE components inside the cell that appeared polarized inside intracellular vesicles demonstrating cellular uptake and trafficking. Further, ultrasound-exposed cells manifested no incorporation of calcein or the release of lactate dehydrogenase. These observations are consistent with a mechanism that suggests that ultrasound is capable of stimulating the intracellular delivery of therapeutic molecules via non-porative mechanisms. Therefore, non-cavitational adjunctive ultrasound offers a novel paradigm in intracellular cargo delivery from PFC nanoparticles.

  12. Massively Parallel Delivery of Large-Sized Cargo into Mammalian Cells with Light Pulses

    PubMed Central

    Wu, Yi-Chien; Wu, Ting-Hsiang; Clemens, Daniel L.; Lee, Bai-Yu; Wen, Ximiao; Horwitz, Marcus A.; Teitell, Michael A.; Chiou, Pei-Yu

    2016-01-01

    We report a high-throughput platform for delivering large cargo into 100,000 cells in 1 min. An array of micro-cavitation bubbles explode in response to laser pulsing, forming pores in adjacent cell membranes, and immediately thereafter, pressurized flows drive slow diffusing cargo through these pores into cells. The platform delivers large cargo including bacteria, enzymes, antibodies, and nanoparticles into diverse cell types with high efficiency and cell viability. We used this platform to explore the intracellular lifestyle of Francisella novicida and discovered that the iglC gene is unexpectedly required for intracellular replication even after phagosome escape into the cell cytosol. PMID:25849636

  13. Fluorescent boronate-based polymer nanoparticles with reactive oxygen species (ROS)-triggered cargo release for drug-delivery applications

    NASA Astrophysics Data System (ADS)

    Jäger, Eliézer; Höcherl, Anita; Janoušková, Olga; Jäger, Alessandro; Hrubý, Martin; Konefał, Rafał; Netopilik, Miloš; Pánek, Jiří; Šlouf, Miroslav; Ulbrich, Karel; Štěpánek, Petr

    2016-03-01

    A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts.A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00791k

  14. Infusion of imaging and therapeutic molecules into the plant virus-based carrier cowpea mosaic virus: cargo-loading and delivery.

    PubMed

    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.

  15. Infusion of imaging and therapeutic molecules into the plant virus-based carrier cowpea mosaic virus: cargo-loading and delivery

    PubMed Central

    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

  16. pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.

    PubMed

    Karabadzhak, Alexander G; An, Ming; Yao, Lan; Langenbacher, Rachel; Moshnikova, Anna; Adochite, Ramona-Cosmina; Andreev, Oleg A; Reshetnyak, Yana K; Engelman, Donald M

    2014-11-21

    We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE peptide has a fluorophore-fluorophore or fluorophore-quencher pair. A pair member is released by disulfide cleavage after insertion into the reducing environment inside a cell, resulting in dequenching of the probe. Thus, the fluorescence of the pHLIP-FIRE probe is enhanced upon cell-insertion in the targeted tissues but is suppressed elsewhere due to quenching. Targeting studies in mice bearing breast tumors show strong signaling by pHLIP-FIRE, with a contrast index of ∼17, demonstrating (i) direct imaging of pHLIP insertion and (ii) cargo translocation in vivo. Imaging and targeted cargo delivery should each have clinical applications.

  17. Kinetics of reciprocating drug delivery to the inner ear.

    PubMed

    Pararas, Erin E Leary; Chen, Zhiqiang; Fiering, Jason; Mescher, Mark J; Kim, Ernest S; McKenna, Michael J; Kujawa, Sharon G; Borenstein, Jeffrey T; Sewell, William F

    2011-06-10

    Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (>5h) or greater distances (>3mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Kinetics of Reciprocating Drug Delivery to the Inner Ear

    PubMed Central

    Leary Pararas, Erin E.; Chen, Zhiqiang; Fiering, Jason; Mescher, Mark J.; Kim, Ernest S.; McKenna, Michael J.; Kujawa, Sharon G.; Borenstein, Jeffrey T.; Sewell, William F.

    2011-01-01

    Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2 h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (>5 h) or greater distances (>3 mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery. PMID:21385596

  19. Light-stimulated cargo release from a core–shell structured nanocomposite for site-specific delivery

    SciTech Connect

    Cai, Yun; Ling, Li; Li, Xiaofang; Chen, Meng; Su, Likai

    2015-03-15

    This paper reported a core–shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe{sub 3}O{sub 4} nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b′]dipyridin-5(5aH)-ylidene)benzene-1, 4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N{sub 2} adsorption/desorption, thermogravimetric analysis, IR, UV–vis absorption and emission spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of “on” and “off” states, controllable release was observed with short release time of ~900 s (90% capacity). - Graphical abstract: A core–shell structured site-specific delivery system with a light switch triggered by yellow light was constructed. Controllable release was observed with short release time of ~900 s (90% capacity). - Highlights: • A core–shell structured site-specific delivery system was constructed. • It consisted of Fe{sub 3}O{sub 4} core and MCM-41 shell grafted with light switch. • This delivery system was triggered by low energy light. • Controllable release was observed with short release time of ~900 s.

  20. Direct cytosolic delivery of cargoes in vivo by a chimera consisting of D- and L-arginine residues.

    PubMed

    Ma, Yan; Gong, Cheng; Ma, Yilong; Fan, Fengkai; Luo, Meijie; Yang, Fei; Zhang, Yu-Hui

    2012-09-10

    The ability of cell-penetrating peptides (CPPs) to deliver a range of membrane-impermeable molecules into living cells makes them attractive potential vehicles for therapeutics. However, in vivo, the efficiency of CPP delivery to the cytosol remains unsatisfactory owing to endosomal entrapment and/or systemic toxicity, which severely restrict their bioavailability and efficacy in in vivo applications. In this study, we developed a series of novel chimeras consisting of various numbers of d- and l-arginine residues and investigated their cellular uptake behaviors and systemic toxicities. We demonstrated that the intracellular distribution, uptake efficiency, and systemic toxicity of these oligoarginines were all significantly affected by the number of d-arginine residues in the peptide sequence. We also found that a hybrid peptide, (rR)(3)R(2), possessed low systemic toxicity, high uptake efficiency, and, remarkably, achieved efficient cytosolic delivery not only in cultured cells but also in living tissue cells in mice after intravenous injection, implying that this heterogeneous motif might have promising applications in the delivery of cargoes of small sizes directed to cytosolic targets in vivo. Our studies into the uptake mechanism of (rR)(3)R(2) indicate that its cellular uptake was not affected by pharmacological or physical inhibitors of endocytosis but by the elimination of the membrane potential, suggesting that (rR)(3)R(2) does not enter the cells via endocytosis but rather through direct membrane translocation driven by the membrane potential. The results here might provide useful guidelines for the design and application of CPPs in drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides

    PubMed Central

    Dixon, James E.; Osman, Gizem; Morris, Gavin E.; Markides, Hareklea; Rotherham, Michael; Bayoussef, Zahia; El Haj, Alicia J.; Denning, Chris; Shakesheff, Kevin M.

    2016-01-01

    Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application. PMID:26733682

  2. Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides.

    PubMed

    Dixon, James E; Osman, Gizem; Morris, Gavin E; Markides, Hareklea; Rotherham, Michael; Bayoussef, Zahia; El Haj, Alicia J; Denning, Chris; Shakesheff, Kevin M

    2016-01-19

    Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application.

  3. Light-stimulated cargo release from a core-shell structured nanocomposite for site-specific delivery

    NASA Astrophysics Data System (ADS)

    Cai, Yun; Ling, Li; Li, Xiaofang; Chen, Meng; Su, Likai

    2015-03-01

    This paper reported a core-shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe3O4 nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b‧]dipyridin-5(5aH)-ylidene)benzene-1,4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N2 adsorption/desorption, thermogravimetric analysis, IR, UV-vis absorption and emission spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of "on" and "off" states, controllable release was observed with short release time of ~900 s (90% capacity).

  4. Intracellular Delivery of Bioactive Cargos to Hard-to-Transfect Cells Using Carbon Nanosyringe Arrays under an Applied Centrifugal g-Force.

    PubMed

    Choi, Minsuk; Lee, Sang Ho; Kim, Won Bae; Gujrati, Vipul; Kim, Daejin; Lee, Jinju; Kim, Jae-Il; Kim, Hyungjun; Saw, Phei Er; Jon, Sangyong

    2016-01-07

    There is considerable interest in developing a common, universal platform for delivering biomacromolecules such as proteins and RNAs into diverse cells with high efficiency. Here, it is shown that carbon nanosyringe arrays (CNSAs) under an applied centrifugal g-force (cf-CNSAs) can deliver diverse bioactive cargos directly into the cytosol of hard-to-transfect cells with relatively high efficiency and reproducibility. The cf-CNSA platform, an optimized version of a previous CNSA-mediated intracellular delivery platform that adds a g-force feature, exhibits more rapid and superior delivery of cargos to various hard-to-transfect cells than is the case in the absence of g-force. Active species, including small interfering RNAs, plasmids, and proteins are successfully transported across plasma membrane barriers into various cells. By overcoming the limitations of currently available transfection methods, the cf-CNSA platform paves the way to universal delivery of a variety of cargos, facilitating the analysis of cellular responses in diverse cell types.

  5. Cargo Delivery into the Brain by in vivo identified Transport Peptides

    PubMed Central

    Urich, Eduard; Schmucki, Roland; Ruderisch, Nadine; Kitas, Eric; Certa, Ulrich; Jacobsen, Helmut; Schweitzer, Christophe; Bergadano, Alessandra; Ebeling, Martin; Loetscher, Hansruedi; Freskgård, Per-Ola

    2015-01-01

    The blood-brain barrier and the blood-cerebrospinal fluid barrier prevent access of biotherapeutics to their targets in the central nervous system and therefore prohibit the effective treatment of neurological disorders. In an attempt to discover novel brain transport vectors in vivo, we injected a T7 phage peptide library and continuously collected blood and cerebrospinal fluid (CSF) using a cisterna magna cannulated conscious rat model. Specific phage clones were highly enriched in the CSF after four rounds of selection. Validation of individual peptide candidates showed CSF enrichments of greater than 1000-fold. The biological activity of peptide-mediated delivery to the brain was confirmed using a BACE1 peptide inhibitor linked to an identified novel transport peptide which led to a 40% reduction of Amyloid-β in CSF. These results indicate that the peptides identified by the in vivo phage selection approach could be useful transporters for systemically administrated large molecules into the brain with therapeutic benefits. PMID:26411801

  6. Stimuli-responsive magnetic nanomicelles as multifunctional heat and cargo delivery vehicles.

    PubMed

    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.

  7. Lipid based drug delivery systems: Kinetics by SANS

    NASA Astrophysics Data System (ADS)

    Uhríková, D.; Teixeira, J.; Hubčík, L.; Búcsi, A.; Kondela, T.; Murugova, T.; Ivankov, O. I.

    2017-05-01

    N,N-dimethyldodecylamine-N-oxide (C12NO) is a surfactant that may exist either in a neutral or protonated form depending on the pH of aqueous solutions. Using small angle X-ray diffraction (SAXD) we demonstrate structural responsivity of C12NO/dioleoylphospha-tidylethanolamine (DOPE)/DNA complexes designed as pH sensitive gene delivery vectors. Small angle neutron scattering (SANS) was employed to follow kinetics of C12NO protonization and DNA binding into C12NO/DOPE/DNA complexes in solution of 150 mM NaCl at acidic condition. SANS data analyzed using paracrystal lamellar model show the formation of complexes with stacking up to ∼32 bilayers, spacing ∼ 62 Å, and lipid bilayer thickness ∼37 Å in 3 minutes after changing pH from 7 to 4. Subsequent structural reorganization of the complexes was observed along 90 minutes of SANS mesurements.

  8. pH-Responsive Dual Cargo Delivery from Mesoporous Silica Nanoparticles with a Metal-latched Nanogate

    PubMed Central

    Tarn, Derrick; Xue, Min; Zink, Jeffrey I.

    2013-01-01

    A nanogate composed of two iminodiacetic acid (IDA) and a metal ion latch was designed, synthesized and assembled on mesoporous silica nanoparticles. This gating mechanism is capable of storing and releasing metal ions and molecules trapped in the pores. Pore openings derivatized with IDA can be latched shut by forming a bis-IDA chelate complex with a metal ion. This system was tested by loading with Hoechst 33342 as the probe cargo molecule, and latching with cobalt, nickel or calcium metal ions. No cargo release was observed in a neutral aqueous environment, but both cargoes were delivered after acid stimulation and/or the addition of a competitively binding ligand. PMID:23391170

  9. In vitro incorporation of a cell-binding protein to a lentiviral vector using an engineered split intein enables targeted delivery of genetic cargo.

    PubMed

    Chamoun-Emanuelli, Ana M; Wright, Gus; Roger, Smith; Münch, Robert C; Buchholz, Christian J; Chen, Zhilei

    2015-12-01

    Gene therapy represents a promising therapeutic paradigm for addressing many disorders, but the absence of a vector that can be robustly and reproducibly functionalized with cell-homing functionality to mediate the delivery of genetic cargo specifically to target cells following systemic administration has stood as a major impediment. In this study, a high-affinity protein-protein pair comprising a splicing-deficient naturally split intein was used as molecular Velcro to append a HER2/neu-binding protein (DARPin) onto the surface of a binding-deficient, fusion-competent lentivirus. HER2/neu-specific lentiviruses created using this in vitro pseudotyping approach were able to deliver their genetic reporter cargo specifically to cells that express the target receptor at high levels in a co-culture. We envision that the described technology could provide a powerful, broadly applicable platform for the incorporation of cell-targeting functionality onto viral vectors.

  10. 33 CFR 105.265 - Security measures for handling cargo.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY MARITIME SECURITY MARITIME SECURITY: FACILITIES Facility Security Requirements § 105.265 Security... to do so, routinely check cargo, cargo transport units, and cargo storage areas within the facility..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo...

  11. 33 CFR 105.265 - Security measures for handling cargo.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY MARITIME SECURITY MARITIME SECURITY: FACILITIES Facility Security Requirements § 105.265 Security... to do so, routinely check cargo, cargo transport units, and cargo storage areas within the facility..., containers, or other cargo transport units entering the facility match the delivery note or equivalent cargo...

  12. Composite dissolving microneedles for coordinated control of antigen and adjuvant delivery kinetics in transcutaneous vaccination.

    PubMed

    Demuth, Peter C; Garcia-Beltran, Wilfredo F; Ai-Ling, Michelle Lim; Hammond, Paula T; Irvine, Darrell J

    2013-01-14

    Transcutaneous administration has the potential to improve therapeutics delivery, providing an approach that is safer and more convenient than traditional alternatives, while offering the opportunity for improved therapeutic efficacy through sustained/controlled drug release. To this end, we demonstrate a microneedle materials platform for rapid implantation of controlled-release polymer depots into the cutaneous tissue. Arrays of microneedles comprised of drug-loaded poly(lactide-co-glycolide) (PLGA) microparticles or solid PLGA tips were prepared with a supporting and rapidly water-soluble poly(acrylic acid) (PAA) matrix. Upon application of microneedle patches to the skin of mice, the microneedles perforated the stratum corneum and epidermis. Penetration of the outer skin layers was followed by rapid dissolution of the PAA binder on contact with the interstitial fluid of the epidermis, implanting the microparticles or solid polymer microneedles in the tissue, which were retained following patch removal. These polymer depots remained in the skin for weeks following application and sustained the release of encapsulated cargos for systemic delivery. To show the utility of this approach we demonstrated the ability of these composite microneedle arrays to deliver a subunit vaccine formulation. In comparison to traditional needle-based vaccination, microneedle delivery gave improved cellular immunity and equivalent generation of serum antibodies, suggesting the potential of this approach for vaccine delivery. However, the flexibility of this system should allow for improved therapeutic delivery in a variety of diverse contexts.

  13. Tri-membrane nanoparticles produced by combining liposome fusion and a novel patchwork of bicelles to overcome endosomal and nuclear membrane barriers to cargo delivery.

    PubMed

    Yamada, Asako; Mitsueda, Asako; Hasan, Mahadi; Ueda, Miho; Hama, Susumu; Warashina, Shota; Nakamura, Takashi; Harashima, Hideyoshi; Kogure, Kentaro

    2016-03-01

    Membrane fusion is a rational strategy for crossing intracellular membranes that present barriers to liposomal nanocarrier-mediated delivery of plasmid DNA into the nucleus of non-dividing cells, such as dendritic cells. Based on this strategy, we previously developed nanocarriers consisting of a nucleic acid core particle coated with four lipid membranes [Akita, et al., Biomaterials, 2009, 30, 2940-2949]. However, including the endosomal membrane and two nuclear membranes, cells possess three intracellular membranous barriers. Thus, after entering the nucleus, nanoparticles coated with four membranes would still have one lipid membrane remaining, and could impede cargo delivery. Until now, coating a core particle with an odd number of lipid membranes was challenging. To produce nanocarriers with an odd number of lipid membranes, we developed a novel coating method involving lipid nano-discs, also known as bicelles, as a material for packaging DNA in a carrier with an odd number of lipid membranes. In this procedure, bicelles fuse to form an outer coating that resembles a patchwork quilt, which allows the preparation of nanoparticles coated with only three lipid membranes. Moreover, the transfection activity of dendritic cells with these three-membrane nanoparticles was higher than that for nanoparticles coated with four lipid membranes. In summary, we developed novel nanoparticles coated with an odd number of lipid membranes using the novel "patchwork-packaging method" to deliver plasmid DNA into the nucleus via membrane fusion.

  14. Spatial organization of the cytoskeleton enhances cargo delivery to specific target areas on the plasma membrane of spherical cells

    NASA Astrophysics Data System (ADS)

    Hafner, Anne E.; Rieger, Heiko

    2016-12-01

    Intracellular transport is vital for the proper functioning and survival of a cell. Cargo (proteins, vesicles, organelles, etc) is transferred from its place of creation to its target locations via molecular motor assisted transport along cytoskeletal filaments. The transport efficiency is strongly affected by the spatial organization of the cytoskeleton, which constitutes an inhomogeneous, complex network. In cells with a centrosome microtubules grow radially from the central microtubule organizing center towards the cell periphery whereas actin filaments form a dense meshwork, the actin cortex, underneath the cell membrane with a broad range of orientations. The emerging ballistic motion along filaments is frequently interrupted due to constricting intersection nodes or cycles of detachment and reattachment processes in the crowded cytoplasm. In order to investigate the efficiency of search strategies established by the cell’s specific spatial organization of the cytoskeleton we formulate a random velocity model with intermittent arrest states. With extensive computer simulations we analyze the dependence of the mean first passage times for narrow escape problems on the structural characteristics of the cytoskeleton, the motor properties and the fraction of time spent in each state. We find that an inhomogeneous architecture with a small width of the actin cortex constitutes an efficient intracellular search strategy.

  15. Oviductosome-Sperm Membrane Interaction in Cargo Delivery: DETECTION OF FUSION AND UNDERLYING MOLECULAR PLAYERS USING THREE-DIMENSIONAL SUPER-RESOLUTION STRUCTURED ILLUMINATION MICROSCOPY (SR-SIM).

    PubMed

    Al-Dossary, Amal A; Bathala, Pradeepthi; Caplan, Jeffrey L; Martin-DeLeon, Patricia A

    2015-07-17

    Oviductosomes ((OVS), exosomes/microvesicles), which deliver the Ca(2+) efflux pump, plasma membrane Ca(2+)ATPase 4 (PMCA4), to sperm are likely to play an important role in sperm fertilizing ability (Al-Dossary, A. A., Strehler, E. E., and Martin-DeLeon, P. A. (2013) PloS one 8, e80181). It is unknown how exosomes/microvesicles deliver transmembrane proteins such as PMCA4 to sperm. Here we define a novel experimental approach for the assessment of the interaction of OVS with sperm at a nanoscale level, using a lipophilic dye (FM4-64FX) and three-dimensional SR/SIM, which has an 8-fold increase in volumetric resolution, compared with conventional confocal microscopy. Coincubation assays detected fusion of prelabeled OVS with sperm, primarily over the head and midpiece. Immunofluorescence revealed oviductosomal delivery of PMCA4a to WT and Pmca4 KO sperm, and also endogenous PMCA4a on the inner acrosomal membrane. Fusion was confirmed by transmission immunoelectron microscopy, showing immunogold particles in OVS, and fusion stalks on sperm membrane. Immunofluorescence colocalized OVS with the αv integrin subunit which, along with CD9, resides primarily on the sperm head and midpiece. In capacitated and acrosome reacted sperm, fusion was significantly (p < 0.001) inhibited by blocking integrin/ligand interactions via antibodies, exogenous ligands (vitronectin and fibronectin), and their RGD recognition motif. Our results provide evidence that receptor/ligand interactions, involving αvβ3 and α5β1integrins on sperm and OVS, facilitate fusion of OVS in the delivery of transmembrane proteins to sperm. The mechanism uncovered is likely to be also involved in cargo delivery of prostasomes, epididymosomes, and uterosomes.

  16. Cargo Assured Access to International Space Station

    NASA Technical Reports Server (NTRS)

    Smith, David A.

    2004-01-01

    Boeing's Cargo Assured Access logistics delivery system will provide a means to transport cargo to/from the International Space Station, Low Earth Orbit and the moon using Expendable Launch Vehicles. For Space Station, this capability will reduce cargo resupply backlog during nominal operations (e.g., supplement Shuttle, Progress, ATV and HTV) and augment cargo resupply capability during contingency operations (e.g., Shuttle delay and/or unavailability of International Partner launch or transfer vehicles). This capability can also provide an autonomous means to deliver cargo to lunar orbit, a lunar orbit refueling and work platform, and a contingency crew safe haven in support of NASA's new Exploration Initiative.

  17. Development of novel recombinant biomimetic chimeric MPG-based peptide as nanocarriers for gene delivery: Imitation of a real cargo.

    PubMed

    Majidi, Asia; Nikkhah, Maryam; Sadeghian, Faranak; Hosseinkhani, Saman

    2016-10-01

    In last decades great efforts have been devoted to the study of development of recombinant peptide based vectors that consist of biological motifs with potential applications in gene therapy. Recombinant Biomimetic Chimeric Vectors (rBCVs) are biopolymeric nanocarriers that are designed to mimic viral features to overcome the cellular obstacles in gene transferring pathway into cell nucleus. In this research, we designed and genetically engineered three novel rBCVs with similar sequences that differed in motifs arrangement and motif abundance: MPG-2H1, 2TMPG-2H1 and 2RMPG-2H1. The MPG as a famous amphipathic cell penetrating peptide is the main segment of these constructs which was studied for the first time in association with truncated histone H1 DNA condensing motif. Through the performance of several physicochemical and biological assays, the rBCVs were remarkably examined regarding transfection efficiency. The main objective of this study is focused on the importance of motif design in transfection efficiency of rBCVs on one hand, and the assessment of correlation between structural features and functionality of motifs on the other hand. The results revealed that all three kinds of rBCVs/pDNA nanoparticles with average sizes of 200nm could overwhelm the cellular obstacles associated with gene transfer, and lead to efficient gene delivery. Furthermore, no significant toxicity was perceived and efficient endosome disruptive activity was obtained. It is noteworthy to say among three mentioned constructs 2RMPG-2H1 showed the highest transfection efficiency. Overall the peptide based vectors hold great promise as a nontoxic and effective gene carrier in vitro and in vivo, besides the rational design possibility as the most vital advantages over the other non-viral gene delivery vectors. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Levodopa microparticles for pulmonary delivery: photodegradation kinetics and LC stability-indicating method.

    PubMed

    Pereira, R L; Paim, C S; Barth, A B; Raffin, R P; Guterres, S S; Schapoval, E E S

    2012-07-01

    Levodopa, (S)-2-amino-3-(3,4-dihydroxyphenyl) propanoic acid, is still considered the gold standard treatment for Parkinson's disease. However, oral levodopa shows poor pharmacokinetics and its efficacy becomes problematic with the progression of the disease. Pulmonary delivery using the association of the polymers: chitosan, hyaluronic acid and HPMC, represents a novel approach to overcome this problem. A stability-indicating liquid chromatography method for the quantitative determination of levodopa microparticles for pulmonary delivery was developed as well as its photodegradation kinetics in solution. The developed and validated method was applied for the analyses of the novel formulation as well as for protocols of stability studies.

  19. Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery

    PubMed Central

    Tong, Xiao; Wang, Zhantong; Sun, Xiaolian; Song, Jibin; Jacobson, Orit; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan

    2016-01-01

    Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer diagnostics and therapy, due to their excellent plasmonic photothermal properties. Tuning the size and aspect ratio of AuNR tailors the localized surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues are transparent, thus enables specific and effective treatment. The AuNR extravasates into tumor interstitium through enhanced permeation and retention (EPR) effect. Efficient AuNR based cancer therapy requires efficient AuNR tumor delivery. However, the size of AuNR can dramatically affect its blood circulation and tumor accumulation. Here we proposed for the first time a systematic framework to investigate the size-dependent kinetics of AuNRs during EPR mediated tumor delivery. By using 64Cu-labeled AuNRs with positron emission tomography (PET) and kinetic modeling, the in vivo uptake and kinetics of 64Cu-AuNR during its blood circulation, tumor accumulation and elimination were studied both in vitro and in vivo. The results of different sized AuNRs were compared and the optimum size of AuNR was suggested for EPR mediated tumor delivery. Our study provides a better understanding of the in vivo behavior of AuNR, which can help future design of nanomaterials for cancer imaging and therapy. PMID:27698939

  20. Controlling drug delivery kinetics from mesoporous titania thin films by pore size and surface energy.

    PubMed

    Karlsson, Johan; Atefyekta, Saba; Andersson, Martin

    2015-01-01

    The osseointegration capacity of bone-anchoring implants can be improved by the use of drugs that are administrated by an inbuilt drug delivery system. However, to attain superior control of drug delivery and to have the ability to administer drugs of varying size, including proteins, further material development of drug carriers is needed. Mesoporous materials have shown great potential in drug delivery applications to provide and maintain a drug concentration within the therapeutic window for the desired period of time. Moreover, drug delivery from coatings consisting of mesoporous titania has shown to be promising to improve healing of bone-anchoring implants. Here we report on how the delivery of an osteoporosis drug, alendronate, can be controlled by altering pore size and surface energy of mesoporous titania thin films. The pore size was varied from 3.4 nm to 7.2 nm by the use of different structure-directing templates and addition of a swelling agent. The surface energy was also altered by grafting dimethylsilane to the pore walls. The drug uptake and release profiles were monitored in situ using quartz crystal microbalance with dissipation (QCM-D) and it was shown that both pore size and surface energy had a profound effect on both the adsorption and release kinetics of alendronate. The QCM-D data provided evidence that the drug delivery from mesoporous titania films is controlled by a binding-diffusion mechanism. The yielded knowledge of release kinetics is crucial in order to improve the in vivo tissue response associated to therapeutic treatments.

  1. Controlling drug delivery kinetics from mesoporous titania thin films by pore size and surface energy

    PubMed Central

    Karlsson, Johan; Atefyekta, Saba; Andersson, Martin

    2015-01-01

    The osseointegration capacity of bone-anchoring implants can be improved by the use of drugs that are administrated by an inbuilt drug delivery system. However, to attain superior control of drug delivery and to have the ability to administer drugs of varying size, including proteins, further material development of drug carriers is needed. Mesoporous materials have shown great potential in drug delivery applications to provide and maintain a drug concentration within the therapeutic window for the desired period of time. Moreover, drug delivery from coatings consisting of mesoporous titania has shown to be promising to improve healing of bone-anchoring implants. Here we report on how the delivery of an osteoporosis drug, alendronate, can be controlled by altering pore size and surface energy of mesoporous titania thin films. The pore size was varied from 3.4 nm to 7.2 nm by the use of different structure-directing templates and addition of a swelling agent. The surface energy was also altered by grafting dimethylsilane to the pore walls. The drug uptake and release profiles were monitored in situ using quartz crystal microbalance with dissipation (QCM-D) and it was shown that both pore size and surface energy had a profound effect on both the adsorption and release kinetics of alendronate. The QCM-D data provided evidence that the drug delivery from mesoporous titania films is controlled by a binding–diffusion mechanism. The yielded knowledge of release kinetics is crucial in order to improve the in vivo tissue response associated to therapeutic treatments. PMID:26185444

  2. Intracellular delivery of peptide cargos using iron oxide based nanoparticles: studies on antitumor efficacy of a BCL-2 converting peptide, NuBCP-9

    NASA Astrophysics Data System (ADS)

    Kumar, Manoj; Singh, Gurpal; Sharma, Sapna; Gupta, Dikshi; Bansal, Vivek; Arora, Vikas; Bhat, Madhusudan; Srivastava, Sandeep K.; Sapra, Sameer; Kharbanda, Surender; Dinda, Amit K.; Singh, Harpal

    2014-11-01

    Delivering peptides into cells targeting the undruggable oncoproteins is an emerging area in cancer therapeutics. Here we report a novel nanoparticle-based delivery system that can transport therapeutic cargos to the intracellular sites without the need for a cell transduction or penetration domain (CPP). In the present study, we have used iron oxide nanoparticles to deliver an oncopeptide, NuBCP-9, targeting the BCL-2 BH3 domain. Citric acid/2-bromo 2-methylpropanoic acid (CA/BMPA)-capped SPIONs were used to immobilize and deliver the NuBCP-9 peptide to the cancer cells without any noticeable off-target effects. Our results have demonstrated that NuBCP-9-SPIONs efficiently penetrate into cancer cells and bind to its intracellular target protein BCL-2. Moreover, significant inhibition of proliferation and substantial induction of cell death were observed when cancer cells were treated with NuBCP-9-SPIONs at different time intervals. Importantly, the IC50 values for killing of breast cancer cells with NuBCP-9-SPIONs were much lower compared to cells treated with the NuBCP-9 peptide linked with a CPP (Arg-8; NuBCP-9-R8). Molecular and biochemical analyses further supported that NuBCP-9-SPIONs killed breast cancer cells by apoptosis-mediated mechanisms. Furthermore, our data demonstrated that administration of NuBCP-9-SPIONs to mice bearing Ehrlich ascites tumors (EAT) was associated with loss of tumorigenicity and extensive apoptosis in tumor tissues. Taken together, these findings show that a non-CPP-tagged peptide can be successfully delivered to undruggable intracellular oncotargets using SPIONs.Delivering peptides into cells targeting the undruggable oncoproteins is an emerging area in cancer therapeutics. Here we report a novel nanoparticle-based delivery system that can transport therapeutic cargos to the intracellular sites without the need for a cell transduction or penetration domain (CPP). In the present study, we have used iron oxide nanoparticles to

  3. Switches for multiple behavioral states and a viral-based approach to non-invasive whole-brain cargo delivery (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Gradinaru, Viviana

    2017-05-01

    Over the past years we have worked on: (1) Viral-based approaches to non-invasive whole-brain cargo delivery: Genetically-encoded tools that can be used to visualize, monitor, and modulate mammalian neurons are revolutionizing neuroscience. These tools are particularly powerful in rodents and invertebrate models where intersectional transgenic strategies are available to restrict their expression to defined cell populations. However, use of genetic tools in non-transgenic animals is often hindered by the lack of vectors capable of safe, efficient, and specific delivery to the desired cellular targets. To begin to address these challenges, we have developed an in vivo Cre-based selection platform (CREATE) for identifying adeno-associated viruses (AAVs) that more efficiently transduce genetically defined cell populations. Our platform's novelty and power arises from the additional selective pressure imparted by a recovery step that amplifies only those capsid variants that have functionally transduced a genetically-defined, Cre-expressing target cell population. The Cre-dependent capsid recovery works within heterogeneous tissue samples without the need for additional steps such as selective capsid recovery approaches that require cell sorting or secondary adenovirus infection. As a first test of the CREATE platform, we selected for viruses that transduced the brain after intravascular delivery and found a novel vector, AAV-PHP.B, that is 40- to 90-fold more efficient at transducing the brain than the current standard, AAV9. AAV-PHP.B transduces most neuronal types and glia across the brain. We also demonstrate here how whole-body tissue clearing can facilitate transduction maps of systemically delivered genes. Since CNS disorders are notoriously challenging due to the restrictive nature of the blood brain barrier our discovery that recombinant vectors can be engineered to overcome this barrier is enabling for the whole field. With the exciting advances in gene

  4. 19 CFR 4.33 - Diversion of cargo.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... VESSELS IN FOREIGN AND DOMESTIC TRADES Landing and Delivery of Cargo § 4.33 Diversion of cargo. (a... vessel may be changed at any time to permit discharge of manifested cargo at any domestic port in lieu of... purposes; and (3) The certified traveling manifest is not altered or added to in any way by the master...

  5. Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

    PubMed Central

    Fu, Yao; Kao, Weiyuan John

    2010-01-01

    Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

  6. Kinetics of early TCR signaling regulate the pathway of lytic granule delivery to the secretory domain

    PubMed Central

    Beal, Allison M.; Anikeeva, Nadia; Varma, Rajat; Cameron, Thomas O.; Vasiliver-Shamis, Gaia; Norris, Philip J.; Dustin, Michael L.; Sykulev, Yuri

    2009-01-01

    SUMMARY Cytolytic granule mediated killing of virus-infected cells is an essential function of cytotoxic T lymphocytes. Analysis of lytic granule delivery shows that the granules can take long or short paths to the secretory domain where they are released. Both paths utilize the same intracellular molecular events, which have different spatial and temporal arrangements in each path and are regulated by the kinetics of downstream Ca2+ mediated signaling. Rapid and robust signaling causes swift granule concentration near the MTOC and subsequent delivery by the polarized MTOC directly to the secretory domain - the shortest and fastest path. Indolent signaling leads to late recruitment of granules that move along microtubules to the periphery of the synapse and then move tangentially to fuse at the outer edge of the secretory domain - a longer path. The short pathway is associated with faster granule release and more efficient killing than the long pathway. PMID:19833088

  7. Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

    PubMed

    Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

    2016-03-01

    Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Controlling hydrogelation kinetics by peptide design for three-dimensional encapsulation and injectable delivery of cells.

    PubMed

    Haines-Butterick, Lisa; Rajagopal, Karthikan; Branco, Monica; Salick, Daphne; Rughani, Ronak; Pilarz, Matthew; Lamm, Matthew S; Pochan, Darrin J; Schneider, Joel P

    2007-05-08

    A peptide-based hydrogelation strategy has been developed that allows homogenous encapsulation and subsequent delivery of C3H10t1/2 mesenchymal stem cells. Structure-based peptide design afforded MAX8, a 20-residue peptide that folds and self-assembles in response to DMEM resulting in mechanically rigid hydrogels. The folding and self-assembly kinetics of MAX8 have been tuned so that when hydrogelation is triggered in the presence of cells, the cells become homogeneously impregnated within the gel. A unique characteristic of these gel-cell constructs is that when an appropriate shear stress is applied, the hydrogel will shear-thin resulting in a low-viscosity gel. However, after the application of shear has stopped, the gel quickly resets and recovers its initial mechanical rigidity in a near quantitative fashion. This property allows gel/cell constructs to be delivered via syringe with precision to target sites. Homogenous cellular distribution and cell viability are unaffected by the shear thinning process and gel/cell constructs stay fixed at the point of introduction, suggesting that these gels may be useful for the delivery of cells to target biological sites in tissue regeneration efforts.

  9. Magnetic glass ceramics for sustained 5-fluorouracil delivery: characterization and evaluation of drug release kinetics.

    PubMed

    Abdel-Hameed, S A M; El-Kady, A M; Marzouk, M A

    2014-11-01

    In the present study, magnetic glass ceramics in the system Fe2O3 ∙ TiO2 ∙ P2O5 ∙ SiO2 ∙ MO (M=Mg, Ca, Mn, Cu, Zn or Ce) are prepared. The effect of adding different cations on the thermal behavior, developed phases, microstructure and magnetic properties is studied using differental thermal analysis (DTA), X-ray diffraction analysis (XRD), transmission electron microscope (TEM), FT-infrared transmission (FT-IR) and vibrating sample magnetometer (VSM) respectively. The magnetic glass ceramics are tested as delivery systems for 5-fluorouracil. Modeling and analysis of release kinetics are addressed. The application of Higuchi square root of time model and the first order release model indicated that, 5-FU is released by diffusion controlled mechanisms, and that its released rate depends greatly on the concentration of loaded drug during the loading stage. The obtained results suggested that, the prepared magnetic glass ceramics can be used for cancer treatment by hyperthermia and/or by localized delivery of therapeutic doses of 5-fluorouracil.

  10. 46 CFR 154.534 - Cargo pumps and cargo compressors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 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...

  11. 46 CFR 154.534 - Cargo pumps and cargo compressors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 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...

  12. 46 CFR 154.534 - Cargo pumps and cargo compressors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 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...

  13. 46 CFR 154.534 - Cargo pumps and cargo compressors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 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...

  14. 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...

  15. Collective navigation of cargo-carrying swarms

    PubMed Central

    Shklarsh, Adi; Finkelshtein, Alin; Ariel, Gil; Kalisman, Oren; Ingham, Colin; Ben-Jacob, Eshel

    2012-01-01

    Much effort has been devoted to the study of swarming and collective navigation of micro-organisms, insects, fish, birds and other organisms, as well as multi-agent simulations and to the study of real robots. It is well known that insect swarms can carry cargo. The studies here are motivated by a less well-known phenomenon: cargo transport by bacteria swarms. We begin with a concise review of how bacteria swarms carry natural, micrometre-scale objects larger than the bacteria (e.g. fungal spores) as well as man-made beads and capsules (for drug delivery). A comparison of the trajectories of virtual beads in simulations (using different putative coupling between the virtual beads and the bacteria) with the observed trajectories of transported fungal spores implies the existence of adaptable coupling. Motivated by these observations, we devised new, multi-agent-based studies of cargo transport by agent swarms. As a first step, we extended previous modelling of collective navigation of simple bacteria-inspired agents in complex terrain, using three putative models of agent–cargo coupling. We found that cargo-carrying swarms can navigate efficiently in a complex landscape. We further investigated how the stability, elasticity and other features of agent–cargo bonds influence the collective motion and the transport of the cargo, and found sharp phase shifts and dual successful strategies for cargo delivery. Further understanding of such mechanisms may provide valuable clues to understand cargo-transport by smart swarms of other organisms as well as by man-made swarming robots. PMID:24312731

  16. Air Cargo Marketing Development

    NASA Technical Reports Server (NTRS)

    Kersey, J. W.

    1972-01-01

    The factors involved in developing a market for air cargo services are discussed. A comparison is made between the passenger traffic problems and those of cargo traffic. Emphasis is placed on distribution analyses which isolates total distribution cost, including logistical costs such as transportation, inventory, materials handling, packaging, and processing. Specific examples of methods for reducing air cargo costs are presented.

  17. Cardiac output, O2 delivery and VO2 kinetics during step exercise in acute normobaric hypoxia.

    PubMed

    Lador, Frédéric; Tam, Enrico; Adami, Alessandra; Kenfack, Marcel Azabji; Bringard, Aurélien; Cautero, Michela; Moia, Christian; Morel, Denis R; Capelli, Carlo; Ferretti, Guido

    2013-04-01

    We hypothesised that phase II time constant (τ2) of alveolar O2 uptake ( [Formula: see text] ) is longer in hypoxia than in normoxia as a consequence of a parallel deceleration of the kinetics of O2 delivery ( [Formula: see text] ). To test this hypothesis, breath-by-breath [Formula: see text] and beat-by-beat [Formula: see text] were measured in eight male subjects (25.4±3.4yy, 1.81±0.05m, 78.8±5.7kg) at the onset of cycling exercise (100W) in normoxia and acute hypoxia ( [Formula: see text] ). Blood lactate ([La]b) accumulation during the exercise transient was also measured. The τ2 for [Formula: see text] was shorter than that for [Formula: see text] in normoxia (8.3±6.8s versus 17.8±3.1s), but not in hypoxia (31.5±21.7s versus 28.4 5.4±5.4s). [La]b was increased in the exercise transient in hypoxia (3.0±0.5mM at exercise versus 1.7±0.2mM at rest), but not in normoxia. We conclude that the slowing down of the [Formula: see text] kinetics generated the longer τ2 for [Formula: see text] in hypoxia, with consequent contribution of anaerobic lactic metabolism to the energy balance in exercise transient, witnessed by the increase in [La]b.

  18. Precise control of the drug kinetics by means of non-invasive magnetic drug delivery system

    NASA Astrophysics Data System (ADS)

    Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

    2013-01-01

    In order to solve the problems of the side effects and medical lowering, has been advanced a study on the drug delivery system (DDS) to accumulate the drugs locally in the body with minimum dosage. The DDS is a system that controls the drug kinetics in the body precisely and accumulates the drug locally at the target part, keeping the drugs at high density. Among the DDS, the magnetic drug delivery system (MDDS) is the one that we studied. This is a technique to accumulate drugs by using the magnetic force as the physical driving force. Our previous researches showed the possibility of the technique of MDDS to accumulate the drugs with higher accumulation rate and locality than the traditional methods. It is necessary to apply a strong external magnetic field and a high magnetic gradient to accumulate the ferromagnetic drugs at a deep diseased part non-invasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the surface of the body locates near the magnet. In this study, we tried to change the magnetic field applied by a superconducting bulk magnet with time, in order to make a constant and strong magnetic field applied in the center of the body and to accumulate the ferromagnetic drugs at the deep target part in the body. First of all, the effect of the surface treatment of the ferromagnetic drugs to prevent its absorption in the normal tissue was examined. Then, to increase the accumulation rate of the ferromagnetic drugs at the target part, the distribution of magnetic field was changed, and the optimum spatial and temporal conditions of magnetic field were examined.

  19. In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life.

    PubMed

    Arnold, Yvonne E; Imanidis, Georgios; Kuentz, Martin

    2012-10-01

    Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, influenced by numerous factors. To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was defined using the reference excipient medium-chain triglycerides. Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay. We identified two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simplified mathematical model provided a good first approximation of initial lipolysis kinetics. Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results.

  20. Site-specific protection and dual labeling of human epidermal growth factor (hEGF) for targeting, imaging, and cargo delivery.

    PubMed

    Sonntag, Michael H; Ibach, Jenny; Nieto, Lidia; Verveer, Peter J; Brunsveld, Luc

    2014-05-12

    Well-defined human epidermal growth factor (hEGF) constructs featuring selectively addressable labels are urgently needed to address outstanding questions regarding hEGF biology. A protein-engineering approach was developed to provide access to hEGF constructs that carry two cysteine-based site-specific orthogonal labeling sites in multi-milligram quantities. Also, a site-selective (de)protection and labeling approach was devised, which allows selective modification of these hEGF constructs. The hEGF, featuring three native disulfide bonds, was expressed featuring additional sulfhydryl groups, in the form of cysteine residues, as orthogonal ligation sites at both the N and C termini. Temporary protection of the N-terminal cysteine unit, in the form of a thiazolidine ring, avoids interference with protein folding and enables sequential labeling in conjunction with the cysteine residue at the C terminus. Based on thus-generated hEGF constructs, sequential and site-specific labeling with a variety of molecular probes could be demonstrated, thus leading to a biological fully functional hEGF with specifically incorporated fluorophores or protein cargo and native cellular targeting and uptake profiles. Thus, this novel strategy provides a robust entry to high-yielding access of hEGF and rapid and easy site-specific and multifunctional dual labeling of this growth factor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. 49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the cargo tank is in service. On cargo tanks equipped with a meter, the meter creep test as outlined... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... may be used for this test. (4) The operator of a cargo tank must check the internal self-closing stop...

  2. 49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the cargo tank is in service. On cargo tanks equipped with a meter, the meter creep test as outlined... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... may be used for this test. (4) The operator of a cargo tank must check the internal self-closing stop...

  3. 49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the cargo tank is in service. On cargo tanks equipped with a meter, the meter creep test as outlined... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery hose... may be used for this test. (4) The operator of a cargo tank must check the internal self-closing stop...

  4. A Preliminary Ship Design Model for Cargo Throughput Optimization

    DTIC Science & Technology

    2014-06-01

    aspect of this collection of information, including suggestions for reducing this burden, to Washington headquarters Services , Directorate for...payload, and range that would give the optimal rate of cargo delivery , or throughput, in a given scenario. A physics based mathematical model is...give the optimal rate of cargo delivery , or throughput, in a given scenario. A physics based mathematical model is developed to display the inter

  5. Multipurpose Cargo Transfer Bag

    NASA Technical Reports Server (NTRS)

    Broyan, James; Baccus, Shelley

    2014-01-01

    The Logistics Reduction (LR) project within the Advanced Exploration Systems (AES) program is tasked with reducing logistical mass and repurposing logistical items. Multipurpose Cargo Transfer Bags (MCTB) have been designed such that they can serve the same purpose as a Cargo Transfer Bag, the suitcase-shaped common logistics carrying bag for Shuttle and the International Space Station. After use as a cargo carrier, a regular CTB becomes trash, whereas the MCTB can be unzipped, unsnapped, and unfolded to be reused. Reuse ideas that have been investigated include partitions, crew quarters, solar radiation storm shelters, acoustic blankets, and forward osmosis water processing.

  6. Adaptation of a 15-ft-dia ribbon parachute and a 73-ft cross main recovery parachute for cargo delivery from high altitude

    SciTech Connect

    Pepper, W.B.; Lucero, H.; Klimas, P.C.; Klein, R.A.; Antkowiak, H.E.

    1984-01-01

    An existing parachute system has been adapted for delivery of a resupply container at high altitudes from aircraft. The parachute system consists of a 15-ft diameter ribbon parachute reefed for 10 seconds and a 73-ft diameter cross parachute reefed for 10 seconds. A solid state recorder in the 2341 1b drop test vehicle was used to obtain deceleration history with time. Two drop tests using the Navy A7 aircraft were conducted at Stallion Site, White Sands Missile Range, New Mexico. Drop release conditions were 250 KCAS at 20,000 ft above sea level from the first test and 230 KCAS at 22,000 ft msl for the second. A new load transfer bridle was designed and tested to release the first stage parachute and replace a costly mechanical load plate.

  7. Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture

    PubMed Central

    2014-01-01

    Background Herpesviruses are ubiquitous pathogens that infect and cause recurrent disease in multiple animal species. Feline herpesvirus-1 (FHV-1), a member of the alphaherpesvirus family, causes respiratory illness and conjunctivitis, and approximately 80% of domestic cats are latently infected. Oral administration of famciclovir or topical application of cidofovir has been shown in masked, placebo-controlled prospective trials to reduce clinical signs and viral shedding in experimentally inoculated cats. However, to the authors’ knowledge, other drugs have not been similarly assessed or were not safe or effective. Likewise, to our knowledge, no drugs have been assessed in a placebo-controlled manner in cats with recrudescent herpetic disease. Controlled-release devices would permit long-term administration of these drugs and enhance compliance. Methods We therefore engineered implantable cylindrical devices made from silicone (MED-4750) impregnated with penciclovir, for long-term, steady-state delivery of this drug. Results Our data show that these devices release penciclovir with a burst of drug delivery until the tenth day of release, then at an average rate of 5.063 ± 1.704 μg per day through the next 50 days with near zero-order kinetics (in comparison to MED-4750-acyclovir devices, which show the same burst kinetics and average 2.236 ± 0.625 μg/day thereafter). Furthermore, these devices suppress primary infection of FHV-1 in a cell culture system. Conclusions The clinical deployment of these silicone-penciclovir devices may allow long-term treatment of FHV-1 infection with a single intervention that could last the life of the host cat. PMID:24558980

  8. Topiramate kinetics during delivery, lactation, and in the neonate: preliminary observations.

    PubMed

    Ohman, Inger; Vitols, Sigurd; Luef, Gerhard; Söderfeldt, Birgitta; Tomson, Torbjörn

    2002-10-01

    To study the pharmacokinetics of topiramate (TPM) during delivery, lactation, and in the neonate. TPM concentrations in plasma and breast milk were measured with fluorescence polarization immunoassay (FPIA) in five women with epilepsy treated with TPM during pregnancy and lactation. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions (24, 48, and 72 h) after delivery. Blood and breast milk also were collected from mothers 2 weeks, and 1 and 3 months postpartum. Blood samples also were drawn from the infants during breast-feeding. Three of the mother-infant pairs were studied both at delivery and during lactation; two contributed with data from delivery only. The umbilical cord plasma/maternal plasma ratios were close to unity, suggesting extensive transplacental transfer of TPM. The mean milk/maternal plasma concentration ratio was 0.86 (range, 0.67-1.1) at 2-3 weeks after delivery. The milk/maternal plasma concentration ratios at sampling 1 and 3 months after delivery were similar (0.86 and 0.69, respectively). Two to 3 weeks after delivery, two of the breast-fed infants had detectable (>0.9 microM) concentrations of TPM, although below the limit of quantification (2.8 microM), and one had an undetectable concentration. Our limited data suggest free passage of TPM over the placenta and an extensive transfer into breast milk. Breast-fed infants had very low TPM concentrations, and no adverse effects were observed in the infants.

  9. Military Air Cargo Containerization.

    DTIC Science & Technology

    1996-05-01

    MILITARY AIR CARGO CONTAINERIZATION GRADUATE RESEARCH PAPER Joseph W. Mancy, Major, USAF AFIT/ GMO /LAL/96J-4 : ."•" ’* ■- ’ DEPARTMENT OF...Approved to public release; Distribution UnHmlted ? DTIC QUALITY INSPECTED 1 AFIT/ GMO /LAL/96J-4 MILITARY AIR CARGO CONTAINERIZATION GRADUATE RESEARCH...PAPER Joseph W. Mancy, Major, USAF AFIT/ GMO /LAL/96J-4 19960617 134 Approved for public release; distribution unlimited The views expressed in this

  10. Novel polymeric nanoparticles for intracellular delivery of peptide cargos: antitumor efficacy of the Bcl-2 conversion peptide NuBCP-9

    PubMed Central

    Kumar, Manoj; Gupta, Dikshi; Singh, Gurpal; Sharma, Sapna; Bhatt, Madhusudan; Prashant, C.K.; Dinda, A.K.; Kharbanda, Surender; Kufe, Donald; Singh, Harpal

    2014-01-01

    The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacological properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anti-cancer peptide NuBCP-9 which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles (NPs) comprised of a polyethylene glycol (PEG)-modified polylactic acid diblock copolymer (NuBCP-9/PLA-PEG), or PEG-polypropylene glycol-PEG-modified PLA - tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the NPs was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these NPs in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/NPs triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins. PMID:24741005

  11. Vesicular Glutamate Transporter 1 Orchestrates Recruitment of Other Synaptic Vesicle Cargo Proteins during Synaptic Vesicle Recycling*

    PubMed Central

    Pan, Ping-Yue; Marrs, Julia; Ryan, Timothy A.

    2015-01-01

    A long standing question in synaptic physiology is how neurotransmitter-filled vesicles are rebuilt after exocytosis. Among the first steps in this process is the endocytic retrieval of the transmembrane proteins that are enriched in synaptic vesicles (SVs). At least six types of transmembrane proteins must be recovered, but the rules for how this multiple cargo selection is accomplished are poorly understood. Among these SV cargos is the vesicular glutamate transporter (vGlut). We show here that vGlut1 has a strong influence on the kinetics of retrieval of half of the known SV cargos and that specifically impairing the endocytosis of vGlut1 in turn slows down other SV cargos, demonstrating that cargo retrieval is a collective cargo-driven process. Finally, we demonstrate that different cargos can be retrieved in the same synapse with different kinetics, suggesting that additional post-endocytic sorting steps likely occur in the nerve terminal. PMID:26224632

  12. Role of non-covalent and covalent interactions in cargo loading capacity and stability of polymeric micelles.

    PubMed

    Ke, Xiyu; Ng, Victor Wee Lin; Ono, Robert J; Chan, Julian M W; Krishnamurthy, Sangeetha; Wang, Ying; Hedrick, James L; Yang, Yi Yan

    2014-11-10

    Polymeric micelles self-assembled from biodegradable amphiphilic block copolymers have been proven to be effective drug delivery carriers that reduce the toxicity and enhance the therapeutic efficacy of free drugs. Several reviews have been reported in the literature to discuss the importance of size/size distribution, stability and drug loading capacity of polymeric micelles for successful in vivo drug delivery. This review is focused on non-covalent and covalent interactions that are employed to enhance cargo loading capacity and in vivo stability, and to achieve nanosize with narrow size distribution. In particular, this review analyzes various non-covalent and covalent interactions and chemistry applied to introduce these interactions to the micellar drug delivery systems, as well as the effects of these interactions on micelle stability, drug loading capacity and release kinetics. Moreover, the factors that influence these interactions and the future research directions of polymeric micelles are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Distinguishing the effects of convective and diffusive O2 delivery on V̇o2 on-kinetics in skeletal muscle contracting at moderate intensity

    PubMed Central

    Spires, Jessica; Gladden, L. Bruce; Grassi, Bruno; Goodwin, Matthew L.; Saidel, Gerald M.

    2013-01-01

    With current techniques, experimental measurements alone cannot characterize the effects of oxygen blood-tissue diffusion on muscle oxygen uptake (V̇o2) kinetics in contracting skeletal muscle. To complement experimental studies, a computational model is used to quantitatively distinguish the contributions of convective oxygen delivery, diffusion into cells, and oxygen utilization to V̇o2 kinetics. The model is validated using previously published experimental V̇o2 kinetics in response to slowed blood flow (Q) on-kinetics in canine muscle (τQ = 20 s, 46 s, and 64 s) [Goodwin ML, Hernández A, Lai N, Cabrera ME, Gladden LB. J Appl Physiol. 112:9–19, 2012]. Distinctive effects of permeability-surface area or diffusive conductance (PS) and Q on V̇o2 kinetics are investigated. Model simulations quantify the relationship between PS and Q, as well as the effects of diffusion associated with PS and Q dynamics on the mean response time of V̇o2. The model indicates that PS and Q are linearly related and that PS increases more with Q when convective delivery is limited by slower Q dynamics. Simulations predict that neither oxygen convective nor diffusive delivery are limiting V̇o2 kinetics in the isolated canine gastrocnemius preparation under normal spontaneous conditions during transitions from rest to moderate (submaximal) energy demand, although both operate close to the tipping point. PMID:23761640

  14. Distinguishing the effects of convective and diffusive O₂ delivery on VO₂ on-kinetics in skeletal muscle contracting at moderate intensity.

    PubMed

    Spires, Jessica; Gladden, L Bruce; Grassi, Bruno; Goodwin, Matthew L; Saidel, Gerald M; Lai, Nicola

    2013-09-01

    With current techniques, experimental measurements alone cannot characterize the effects of oxygen blood-tissue diffusion on muscle oxygen uptake (Vo₂) kinetics in contracting skeletal muscle. To complement experimental studies, a computational model is used to quantitatively distinguish the contributions of convective oxygen delivery, diffusion into cells, and oxygen utilization to Vo₂ kinetics. The model is validated using previously published experimental Vo₂ kinetics in response to slowed blood flow (Q) on-kinetics in canine muscle (τQ = 20 s, 46 s, and 64 s) [Goodwin ML, Hernández A, Lai N, Cabrera ME, Gladden LB. J Appl Physiol. 112:9-19, 2012]. Distinctive effects of permeability-surface area or diffusive conductance (PS) and Q on Vo₂ kinetics are investigated. Model simulations quantify the relationship between PS and Q, as well as the effects of diffusion associated with PS and Q dynamics on the mean response time of Vo₂. The model indicates that PS and Q are linearly related and that PS increases more with Q when convective delivery is limited by slower Q dynamics. Simulations predict that neither oxygen convective nor diffusive delivery are limiting Vo₂ kinetics in the isolated canine gastrocnemius preparation under normal spontaneous conditions during transitions from rest to moderate (submaximal) energy demand, although both operate close to the tipping point.

  15. Controlled delivery of nanosuspensions from osmotic pumps: zero order and non-zero order kinetics.

    PubMed

    Hill, Alexandra; Geissler, Simon; Weigandt, Markus; Mäder, Karsten

    2012-03-28

    Nanosuspensions have gained great interest in the last decade as a formulation tool for poorly soluble drugs. By decreasing particle sizes nanosuspensions enhance dissolution rate and bioavailability of the active pharmaceutical ingredient. Micro-osmotic pumps are widely used in experimental pharmacology and offer a tool of interest for the sustained release of nanosuspensions via the intraperitoneal or subcutaneous application site. The purpose of the present study was to investigate in-vitro the influence of (1) nanosuspension viscosity, (2) pump orifice position and (3) formulation osmolality on the delivery behavior of formulations in implantable osmotic systems. Therefore fenofibrate nanosuspension, methylene blue and fluorescein sodium solutions were chosen as model formulations. They were released in water or isotonic saline solution and drug/dye concentrations were determined by HPLC/UV. Release of nanosuspension particles in low viscous formulations resulted in a burst whereas increasing the viscosity led to the expected zero order delivery. Pumps with upward-positioned orifices released the nanosuspension in a zero order manner. Within the release of dyes, constant delivery could be ensured up to an osmolality of 486 mO sm/kg; above this value premature release of formulation was observed. The results indicate the requirement of in-vitro experiments prior to in-vivo animal testing for determining the release profiles of osmotic pumps.

  16. Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics.

    PubMed

    Buyukozturk, Fulden; Benneyan, James C; Carrier, Rebecca L

    2010-02-25

    Lipid based drug delivery systems, and in particular self-emulsifying drug delivery systems (SEDDS), show great potential for enhancing oral bioavailability but have not been broadly applied, largely due to lack of general formulation guidance. To help understand how formulation design influences physicochemical emulsion properties and associated function in the gastrointestinal environment, a range of twenty-seven representative self-emulsifying formulations were investigated. Two key functions of emulsion-based drug delivery systems, permeability enhancement and drug release, were studied and statistically related to three formulation properties - oil structure, surfactant hydrophilic liphophilic balance (HLB) values, and surfactant-to-oil ratio. Three surfactants with HLB values ranging from 10 to 15 and three structurally different oils (long chain triglyceride, medium chain triglyceride, and propylene glycol dicaprylate/dicaprate) were combined at three different weight ratios (1:1, 5:1, 9:1). Unstable formulations of low HLB surfactant (HLB=10) had a toxic effect on cells at high (1:1) surfactant concentrations, indicating the importance of formulation stability for minimizing toxicity. Results also indicate that high HLB surfactant (Tween 80) loosens tight junction at high (1:1) surfactant concentrations. Release coefficients for each emulsion system were calculated. Incorporation of a long chain triglyceride (Soybean oil) as the oil phase increased the drug release rate constant. These results help establish an initial foundation for relating emulsion function to formulation design and enabling bioavailability optimization across a broad, representative range of SEDDS formulations.

  17. 33 CFR 401.32 - Cargo booms-deck cargo.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Cargo booms-deck cargo. 401.32 Section 401.32 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.32 Cargo booms...

  18. Stochastic Movement of Multiple Motor Transported Cargo

    NASA Astrophysics Data System (ADS)

    Ando, David; Gopinathan, Ajay; Xu, Jing

    2015-03-01

    Experimental observations of cargo position during transport by multiple motors are determined by several coupled stochastic processes. During collective transport, each motor can transition between multiple kinetic states, with the state of each motor influencing the states of the others via mechanical coupling through a common cargo. We measured the motion of a micron sized bead as it is transported by two kinesin motors along a single microtubule track, focusing on cargo displacements which are both axial and transverse to the microtubule. We model the effects of inter-motor interference and the state of each motor throughout time, and back out motor properties using a systematic comparison of experimental observations with simulated model traces over a wide parameter space. Our model captures a surface-associated mode of kinesin, which is only accessible via inter-motor interference in groups, in which kinesin diffuses along the microtubule surface and rapidly ``hops'' between protofilaments without dissociating from the microtubule. This enhances local exploration of the microtubule surface, possibly enabling cellular cargos to overcome macromolecular crowding and to navigate obstacles along micro- tubule tracks without sacrificing overall travel distance.

  19. Effects of protein molecular weight on the intrinsic material properties and release kinetics of wet spun polymeric microfiber delivery systems.

    PubMed

    Lavin, Danya M; Zhang, Linda; Furtado, Stacia; Hopkins, Richard A; Mathiowitz, Edith

    2013-01-01

    Wet spun microfibers have great potential for the design of multifunctional controlled release scaffolds. Understanding aspects of drug delivery and mechanical strength, specific to protein molecular weight, may aid in the optimization and development of wet spun fiber platforms. This study investigated the intrinsic material properties and release kinetics of poly(l-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA) wet spun microfibers encapsulating proteins with varying molecular weights. A cryogenic emulsion technique developed in our laboratory was used to encapsulate insulin (5.8 kDa), lysozyme (14.3 kDa) and bovine serum albumin (BSA, 66.0 kDa) within wet spun microfibers (~100 μm). Protein loading was found to significantly influence mechanical strength and drug release kinetics of PLGA and PLLA microfibers in a molecular-weight-dependent manner. BSA encapsulation resulted in the most significant decrease in strength and ductility for both PLGA and PLLA microfibers. Interestingly, BSA-loaded PLGA microfibers had a twofold increase (8±2 MPa to 16±1 MPa) in tensile strength and a fourfold increase (3±1% to 12±6%) in elongation until failure in comparison to PLLA microfibers. PLGA and PLLA microfibers exhibited prolonged protein release up to 63 days in vitro. Further analysis with the Korsmeyer-Peppas kinetic model determined that the mechanism of protein release was dependent on Fickian diffusion. These results emphasize the critical role protein molecular weight has on the properties of wet spun filaments, highlighting the importance of designing small molecular analogues to replace growth factors with large molecular weights.

  20. 46 CFR 111.106-13 - Cargo handling devices or cargo pump rooms handling flammable or combustible cargoes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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... classification of such areas. (c) Cargo pump rooms must be isolated from all sources of vapor ignition...

  1. Thermodynamic and Kinetic Aspects Involved in the Development of Nanocarriers and Drug Delivery Systems Based on Cationic Biopolymers.

    PubMed

    Bianco, Ismael D; Alasino, Roxana V; Leonhard, Victoria; Beltramo, Dante M

    2016-01-01

    During the last years we have seen an increasing number of reports describing new properties and potential applications of cationic polymers and derived nanostructures. This review gives a summary of their applications in drug delivery, the preparation methods for nano and microstructures and will attempt to give a glimpse on how their structure, chemical composition and properties may be affected or modulated as to make them suitable for an intended application as drug delivery nanocarriers. The compositional complexity with the existence of several reacting groups makes cationic nanostructures critically sensitive to the contribution of thermodynamic and kinetic parameters in the determination of the type and stability of a particular structure and its ability to respond to changes in environmental conditions in the right time frame. Curiously, and contrarily to what could be expected, despite the fact that cationic polymers can form strong electrostatic interactions the contribution of the entropic component has been often found to be very important for their association with negatively charged supramolecular structures. Some general considerations indicate that when considering a complex multimolecular system like a nanocarrier containing an active ingredient it is frequently possible to find conditions under which enthalpic and entropic contributions are compensated leading to stable structures with a marginal thermodynamic stability (free energy change close to zero) which make them able to respond relatively fast to changes in the environmental conditions and therefore suitable for the design of smart drug delivery systems. Like with other nanocarriers, it should always be kept in mind that the properties of cationic nanocarriers will depend not only on their chemical composition but also on the properties of the structures formed by them.

  2. The Economics of Air Cargo

    NASA Technical Reports Server (NTRS)

    Kersey, J. W.

    1972-01-01

    The economic factors involved in air cargo operations and air cargo marketing development are discussed. Specific steps which are followed by various airports to reduce operating costs are described. The economics of cargo handling within an airline are analyzed with respect to: (1) paperwork costs, (2) terminal costs, (3) line haul costs, and (4) claims costs.

  3. Long-range cargo transport on crowded microtubules: The motor jamming mechanism

    NASA Astrophysics Data System (ADS)

    Rossi, Lucas W.; Radtke, Paul K.; Goldman, Carla

    2014-05-01

    The hopping model for cargo transport by molecular motors introduced in Goldman and Sena (2009), Goldman (2010) is extended here in order to incorporate the movement of cargo-motor complexes (C-MC). Hopping processes in this context express the possibility for cargo to be exchanged between neighboring motors at a microtubule where the transport takes place. Jamming of motors is essential for cargos to execute long-range movement in this way. Results from computer simulations accompanied by a mean-field analysis of the extended model confirm our previous analytical results and suggests that an interplay between cargo hopping and the movement of the C-MC’s would control the efficiency of cargo transfer and cargo delivery in these model systems.

  4. Zero g manual cargo handling

    NASA Technical Reports Server (NTRS)

    Spady, A. A., Jr.; Beasley, G. P.

    1972-01-01

    A series of studies were conducted utilizing a water-immersion simulator facility to better define the cargo that can realistically be handled by man. The initial phase of the program was a parametric study to define man's intravehicular (IV) cargo transfer capabilities, and its results are reported. Additional phases of the study, deal with: (1) man's ability to perform extravehicular (EV) cargo transfer, (2) the ability to transfer cargo through a 1.5 m (5-foot) diameter tunnel (IV), and (3) the utilization of electroadhesive/electromagnetic mobility aids for both IV and EV self-locomotion and cargo transfer.

  5. CargoTIPS: an innovative approach to combating cargo theft

    NASA Astrophysics Data System (ADS)

    Toth, Gail E.

    1998-12-01

    Cargo theft has been estimated by the Federal Bureau o Investigations to be 6 billion annually, while others believe it to be more than 10 billion annually. Opportunistic thieves, street gangs, traditional organized crime groups, and new organized crime groups have been targeting cargo. They steal from warehouses, terminals, equipment, truck stops, or any place where freight comes to a rest. With zero inventory levels, our trailers have become virtual warehouses on wheels and easy targets for thieves. Without information and communication cargo thieves can thrive. The industry and law enforcement are forced into being reactive instead of developing proactive policies and procedures. Cargo thieves cross town lines, county lines, state lines and country borders. This makes communication within the law enforcement community imperative. CargoTIPS (cargo theft information processing system) was developed in response to the need for cargo theft information. The system allows us to collect cargo theft statistics to analyze the problem, assess the threat and develop a response on a national level. CargoTIPS includes a bulletin board, which allows users to communicate with each other, pass on alerts or seek information. The system is also used as an investigative tool. CargoTIPS can identify the mode of transportation (truck, small parcel, air, rail or ocean). It was designed to take in international data. Currently the system has identified that food products are the number one targeted commodity, followed by electronic products and third, computers and computer parts.

  6. Iontophoretic transport kinetics of ketorolac in vitro and in vivo: demonstrating local enhanced topical drug delivery to muscle.

    PubMed

    Gratieri, Taís; Pujol-Bello, Ester; Gelfuso, Guilherme M; de Souza, Joel G; Lopez, Renata F V; Kalia, Yogeshvar N

    2014-02-01

    The objective of the study was to investigate the iontophoretic delivery kinetics of ketorolac (KT), a highly potent NSAID and peripherally-acting analgesic that is currently indicated to treat moderate to severe acute pain. It was envisaged that, depending on the amounts delivered, transdermal iontophoretic administration might have two distinct therapeutic applications: (i) more effective and faster local therapy with shorter onset times (e.g. to treat trauma-related pain/inflammation in muscle) or (ii) a non-parenteral, gastrointestinal tract sparing approach for systemic pain relief. The first part of the study investigated the effect of experimental conditions on KT iontophoresis using porcine and human skin in vitro. These results demonstrated that KT electrotransport was linearly dependent on current density - from 0.1875 to 0.5mA/cm(2) - (r(2)>0.99) and drug concentration - from 5 to 20mg/ml (r(2)>0.99). Iontophoretic permeation of KT from a 2% hydroxymethyl cellulose gel was comparable to that from an aqueous solution with equivalent drug loading (584.59±114.67 and 462.05±66.56μg/cm(2), respectively). Cumulative permeation (462.05±66.56 and 416.28±95.71μg/cm(2)) and steady state flux (106.72±11.70 and 94.28±15.47μg/cm(2)h), across porcine and human skin, were statistically equivalent confirming the validity of the model. Based on the results in vitro, it was decided to focus on topical rather than systemic applications of KT iontophoresis in vivo. Subsequent experiments, in male Wistar rats, investigated the local enhancement of KT delivery to muscle by iontophoresis. Drug biodistribution was assessed in skin, in the biceps femoris muscle beneath the site of iontophoresis ('treated muscle'; TM), in the contralateral muscle ('non-treated muscle'; NTM) and in plasma (P). Passive topical delivery and oral administration served as negative and positive controls, respectively. Iontophoretic administration for 30min was superior to passive topical

  7. The Cargo Transfer Vehicle

    NASA Astrophysics Data System (ADS)

    Rourke, K. H.

    1992-03-01

    NASA's Cargo Transfer Vehicle is a key element of the National Launch System currently under definition by a joint USAF and NASA development program. The CTV reference mission and configuration are described. Key mission and system requirements are analyzed and summarized including CTV electrical power and energy, main engine thrust, RCS configurations. Methods of control system validation using full 6DoF simulations are presented.

  8. Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

    PubMed

    Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

    2016-07-01

    Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated.

  9. In Vivo Fluorescence Resonance Energy Transfer Imaging for Targeted Anti-Cancer Drug Delivery Kinetics

    NASA Astrophysics Data System (ADS)

    Webb, Kevin; Gaind, Vaibhav; Tsai, Hsiaorho; Bentz, Brian; Chelvam, Venkatesh; Low, Philip

    2012-02-01

    We describe an approach for the evaluation of targeted anti-cancer drug delivery in vivo. The method emulates the drug release and activation process through acceptor release from a targeted donor-acceptor pair that exhibits fluorescence resonance energy transfer (FRET). In this case, folate targeting of the cancer cells is used - 40 % of all human cancers, including ovarian, lung, breast, kidney, brain and colon cancer, over-express folate receptors. We demonstrate the reconstruction of the spatially-dependent FRET parameters in a mouse model and in tissue phantoms. The FRET parameterization is incorporated into a source for a diffusion equation model for photon transport in tissue, in a variant of optical diffusion tomography (ODT) called FRET-ODT. In addition to the spatially-dependent tissue parameters in the diffusion model (absorption and diffusion coefficients), the FRET parameters (donor-acceptor distance and yield) are imaged as a function of position. Modulated light measurements are made with various laser excitation positions and a gated camera. More generally, our method provides a new vehicle for studying disease at the molecular level by imaging FRET parameters in deep tissue, and allows the nanometer FRET ruler to be utilized in deep tissue.

  10. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  11. Bacterial Growth Kinetics under a Novel Flexible Methacrylate Dressing Serving as a Drug Delivery Vehicle for Antiseptics

    PubMed Central

    Forstner, Christina; Leitgeb, Johannes; Schuster, Rupert; Dosch, Verena; Kramer, Axel; Cutting, Keith F.; Leaper, David J.; Assadian, Ojan

    2013-01-01

    A flexible methacrylate powder dressing (Altrazeal®) transforms into a wound contour conforming matrix once in contact with wound exudate. We hypothesised that it may also serve as a drug delivery vehicle for antiseptics. The antimicrobial efficacy and influence on bacterial growth kinetics in combination with three antiseptics was investigated in an in vitro porcine wound model. Standardized in vitro wounds were contaminated with Staphylococcus aureus (MRSA; ATCC 33591) and divided into six groups: no dressing (negative control), methacrylate dressing alone, and combinations with application of 0.02% Polyhexamethylene Biguanide (PHMB), 0.4% PHMB, 0.1% PHMB + 0.1% betaine, 7.7 mg/mL Povidone-iodine (PVP-iodine), and 0.1% Octenidine-dihydrochloride (OCT) + 2% phenoxyethanol. Bacterial load per gram tissue was measured over five days. The highest reduction was observed with PVP-iodine at 24 h to log10 1.43 cfu/g, followed by OCT at 48 h to log10 2.41 cfu/g. Whilst 0.02% PHMB resulted in a stable bacterial load over 120 h to log10 4.00 cfu/g over 120 h, 0.1% PHMB + 0.1% betaine inhibited growth during the first 48 h, with slightly increasing bacterial numbers up to log10 5.38 cfu/g at 120 h. These results indicate that this flexible methacrylate dressing can be loaded with various antiseptics serving as drug delivery system. Depending on the selected combination, an individually shaped and controlled antibacterial effect may be achieved using the same type of wound dressing. PMID:23698780

  12. 19 CFR 4.34 - Prematurely discharged, overcarried, and undelivered cargo.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cargo for domestic ports. The substitute traveling manifest, carried forward from port to port by the... SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Landing and Delivery of Cargo... destination and was overcarried to another domestic port through error or emergency, the port director may...

  13. 19 CFR 4.32 - Vessels in distress; landing of cargo.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Vessels in distress; landing of cargo. 4.32 Section 4.32 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY VESSELS IN FOREIGN AND DOMESTIC TRADES Landing and Delivery of Cargo § 4.32...

  14. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization.

    PubMed

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  15. Polycaprolactone/maltodextrin nanocarrier for intracellular drug delivery: formulation, uptake mechanism, internalization kinetics, and subcellular localization

    PubMed Central

    Korang-Yeboah, Maxwell; Gorantla, Yamini; Paulos, Simon A; Sharma, Pankaj; Chaudhary, Jaideep; Palaniappan, Ravi

    2015-01-01

    Prostate cancer (PCa) disease progression is associated with significant changes in intracellular and extracellular proteins, intracellular signaling mechanism, and cancer cell phenotype. These changes may have direct impact on the cellular interactions with nanocarriers; hence, there is the need for a much-detailed understanding, as nanocarrier cellular internalization and intracellular sorting mechanism correlate directly with bioavailability and clinical efficacy. In this study, we report the differences in the rate and mechanism of cellular internalization of a biocompatible polycaprolactone (PCL)/maltodextrin (MD) nanocarrier system for intracellular drug delivery in LNCaP, PC3, and DU145 PCa cell lines. PCL/MD nanocarriers were designed and characterized. PCL/MD nanocarriers significantly increased the intracellular concentration of coumarin-6 and fluorescein isothiocyanate-labeled bovine serum albumin, a model hydrophobic and large molecule, respectively. Fluorescence microscopy and flow cytometry analysis revealed rapid internalization of the nanocarrier. The extent of nanocarrier cellular internalization correlated directly with cell line aggressiveness. PCL/MD internalization was highest in PC3 followed by DU145 and LNCaP, respectively. Uptake in all PCa cell lines was metabolically dependent. Extraction of endogenous cholesterol by methyl-β-cyclodextrin reduced uptake by 75%±4.53% in PC3, 64%±6.01% in LNCaP, and 50%±4.50% in DU145, indicating the involvement of endogenous cholesterol in cellular internalization. Internalization of the nanocarrier in LNCaP was mediated mainly by macropinocytosis and clathrin-independent pathways, while internalization in PC3 and DU145 involved clathrin-mediated endocytosis, clathrin-independent pathways, and macropinocytosis. Fluorescence microscopy showed a very diffused and non-compartmentalized subcellular localization of the PCL/MD nanocarriers with possible intranuclear localization and minor colocalization in

  16. Acoustic Multipurpose Cargo Transfer Bag

    NASA Technical Reports Server (NTRS)

    Baccus, Shelley

    2015-01-01

    The Logistics Reduction (LR) project within the Advanced Exploration Systems (AES) program is tasked with reducing logistical mass and repurposing logistical items. Multipurpose Cargo Transfer Bags (MCTB) are designed to be the same external volume as a regular cargo transfer bag, the common logistics carrier for the International Space Station. After use as a cargo bag, the MCTB can be unzipped and unfolded to be reused. This Acoustic MCTBs transform into acoustic blankets after the initial logistics carrying objective is complete.

  17. External tank aft cargo carrier

    NASA Technical Reports Server (NTRS)

    Mobley, T. B.

    1984-01-01

    The External Tank (ET) Aft Cargo Carrier (ACC) is a low cost, low risk augmentation of the Space Transportation System (STS). It almost doubles the cargo volume of the STS while minimally impacting other STS elements (orbiter, ET and solid rocket boosters SRBs, launch facilities and STS operations. In addition to increasing the potential volume of cargo carried on a Shuttle launch, the ACC provides the following additional benefits: (1) Increased STS competitiveness for payloads; (2) Increased cargo manifest flexibility; (3) Increased spacecraft design options; (4) Alternate manifesting for special payloads; and (5) Future space platform/station design options.

  18. 22 CFR 228.55 - Delivery services.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Delivery services. 228.55 Section 228.55... COMMODITIES AND SERVICES FINANCED BY USAID Waivers § 228.55 Delivery services. (a) Ocean transportation. A... case of bulk cargoes and large cargoes carried by liners; (2) Eligible vessels provide liner...

  19. Audible Noise Design of ISS Cargo Module "Cygnus"

    NASA Astrophysics Data System (ADS)

    Destefanis, Stefano; Paron, Alberto; Bandini, Flavio

    2014-06-01

    Orbital developed the Cygnus advanced manoeuvring spacecraft to demonstrate cargo delivery services under a NASA Commercial Orbital Transportation Services (COTS) Space Act Agreement.In addition to the COTS development and demonstration program, Orbital will utilize Cygnus to perform ISS resupply flights under the Commercial Resupply Service (CRS) contract.Starting in January 2014 Orbital launched its first of eight missions to deliver approximately 20,000 kilograms of cargo to the ISS (International Space Station). Cygnus will carry crew supplies, spares and scientific experiments to the ISS.Cygnus consists of a common service module and a pressurized cargo module. The pressurized cargo module is based on the Multi-Purpose Logistics Module (MPLM), developed by Thales Alenia Space for NASA. Since Cygnus pressurized cargo module will host astronauts performing daily tasks, it is required to be compliant with NASA guidelines related to acoustic comfort (working areas noise not to exceed NC-50 requirement) and safety (caution and warning alarms audibility).The main source of noise inside Cygnus is the ventilation fan, which happens to be the same model already installed on the ATV (Automated Transfer Vehicle) cargo module: however, the strategy adopted to limit its acoustic disturbance had to be differently tailored.This paper presents the activities (assumptions, design, characterization, testing) that led to define the type of noise control devices used on Cygnus, up to its first successful flight (module labelled "PCM0") to the ISS, where it reached 2nd place in the "quietest visiting modules" ranking.

  20. 46 CFR 154.315 - Cargo pump and cargo compressor rooms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 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...

  1. 46 CFR 154.315 - Cargo pump and cargo compressor rooms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 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...

  2. 46 CFR 154.315 - Cargo pump and cargo compressor rooms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 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...

  3. 46 CFR 154.315 - Cargo pump and cargo compressor rooms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 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...

  4. 46 CFR 154.1810 - Cargo manual.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... or condensate return system. (iii) Cargo tank cool-down system. (iv) Cargo tank warm-up or... during the voyage. (12) A description of cargo tank cool-down and warm-up operations including purging...

  5. 46 CFR 154.1810 - Cargo manual.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... or condensate return system. (iii) Cargo tank cool-down system. (iv) Cargo tank warm-up or... during the voyage. (12) A description of cargo tank cool-down and warm-up operations including purging...

  6. 46 CFR 154.1810 - Cargo manual.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... or condensate return system. (iii) Cargo tank cool-down system. (iv) Cargo tank warm-up or... during the voyage. (12) A description of cargo tank cool-down and warm-up operations including purging...

  7. 46 CFR 154.1810 - Cargo manual.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... or condensate return system. (iii) Cargo tank cool-down system. (iv) Cargo tank warm-up or... during the voyage. (12) A description of cargo tank cool-down and warm-up operations including purging...

  8. Cargo-cult training

    NASA Astrophysics Data System (ADS)

    Magueijo, João

    2009-12-01

    Richard Feynman, in one of his famous rants, evoked as a metaphor what he called "cargo-cult science". During the Second World War, the indigenous people of the South Pacific became accustomed to US Air Force planes landing on their islands, invariably bringing a profusion of desirable goods and tasty foods. When the war ended, they were distressed by the discontinuation of this popular service. So, they decided to take action. They cleared elongated patches of land to make them look like runways. They lit wood fires where they had seen electric floodlights guiding in the planes. They built a wooden shack and made a man sit inside with two halves of a coconut on each ear and bamboo bars sticking out like antennas: he was the "air controller". And they waited for the planes to return.

  9. Magnetic-resonance imaging for kinetic analysis of permeability changes during focused ultrasound-induced blood-brain barrier opening and brain drug delivery.

    PubMed

    Chai, Wen-Yen; Chu, Po-Chun; Tsai, Meng-Yen; Lin, Yu-Chun; Wang, Jiun-Jie; Wei, Kuo-Chen; Wai, Yau-Yau; Liu, Hao-Li

    2014-10-28

    Focused ultrasound (FUS) with the presence of microbubbles has been shown to induce transient and local opening of the blood-brain barrier (BBB) for the delivery of therapeutic molecules which normally cannot penetrate into the brain. The success of FUS brain-drug delivery relies on its integration with in-vivo imaging to monitor kinetic change of therapeutic molecules into the brain. In this study, we developed a dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) technique for kinetic analysis of delivered molecules during FUS-BBB opening. Three kinetic parameters (Ktrans, Ve, Kep) were characterized dynamically to describe BBB-permeability at two FUS exposure conditions (0.4 or 0.8MPa) over 24h. Ktrans, defined as the influx volume transfer constant from plasma to EES, and Ve, the EES volume fraction, were both found to be pressure-dependent. Ktrans and Ve showed a peak increase of 0.0086-0.0131min(-1) (for 0.4-0.8MPa pressure), and 0.0431-0.0692, respectively, immediately after FUS exposure. Both parameters subsequently decreased exponentially as a function of time, with estimated half-lives of decay of 2.89-5.3 and 2.2-4.93h, respectively. The kinetics of Kep, defined as the efflux rate constant from the extracellular extravascular space (EES) to the plasma, were complementary to Ktrans, with an initial decrease from 0.2010 to 0.1901min(-1) followed by a significantly longer recovery time (half-life of 17.39-99.92h). Our observations strongly supported the existence of imbalanced and mismatched kinetics of influx (Ktrans) and efflux (Kep) between the plasma and EES, indicating the existence of directional permeability during FUS-BBB opening. We further showed that kinetic change determined by DCE-MRI correlated well with the concentration of Evans Blue (EB)-albumin (coefficient of 0.74-0.89). These findings suggest that MRI kinetic monitoring may serve as an alternative method for in-vivo monitoring of pharmacokinetics and pharmacodynamics (PK

  10. Polymeric colloidal particulate systems: intelligent tools for intracellular targeting of antileishmanial cargos.

    PubMed

    Asthana, Shalini; Gupta, Pramod K; Chaurasia, Mohini; Dube, Anuradha; Chourasia, Manish K

    2013-12-01

    Targeted cargo delivery systems can overcome drawbacks associated with antileishmanials delivery, by defeating challenges of physiological barriers. Various colloidal particulate systems have been developed in the past; few of them even achieved success in the market, but still are limited in some ways. This review is focused on the pathobiology of leishmaniasis, interactions of particulate systems with biological environment, targeting strategies along with current conventional and vaccine therapies with special emphasis on polymeric nanotechnology for effective antileishmanial cargo delivery. The problems concerned with limited accessibility of chemotherapeutic cargos in conventional modes to Leishmania-harboring macrophages, their toxicity, and resistant parasitic strain development can be sorted out through target-specific delivery of cargos. Vaccination is another therapeutic approach employing antigen alone or adjuvant combinations delivered by means of a carrier, and can provide preventive measures against human leishmaniasis (HL). Therefore, there is an urgent need of designing site-specific antileishmanial cargo carriers for safe and effective management of HL. Among various colloidal carriers, polymeric particulate systems hold tremendous potential as an effective delivery tool by providing control over spatial and temporal distribution of cargos after systemic or localized administration along with enhancing their stability profile at a comparatively cost-effective price leading to improved chances of commercial applicability.

  11. 49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

    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 for cargo personnel in the United States. This section applies in the United States to each aircraft...

  12. 49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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 for cargo personnel in the United States. This section applies in the United States to each aircraft...

  13. Optimizing an undulating magnetic microswimmer for cargo towing.

    PubMed

    Gutman, Emiliya; Or, Yizhar

    2016-06-01

    One of the promising capabilities of magnetic microswimmers is towing a cargo, which can be used for targeted drug delivery or performing tissue biopsy. A key question is what should be the optimal size ratio between the cargo and the swimmer's flexible tail. This question is addressed here for the simplest theoretical model of a magnetic microswimmer undergoing planar undulations-a spherical load connected by a torsion spring to a rigid slender link. The swimmer's dynamic is formulated and leading-order expressions for its motion are obtained explicitly under small-amplitude approximation. Optimal combinations of magnetic actuation frequency, torsion stiffness, and tail length for maximizing displacement, average speed, or energetic efficiency are obtained. The theoretical results are compared with reported experiments in several types of cargo-towing magnetic microswimmers.

  14. Optimizing an undulating magnetic microswimmer for cargo towing

    NASA Astrophysics Data System (ADS)

    Gutman, Emiliya; Or, Yizhar

    2016-06-01

    One of the promising capabilities of magnetic microswimmers is towing a cargo, which can be used for targeted drug delivery or performing tissue biopsy. A key question is what should be the optimal size ratio between the cargo and the swimmer's flexible tail. This question is addressed here for the simplest theoretical model of a magnetic microswimmer undergoing planar undulations—a spherical load connected by a torsion spring to a rigid slender link. The swimmer's dynamic is formulated and leading-order expressions for its motion are obtained explicitly under small-amplitude approximation. Optimal combinations of magnetic actuation frequency, torsion stiffness, and tail length for maximizing displacement, average speed, or energetic efficiency are obtained. The theoretical results are compared with reported experiments in several types of cargo-towing magnetic microswimmers.

  15. Multiscale Kinetic Modeling of Liposomal Doxorubicin Delivery Quantifies the Role of Tumor and Drug-Specific Parameters in Local Delivery to Tumors

    PubMed Central

    Hendriks, B S; Reynolds, J G; Klinz, S G; Geretti, E; Lee, H; Leonard, S C; Gaddy, D F; Espelin, C W; Nielsen, U B; Wickham, T J

    2012-01-01

    Nanoparticle encapsulation has been used as a means to manipulate the pharmacokinetic (PK) and safety profile of drugs in oncology. Using pegylated liposomal doxorubicin (PLD) vs. conventional doxorubicin as a model system, we developed and experimentally validated a multiscale computational model of liposomal drug delivery. We demonstrated that, for varying tumor transport properties, there is a regimen where liposomal and conventional doxorubicin deliver identical amounts of doxorubicin to tumor cell nuclei. In mice, typical tumor properties consistently favor improved delivery via liposomes relative to free drug. However, in humans, we predict that some tumors will have properties wherein liposomal delivery delivers the identical amount of drug to its target relative to dosing with free drug. The ability to identify tumor types and/or individual patient tumors with high degree of liposome deposition may be critical for optimizing the success of nanoparticle and liposomal anticancer therapeutics. PMID:23835797

  16. Vacuolar Transport in Tobacco Leaf Epidermis Cells Involves a Single Route for Soluble Cargo and Multiple Routes for Membrane Cargo[W

    PubMed Central

    Bottanelli, Francesca; Foresti, Ombretta; Hanton, Sally; Denecke, Jürgen

    2011-01-01

    We tested if different classes of vacuolar cargo reach the vacuole via distinct mechanisms by interference at multiple steps along the transport route. We show that nucleotide-free mutants of low molecular weight GTPases, including Rab11, the Rab5 members Rha1 and Ara6, and the tonoplast-resident Rab7, caused induced secretion of both lytic and storage vacuolar cargo. In situ analysis in leaf epidermis cells indicates a sequential action of Rab11, Rab5, and Rab7 GTPases. Compared with Rab5 members, mutant Rab11 mediates an early transport defect interfering with the arrival of cargo at prevacuoles, while mutant Rab7 inhibits the final delivery to the vacuole and increases cargo levels in prevacuoles. In contrast with soluble cargo, membrane cargo may follow different routes. Tonoplast targeting of an α-TIP chimera was impaired by nucleotide-free Rha1, Ara6, and Rab7 similar to soluble cargo. By contrast, the tail-anchored tonoplast SNARE Vam3 shares only the Rab7-mediated vacuolar deposition step. The most marked difference was observed for the calcineurin binding protein CBL6, which was insensitive to all Rab mutants tested. Unlike soluble cargo, α-TIP and Vam3, CBL6 transport to the vacuole was COPII independent. The results indicate that soluble vacuolar proteins follow a single route to vacuoles, while membrane spanning proteins may use at least three different transport mechanisms. PMID:21856792

  17. 46 CFR 153.930 - Cargo antidotes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo antidotes. 153.930 Section 153.930 Shipping COAST... Cargo antidotes. No person may operate a tankship that carries a cargo listed in Table 1 unless the tankship has on board the antidotes described for the cargo in the Medical First Aid Guide for Use...

  18. 46 CFR 151.03-9 - Cargo.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo. 151.03-9 Section 151.03-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-9 Cargo. This term means any liquid, gas or solid having one...

  19. 46 CFR 151.03-9 - Cargo.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo. 151.03-9 Section 151.03-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-9 Cargo. This term means any liquid, gas or solid having one...

  20. 46 CFR 151.03-9 - Cargo.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo. 151.03-9 Section 151.03-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-9 Cargo. This term means any liquid, gas or solid having one...

  1. 46 CFR 151.03-9 - Cargo.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo. 151.03-9 Section 151.03-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-9 Cargo. This term means any liquid, gas or solid having one...

  2. 46 CFR 151.03-9 - Cargo.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo. 151.03-9 Section 151.03-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-9 Cargo. This term means any liquid, gas or solid having one...

  3. 29 CFR 1918.84 - Bulling cargo.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 7 2012-07-01 2012-07-01 false Bulling cargo. 1918.84 Section 1918.84 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo shall be done with the bull line led directly from the heel block. However, bulling may be done from...

  4. 29 CFR 1918.84 - Bulling cargo.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 7 2013-07-01 2013-07-01 false Bulling cargo. 1918.84 Section 1918.84 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo shall be done with the bull line led directly from the heel block. However, bulling may be done from...

  5. 29 CFR 1918.84 - Bulling cargo.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 7 2014-07-01 2014-07-01 false Bulling cargo. 1918.84 Section 1918.84 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo shall be done with the bull line led directly from the heel block. However, bulling may be done from...

  6. 29 CFR 1918.84 - Bulling cargo.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false Bulling cargo. 1918.84 Section 1918.84 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo shall be done with the bull line led directly from the heel block. However, bulling may be done from...

  7. 29 CFR 1918.84 - Bulling cargo.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 7 2011-07-01 2011-07-01 false Bulling cargo. 1918.84 Section 1918.84 Labor Regulations...) SAFETY AND HEALTH REGULATIONS FOR LONGSHORING Handling Cargo § 1918.84 Bulling cargo. (a) Bulling cargo shall be done with the bull line led directly from the heel block. However, bulling may be done from...

  8. 46 CFR 153.907 - Cargo information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...: (1) The name of the cargo as listed in table 1. (2) A description of the cargo's appearance and color... listed in Table 4 of Part 154 of this chapter or § 30.25-1 of this chapter if the cargo is listed in one of these two tables. (2) The name of the cargo prescribed in the letter authorizing carriage of...

  9. 46 CFR 64.97 - Cargo hose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Cargo hose. 64.97 Section 64.97 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Cargo Handling System § 64.97 Cargo hose. Each hose assembly, consisting of couplings and a...

  10. 46 CFR 64.97 - Cargo hose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Cargo hose. 64.97 Section 64.97 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Cargo Handling System § 64.97 Cargo hose. Each hose assembly, consisting of couplings and a...

  11. 46 CFR 64.97 - Cargo hose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Cargo hose. 64.97 Section 64.97 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Cargo Handling System § 64.97 Cargo hose. Each hose assembly, consisting of couplings and a...

  12. 46 CFR 64.97 - Cargo hose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Cargo hose. 64.97 Section 64.97 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Cargo Handling System § 64.97 Cargo hose. Each hose assembly, consisting of couplings and a...

  13. 46 CFR 64.97 - Cargo hose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Cargo hose. 64.97 Section 64.97 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND CARGO HANDLING SYSTEMS Cargo Handling System § 64.97 Cargo hose. Each hose assembly, consisting of couplings and a...

  14. Nuclear cargo detector

    DOEpatents

    Christo, Steven Basil

    2006-12-19

    Apparatus for the inspection of cargo containers for nuclear materials comprising one or more arrays of modules comprising grounded, closed conductive tubes filled with an ionizing gas mixture such as, but not limited to, Argon:CO.sub.2. A wire is suspended along each tube axis and electrically connected at both ends of the tube. A positive, dc high voltage is supplied to one end of the wire and an amplifier is attached to the other end through a capacitance to decouple the amplifier from the high voltage. X-rays, gamma rays or neutrons produced by nuclear material and passing through the tube ionize the gas. The electrons from the gas ionization process are accelerated toward the wire surface due to the wire's electrical potential. The acceleration of the electrons near the wire's surface is sufficient to ionize more gas and produce an amplification of electrons/ions that create a surge of current large enough to be detectable by the amplifier. Means are also provided for a warning device coupled to the amplifier.

  15. X-ray cargo inspection

    NASA Astrophysics Data System (ADS)

    Ries, Hermann; Hemp, Fred; Koch, Cornelius

    1994-10-01

    Increasing world trade, besides others, means to take care for a continuous flow of cargo. This is important if politicians want to improve a country's economy. There are a lot of technical means assisting to speed up the handling of the huge amount of cargo. But, just taking care for a fast handling of merchandise means to support the fraudulent and often dangerous activities of criminal syndicates and organizations. Responsible governmental officials are now supported in fulfilling their difficult task.

  16. GNeosomes: Highly Lysosomotropic Nanoassemblies for Lysosomal Delivery.

    PubMed

    Wexselblatt, Ezequiel; Esko, Jeffrey D; Tor, Yitzhak

    2015-01-01

    GNeosomes, lysosomotropic lipid vesicles decorated with guanidinoneomycin, can encapsulate and facilitate the cellular internalization and lysosomal delivery of cargo ranging from small molecules to high molecular weight proteins, in a process that is exclusively dependent on cell surface glycosaminoglycans. Their cellular uptake mechanism and co-localization with lysosomes, as well as the delivery, release, and activity of internalized cargo, are quantified. GNeosomes are proposed as a universal platform for lysosomal delivery with potential as a basic research tool and a therapeutic vehicle.

  17. 46 CFR 154.901 - Atmospheric control within cargo tanks and cargo piping systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Atmospheric control within cargo tanks and cargo piping... BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... within cargo tanks and cargo piping systems. (a) Each vessel must have a piping system for purging each...

  18. 46 CFR 154.901 - Atmospheric control within cargo tanks and cargo piping systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Atmospheric control within cargo tanks and cargo piping... BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... within cargo tanks and cargo piping systems. (a) Each vessel must have a piping system for purging each...

  19. 46 CFR 154.901 - Atmospheric control within cargo tanks and cargo piping systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Atmospheric control within cargo tanks and cargo piping... BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design... within cargo tanks and cargo piping systems. (a) Each vessel must have a piping system for purging each...

  20. Dual-controlled drug delivery across biodegradable copolymer. I. Delivery kinetics of levonorgestrel and estradiol through (caprolactone/lactide) block copolymer.

    PubMed

    Ye, W P; Chien, Y W

    1996-04-01

    Four block copolymers of caprolactone (CL) and dl-lactide (LA) with varying weight fractions were synthesized by living polymerization in the presence of Al/Zn bimetallic alkoxide complex. The solubility of levonorgestrel (LNG) and estradiol (E2) in the copolymers was evaluated and found to increase exponentially with CL mole fraction. Their aqueous solubilities were also studied and observed to increase linearly with the concentration of benzalkonium chloride (BAC), a solubilizer. The kinetics of LNG and E2 permeation through the copolymer membranes were studied and observed to follow a zero-order kinetics, and the permeation rates obtained were noted to be a function of copolymer composition. The release kinetics through the copolymer matrix were also studied and noted to follow a matrix-diffusion process, and the release flux was found to be dependent on copolymer composition. Permeation rates and release fluxes at steady state as well as the permeability and solubility of LNG and E2 in the copolymers suggest that these permeation parameters are affected by copolymer composition, which increase as the CL/LA ratio in the copolymer was increased.

  1. Sildenafil improves microvascular O2 delivery-to-utilization matching and accelerates exercise O2 uptake kinetics in chronic heart failure.

    PubMed

    Sperandio, Priscila A; Oliveira, Mayron F; Rodrigues, Miguel K; Berton, Danilo C; Treptow, Erika; Nery, Luiz E; Almeida, Dirceu R; Neder, J Alberto

    2012-12-15

    Nitric oxide (NO) can temporally and spatially match microvascular oxygen (O(2)) delivery (Qo(2mv)) to O(2) uptake (Vo(2)) in the skeletal muscle, a crucial adjustment-to-exercise tolerance that is impaired in chronic heart failure (CHF). To investigate the effects of NO bioavailability induced by sildenafil intake on muscle Qo(2mv)-to-O(2) utilization matching and Vo(2) kinetics, 10 males with CHF (ejection fraction = 27 ± 6%) undertook constant work-rate exercise (70-80% peak). Breath-by-breath Vo(2), fractional O(2)extraction in the vastus lateralis {∼deoxygenated hemoglobin + myoglobin ([deoxy-Hb + Mb]) by near-infrared spectroscopy}, and cardiac output (CO) were evaluated after sildenafil (50 mg) or placebo. Sildenafil increased exercise tolerance compared with placebo by ∼20%, an effect that was related to faster on- and off-exercise Vo(2) kinetics (P < 0.05). Active treatment, however, failed to accelerate CO dynamics (P > 0.05). On-exercise [deoxy-Hb + Mb] kinetics were slowed by sildenafil (∼25%), and a subsequent response "overshoot" (n = 8) was significantly lessened or even abolished. In contrast, [deoxy-Hb + Mb] recovery was faster with sildenafil (∼15%). Improvements in muscle oxygenation with sildenafil were related to faster on-exercise Vo(2) kinetics, blunted oscillations in ventilation (n = 9), and greater exercise capacity (P < 0.05). Sildenafil intake enhanced intramuscular Qo(2mv)-to-Vo(2) matching with beneficial effects on Vo(2) kinetics and exercise tolerance in CHF. The lack of effect on CO suggests that improvement in blood flow to and within skeletal muscles underlies these effects.

  2. Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

    PubMed

    Sengbusch, E; Pérez-Andújar, A; DeLuca, P M; Mackie, T R

    2009-02-01

    Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the

  3. Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy

    PubMed Central

    Sengbusch, E.; Pérez-Andújar, A.; DeLuca, P. M.; Mackie, T. R.

    2009-01-01

    Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180° continuous arc proton therapy and for 180° split arc proton therapy (two 90° arcs) using CT# profiles from the Pinnacle™ (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic

  4. Synaptic activation modifies microtubules underlying transport of postsynaptic cargo.

    PubMed

    Maas, Christoph; Belgardt, Dorthe; Lee, Han Kyu; Heisler, Frank F; Lappe-Siefke, Corinna; Magiera, Maria M; van Dijk, Juliette; Hausrat, Torben J; Janke, Carsten; Kneussel, Matthias

    2009-05-26

    Synaptic plasticity, the ability of synapses to change in strength, requires alterations in synaptic molecule compositions over time, and synapses undergo selective modifications on stimulation. Molecular motors operate in sorting/transport of neuronal proteins; however, the targeting mechanisms that guide and direct cargo delivery remain elusive. We addressed the impact of synaptic transmission on the regulation of intracellular microtubule (MT)-based transport. We show that increased neuronal activity, as induced through GlyR activity blockade, facilitates tubulin polyglutamylation, a posttranslational modification thought to represent a molecular traffic sign for transport. Also, GlyR activity blockade alters the binding of the MT-associated protein MAP2 to MTs. By using the kinesin (KIF5) and the postsynaptic protein gephyrin as models, we show that such changes of MT tracks are accompanied by reduced motor protein mobility and cargo delivery into neurites. Notably, the observed neurite targeting deficits are prevented on functional depletion or gene expression knockdown of neuronal polyglutamylase. Our data suggest a previously undescribed concept of synaptic transmission regulating MT-dependent cargo delivery.

  5. Evaluation of the cell survival curve under radiation exposure based on the kinetics of lesions in relation to dose-delivery time

    PubMed Central

    Matsuya, Yusuke; Tsutsumi, Kaori; Sasaki, Kohei; Date, Hiroyuki

    2015-01-01

    We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric–kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate. PMID:25355708

  6. Evaluation of the cell survival curve under radiation exposure based on the kinetics of lesions in relation to dose-delivery time.

    PubMed

    Matsuya, Yusuke; Tsutsumi, Kaori; Sasaki, Kohei; Date, Hiroyuki

    2015-01-01

    We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric-kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  7. 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.

  8. OA-7 Late Cargo Loading

    NASA Image and Video Library

    2017-03-03

    Inside the Payload Hazardous Servicing Facility at NASA's Kennedy Space Center in Florida, technicians perform the late cargo installation in the Orbital ATK Cygnus pressurized cargo module. The Orbital ATK CRS-7 commercial resupply services mission to the International Space Station is scheduled to launch atop a United Launch Alliance Atlas V rocket from Space Launch Complex 41 at Cape Canaveral Air Force Station targeted for March 24, 2017. Cygnus will deliver 7,600 pounds of supplies, equipment and scientific research materials to the space station.

  9. Cargo recognition and cargo-mediated regulation of unconventional myosins.

    PubMed

    Lu, Qing; Li, Jianchao; Zhang, Mingjie

    2014-10-21

    Organized motions are hallmarks of living organisms. Such motions range from collective cell movements during development and muscle contractions at the macroscopic scale all the way down to cellular cargo (e.g., various biomolecules and organelles) transportation and mechanoforce sensing at more microscopic scales. Energy required for these biological motions is almost invariably provided by cellular chemical fuels in the form of nucleotide triphosphate. Biological systems have designed a group of nanoscale engines, known as molecular motors, to convert cellular chemical fuels into mechanical energy. Molecular motors come in various forms including cytoskeleton motors (myosin, kinesin, and dynein), nucleic-acid-based motors, cellular membrane-based rotary motors, and so on. The main focus of this Account is one subfamily of actin filament-based motors called unconventional myosins (other than muscle myosin II, the remaining myosins are collectively referred to as unconventional myosins). In general, myosins can use ATP to fuel two types of mechanomotions: dynamic tethering actin filaments with various cellular compartments or structures and actin filament-based intracellular transport. In contrast to rich knowledge accumulated over many decades on ATP hydrolyzing motor heads and their interactions with actin filaments, how various myosins recognize their specific cargoes and whether and how cargoes can in return regulate functions of motors are less understood. Nonetheless, a series of biochemical and structural investigations in the past few years, including works from our own laboratory, begin to shed lights on these latter questions. Some myosins (e.g., myosin-VI) can function both as cellular transporters and as mechanical tethers. To function as a processive transporter, myosins need to form dimers or multimers. To be a mechanical tether, a monomeric myosin is sufficient. It has been shown for myosin-VI that its cellular cargo proteins can play critical roles

  10. Studies on silicon NMR characterization and kinetic modeling of the structural evolution of siloxane-based materials and their applications in drug delivery and adsorption

    NASA Astrophysics Data System (ADS)

    Ambati, Jyothirmai

    This dissertation presents studies of the synthetic processes and applications of siloxane-based materials. Kinetic investigations of bridged organoalkoxysilanes that are precursors to organic-inorganic hybrid polysilsesquioxanes are a primary focus. Quick gelation despite extensive cyclization is found during the polymerization of bridged silane precursors except for silanes with certain short bridges. This work is an attempt to characterize and understand some of the distinct features of bridged silanes using experimental characterization, kinetic modeling and simulation. In addition to this, the dissertation shows how the properties of siloxane-materials can be engineered for drug delivery and adsorption. The phase behavior of polymerizing mixtures is first investigated to identify the solutions that favor kinetic characterization. Microphase separation is found to cause gradual loss of NMR signal for certain initial compositions. Distortionless Enhancement by Polarization Transfer 29Si NMR is employed to identify the products of polymerization of some short-bridged silanes under no signal loss conditions. This technique requires knowing indirect 29Si-1H scalar coupling constants which sometimes cannot be measured due to second-order effects. However, the B3LYP density functional method with 6-31G basis set is found to predict accurate 29Si- 1H coupling constants of organoalkoxysilanes and siloxanes. The scalar coupling constants thus estimated are employed to resolve non-trivial coupled NMR spectra and quantitative kinetic modeling is performed using the DEPT Si NMR transients. In order to investigate the role of the organic bridging group, the structural evolution of bridged and non-bridged silanes are compared using Monte Carlo simulations. Kinetic and simulation models suggest that cyclization plays a key role right from the onset of polymerization for bridged silanes even more than in non-bridged silanes. The simulations indicate that the carbosiloxane

  11. 46 CFR 154.235 - Cargo tank location.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo... extents of damage must be measured to the inner hull. (d) For type IIG, IIPG, and IIIG hulls, cargo...

  12. 46 CFR 154.235 - Cargo tank location.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo... extents of damage must be measured to the inner hull. (d) For type IIG, IIPG, and IIIG hulls, cargo...

  13. 46 CFR 154.235 - Cargo tank location.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo... extents of damage must be measured to the inner hull. (d) For type IIG, IIPG, and IIIG hulls, cargo...

  14. 46 CFR 154.235 - Cargo tank location.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo... extents of damage must be measured to the inner hull. (d) For type IIG, IIPG, and IIIG hulls, cargo...

  15. Aircraft Cargo Compartment Fire Test Simulation Program

    NASA Technical Reports Server (NTRS)

    Blumke, R. E.

    1977-01-01

    The objective of the test was to assess fire containment and fire extinguishment in the cargo by reducing the ventilation through the cargo compartment. Parameters which were measured included ignition time, burnthrough time, and physical damage to the cargo liner, composition of selected combustible gases, temperature-time histories, heat flux, and detector response. The ignitor load was made of a typical cargo consisting of filled cardboard cartons occupying 50% of the compartment volume.

  16. Russian Cargo Craft Final Undocking

    NASA Image and Video Library

    The ISS Progress 47 resupply vehicle, loaded with trash, undocked from the International Space Station’s Pirs docking compartment for the final time July 30 at 5:19 p.m. EDT. The cargo ship undo...

  17. 46 CFR 154.901 - Atmospheric control within cargo tanks and cargo piping systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Atmospheric control within cargo tanks and cargo piping... BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Atmospheric Control in Cargo Containment Systems § 154.901 Atmospheric...

  18. 46 CFR 153.908 - Cargo viscosity and melting point information; measuring cargo temperature during discharge...

    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...

  19. 46 CFR 153.908 - Cargo viscosity and melting point information; measuring cargo temperature during discharge...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 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...

  20. 46 CFR 153.908 - Cargo viscosity and melting point information; measuring cargo temperature during discharge...

    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...

  1. 46 CFR 153.908 - Cargo viscosity and melting point information; measuring cargo temperature during discharge...

    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...

  2. Polymeric drugs with prolonged sustained delivery of specific anti-aggregant agents for platelets: kinetic analysis of the release mechanism.

    PubMed

    Gallardo, Alberto; Rodríguez, Gema; Fernández, Mar; Aguilar, María Rosa; San Román, Julio

    2004-01-01

    The in vitro aqueous behaviour of a metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate (THEMA)/N,N'-dimethylacrylamide (DMA) copolymer with a THEMA molar content of 39% (labeled THDMA39) has been investigated. This composition has been selected to achieve a system able to keep both the non-water solubility during the release and the resorbability (and the water solubility) after the completion of the drug release. This copolymer exhibited, at pH 7.4, a constant release during several months, very interesting for a long term treatments required for the application of some cardiovascular devices. A kinetic model has been developed to explain the pseudo-zero-order kinetics of the release process. This model, which considers (from the aqueous studies) a linear increase with time of the amount of water present in the polymeric matrix, has been able to fit adequately the experimental data.

  3. 46 CFR 153.907 - Cargo information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo information. 153.907 Section 153.907 Shipping... Information § 153.907 Cargo information. (a) The master shall ensure that the following information for each... process for the vessel. (b) The master shall make sure that the following information for cargoes other...

  4. 76 FR 53080 - Air Cargo Screening; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-25

    ...-6, 1549-1] RIN 1652-AA64 Air Cargo Screening; Correction AGENCY: Transportation Security... Administration (TSA) is correcting the Air Cargo Screening final rule published in the Federal Register on August 18, 2011. The final rule amended two provisions of the Air Cargo Screening interim final rule...

  5. Determination of high-risk cargo

    NASA Astrophysics Data System (ADS)

    Morris, Leo A.; Smith, Douglas E.; Khan, Siraj M.

    1994-10-01

    The approach and methodology used in the determination of the type of cargo containing concealments of commercial quantities of narcotics such as cocaine and heroin is described. This high-risk cargo enters the United States through border crossings at land, seaports and airports. The volume and variety of cargos make it a complex and challenging task for the U.S. Customs Service.

  6. Cargo-shell and cargo-cargo couplings govern the mechanics of artificially loaded virus-derived cages

    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

  7. Effect of initial pBMP-9 loading and collagen concentration on the kinetics of peptide release and a mathematical model of the delivery system.

    PubMed

    Lauzon, Marc-Antoine; Marcos, Bernard; Faucheux, Nathalie

    2014-05-28

    Type I collagen is one of the most widely used materials for drug delivery in tissue repair. It is the reference carrier for delivering growth factors like bone morphogenetic proteins (BMPs such as BMP-2 and BMP-7) for bone repair. Since BMPs are expensive to produce, we have developed a peptide derived from BMP-9 (pBMP-9) that is 300 times less expensive than the entire protein while still promoting osteogenic differentiation. We have now evaluated the effects of the collagen concentration and the initial pBMP-9 load on peptide release. We then developed a model of pBMP-9 release kinetics by finite differences using a system based on Fick's second law in which the interactions between the peptide and collagen fibers are assumed to follow Langmuir adsorption kinetics. The Langmuir isotherms suggest that the structure of the collagen gel influences the strength of its electrostatic interaction with the peptide, since increasing the collagen concentration decreased the affinity of pBMP-9 for the collagen. The resulting model of the mechanism accurately reflects the experimental data and the parameters estimated indicate that the diffusivities with the different collagen concentrations are similar, whereas the mass transfer coefficient increases with the collagen concentration. The results also indicate that perfect sink conditions cannot be assumed and suggest the presence of an optimal collagen concentration. Finally, we have correlated our conclusions with the differences in collagen fiber organization observed by transmission electron microscopy.

  8. Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

    NASA Astrophysics Data System (ADS)

    Sasikumar, Swamiappan

    2013-09-01

    Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

  9. 46 CFR 153.957 - Persons in charge of transferring liquid cargo in bulk or cleaning cargo tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... safely transfer liquid cargo in bulk or to safely clean cargo tanks; (2) Each transfer of liquid cargo in... or cleaning cargo tanks. 153.957 Section 153.957 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... transferring liquid cargo in bulk or cleaning cargo tanks. (a) The owner and operator of the vessel, and his...

  10. Thermoresponsive microcapsules for controlled release of hydrophilic cargo

    NASA Astrophysics Data System (ADS)

    Amstad, Esther; Weitz, David

    2012-02-01

    Thermoresponsive microcapsules that collapse upon increasing the temperature above their lower critical solution temperature (LCST) such as poly(N-isopropyl acrylamide) (PNIPAM) capsules are well known. However, capsules consisting of thermoresponsive polymers that possess an upper critical solution temperature (UCST) and therefore swell upon increasing the temperature above their UCST are scarce. We will present a microfluidic method to assemble thermoresponsive poly([2-(methacryloyloxy)-ethyl]-dimethyl-[3-sulfopropyl-ammoniumhzdroxide) (PMEDSH) microcapsules that have UCST. These capsules are in a collapsed state at room temperature and become highly water permeable upon increasing the temperature above the UCST. To simultaneously allow for encapsulation of hydrophilic cargo and enable the water based polymerization reaction of the PMEDSH shell, these microcapsules are assembled as water/water/oil emulsions using capillary microfluidic devices. The resulting PMEDSH microcapsules are envisaged as delivery vehicles and microreactors that allow for temperature induced controlled release of hydrophilic cargo. .

  11. Advanced propulsion options for the Mars cargo mission

    NASA Technical Reports Server (NTRS)

    Frisbee, Robert H.; Blandino, John J.; Sercel, Joel C.; Sargent, Mark S.; Gowda, Nandini

    1990-01-01

    Several advanced propulsion options for a split-mission piloted Mars exploration scenario are presented. The primary study focus is on identifying concepts that can reduce total initial mass in low earth orbit (IMLEO) for the cargo delivery portion of the mission; in addition, concepts that can reduce the trip time of the piloted option are assessed. The propulsion options considered are nuclear thermal propulsion, solar sails, multimegawatt-class nuclear electric propulsion, solar electric propulsion, magnetic sails, mass drivers, rail guns, solar thermal rockets, beamed-energy propulsion systems, and tethers. For the cargo mission, solar sails are found to provide the greatest mass savings over the baseline chemical system, although they suffer from having very long trip times; a good performance compromise between a low IMLEO and a short trip time can be obtained using multimegawatt-class nuclear electric propulsion systems.

  12. Solar electric propulsion cargo spacecraft for Mars missions

    NASA Astrophysics Data System (ADS)

    One of the topics available to the 1990-91 Aerospace Engineering senior class was the development of a preliminary design of an unmanned cargo ferry that would support the Mars mission by bringing equipment and supplies from a low Earth orbit (LEO) to a low Mars orbit (LMO). Several previous studies initiated by NASA have indicated that low-thrust transportation systems seem to offer the best performance for Mars missions. Such systems are characterized by long spiral times during escape and capture maneuvers, high payload mass fractions, and, typically, low propellant mass fractions. Of two main low-thrust candidates, nuclear electric propulsion (NEP) and solar electric propulsion (SEP), only the first one received extensive consideration because it seemed to represent the most promising concept for a manned mission to Mars. However, any sustained Mars initiative will have to include an unmanned cargo transportation system, for which an SEP concept deserves very careful consideration. The key assumptions and requirements established in cooperation with the Space Exploration Initiative office at the NASA Langley Research Center were (1) vehicle is assembled at the Space Station Freedom (SSF); (2) Earth-to-orbit delivery of the vehicle components, propellant, and payload is via shuttle-C; (3) vehicle's cargo mass is 61,000 kg; (4) vehicle delivers cargo to LMO at an altitude of 500 km and inclination of 70 deg; (5) vehicle returns (without cargo) to SSF; (6) vehicle should be reusable for at least three missions; and (7) vehicle is powered by ion argon thrusters. Two configurations were developed by two student teams, working mostly independently.

  13. Solar electric propulsion cargo spacecraft for Mars missions

    NASA Technical Reports Server (NTRS)

    1991-01-01

    One of the topics available to the 1990-91 Aerospace Engineering senior class was the development of a preliminary design of an unmanned cargo ferry that would support the Mars mission by bringing equipment and supplies from a low Earth orbit (LEO) to a low Mars orbit (LMO). Several previous studies initiated by NASA have indicated that low-thrust transportation systems seem to offer the best performance for Mars missions. Such systems are characterized by long spiral times during escape and capture maneuvers, high payload mass fractions, and, typically, low propellant mass fractions. Of two main low-thrust candidates, nuclear electric propulsion (NEP) and solar electric propulsion (SEP), only the first one received extensive consideration because it seemed to represent the most promising concept for a manned mission to Mars. However, any sustained Mars initiative will have to include an unmanned cargo transportation system, for which an SEP concept deserves very careful consideration. The key assumptions and requirements established in cooperation with the Space Exploration Initiative office at the NASA Langley Research Center were (1) vehicle is assembled at the Space Station Freedom (SSF); (2) Earth-to-orbit delivery of the vehicle components, propellant, and payload is via shuttle-C; (3) vehicle's cargo mass is 61,000 kg; (4) vehicle delivers cargo to LMO at an altitude of 500 km and inclination of 70 deg; (5) vehicle returns (without cargo) to SSF; (6) vehicle should be reusable for at least three missions; and (7) vehicle is powered by ion argon thrusters. Two configurations were developed by two student teams, working mostly independently.

  14. Proteomics characterization of exosome cargo.

    PubMed

    Schey, Kevin L; Luther, J Matthew; Rose, Kristie L

    2015-10-01

    Characterization of exosomal cargo is of significant interest because this cargo can provide clues to exosome biogenesis, targeting, and cellular effects and may be a source of biomarkers for disease diagnosis, prognosis and response to treatment. With recent improvements in proteomics technologies, both qualitative and quantitative characterization of exosomal proteins is possible. Here we provide a brief review of exosome proteomics studies and provide detailed protocols for global qualitative, global quantitative, and targeted quantitative analysis of exosomal proteins. In addition, we provide an example application of a standard global quantitative analysis followed by validation via a targeted quantitative analysis of urine exosome samples from human patients. Advantages and limitations of each method are discussed as well as future directions for exosome proteomics analysis.

  15. Proteomics Characterization of Exosome Cargo

    PubMed Central

    Schey, Kevin L.; Luther, J. Matthew; Rose, Kristie L.

    2015-01-01

    Characterization of exosomal cargo is of significant interest because this cargo can provide clues to exosome biogenesis, targeting, and cellular effects and may be a source of biomarkers for disease diagnosis, prognosis and response to treatment. With recent improvements in proteomics technologies, both qualitative and quantitative characterization of exosomal proteins is possible. Here we provide a brief review of exosome proteomics studies and provide detailed protocols for global qualitative, global quantitative, and targeted quantitative analysis of exosomal proteins. In addition, we provide an example application of a standard global quantitative analysis followed by validation via a targeted quantitative analysis of urine exosome samples from human patients. Advantages and limitations of each method are discussed as well as future directions for exosome proteomics analysis. PMID:25837312

  16. OA-7 Cargo Module Loading

    NASA Image and Video Library

    2017-02-07

    In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, technicians and engineers load thousands of pounds of supplies, equipment and scientific research materials aboard a Cygnus spacecraft's pressurized cargo module (PCM) for the Orbital ATK CRS-7 mission to the International Space Station. Scheduled to launch on March 19, 2017, the commercial resupply services mission will lift off atop a United Launch Alliance Atlas V rocket from Space launch Complex 41 at Cape Canaveral Air Force Station.

  17. OA-7 Cargo Module Loading

    NASA Image and Video Library

    2017-02-07

    In the Space Station Processing Facility at NASA's Kennedy Space Center in Florida, thousands of pounds of supplies, equipment and scientific research materials are prepared for loading aboard a Cygnus spacecraft's pressurized cargo module (PCM) for the Orbital ATK CRS-7 mission to the International Space Station. Scheduled to launch on March 19, 2017, the commercial resupply services mission will lift off atop a United Launch Alliance Atlas V rocket from Space launch Complex 41 at Cape Canaveral Air Force Station.

  18. Nonlinear absorption kinetics of self-emulsifying drug delivery systems (SEDDS) containing tocotrienols as lipophilic molecules: in vivo and in vitro studies.

    PubMed

    Alqahtani, Saeed; Alayoubi, Alaadin; Nazzal, Sami; Sylvester, Paul W; Kaddoumi, Amal

    2013-07-01

    Self-emulsifying drug delivery systems (SEDDS) have been broadly used to promote the oral absorption of poorly water-soluble drugs. The purpose of the current study was to evaluate the in vivo oral bioavailability of vitamin E isoforms, δ-tocotrienol (δ-T3) and γ-tocotrienol (γ-T3) administered as SEDDS, as compared to commercially available UNIQUE E® Tocotrienols capsules. Results from studies in rats showed that low dose treatment with δ-T3 (90%) and γ-T3 (10%) formulated SEDDS showed bioavailability of 31.5% and 332%, respectively. However, bioavailability showed a progressive decrease with increased treatment dose that displayed nonlinear absorption kinetics. Additional in vitro studies examining cellular uptake studies in Caco 2 cells revealed that the SEDDS formulation increased passive permeability of δ-T3 and γ-T3 by threefold as compared to the commercial capsule formulation. These studies also showed that free surfactants decreased δ-T3 and γ-T3 absorption. Specifically, combined treatment cremophor EL or labrasol with tocotrienols caused a 60-85% reduction in the cellular uptake of δ-T3 and γ-T3 and these effects appear to result from surfactant-induced inhibition of the δ-T3 and γ-T3 transport protein Niemann-Pick C1-like 1 (NPC1L1). In summary, results showed that SEDDS formulation significantly increases the absorption and bioavailability δ-T3 and γ-T3. However, this effect is self-limiting because treatment with increasing doses of SEDDS appears to be associated with a corresponding increase in free surfactants levels that directly and negatively impact tocotrienol transport protein function and results in nonlinear absorption kinetics and a progressive decrease in δ-T3 and γ-T3 absorption and bioavailability.

  19. Communication: Cargo towing by artificial swimmers

    NASA Astrophysics Data System (ADS)

    Debnath, Debajyoti; Ghosh, Pulak K.; Li, Yunyun; Marchesoni, Fabio; Li, Baowen

    2016-11-01

    An active swimmer can tow a passive cargo by binding it to form a self-propelling dimer. The orientation of the cargo relative to the axis of the active dimer's head is determined by the hydrodynamic interactions associated with the propulsion mechanism of the latter. We show how the tower-cargo angular configuration greatly influences the dimer's diffusivity and, therefore, the efficiency of the active swimmer as a micro-towing motor.

  20. 49 CFR 180.416 - Discharge system inspection and maintenance program for cargo tanks transporting liquefied...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Cargo Tanks § 180.416 Discharge system inspection and maintenance program for... unloading. (d) Monthly inspections and tests. (1) The operator must visually inspect each delivery...

  1. Preparation, characterization, release kinetics, and in vitro cytotoxicity of calcium silicate cement as a risedronate delivery system.

    PubMed

    Gong, Tianxing; Wang, Zhiqin; Zhang, Yubiao; Sun, Changshan; Yang, Quanzu; Troczynski, Tom; Häfeli, Urs O

    2014-07-01

    Injectable bone cements have been well characterized and studied in non-load bearing bone fixation and bone screw augmentation applications. Current calcium phosphate cement or poly(methyl methacrylate) cement have drawbacks like low mechanical strength and in situ exothermic properties. This leads especially in patients with osteoporosis to worsening contact between implant and bone and can finally lead to implant failure. To improve these properties, a calcium silicate cement (CSC) was prepared, which additionally contained the bisphosphonate risedronate (RA) to promote osteoblast function. Cement setting rate and compressive strength were measured and found to be reduced by RA above 0.5 wt%. X-ray diffraction, Rietveld refinement analysis, scanning electron microscopy, and porosity measurements by gas sorption revealed that RA reduces calcium silicate hydrate gel formation and changes the cement's microstructure. Cumulative release profiles of RA from CSC up to 6 months into phosphate buffer solution were analyzed by high-performance liquid chromatography, and the results were compared with theoretical release curves obtained from the Higuchi equation. Fourier transform infrared spectra measurements and drug release studies indicate that calcium-RA formed within the cement, from which the drug can be slowly released over time. An investigation of the cytotoxicity of the RA-CSC systems upon osteoblast-like cells showed no toxic effects of concentrations up to 2%. The delivery of RA from within a CSC might thus be a valuable and biocompatible new approach to locally deliver RA and to reconstruct and/or repair osteoporosis-related bone fractures.

  2. Turboprop cargo aircraft systems study

    NASA Technical Reports Server (NTRS)

    Muehlbauer, J. C.; Hewell, J. G., Jr.; Lindenbaum, S. P.; Randall, C. C.; Searle, N.; Stone, R. G., Jr.

    1981-01-01

    The effects of using advanced turboprop propulsion systems to reduce the fuel consumption and direct operating costs of cargo aircraft were studied, and the impact of these systems on aircraft noise and noise prints around a terminal area was determined. Parametric variations of aircraft and propeller characteristics were investigated to determine their effects on noiseprint areas, fuel consumption, and direct operating costs. From these results, three aircraft designs were selected and subjected to design refinements and sensitivity analyses. Three competitive turbofan aircraft were also defined from parametric studies to provide a basis for comparing the two types of propulsion.

  3. 46 CFR 153.285 - Valving for cargo pump manifolds.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo lines serving different tanks enter a pumproom and connect to the same pump: (1) Each cargo line...

  4. 46 CFR 153.285 - Valving for cargo pump manifolds.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo lines serving different tanks enter a pumproom and connect to the same pump: (1) Each cargo line...

  5. 46 CFR 153.285 - Valving for cargo pump manifolds.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo lines serving different tanks enter a pumproom and connect to the same pump: (1) Each cargo line...

  6. 46 CFR 153.333 - Cargo pump discharge pressure gauge.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153.333 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES... Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room...

  7. 46 CFR 153.333 - Cargo pump discharge pressure gauge.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153.333 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES... Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room...

  8. 46 CFR 153.333 - Cargo pump discharge pressure gauge.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153.333 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES... Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room...

  9. 46 CFR 153.285 - Valving for cargo pump manifolds.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Valving for cargo pump manifolds. 153.285 Section 153... Piping Systems and Cargo Handling Equipment § 153.285 Valving for cargo pump manifolds. (a) When cargo lines serving different tanks enter a pumproom and connect to the same pump: (1) Each cargo line...

  10. 46 CFR 154.554 - Cargo hose: Bursting pressure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo hose: Bursting pressure. 154.554 Section 154.554... Hose § 154.554 Cargo hose: Bursting pressure. Cargo hose that may be exposed to the pressure in the cargo tank, the cargo pump discharge, or the vapor compressor discharge must have a bursting pressure...

  11. 46 CFR 154.554 - Cargo hose: Bursting pressure.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo hose: Bursting pressure. 154.554 Section 154.554... Hose § 154.554 Cargo hose: Bursting pressure. Cargo hose that may be exposed to the pressure in the cargo tank, the cargo pump discharge, or the vapor compressor discharge must have a bursting pressure...

  12. 46 CFR 154.554 - Cargo hose: Bursting pressure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo hose: Bursting pressure. 154.554 Section 154.554... Hose § 154.554 Cargo hose: Bursting pressure. Cargo hose that may be exposed to the pressure in the cargo tank, the cargo pump discharge, or the vapor compressor discharge must have a bursting pressure...

  13. 46 CFR 154.554 - Cargo hose: Bursting pressure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo hose: Bursting pressure. 154.554 Section 154.554... Hose § 154.554 Cargo hose: Bursting pressure. Cargo hose that may be exposed to the pressure in the cargo tank, the cargo pump discharge, or the vapor compressor discharge must have a bursting pressure...

  14. 46 CFR 154.476 - Cargo transfer devices and means.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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... of cargo transfer, such as another pump or gas pressurization. (b) If cargo is transferred by...

  15. 46 CFR 154.476 - Cargo transfer devices and means.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 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... of cargo transfer, such as another pump or gas pressurization. (b) If cargo is transferred by...

  16. 46 CFR 154.476 - Cargo transfer devices and means.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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... of cargo transfer, such as another pump or gas pressurization. (b) If cargo is transferred by...

  17. 46 CFR 154.476 - Cargo transfer devices and means.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 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... of cargo transfer, such as another pump or gas pressurization. (b) If cargo is transferred by...

  18. 46 CFR 154.1834 - Cargo transfer piping.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo transfer piping. 154.1834 Section 154.1834 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... piping. The person in charge of cargo transfer shall ensure that cargo is transferred to or from a cargo...

  19. 46 CFR 154.1834 - Cargo transfer piping.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo transfer piping. 154.1834 Section 154.1834 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... piping. The person in charge of cargo transfer shall ensure that cargo is transferred to or from a cargo...

  20. 46 CFR 154.1834 - Cargo transfer piping.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo transfer piping. 154.1834 Section 154.1834 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... piping. The person in charge of cargo transfer shall ensure that cargo is transferred to or from a cargo...

  1. 46 CFR 154.1834 - Cargo transfer piping.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo transfer piping. 154.1834 Section 154.1834 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... piping. The person in charge of cargo transfer shall ensure that cargo is transferred to or from a cargo...

  2. 46 CFR 154.1834 - Cargo transfer piping.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo transfer piping. 154.1834 Section 154.1834 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... piping. The person in charge of cargo transfer shall ensure that cargo is transferred to or from a cargo...

  3. 46 CFR 151.20-10 - Cargo system instrumentation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo system instrumentation. 151.20-10 Section 151.20... BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-10 Cargo system... be located at the cargo handling control station or another approved location. (b) Where required...

  4. 46 CFR 151.20-10 - Cargo system instrumentation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo system instrumentation. 151.20-10 Section 151.20... BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Transfer § 151.20-10 Cargo system... be located at the cargo handling control station or another approved location. (b) Where required...

  5. Optimizing an undulating magnetic microswimmer for cargo towing

    NASA Astrophysics Data System (ADS)

    Or, Yizhar; Gutman, Emiliya

    2015-11-01

    One of the promising applications of robotic microswimmers is towing a cargo for controlled drug delivery, micro-surgery or tumor detection. This capability has been demonstrated by the magnetically-actuated microswimmer of Dreyfus et al. [Nature 2005] in which a red blood cell was attached to a chain of magnetic beads connected by flexible DNA links. A key question is what should be the optimal size of the magnetic tail for towing a given cargo. This question is addressed here for the simplest theoretical model of a magnetic microswimmer under planar undulations - a spherical load connected by a torsion spring to a magnetized rigid slender link. The swimmer's dynamics is formulated assuming negligible hydrodynamic interaction and leading-order expressions for the resulting motion are obtained explicitly under small amplitude approximation. Optimal combinations of magnetic actuation frequency, torsion stiffness, and tail length for maximizing displacement or average speed are obtained. The theoretical results are compared with several reported magnetic microswimmers, and also agree qualitatively with recent results on cargo towing by screw rotation of magnetic helical tails [Walker et al., ACS Nano Letters 2015]. This work is supported by the Israeli Science Foundation (ISF) under Grant No. 567/14.

  6. A Novel Multilayered RFID Tagged Cargo Integrity Assurance Scheme

    PubMed Central

    Yang, Ming Hour; Luo, Jia Ning; Lu, Shao Yong

    2015-01-01

    To minimize cargo theft during transport, mobile radio frequency identification (RFID) grouping proof methods are generally employed to ensure the integrity of entire cargo loads. However, conventional grouping proofs cannot simultaneously generate grouping proofs for a specific group of RFID tags. The most serious problem of these methods is that nonexistent tags are included in the grouping proofs because of the considerable amount of time it takes to scan a high number of tags. Thus, applying grouping proof methods in the current logistics industry is difficult. To solve this problem, this paper proposes a method for generating multilayered offline grouping proofs. The proposed method provides tag anonymity; moreover, resolving disputes between recipients and transporters over the integrity of cargo deliveries can be expedited by generating grouping proofs and automatically authenticating the consistency between the receipt proof and pick proof. The proposed method can also protect against replay attacks, multi-session attacks, and concurrency attacks. Finally, experimental results verify that, compared with other methods for generating grouping proofs, the proposed method can efficiently generate offline grouping proofs involving several parties in a supply chain using mobile RFID. PMID:26512673

  7. 46 CFR 154.901 - Atmospheric control within cargo tanks and cargo piping systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... within cargo tanks and cargo piping systems. (a) Each vessel must have a piping system for purging each... remaining after purging. (c) For cargo tanks certificated to carry flammable gases, the piping system must allow purging the tank of flammable vapors before air is introduced and purging the tank of air...

  8. 46 CFR 154.315 - Cargo pump and cargo compressor rooms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... compressors are driven by a prime mover in an adjacent gas safe space: (1) The bulkhead or deck must be... 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...

  9. Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device

    PubMed Central

    Amante, Dinah H.; Smith, Trevor R.F.; Mendoza, Janess M.; Schultheis, Katherine; McCoy, Jay R.; Khan, Amir S.; Sardesai, Niranjan Y.; Broderick, Kate E.

    2015-01-01

    The CELLECTRA-3P dermal electroporation device (Inovio Pharmaceuticals, Plymouth Meeting, PA) has been evaluated in the clinic and shown to enhance the delivery of an influenza DNA vaccine. To understand the mechanism by which this device aids in enhancing the host immune response to DNA vaccines we investigated the expression kinetics and localization of a reporter plasmid (pGFP) delivered via the CELLECTRA-3P. Histological analysis revealed green fluorescent protein (GFP) expression as early as 1 hr posttreatment in the epidermal and dermal layers, and as early as 2 hr posttreatment in the subdermal layers. Immunofluorescence techniques identified keratinocytes, fibrocytes, dendritic-like cells, adipocytes, and myocytes as the principal cell populations transfected. We proceeded to demonstrate elicitation of robust host immune responses after plasmid DNA (pDNA) vaccination. In guinea pigs equivalent humoral (antibody binding titers) immune responses were observed between protocols using either CELLECTRA-3P or intramuscular electroporation to deliver the DNA vaccine. In nonhuman primates, robust interferon-γ enzyme-linked immunospot and protective levels of hemagglutination inhibition titers after pDNA vaccination were observed in groups treated with the CELLECTRA-3P. In conclusion, these findings may assist in the future to design efficient, tolerable DNA vaccination strategies for the clinic. PMID:26222896

  10. 49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION... 49 Transportation 9 2014-10-01 2014-10-01 false Access to cargo and cargo screening: Security... aircraft; or who performs certain functions related to the transportation, dispatch, or security of...

  11. 49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION... 49 Transportation 9 2013-10-01 2013-10-01 false Access to cargo and cargo screening: Security... aircraft; or who performs certain functions related to the transportation, dispatch, or security of...

  12. 49 CFR 1544.228 - Access to cargo and cargo screening: Security threat assessments for cargo personnel in the...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION... 49 Transportation 9 2012-10-01 2012-10-01 false Access to cargo and cargo screening: Security... aircraft; or who performs certain functions related to the transportation, dispatch, or security of...

  13. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy

    PubMed Central

    Mancias, Joseph D.; Wang, Xiaoxu; Gygi, Steven P.; Harper, J. Wade; Kimmelman, Alec C.

    2014-01-01

    Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration1,2. Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo including organelles, proteins, or intracellular pathogens are targeted for selective autophagy is limited3. We employed quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins, including cargo receptors. Like known cargo receptors, NCOA4 was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species4 but is degraded via autophagy to release iron5,6 through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin leads to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy) critical for iron homeostasis and provides a resource for further dissection of autophagosomal cargo-receptor connectivity. PMID:24695223

  14. Development of Nanoparticles Incorporating a Novel Liposomal Membrane Destabilization Peptide for Efficient Release of Cargos into Cancer Cells

    PubMed Central

    Ohgita, Takashi; Kogure, Kentaro

    2014-01-01

    In anti-cancer therapy mediated by a nanoparticle-based drug delivery system (DDS), overall efficacy depends on the release efficiency of cargos from the nanoparticles in the cancer cells as well as the specificity of delivery to tumor tissue. However, conventional liposome-based DDS have no mechanism for specifically releasing the encapsulated cargos inside the cancer cells. To overcome this barrier, we developed nanoparticles containing a novel liposomal membrane destabilization peptide (LMDP) that can destabilize membranes by cleavage with intramembranous proteases on/in cancer cells. Calcein encapsulated in liposomes modified with LMDP (LMDP-lipo) was effectively released in the presence of a membrane fraction containing an LMDP-cleavable protease. The release was inhibited by a protease inhibitor, suggesting that LMDP-lipo could effectively release its cargo into cells in response to a cancer-specific protease. Moreover, when LMDP-lipo contained fusogenic lipids, the release of cargo was accelerated, suggesting that the fusion of LMDP-lipo with cellular membranes was the initial step in the intracellular delivery. Time-lapse microscopic observations showed that the release of cargo from LMDP-lipo occurred immediately after association of LMDP-lipo with target cells. Consequently, LMDP-lipo could be a useful nanoparticle capable of effective release of cargos specifically into targeted cancer cells. PMID:25343714

  15. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Segregation of cargo from surrounding waters (Line 1 of Table 151.05). i=Skin of vessel (single skin) only required. Cargo tank wall can be vessel's hull. ii=Double skin required. Cargo tank wall cannot be...

  16. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Segregation of cargo from surrounding waters (Line 1 of Table 151.05). i = Skin of vessel (single skin) only required. Cargo tank wall can be vessel's hull. ii = Double skin required. Cargo tank wall cannot be...

  17. 19 CFR 122.115 - Labeling of cargo.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AIR COMMERCE REGULATIONS Transit Air Cargo Manifest (TACM) Procedures § 122.115 Labeling of cargo. A warning label, as required by § 18.4(e) of this chapter, shall be attached to all transit air cargo...

  18. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Segregation of cargo from surrounding waters (Line 1 of Table 151.05). i=Skin of vessel (single skin) only required. Cargo tank wall can be vessel's hull. ii=Double skin required. Cargo tank wall cannot be vessel's...

  19. 14 CFR 29.787 - Cargo and baggage compartments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Personnel and Cargo Accommodations § 29.787 Cargo and baggage compartments. (a) Each cargo and baggage compartment must be...

  20. 14 CFR 27.787 - Cargo and baggage compartments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Personnel and Cargo Accommodations § 27.787 Cargo and baggage compartments. (a) Each cargo and baggage compartment must be...

  1. 46 CFR 28.885 - Cargo gear.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 1 2012-10-01 2012-10-01 false Cargo gear. 28.885 Section 28.885 Shipping COAST GUARD... Aleutian Trade Act Vessels § 28.885 Cargo gear. (a) The safe working load (SWL) for the assembled gear... the load the gear is approved to lift, excluding the weight of the gear itself. (b) All wire...

  2. 46 CFR 28.885 - Cargo gear.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 1 2014-10-01 2014-10-01 false Cargo gear. 28.885 Section 28.885 Shipping COAST GUARD... Aleutian Trade Act Vessels § 28.885 Cargo gear. (a) The safe working load (SWL) for the assembled gear... the load the gear is approved to lift, excluding the weight of the gear itself. (b) All wire...

  3. 46 CFR 28.885 - Cargo gear.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 1 2013-10-01 2013-10-01 false Cargo gear. 28.885 Section 28.885 Shipping COAST GUARD... Aleutian Trade Act Vessels § 28.885 Cargo gear. (a) The safe working load (SWL) for the assembled gear... the load the gear is approved to lift, excluding the weight of the gear itself. (b) All wire...

  4. 46 CFR 28.885 - Cargo gear.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Cargo gear. 28.885 Section 28.885 Shipping COAST GUARD... Aleutian Trade Act Vessels § 28.885 Cargo gear. (a) The safe working load (SWL) for the assembled gear... the load the gear is approved to lift, excluding the weight of the gear itself. (b) All wire...

  5. 46 CFR 28.885 - Cargo gear.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Cargo gear. 28.885 Section 28.885 Shipping COAST GUARD... Aleutian Trade Act Vessels § 28.885 Cargo gear. (a) The safe working load (SWL) for the assembled gear... the load the gear is approved to lift, excluding the weight of the gear itself. (b) All wire...

  6. 49 CFR 172.328 - Cargo tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SECURITY PLANS Marking § 172.328 Cargo tanks. (a) Providing and affixing identification numbers. Unless a cargo tank is already marked with the identification numbers required by this subpart, the identification numbers must be provided or affixed as follows: (1) A person who offers a hazardous material to a...

  7. 46 CFR 45.179 - Cargo limitations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Cargo limitations. 45.179 Section 45.179 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Unmanned River... cargoes, even in drums or tank containers, may not be carried. (b) Hazardous materials, as defined in part...

  8. 46 CFR 45.179 - Cargo limitations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Cargo limitations. 45.179 Section 45.179 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES Unmanned River... cargoes, even in drums or tank containers, may not be carried. (b) Hazardous materials, as defined in part...

  9. 76 FR 51847 - Air Cargo Screening

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... Transportation Security Administration (TSA) establish a system to screen 100 percent of cargo transported on... Facilities (CCSFs) to screen cargo prior to transport on passenger aircraft. Under the IFR, each CCSF... certification is appropriate. The IFR also required that if an aircraft operator or foreign air carrier screens...

  10. 48 CFR 470.203 - Cargo preference.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Cargo preference. 470.203 Section 470.203 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE FOOD ASSISTANCE PROGRAMS COMMODITY ACQUISITIONS 470.203 Cargo preference. An agency having responsibility under this subpart shall...

  11. Effects of dose-delivery time structure on biological effectiveness for therapeutic carbon-ion beams evaluated with microdosimetric kinetic model.

    PubMed

    Inaniwa, Taku; Suzuki, Masao; Furukawa, Takuji; Kase, Yuki; Kanematsu, Nobuyuki; Shirai, Toshiyuki; Hawkins, Roland B

    2013-07-01

    Treatment plans of carbon-ion radiotherapy have been made on the assumption that the beams are delivered instantaneously irrespective to the dose delivery time as well as the interruption time. The advanced therapeutic techniques such as a hypofractionation and a respiratory gating usually require more time to deliver a fractioned dose than conventional techniques. The purpose of this study was to investigate the effects of dose-delivery time structure on biological effectiveness in carbon-ion radiotherapy. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions caused in the DNA were reanalyzed and applied to continuous or interrupted irradiation with therapeutic carbon-ion beams. The rate constants characterizing the time of the primary nonlethal lesions to repair or to convert to lethal lesion were experimentally determined for human salivary gland (HSG) tumor cells. Treatment plans were made for a patient case on the assumption that the beam is delivered instantaneously. The RBE weighted absorbed doses of 2.65, 3.45 and 6.86 Gy (RBE) was prescribed to the target. These plans were recalculated by varying the dose delivery time and the interruption time ranging from 1-60 min based on the MKM with the determined parameters. The sum of rate constants for nonlethal lesion to repair a and to convert to lethal lesion c, (a + c), is 2.19 ± 0.40 h⁻¹. The biological effectiveness in the target decreases with the dose delivery time T in continuous irradiation compared to the planned one due to the repair of nonlethal lesions during the irradiation. The biological effectiveness in terms of equivalent acute dose decreases to 99.7% and 96.4% for T = 3 and 60 min in 2.65 Gy (RBE), 99.5% and 94.3% in 4.35 Gy (RBE), and 99.4% and 91.7% in 6.86 Gy (RBE), respectively. For all the cases, the decrease of biological effectiveness is larger at the proximal side with low-LET than the distal side with high-LET. Similar reductions of biological

  12. OA-7 Cargo Module Arrival

    NASA Image and Video Library

    2017-01-09

    The Orbital ATK OA-7 Cygnus spacecraft's pressurized cargo module (PCM) arrives at the Space Station Processing Facility of NASA's Kennedy Space Center in Florida. The PCM is sealed in an environmentally controlled shipping container, pulled in by truck on a low-boy flatbed trailer. Scheduled to launch in March 2017, the Orbital ATK OA-7 mission will lift off atop a United Launch Alliance Atlas V rocket from Space launch Complex 41 at Cape Canaveral Air Force Station. The commercial resupply services mission to the International Space Station will deliver thousands of pounds of supplies, equipment and scientific research materials that improve life on Earth and drive progress toward future space exploration.

  13. 46 CFR 105.25-10 - Cargo pumping installation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... COMMERCIAL FISHING VESSELS DISPENSING PETROLEUM PRODUCTS Additional Requirements-When Cargo Tanks Are... cargo tank compartment unless the drive system is outside the compartment. (b) Suction pipelines from...

  14. 46 CFR 105.25-10 - Cargo pumping installation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... COMMERCIAL FISHING VESSELS DISPENSING PETROLEUM PRODUCTS Additional Requirements-When Cargo Tanks Are... cargo tank compartment unless the drive system is outside the compartment. (b) Suction pipelines from...

  15. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    DOE PAGES

    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

  16. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    SciTech Connect

    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

    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, 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.

  17. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    PubMed

    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.

  18. Characterizing the composition of molecular motors on moving axonal cargo using "cargo mapping" analysis.

    PubMed

    Neumann, Sylvia; Campbell, George E; Szpankowski, Lukasz; Goldstein, Lawrence S B; Encalada, Sandra E

    2014-10-30

    Understanding the mechanisms by which molecular motors coordinate their activities to transport vesicular cargoes within neurons requires the quantitative analysis of motor/cargo associations at the single vesicle level. The goal of this protocol is to use quantitative fluorescence microscopy to correlate ("map") the position and directionality of movement of live cargo to the composition and relative amounts of motors associated with the same cargo. "Cargo mapping" consists of live imaging of fluorescently labeled cargoes moving in axons cultured on microfluidic devices, followed by chemical fixation during recording of live movement, and subsequent immunofluorescence (IF) staining of the exact same axonal regions with antibodies against motors. Colocalization between cargoes and their associated motors is assessed by assigning sub-pixel position coordinates to motor and cargo channels, by fitting Gaussian functions to the diffraction-limited point spread functions representing individual fluorescent point sources. Fixed cargo and motor images are subsequently superimposed to plots of cargo movement, to "map" them to their tracked trajectories. The strength of this protocol is the combination of live and IF data to record both the transport of vesicular cargoes in live cells and to determine the motors associated to these exact same vesicles. This technique overcomes previous challenges that use biochemical methods to determine the average motor composition of purified heterogeneous bulk vesicle populations, as these methods do not reveal compositions on single moving cargoes. Furthermore, this protocol can be adapted for the analysis of other transport and/or trafficking pathways in other cell types to correlate the movement of individual intracellular structures with their protein composition. Limitations of this protocol are the relatively low throughput due to low transfection efficiencies of cultured primary neurons and a limited field of view available for

  19. Improving the Endosomal Escape of Cell-Penetrating Peptides and Their Cargos: Strategies and Challenges

    PubMed Central

    Erazo-Oliveras, Alfredo; Muthukrishnan, Nandhini; Baker, Ryan; Wang, Ting-Yi; Pellois, Jean-Philippe

    2012-01-01

    Cell penetrating peptides (CPPs) can deliver cell-impermeable therapeutic cargos into cells. In particular, CPP-cargo conjugates tend to accumulate inside cells by endocytosis. However, they often remain trapped inside endocytic organelles and fail to reach the cytosolic space of cells efficiently. In this review, the evidence for CPP-mediated endosomal escape is discussed. In addition, several strategies that have been utilized to enhance the endosomal escape of CPP-cargos are described. The recent development of branched systems that display multiple copies of a CPP is presented. The use of viral or synthetic peptides that can disrupt the endosomal membrane upon activation by the low pH of endosomes is also discussed. Finally, we survey how CPPs labeled with chromophores can be used in combination with light to stimulate endosomal lysis. The mechanisms and challenges associated with these intracellular delivery methodologies are discussed. PMID:24223492

  20. Mechanized azobenzene-functionalized zirconium metal-organic framework for on-command cargo release

    PubMed Central

    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

  1. Mechanized azobenzene-functionalized zirconium metal-organic framework for on-command cargo release.

    PubMed

    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.

  2. 46 CFR 98.30-11 - Cargo pumps.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Cargo pumps. 98.30-11 Section 98.30-11 Shipping COAST..., ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Portable Tanks § 98.30-11 Cargo pumps. No person may operate a cargo pump to transfer a product to or from a portable tank unless the...

  3. 46 CFR 98.30-11 - Cargo pumps.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Cargo pumps. 98.30-11 Section 98.30-11 Shipping COAST..., ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Portable Tanks § 98.30-11 Cargo pumps. No person may operate a cargo pump to transfer a product to or from a portable tank unless the...

  4. 46 CFR 98.30-11 - Cargo pumps.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Cargo pumps. 98.30-11 Section 98.30-11 Shipping COAST..., ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Portable Tanks § 98.30-11 Cargo pumps. No person may operate a cargo pump to transfer a product to or from a portable tank unless the...

  5. 46 CFR 105.25-10 - Cargo pumping installation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... COMMERCIAL FISHING VESSELS DISPENSING PETROLEUM PRODUCTS Additional Requirements-When Cargo Tanks Are Installed Below Decks § 105.25-10 Cargo pumping installation. (a) Cargo pumps shall not be installed in the... cargo tanks shall be run directly to the pump, but not through working or crew spaces of vessel....

  6. 46 CFR 148.450 - Cargoes subject to liquefaction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... moisture limit. (2) Moisture migration is the movement of moisture by settling and consolidation of a... that— (1) A cargo containing a liquid is not stowed in the same cargo space with a cargo subject to liquefaction; and (2) Precautions are taken to prevent the entry of liquids into a cargo space containing a...

  7. 46 CFR 154.412 - Cargo tank corrosion allowance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo tank corrosion allowance. 154.412 Section 154.412... Containment Systems § 154.412 Cargo tank corrosion allowance. A cargo tank must be designed with a corrosion...) carries a cargo that corrodes the tank material. Note: Corrosion allowance for independent tank type C...

  8. 46 CFR 154.412 - Cargo tank corrosion allowance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo tank corrosion allowance. 154.412 Section 154.412... Containment Systems § 154.412 Cargo tank corrosion allowance. A cargo tank must be designed with a corrosion...) carries a cargo that corrodes the tank material. Note: Corrosion allowance for independent tank type C...

  9. 46 CFR 98.30-11 - Cargo pumps.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Cargo pumps. 98.30-11 Section 98.30-11 Shipping COAST..., ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Portable Tanks § 98.30-11 Cargo pumps. No person may operate a cargo pump to transfer a product to or from a portable tank unless the...

  10. 46 CFR 154.560 - Cargo hose: Prototype test.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo hose: Prototype test. 154.560 Section 154.560 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo Hose § 154.560 Cargo hose: Prototype test...

  11. 46 CFR 153.1020 - Unusually toxic cargoes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... cargo. (c) No person may discharge overboard condensed steam from the heating system of a cargo... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Operations Special Cargo... section in Table 1 unless the cargo's piping and venting systems are separated from piping and venting...

  12. 46 CFR 153.333 - Cargo pump discharge pressure gauge.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must have a discharge pressure gauge outside the pumproom....

  13. 46 CFR 154.556 - Cargo hose: Maximum working pressure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo hose: Maximum working pressure. 154.556 Section... Equipment Cargo Hose § 154.556 Cargo hose: Maximum working pressure. A cargo hose must have a maximum working pressure not less than the maximum pressure to which it may be subjected and at least 1034...

  14. 29 CFR 1918.87 - Ship's cargo elevators.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 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...

  15. 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...

  16. 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...

  17. 46 CFR 154.320 - Cargo control stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Arrangements § 154.320 Cargo control stations. (a) Cargo control stations must be above the weather deck. (b) If a cargo control station is in accommodation, service, or control spaces or has access to such a... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo control stations. 154.320 Section 154.320 Shipping...

  18. 46 CFR 154.412 - Cargo tank corrosion allowance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo tank corrosion allowance. 154.412 Section 154.412... Containment Systems § 154.412 Cargo tank corrosion allowance. A cargo tank must be designed with a corrosion...) carries a cargo that corrodes the tank material. Note: Corrosion allowance for independent tank type C is...

  19. 46 CFR 154.412 - Cargo tank corrosion allowance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo tank corrosion allowance. 154.412 Section 154.412... Containment Systems § 154.412 Cargo tank corrosion allowance. A cargo tank must be designed with a corrosion...) carries a cargo that corrodes the tank material. Note: Corrosion allowance for independent tank type C is...

  20. 46 CFR 154.412 - Cargo tank corrosion allowance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo tank corrosion allowance. 154.412 Section 154.412... Containment Systems § 154.412 Cargo tank corrosion allowance. A cargo tank must be designed with a corrosion...) carries a cargo that corrodes the tank material. Note: Corrosion allowance for independent tank type C is...

  1. 46 CFR 153.333 - Cargo pump discharge pressure gauge.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo pump discharge pressure gauge. 153.333 Section 153... Cargo Pumprooms § 153.333 Cargo pump discharge pressure gauge. Each cargo pump within a pump-room must have a discharge pressure gauge outside the pumproom....

  2. 46 CFR 154.556 - Cargo hose: Maximum working pressure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo hose: Maximum working pressure. 154.556 Section... Equipment Cargo Hose § 154.556 Cargo hose: Maximum working pressure. A cargo hose must have a maximum working pressure not less than the maximum pressure to which it may be subjected and at least 1034...

  3. 46 CFR 154.1828 - Spaces containing cargo vapor: Entry.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Spaces containing cargo vapor: Entry. 154.1828 Section... Spaces containing cargo vapor: Entry. (a) No person may enter a cargo handling space without the... allowing anyone to enter a cargo handling space, the master shall ensure that: (1) The space is free of...

  4. 46 CFR 151.20-5 - Cargo system valving requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... meet the requirements listed below. Cargo tanks, whether gravity or pressure vessel type, for cargoes... tank is insulated) shall be provided with a valving system designated as Gravity-1. Cargo tanks, whether gravity or pressure vessel type, for cargoes which are carried below ambient temperature and whose...

  5. 46 CFR 151.20-5 - Cargo system valving requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... meet the requirements listed below. Cargo tanks, whether gravity or pressure vessel type, for cargoes... tank is insulated) shall be provided with a valving system designated as Gravity-1. Cargo tanks, whether gravity or pressure vessel type, for cargoes which are carried below ambient temperature and whose...

  6. 46 CFR 153.975 - Preparation for cargo transfer.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Preparation for cargo transfer. 153.975 Section 153.975 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.975 Preparation for cargo transfer. The person in charge of cargo transfer may not...

  7. 46 CFR 153.975 - Preparation for cargo transfer.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Preparation for cargo transfer. 153.975 Section 153.975 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.975 Preparation for cargo transfer. The person in charge of cargo transfer may not...

  8. 46 CFR 153.975 - Preparation for cargo transfer.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Preparation for cargo transfer. 153.975 Section 153.975 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.975 Preparation for cargo transfer. The person in charge of cargo transfer may not...

  9. 46 CFR 153.975 - Preparation for cargo transfer.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Preparation for cargo transfer. 153.975 Section 153.975 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.975 Preparation for cargo transfer. The person in charge of cargo transfer may not...

  10. 46 CFR 153.975 - Preparation for cargo transfer.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Preparation for cargo transfer. 153.975 Section 153.975 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.975 Preparation for cargo transfer. The person in charge of cargo transfer may not...

  11. 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...

  12. 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...

  13. 46 CFR 153.316 - Special cargo pumproom ventilation rate.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Special cargo pumproom ventilation rate. 153.316 Section... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Handling Space Ventilation § 153.316 Special cargo pumproom ventilation rate. When Table...

  14. 46 CFR 153.316 - Special cargo pumproom ventilation rate.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Special cargo pumproom ventilation rate. 153.316 Section... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Handling Space Ventilation § 153.316 Special cargo pumproom ventilation rate. When Table...

  15. 46 CFR 153.316 - Special cargo pumproom ventilation rate.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Special cargo pumproom ventilation rate. 153.316 Section... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Handling Space Ventilation § 153.316 Special cargo pumproom ventilation rate. When Table...

  16. 46 CFR 153.316 - Special cargo pumproom ventilation rate.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Special cargo pumproom ventilation rate. 153.316 Section... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Handling Space Ventilation § 153.316 Special cargo pumproom ventilation rate. When Table...

  17. 46 CFR 153.316 - Special cargo pumproom ventilation rate.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Special cargo pumproom ventilation rate. 153.316 Section... CARGOES SHIPS CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Handling Space Ventilation § 153.316 Special cargo pumproom ventilation rate. When Table...

  18. 46 CFR 154.1814 - Cargo information cards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo information cards. 154.1814 Section 154.1814... cards. (a) No person may operate a vessel unless a cargo information card for each cargo being... ensure that a set of information cards is in the possession of the terminal's person in charge of cargo...

  19. 46 CFR 154.1814 - Cargo information cards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo information cards. 154.1814 Section 154.1814... cards. (a) No person may operate a vessel unless a cargo information card for each cargo being... ensure that a set of information cards is in the possession of the terminal's person in charge of cargo...

  20. 46 CFR 154.1814 - Cargo information cards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo information cards. 154.1814 Section 154.1814... cards. (a) No person may operate a vessel unless a cargo information card for each cargo being... ensure that a set of information cards is in the possession of the terminal's person in charge of cargo...

  1. 46 CFR 154.1814 - Cargo information cards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo information cards. 154.1814 Section 154.1814... cards. (a) No person may operate a vessel unless a cargo information card for each cargo being... ensure that a set of information cards is in the possession of the terminal's person in charge of cargo...

  2. 46 CFR 154.1814 - Cargo information cards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo information cards. 154.1814 Section 154.1814... cards. (a) No person may operate a vessel unless a cargo information card for each cargo being... ensure that a set of information cards is in the possession of the terminal's person in charge of cargo...

  3. 46 CFR 154.310 - Cargo piping systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo piping systems. 154.310 Section 154.310 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS... Arrangements § 154.310 Cargo piping systems. Cargo liquid or vapor piping must: (a) Be separated from other...

  4. 46 CFR 154.538 - Cargo transfer connection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo transfer connection. 154.538 Section 154.538 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.538 Cargo transfer connection. A cargo transfer connection must have...

  5. 46 CFR 154.500 - Cargo and process piping standards.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo and process piping standards. 154.500 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.500 Cargo and process piping standards. The cargo liquid...

  6. 46 CFR 154.538 - Cargo transfer connection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo transfer connection. 154.538 Section 154.538 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.538 Cargo transfer connection. A cargo transfer connection must have...

  7. 46 CFR 154.538 - Cargo transfer connection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo transfer connection. 154.538 Section 154.538 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.538 Cargo transfer connection. A cargo transfer connection must have...

  8. 46 CFR 154.538 - Cargo transfer connection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo transfer connection. 154.538 Section 154.538 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.538 Cargo transfer connection. A cargo transfer connection must have...

  9. 46 CFR 154.310 - Cargo piping systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo piping systems. 154.310 Section 154.310 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS... Arrangements § 154.310 Cargo piping systems. Cargo liquid or vapor piping must: (a) Be separated from other...

  10. 46 CFR 154.500 - Cargo and process piping standards.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo and process piping standards. 154.500 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.500 Cargo and process piping standards. The cargo liquid...

  11. 46 CFR 154.500 - Cargo and process piping standards.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo and process piping standards. 154.500 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.500 Cargo and process piping standards. The cargo liquid...

  12. 46 CFR 154.538 - Cargo transfer connection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo transfer connection. 154.538 Section 154.538 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.538 Cargo transfer connection. A cargo transfer connection must have...

  13. 46 CFR 154.500 - Cargo and process piping standards.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo and process piping standards. 154.500 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.500 Cargo and process piping standards. The cargo liquid...

  14. 46 CFR 154.500 - Cargo and process piping standards.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo and process piping standards. 154.500 Section 154... SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and Equipment Cargo and Process Piping Systems § 154.500 Cargo and process piping standards. The cargo liquid...

  15. 46 CFR 154.310 - Cargo piping systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo piping systems. 154.310 Section 154.310 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS... Arrangements § 154.310 Cargo piping systems. Cargo liquid or vapor piping must: (a) Be separated from other...

  16. Cargo/Logistics Airlift System Study (CLASS), Executive Summary

    NASA Technical Reports Server (NTRS)

    Norman, J. M.; Henderson, R. D.; Macey, F. C.; Tuttle, R. P.

    1978-01-01

    The current air cargo system is analyzed along with advanced air cargo systems studies. A forecast of advanced air cargo system demand is presented with cost estimates. It is concluded that there is a need for a dedicated advance air cargo system, and with application of advanced technology, reductions of 45% in air freight rates may be achieved.

  17. 46 CFR 154.1828 - Spaces containing cargo vapor: Entry.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Spaces containing cargo vapor: Entry. 154.1828 Section... Spaces containing cargo vapor: Entry. (a) No person may enter a cargo handling space without the... allowing anyone to enter a cargo handling space, the master shall ensure that: (1) The space is free...

  18. 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... Survival Capability and Cargo Tank Location § 154.235 Cargo tank location. (a) For type IG hulls, cargo tanks must be located inboard of: (1) The transverse extent of damage for collision...

  19. 46 CFR 153.251 - Independent cargo tanks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Independent cargo tanks. 153.251 Section 153.251... CARRYING BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.251 Independent cargo tanks. All independent cargo tank must meet § 38.05-10 (a)(1), (b), (d),...

  20. 46 CFR 153.254 - Cargo tank access.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo tank access. 153.254 Section 153.254 Shipping... BULK LIQUID, LIQUEFIED GAS, OR COMPRESSED GAS HAZARDOUS MATERIALS Design and Equipment Cargo Tanks § 153.254 Cargo tank access. (a) A cargo tank must have at least one covered manhole opening into...

  1. IP-1 Certification of Cargo Containers

    SciTech Connect

    Hagler, Lisle

    2010-10-05

    The purpose and scope of this engineering note is to demonstrate that the structural design of the cargo container complies with the IP-1 container requirements of 49 CFR 173.410 as required by CFR 173.411.

  2. 46 CFR 45.137 - Cargo ports.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....137 Cargo ports. (a) Unless otherwise authorized by the Commandant, the lower edge of any opening for... is drawn parallel to the freeboard deck at side and has as its lowest point the upper edge of the...

  3. 46 CFR 45.137 - Cargo ports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....137 Cargo ports. (a) Unless otherwise authorized by the Commandant, the lower edge of any opening for... is drawn parallel to the freeboard deck at side and has as its lowest point the upper edge of the...

  4. European Cargo Ship Launches to Station

    NASA Image and Video Library

    The European Space Agency's (ESA) fourth Automated Transfer Vehicle cargo craft (ATV-4) launched atop an Ariane 5 rocket from Kourou, French Guiana at 5:52 p.m. EDT on Wednesday to begin a 10-day t...

  5. 49 CFR 172.328 - Cargo tanks.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... constructed of quenched and tempered steel; or (2) “NQT”, if the cargo tank is constructed of other than quenched and tempered steel. (d) After October 3, 2005, each on-vehicle manually-activated remote...

  6. ISS Update: ATV-3 Cargo Transfer Activities

    NASA Image and Video Library

    NASA Public Affairs Officer Dan Huot interviews Michael Ferullo, ATV-3 Lead Inventory and Stowage Officer. Transferring cargo to and from a docked resupply ship is a complex and time-consuming acti...

  7. Voyager Special Cargo: The Golden Record

    NASA Image and Video Library

    2011-04-29

    This image highlights the special cargo onboard NASA Voyager spacecraft: the Golden Record. Each of the two Voyager spacecraft launched in 1977 carry a 12-inch gold-plated phonograph record with images and sounds from Earth.

  8. Low Energy Accelerators for Cargo Inspection

    NASA Astrophysics Data System (ADS)

    Tang, Chuanxiang

    Cargo inspection by X-rays has become essential for seaports and airports. With the emphasis on homeland security issues, the identification of dangerous things, such as explosive items and nuclear materials, is the key feature of a cargo inspection system. And new technologies based on dual energy X-rays, neutrons and monoenergetic X-rays have been studied to achieve sufficiently good material identification. An interpretation of the principle of X-ray cargo inspection technology and the features of X-ray sources are presented in this article. As most of the X-ray sources are based on RF electron linear accelerators (linacs), we give a relatively detailed description of the principle and characteristics of linacs. Cargo inspection technologies based on neutron imaging, neutron analysis, nuclear resonance fluorescence and computer tomography are also mentioned here. The main vendors and their products are summarized at the end of the article.

  9. System for inspection of stacked cargo containers

    SciTech Connect

    Derenzo, Stephen

    2011-08-16

    The present invention relates to a system for inspection of stacked cargo containers. One embodiment of the invention generally comprises a plurality of stacked cargo containers arranged in rows or tiers, each container having a top, a bottom a first side, a second side, a front end, and a back end; a plurality of spacers arranged in rows or tiers; one or more mobile inspection devices for inspecting the cargo containers, wherein the one or more inspection devices are removeably disposed within the spacers, the inspection means configured to move through the spacers to detect radiation within the containers. The invented system can also be configured to inspect the cargo containers for a variety of other potentially hazardous materials including but not limited to explosive and chemical threats.

  10. KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Donatello is suspended by cables over the payload canister in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Donatello is suspended by cables over the payload canister in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  11. KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers confirm the Multi-Purpose Logistics Module Donatello is safely in place on a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello, is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers confirm the Multi-Purpose Logistics Module Donatello is safely in place on a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello, is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  12. KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, the Multi-Purpose Logistics Module Donatello is slowly lowered toward a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, the Multi-Purpose Logistics Module Donatello is slowly lowered toward a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  13. KENNEDY SPACE CENTER, FLA. - This view reveals all three Multi-Purpose Logistics Modules on the floor of the Space Station Processing Facility. This is the first time all three - Leonardo, Raffaello and Donatello -- have been in one location. Donatello has been stored in the Operations and Checkout Building since its arrival at KSC and was brought into the SSPF for routine testing. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-18

    KENNEDY SPACE CENTER, FLA. - This view reveals all three Multi-Purpose Logistics Modules on the floor of the Space Station Processing Facility. This is the first time all three - Leonardo, Raffaello and Donatello -- have been in one location. Donatello has been stored in the Operations and Checkout Building since its arrival at KSC and was brought into the SSPF for routine testing. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  14. KENNEDY SPACE CENTER, FLA. - All three Multi-Purpose Logistics Modules are on the floor of the Space Station Processing Facility. This is the first time the three - Leonardo, Raffaello and Donatello -- have been in one location. Donatello has been stored in the Operations and Checkout Building since its arrival at KSC and was brought into the SSPF for routine testing. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-18

    KENNEDY SPACE CENTER, FLA. - All three Multi-Purpose Logistics Modules are on the floor of the Space Station Processing Facility. This is the first time the three - Leonardo, Raffaello and Donatello -- have been in one location. Donatello has been stored in the Operations and Checkout Building since its arrival at KSC and was brought into the SSPF for routine testing. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  15. KENNEDY SPACE CENTER, FLA. - Workers in the Space Station Processing Facility secure the Multi-Purpose Logistics Module Raffaello onto a new work stand. Raffaello is the second MPLM built by the Italian Space Agency, serving as a reusable logistics carrier and primary delivery system to resupply and return station cargo requiring a pressurized environment. It has been moved to allow the third MPLM, Donatello, to be brought in for routine testing. Donatello has been stored in the Operations and Checkout Building. This is the first time all three MPLMs are in the SSPF; the other one is the Leonardo. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-10

    KENNEDY SPACE CENTER, FLA. - Workers in the Space Station Processing Facility secure the Multi-Purpose Logistics Module Raffaello onto a new work stand. Raffaello is the second MPLM built by the Italian Space Agency, serving as a reusable logistics carrier and primary delivery system to resupply and return station cargo requiring a pressurized environment. It has been moved to allow the third MPLM, Donatello, to be brought in for routine testing. Donatello has been stored in the Operations and Checkout Building. This is the first time all three MPLMs are in the SSPF; the other one is the Leonardo. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  16. KENNEDY SPACE CENTER, FLA. - Overhead cables carry the Multi-Purpose Logistics Module Donatello from the payload canister (lower right) to a work stand in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - Overhead cables carry the Multi-Purpose Logistics Module Donatello from the payload canister (lower right) to a work stand in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  17. KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Donatello is moved away from the payload canister in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Donatello is moved away from the payload canister in the Space Station Processing Facility. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  18. KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers help the Multi-Purpose Logistics Module Donatello settle onto a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello, is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers help the Multi-Purpose Logistics Module Donatello settle onto a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello, is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  19. KENNEDY SPACE CENTER, FLA. - Workers on the floor of the Space Station Processing Facility watch as overhead cables carry the Multi-Purpose Logistics Module Donatello to a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-13

    KENNEDY SPACE CENTER, FLA. - Workers on the floor of the Space Station Processing Facility watch as overhead cables carry the Multi-Purpose Logistics Module Donatello to a work stand. Previously housed in the Operations and Checkout Building, Donatello was brought into the SSPF for routine testing. This is the first time all three MPLMs (Donatello, Raffaello and Leonardo) are in the SSPF. The MPLMs were built by the Italian Space Agency, to serve as reusable logistics carriers and the primary delivery system to resupply and return station cargo requiring a pressurized environment. The third MPLM, Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  20. KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Raffaello moves away from its stand in the Space Station Processing Facility. Raffaello is the second MPLM built by the Italian Space Agency, serving as a reusable logistics carrier and primary delivery system to resupply and return station cargo requiring a pressurized environment. It is being moved to allow the third MPLM, Donatello, to be brought in for routine testing. Donatello has been stored in the Operations and Checkout Building. This is the first time all three MPLMs are in the SSPF; the other one is the Leonardo. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

    NASA Image and Video Library

    2004-02-10

    KENNEDY SPACE CENTER, FLA. - The Multi-Purpose Logistics Module Raffaello moves away from its stand in the Space Station Processing Facility. Raffaello is the second MPLM built by the Italian Space Agency, serving as a reusable logistics carrier and primary delivery system to resupply and return station cargo requiring a pressurized environment. It is being moved to allow the third MPLM, Donatello, to be brought in for routine testing. Donatello has been stored in the Operations and Checkout Building. This is the first time all three MPLMs are in the SSPF; the other one is the Leonardo. Raffaello is scheduled to fly on Space Shuttle Atlantis on mission STS-114.

  1. A Family of Tetraspans Organizes Cargo for Sorting into Multivesicular Bodies

    PubMed Central

    MacDonald, Chris; Payne, Johanna A.; Aboian, Mariam; Smith, William; Katzmann, David J.; Piper, Robert C.

    2015-01-01

    SUMMARY The abundance of cell surface membrane proteins is regulated by internalization and delivery into intralumenal vesicles (ILVs) of multivesicular bodies (MVB). Many cargoes are ubiquitinated, allowing access to an ESCRT-dependent pathway into MVBs. Yet, how non-ubiquitinated proteins, such as Glycosylphosphatidylinisotol-anchored proteins, enter MVBs is unclear, supporting the possibility of mechanistically distinct ILV biogenesis pathways. Here we show a family of highly ubiquitinated tetraspan Cos proteins provide a Ub-signal in trans, allowing sorting of non-ubiquitinated MVB cargo into the canonical ESCRT- and Ub-dependent pathway. Cos proteins create discrete endosomal subdomains that concentrate Ub-cargo prior to their envelopment into ILVs and the activity of Cos proteins is required not only for efficient sorting of canonical Ub-cargo but is also essential for sorting non-ubiquitinated cargo into MVBs. Expression of these proteins increases during nutrient stress though a NAD+/Sir2-dpendent mechanism that in turn accelerates the down-regulation of a broad range of cell surface proteins. PMID:25942624

  2. Survey of air cargo forecasting techniques

    NASA Technical Reports Server (NTRS)

    Kuhlthan, A. R.; Vermuri, R. S.

    1978-01-01

    Forecasting techniques currently in use in estimating or predicting the demand for air cargo in various markets are discussed with emphasis on the fundamentals of the different forecasting approaches. References to specific studies are cited when appropriate. The effectiveness of current methods is evaluated and several prospects for future activities or approaches are suggested. Appendices contain summary type analyses of about 50 specific publications on forecasting, and selected bibliographies on air cargo forecasting, air passenger demand forecasting, and general demand and modalsplit modeling.

  3. Software For Nearly Optimal Packing Of Cargo

    NASA Technical Reports Server (NTRS)

    Fennel, Theron R.; Daughtrey, Rodney S.; Schwaab, Doug G.

    1994-01-01

    PACKMAN computer program used to find nearly optimal arrangements of cargo items in storage containers, subject to such multiple packing objectives as utilization of volumes of containers, utilization of containers up to limits on weights, and other considerations. Automatic packing algorithm employed attempts to find best positioning of cargo items in container, such that volume and weight capacity of container both utilized to maximum extent possible. Written in Common LISP.

  4. Software For Nearly Optimal Packing Of Cargo

    NASA Technical Reports Server (NTRS)

    Fennel, Theron R.; Daughtrey, Rodney S.; Schwaab, Doug G.

    1994-01-01

    PACKMAN computer program used to find nearly optimal arrangements of cargo items in storage containers, subject to such multiple packing objectives as utilization of volumes of containers, utilization of containers up to limits on weights, and other considerations. Automatic packing algorithm employed attempts to find best positioning of cargo items in container, such that volume and weight capacity of container both utilized to maximum extent possible. Written in Common LISP.

  5. San Francisco Bay Area Cargo Forecast.

    DTIC Science & Technology

    1981-06-01

    Though sugar manufacturers face competition from non-nutritive sweetners, high fructose corn syrups , and foreign suppliers, the Hawaiian-San...approach, provides background on recent levels of trade, and presents the baseline, high , and low forecasts for 1985, 1990, 2000 and 2020. The major...cargo sectors is cargo that would be carried by high technology ships such as Ro/Ro vessels and barge carriers. In recent years, these vessel designs

  6. Characterizing X-ray Attenuation of Containerized Cargo

    SciTech Connect

    Birrer, N.; Divin, C.; Glenn, S.; Martz, H.; Wang, G.

    2016-08-02

    X-ray inspection systems can be used to detect radiological and nuclear threats in imported cargo. In order to better understand performance of these systems, the attenuation characteristics of imported cargo need to be determined. This project focused on developing image processing algorithms for segmenting cargo and using x-ray attenuation to quantify equivalent steel thickness to determine cargo density. These algorithms were applied to over 450 cargo radiographs. The results are summarized in this report.

  7. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  8. 49 CFR 392.9 - Inspection of cargo, cargo securement devices and systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... motor vehicle's cargo and its load securement devices during the course of transportation and make any... its cargo or to the driver of a commercial motor vehicle that has been loaded in a manner that makes...) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY...

  9. 49 CFR 392.9 - Inspection of cargo, cargo securement devices and systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... motor vehicle's cargo and its load securement devices during the course of transportation and make any... its cargo or to the driver of a commercial motor vehicle that has been loaded in a manner that makes...) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY...

  10. Polyethylene glycol-based protein nanocapsules for functional delivery of a differentiation transcription factor.

    PubMed

    Biswas, Anuradha; Liu, Ying; Liu, Tianfei; Fan, Guoping; Tang, Yi

    2012-07-01

    Transcription factors (TFs) can direct cell fate by binding to DNA and regulating gene transcription. Controlling the intracellular levels of specific TFs can therefore enable reprogramming of cellular function and differentiation. Direct delivery of recombinant TFs to target cells can thus have widespread therapeutic value, but has remained challenging due to structural fragility of TFs and inefficient membrane transduction. Here we describe the functional delivery of TFs using degradable polymeric nanocapsules to drive cellular differentiation. The nanocapsules were synthesized with poly(ethylene) glycol (PEG)-based monomers and intracellularly-degradable crosslinkers. Physical properties and release kinetics of the nanocapsules were optimized through tuning of monomer and crosslinker ratios to achieve enhanced delivery of cargo destined for the nuclei. The nanocapsules did not display cytotoxicity in primary cell lines up to concentrations of 5 μm. A recombinant myogenic transcription factor, MyoD, was delivered to the nuclei of myoblast cells using degradable nanocapsules to induce myogenic differentiation. MyoD was confirmed to be delivered to the nuclei of myoblasts using confocal microscopy and was demonstrated to be active in transcription through a luciferase-based reporter assay. More importantly, delivered MyoD was able to drive myoblast differentiation as evidenced by the hallmark elongated and multinuclear morphology of myotubes. The activation of downstream cascade was also confirmed through immunostaining of late myogenic markers myogenin and My-HC. The efficiency of differentiation achieved via nanocapsule delivery is significantly higher than that of native MyoD, and is comparable to that of plasmid transfection. The encapsulated MyoD can also withstand prolonged protease treatment and remain functional. The ease of preparation, biocompatibility and effective cargo delivery make the polymeric nanocapsule a useful tool to deliver a variety of

  11. Dual Transport Process for Targeted Delivery in Porous Media

    NASA Astrophysics Data System (ADS)

    Deng, W.; Fan, J.

    2015-12-01

    The targeted delivery in porous media is a promising technology to encapsulate the solute (i.e., the cargo) in colloid-like microcapsules (i.e., the carriers), transport the microcapsules in the targeted location in porous media, and then release the solute. While extensive literatures and applications about the drug delivery in human and animal bodies exist, the targeted delivery using similar delivery carriers in subsurface porous media is not well understood. The dual transport process study is an explorative study for the targeted delivery in porous media. While the colloid transport is dominated by the advection process and the solute transport is dominated by the advection-dispersion, the dual transport process is the process with the first step of carrier transport, which is dominated by advection, and then after the release of cargo, the transport of cargo is dominated by advection-dispersion. By applying the random walk particle tracking (RWPT) approach, we investigate how the carriers transport in porous media and how the cargo release mechanisms affect the cargo distribution for the targeted delivery in various patterns of porous media. The RWPT numerical model will be verified against the experimental results of dual transport process in packed-disk 2D micromodels. The understanding of the mechanism of dual transport process is crucial to achieve the potential applications of targeted delivery in improved oil and gas recovery, CO2 sequestration, environmental remediation, and soil biomediation.

  12. Motility states in bidirectional cargo transport

    NASA Astrophysics Data System (ADS)

    Klein, Sarah; Appert-Rolland, Cécile; Santen, Ludger

    2015-09-01

    Intracellular cargos which are transported by molecular motors move stochastically along cytoskeleton filaments. In particular for bidirectionally transported cargos it is an open question whether the characteristics of their motion can result from pure stochastic fluctuations or whether some coordination of the motors is needed. The results of a mean-field (MF) model of cargo-motors dynamics proposed by Müller et al. (Müller M. J. et al., Proc. Natl. Acad. Sci. U.S.A., 105 (2008) 4609) suggest the existence of states which are characterized by a symmetric bimodal distribution of cargo velocities. These states would result from a stochastic tug of war. Here we analyze the influence of the MF assumption on the cargo motion by considering a model that takes explicitly the position of each motor into account. We find that those states with symmetric bimodal distributions then disappear. As the MF model implicitly assumes some stepping synchronization between motors, we introduce a partial synchronization via an artificial mutual motor-motor activation, and show that the results of the MF model are then recovered but, even in this favorable case, only in the limit of a strong motor-motor activation and of a high number of motors. We conclude that the MF assumption is not relevant for intracellular transport.

  13. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  14. The promise of air cargo: System aspects and vehicle design

    NASA Technical Reports Server (NTRS)

    Whitehead, A. H., Jr.

    1976-01-01

    The current operation of the air cargo system is reviewed. An assessment of the future of air cargo is provided by: (1) analyzing statistics and trends, (2) by noting system problems and inefficiencies, (3) by analyzing characteristics of 'air eligible' commodities, and (4) by showing the promise of new technology for future cargo aircraft with significant improvements in costs and efficiency. The following topics are discussed: (1) air cargo demand forecasts; (2) economics of air cargo transport; (3) the integrated air cargo system; (4) evolution of airfreighter design; and (5) the span distributed load concept.

  15. Characterizing Complexity of Containerized Cargo X-ray Images

    SciTech Connect

    Wang, Guangxing; Martz, Harry; Glenn, Steven; Divin, Charles; Birrer, Nat

    2016-08-19

    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.

  16. Maleimide cross-linked bioactive PEG hydrogel exhibits improved reaction kinetics and cross-linking for cell encapsulation and in-situ delivery

    PubMed Central

    Phelps, Edward A.; Enemchukwu, Nduka O.; Fiore, Vincent F.; Sy, Jay C.; Murthy, Niren; Sulchek, Todd A.; Barker, Thomas H.

    2012-01-01

    Engineered polyethylene glycol-maleimide matrices for regenerative medicine exhibit improved reaction efficiency and wider range of Young’s moduli by utilizing maleimide cross-linking chemistry. This hydrogel chemistry is advantageous for cell delivery due to the mild reaction that occurs rapidly enough for in situ delivery, while easily lending itself to “plug-and-play” design variations such as incorporation of enzyme-cleavable cross-links and cell-adhesion peptides. PMID:22174081

  17. Design of a spanloader cargo aircraft

    NASA Technical Reports Server (NTRS)

    Weisshaar, Terrence A.

    1989-01-01

    The design features of an aircraft capable of fulfilling a long haul, high capacity cargo mission are described. This span-loading aircraft, or flying wing, is capable of carrying extremely large payloads and is expected to be in demand to replace the slow-moving cargo ships currently in use. The spanloader seeks to reduce empty weight by eliminating the aircraft fuselage. Disadvantages are the thickness of the cargo-containing wing, and resulting stability and control problems. The spanloader presented here has a small fuselage, low-aspect ratio wings, winglets, and uses six turbofan engines for propulsion. It will have a payload capacity of 300,000 pounds plus 30 first class passengers and 6 crew members. Its projected market is transportation of freight from Europe and the U.S.A. to countries in the Pacific Basin. Cost estimates support its economic feasibility.

  18. How neurosecretory vesicles release their cargo.

    PubMed

    Scalettar, Bethe A

    2006-04-01

    Neurons and related cell types often contain two major classes of neurosecretory vesicles, synaptic vesicles (SVs) and dense-core granules (DCGs), which store and release distinct cargo. SVs store and release classic neurotransmitters, which facilitate propagation of action potentials across the synaptic cleft, whereas DCGs transport, store, and release hormones, proteins, and neuropeptides, which facilitate neuronal survival, synaptic transmission, and learning. Over the past few years, there has been a major surge in our understanding of many of the key molecular mechanisms underlying cargo release from SVs and DCGs. This surge has been driven largely by the use of fluorescence microscopy (especially total internal reflection fluorescence microscopy) to visualize SVs or DCGs in living cells. This review highlights some of the recent insights into cargo release from neurosecretory vesicles provided by fluorescence microscopy, with emphasis on DCGs.

  19. 14 CFR 23.787 - Baggage and cargo compartments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... inertial load factor is 9g and assuming the maximum allowed baggage or cargo weight for the compartment. (b... means to protect the occupants from injury when the baggage or cargo is subjected to the inertial...

  20. 14 CFR 23.787 - Baggage and cargo compartments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... inertial load factor is 9g and assuming the maximum allowed baggage or cargo weight for the compartment. (b... means to protect the occupants from injury when the baggage or cargo is subjected to the inertial...

  1. 14 CFR 23.787 - Baggage and cargo compartments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... inertial load factor is 9g and assuming the maximum allowed baggage or cargo weight for the compartment. (b... means to protect the occupants from injury when the baggage or cargo is subjected to the inertial...

  2. 14 CFR 23.787 - Baggage and cargo compartments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... inertial load factor is 9g and assuming the maximum allowed baggage or cargo weight for the compartment. (b... means to protect the occupants from injury when the baggage or cargo is subjected to the inertial...

  3. 14 CFR 23.787 - Baggage and cargo compartments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... inertial load factor is 9g and assuming the maximum allowed baggage or cargo weight for the compartment. (b... means to protect the occupants from injury when the baggage or cargo is subjected to the inertial...

  4. 41 CFR 102-117.140 - What is cargo preference?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-borne cargo that moves internationally be transported on U.S. flag vessels. Deviations or waivers from the cargo preference laws must be approved by: Department of Transportation, Maritime Administration...

  5. 41 CFR 102-117.140 - What is cargo preference?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-borne cargo that moves internationally be transported on U.S. flag vessels. Deviations or waivers from the cargo preference laws must be approved by: Department of Transportation, Maritime Administration...

  6. 41 CFR 102-117.140 - What is cargo preference?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-borne cargo that moves internationally be transported on U.S. flag vessels. Deviations or waivers from the cargo preference laws must be approved by: Department of Transportation, Maritime Administration...

  7. 41 CFR 102-117.140 - What is cargo preference?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-borne cargo that moves internationally be transported on U.S. flag vessels. Deviations or waivers from the cargo preference laws must be approved by: Department of Transportation Maritime Administration...

  8. 46 CFR 64.89 - Cargo pump unit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... with the product to be pumped. (d) A diesel engine that is used to drive a cargo pump must have a spark...) The cargo pump power unit must be— (1) Diesel; (2) Hydraulic; (3) Pneumatic; or (4) Electric. (c)...

  9. 46 CFR 64.89 - Cargo pump unit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... with the product to be pumped. (d) A diesel engine that is used to drive a cargo pump must have a spark...) The cargo pump power unit must be— (1) Diesel; (2) Hydraulic; (3) Pneumatic; or (4) Electric. (c)...

  10. 46 CFR 64.89 - Cargo pump unit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... with the product to be pumped. (d) A diesel engine that is used to drive a cargo pump must have a spark...) The cargo pump power unit must be— (1) Diesel; (2) Hydraulic; (3) Pneumatic; or (4) Electric. (c)...

  11. 46 CFR 64.89 - Cargo pump unit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... with the product to be pumped. (d) A diesel engine that is used to drive a cargo pump must have a spark...) The cargo pump power unit must be— (1) Diesel; (2) Hydraulic; (3) Pneumatic; or (4) Electric. (c)...

  12. 46 CFR 64.89 - Cargo pump unit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... with the product to be pumped. (d) A diesel engine that is used to drive a cargo pump must have a spark...) The cargo pump power unit must be— (1) Diesel; (2) Hydraulic; (3) Pneumatic; or (4) Electric. (c)...

  13. 46 CFR 172.087 - Cargo loading assumptions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PERTAINING TO BULK CARGOES Special Rules Pertaining to a Barge That Carries a Hazardous Liquid Regulated... this subpart must be done for cargo weights and densities up to and including the maximum that is to be...

  14. 46 CFR 172.087 - Cargo loading assumptions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PERTAINING TO BULK CARGOES Special Rules Pertaining to a Barge That Carries a Hazardous Liquid Regulated... this subpart must be done for cargo weights and densities up to and including the maximum that is to be...

  15. 46 CFR 172.087 - Cargo loading assumptions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PERTAINING TO BULK CARGOES Special Rules Pertaining to a Barge That Carries a Hazardous Liquid Regulated... this subpart must be done for cargo weights and densities up to and including the maximum that is to be...

  16. 46 CFR 172.087 - Cargo loading assumptions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PERTAINING TO BULK CARGOES Special Rules Pertaining to a Barge That Carries a Hazardous Liquid Regulated... this subpart must be done for cargo weights and densities up to and including the maximum that is to be...

  17. 46 CFR 153.935a - Storage of cargo samples.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS...: (1) A designated and ventilated space in the cargo area of the vessel; or (2) An area approved by the... part 150, subpart A)....

  18. 49 CFR 176.39 - Inspection of cargo.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... hazardous materials performed. (b) Unmanned and magazine vessels. An inspection of the cargo must be made... and stowing the cargo on the unmanned vessels or the individual in charge in the case of a...

  19. 49 CFR 176.39 - Inspection of cargo.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... hazardous materials performed. (b) Unmanned and magazine vessels. An inspection of the cargo must be made... and stowing the cargo on the unmanned vessels or the individual in charge in the case of a...

  20. 49 CFR 176.39 - Inspection of cargo.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... hazardous materials performed. (b) Unmanned and magazine vessels. An inspection of the cargo must be made... and stowing the cargo on the unmanned vessels or the individual in charge in the case of a...

  1. 49 CFR 176.39 - Inspection of cargo.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... hazardous materials performed. (b) Unmanned and magazine vessels. An inspection of the cargo must be made... and stowing the cargo on the unmanned vessels or the individual in charge in the case of a magazine...

  2. Assembly and Transport of Microscopic Cargos via Reconfigurable Photoactivated Magnetic Microdockers.

    PubMed

    Martinez-Pedrero, Fernando; Massana-Cid, Helena; Tierno, Pietro

    2017-05-01

    The realization of micromotors able to dock and transport microscopic objects in a fluid medium has direct applications toward the delivery of drugs and chemicals in small channels and pores, and the realization of functional wireless microrobots in lab-on-a-chip technology. A simple and general method to tow microscopic particles in water by using remotely controllable light-activated hematite microdockers is demonstrated. These anisotropic ferromagnetic particles can be synthesized in bulk and present the remarkable ability to be activated by light while independently manipulated via external fields. The photoactivation process induces a phoretic flow capable to attract cargos toward the surface of the propellers, while a rotating magnetic field is used to transport the composite particles to any location of the experimental platform. The method allows the assembling of small colloidal clusters of various sizes, composed by a skeleton of mobile magnetic dockers, which cooperatively keep, transport, and release the microscopic cargos. The possibility to easily reconfigure in situ the location of the docker above the cargo is demonstrated, which enables optimize transport and cargo release operations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. 46 CFR 154.405 - Design vapor pressure (Po) of a cargo tank.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Design, Construction and... cargo tank has no temperature control for the cargo; and (2) The vapor pressure of the cargo results...

  4. 49 CFR 172.448 - CARGO AIRCRAFT ONLY label.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false CARGO AIRCRAFT ONLY label. 172.448 Section 172.448... SECURITY PLANS Labeling § 172.448 CARGO AIRCRAFT ONLY label. (a) Except for size and color, the CARGO AIRCRAFT ONLY label must be as follows: ER14JA09.001 (b) The CARGO AIRCRAFT ONLY label must be black on...

  5. 49 CFR 172.448 - CARGO AIRCRAFT ONLY label.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false CARGO AIRCRAFT ONLY label. 172.448 Section 172.448... SECURITY PLANS Labeling § 172.448 CARGO AIRCRAFT ONLY label. (a) Except for size and color, the CARGO AIRCRAFT ONLY label must be as follows: ER14JA09.001 (b) The CARGO AIRCRAFT ONLY label must be black on...

  6. 49 CFR 172.448 - CARGO AIRCRAFT ONLY label.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false CARGO AIRCRAFT ONLY label. 172.448 Section 172.448... SECURITY PLANS Labeling § 172.448 CARGO AIRCRAFT ONLY label. (a) Except for size and color, the CARGO AIRCRAFT ONLY label must be as follows: ER14JA09.001 (b) The CARGO AIRCRAFT ONLY label must be black on...

  7. 49 CFR 172.448 - CARGO AIRCRAFT ONLY label.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false CARGO AIRCRAFT ONLY label. 172.448 Section 172.448... SECURITY PLANS Labeling § 172.448 CARGO AIRCRAFT ONLY label. (a) Except for size and color, the CARGO AIRCRAFT ONLY label must be as follows: ER14JA09.001 (b) The CARGO AIRCRAFT ONLY label must be black on...

  8. 49 CFR 172.448 - CARGO AIRCRAFT ONLY label.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false CARGO AIRCRAFT ONLY label. 172.448 Section 172.448... SECURITY PLANS Labeling § 172.448 CARGO AIRCRAFT ONLY label. (a) Except for size and color, the CARGO AIRCRAFT ONLY label must be as follows: ER14JA09.001 (b) The CARGO AIRCRAFT ONLY label must be black on an...

  9. 78 FR 68784 - Cargo Securing Manuals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... an extension because the cargo loss record of coastwise trade does not justify the regulatory costs... be feasible due to cost and surveyor availability. A seagoing barge operator agreed that it would be... high cost of hiring surveyors. Four commenters commented on Option 4. Option 4 proposed...

  10. Inspection of cargo containers using gamma radiation

    NASA Astrophysics Data System (ADS)

    Hussein, Esam M. A.; Gokhale, Prasad; Arendtsz, Nina V.; Lawrence, Andre H.

    1997-02-01

    This paper investigate, with the aid of Monte Carlo simulations and laboratory experiments, a technique for the detection of narcotics in large cargo containers using gamma-radiation. The transmission and back-scattering of photons, at different energies, is used to provide information useful for identifying the presence of bulk quantities of commonly encountered narcotics.

  11. 49 CFR 172.328 - Cargo tanks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Cargo tanks. 172.328 Section 172.328 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS HAZARDOUS MATERIALS TABLE,...

  12. 49 CFR 172.328 - Cargo tanks.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Cargo tanks. 172.328 Section 172.328 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS HAZARDOUS MATERIALS TABLE,...

  13. 49 CFR 172.328 - Cargo tanks.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Cargo tanks. 172.328 Section 172.328 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS HAZARDOUS MATERIALS TABLE,...

  14. Marine cargo imports and forest pest introductions

    Treesearch

    F.H. Koch

    2009-01-01

    A major pathway for the introduction of nonindigenous forest pests is accidental transport on cargo imported from overseas. Diseases may be brought into the United States via commercial trade of nursery stock or other live plant material, as has been suggested for Phytophthora ramorum, the pathogen that causes sudden oak death (Ivors and others 2006). Insects may...

  15. Cargo selectivity of yeast sorting nexins.

    PubMed

    Bean, Björn D M; Davey, Michael; Conibear, Elizabeth

    2017-02-01

    Sorting nexins are PX domain-containing proteins that bind phospholipids and often act in membrane trafficking where they help to select cargo. However, the functions and cargo specificities of many sorting nexins are unknown. Here, a high-throughput imaging screen was used to identify new sorting nexin cargo in the yeast Saccharomyces cerevisiae. Deletions of 9 different sorting nexins were screened for mislocalization of a set of green fluorescent protein (GFP)-tagged membrane proteins found at the plasma membrane, Golgi or endosomes. This identified 27 proteins that require 1 or more sorting nexins for their correct localization, 23 of which represent novel sorting nexin cargo. Nine hits whose sorting was dependent on Snx4, the sorting nexin-containing retromer complex, or both retromer and Snx3, were examined in detail to search for potential sorting motifs. We identified cytosolic domains of Ear1, Ymd8 and Ymr010w that conferred retromer-dependent sorting on a chimeric reporter and identified conserved residues required for this sorting in a functional assay. This work defined a consensus sequence for retromer and Snx3-dependent sorting.

  16. 46 CFR 151.45-6 - Maximum amount of cargo.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... insulated, or 115 °F if uninsulated. If specific filling densities are designated in Subpart 151.50 of this...=Maximum volume to which tank may be loaded. V =Volume of tank. d r=Density of cargo at the temperature required for a cargo vapor pressure equal to the relief valve setting. d L=Density of cargo at the loading...

  17. 46 CFR 162.050-25 - Cargo monitor: Design specification.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 6 2011-10-01 2011-10-01 false Cargo monitor: Design specification. 162.050-25 Section....050-25 Cargo monitor: Design specification. (a) This section contains requirements that apply to cargo monitors. (b) Each monitor must be designed so that it is calibrated by a means that does not involve...

  18. Cargo/Logistics Airlift System Study (CLASS), Volume 1

    NASA Technical Reports Server (NTRS)

    Norman, J. M.; Henderson, R. D.; Macey, F. C.; Tuttle, R. P.

    1978-01-01

    Current and advanced air cargo systems are evaluated using industrial and consumer statistics. Market and commodity characteristics that influence the use of the air mode are discussed along with a comparison of air and surface mode on typical routes. Results of on-site surveys of cargo processing facilities at airports are presented, and institutional controls and influences on air cargo operations are considered.

  19. 46 CFR 154.1816 - Cargo location plan.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo location plan. 154.1816 Section 154.1816 Shipping... FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Operations § 154.1816 Cargo location plan. The master shall ensure that: (a) A cargo location plan is prepared that gives: (1) The location and...

  20. 46 CFR 154.195 - Aluminum cargo tank: Steel enclosure.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Aluminum cargo tank: Steel enclosure. 154.195 Section... Equipment Hull Structure § 154.195 Aluminum cargo tank: Steel enclosure. (a) An aluminum cargo tank and its dome must be enclosed by the vessel's hull structure or a separate steel cover. (b) The steel cover...

  1. 46 CFR 154.195 - Aluminum cargo tank: Steel enclosure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Aluminum cargo tank: Steel enclosure. 154.195 Section... Equipment Hull Structure § 154.195 Aluminum cargo tank: Steel enclosure. (a) An aluminum cargo tank and its dome must be enclosed by the vessel's hull structure or a separate steel cover. (b) The steel cover...

  2. 46 CFR 154.195 - Aluminum cargo tank: Steel enclosure.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Aluminum cargo tank: Steel enclosure. 154.195 Section... Equipment Hull Structure § 154.195 Aluminum cargo tank: Steel enclosure. (a) An aluminum cargo tank and its dome must be enclosed by the vessel's hull structure or a separate steel cover. (b) The steel cover...

  3. 46 CFR 154.195 - Aluminum cargo tank: Steel enclosure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Aluminum cargo tank: Steel enclosure. 154.195 Section... Equipment Hull Structure § 154.195 Aluminum cargo tank: Steel enclosure. (a) An aluminum cargo tank and its dome must be enclosed by the vessel's hull structure or a separate steel cover. (b) The steel cover...

  4. 46 CFR 154.195 - Aluminum cargo tank: Steel enclosure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Aluminum cargo tank: Steel enclosure. 154.195 Section... Equipment Hull Structure § 154.195 Aluminum cargo tank: Steel enclosure. (a) An aluminum cargo tank and its dome must be enclosed by the vessel's hull structure or a separate steel cover. (b) The steel cover...

  5. 46 CFR 148.435 - Electrical circuits in cargo holds.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Electrical circuits in cargo holds. 148.435 Section 148... circuits in cargo holds. During transport of a material that Table 148.10 of this part associates with a reference to this section, each electrical circuit terminating in a cargo hold containing the material must...

  6. 46 CFR 148.435 - Electrical circuits in cargo holds.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Electrical circuits in cargo holds. 148.435 Section 148... circuits in cargo holds. During transport of a material that Table 148.10 of this part associates with a reference to this section, each electrical circuit terminating in a cargo hold containing the material must...

  7. 46 CFR 148.435 - Electrical circuits in cargo holds.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Electrical circuits in cargo holds. 148.435 Section 148... circuits in cargo holds. During transport of a material that Table 148.10 of this part associates with a reference to this section, each electrical circuit terminating in a cargo hold containing the material must...

  8. 33 CFR 104.275 - Security measures for handling cargo.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... vessel, are specified in order to: (1) Deter tampering; (2) Prevent cargo that is not meant for carriage... additional security measures may include: (1) Increasing the frequency and detail of checking cargo and cargo... car-carriers, RO-RO, and passenger vessels; (4) In liaison with the facility, increasing frequency and...

  9. 46 CFR 153.440 - Cargo temperature sensors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo temperature sensors. 153.440 Section 153.440 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Temperature Control Systems § 153.440 Cargo temperature sensors. (a) Except as prescribed in paragraph (c)...

  10. 46 CFR 153.440 - Cargo temperature sensors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo temperature sensors. 153.440 Section 153.440 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Temperature Control Systems § 153.440 Cargo temperature sensors. (a) Except as prescribed in paragraph (c)...

  11. 33 CFR 157.23 - Cargo and ballast system information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.23 Cargo and ballast system information. (a... automatic and manual operation of the cargo and ballast system in the vessel. (b) The format and information... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Cargo and ballast...

  12. 33 CFR 157.23 - Cargo and ballast system information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.23 Cargo and ballast system information. (a... automatic and manual operation of the cargo and ballast system in the vessel. (b) The format and information... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Cargo and ballast...

  13. 33 CFR 157.23 - Cargo and ballast system information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.23 Cargo and ballast system information. (a... automatic and manual operation of the cargo and ballast system in the vessel. (b) The format and information... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Cargo and ballast...

  14. 33 CFR 157.23 - Cargo and ballast system information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.23 Cargo and ballast system information. (a... automatic and manual operation of the cargo and ballast system in the vessel. (b) The format and information... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Cargo and ballast...

  15. 46 CFR 154.408 - Cargo tank external pressure load.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo tank external pressure load. 154.408 Section 154... Equipment Cargo Containment Systems § 154.408 Cargo tank external pressure load. For the calculation required under § 154.406 (a)(2) and (b), the external pressure load must be the difference between...

  16. 46 CFR 308.511 - Cancellation of Open Cargo Policy.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 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 Ii-Open Policy War Risk Cargo Insurance § 308.511 Cancellation of...

  17. 46 CFR 154.407 - Cargo tank internal pressure head.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo tank internal pressure head. 154.407 Section 154... Equipment Cargo Containment Systems § 154.407 Cargo tank internal pressure head. (a) For the calculation required under § 154.406(a)(1) and (b), the internal pressure head (heq), must be determined from...

  18. 46 CFR 154.407 - Cargo tank internal pressure head.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo tank internal pressure head. 154.407 Section 154... Equipment Cargo Containment Systems § 154.407 Cargo tank internal pressure head. (a) For the calculation required under § 154.406(a)(1) and (b), the internal pressure head (heq), must be determined from...

  19. 46 CFR 111.105-29 - Combustible liquid cargo carriers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Combustible liquid cargo carriers. 111.105-29 Section... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-29 Combustible liquid cargo carriers. (a) Each vessel that carries combustible liquid cargo with a closed-cup flashpoint of 60 degrees...

  20. 46 CFR 127.650 - Bulk liquid cargo limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Bulk liquid cargo limitations. 127.650 Section 127.650... liquid cargo limitations. Notwithstanding § 125.110 of this subchapter, no OSV carrying more than 240 total persons may carry flammable or combustible liquid cargoes of Grade D or higher in bulk....

  1. 46 CFR 111.105-29 - Combustible liquid cargo carriers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Combustible liquid cargo carriers. 111.105-29 Section... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-29 Combustible liquid cargo carriers. (a) Each vessel that carries combustible liquid cargo with a closed-cup flashpoint of 60 degrees...

  2. 46 CFR 111.105-29 - Combustible liquid cargo carriers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Combustible liquid cargo carriers. 111.105-29 Section... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-29 Combustible liquid cargo carriers. (a) Each vessel that carries combustible liquid cargo with a closed-cup flashpoint of 60 degrees...

  3. 46 CFR 111.105-29 - Combustible liquid cargo carriers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Combustible liquid cargo carriers. 111.105-29 Section... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-29 Combustible liquid cargo carriers. (a) Each vessel that carries combustible liquid cargo with a closed-cup flashpoint of 60 degrees...

  4. 46 CFR 111.105-29 - Combustible liquid cargo carriers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Combustible liquid cargo carriers. 111.105-29 Section... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Hazardous Locations § 111.105-29 Combustible liquid cargo carriers. (a) Each vessel that carries combustible liquid cargo with a closed-cup flashpoint of 60 degrees...

  5. 46 CFR 151.50-5 - Cargoes having toxic properties.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargoes having toxic properties. 151.50-5 Section 151.50... BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-5 Cargoes having... transporting liquids having a Reid vapor pressure exceeding 14 pounds per square inch absolute or vented at...

  6. 46 CFR 151.50-5 - Cargoes having toxic properties.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargoes having toxic properties. 151.50-5 Section 151.50... BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Special Requirements § 151.50-5 Cargoes having... transporting liquids having a Reid vapor pressure exceeding 14 pounds per square inch absolute or vented at...

  7. 46 CFR 154.1828 - Spaces containing cargo vapor: Entry.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Spaces containing cargo vapor: Entry. 154.1828 Section 154.1828 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS FOR SELF-PROPELLED VESSELS CARRYING BULK LIQUEFIED GASES Operations § 154.1828 Spaces containing cargo vapor: Entry. (a) No...

  8. 46 CFR 154.310 - Cargo piping systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo piping systems. 154.310 Section 154.310 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY STANDARDS... under § 154.703, not enter or pass through a machinery space other than a cargo pump or compressor...

  9. 46 CFR 69.67 - Marking of cargo spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Marking of cargo spaces. 69.67 Section 69.67 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.67 Marking of cargo spaces. Cargo spaces used in...

  10. 46 CFR 151.25-2 - Cargo handling space.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Cargo handling space. 151.25-2 Section 151.25-2 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Environmental Control § 151.25-2 Cargo handling space. Pump rooms, compressor rooms, refrigeration rooms, heating rooms, instrument rooms or other closed spaces...

  11. 46 CFR 154.1850 - Entering cargo handling spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Entering cargo handling spaces. 154.1850 Section 154... cargo handling spaces. (a) The master shall ensure that the ventilation system under § 154.1200 is in operation for 30 minutes before a person enters one of the following: (1) Spaces containing cargo pumps...

  12. 46 CFR 154.1850 - Entering cargo handling spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Entering cargo handling spaces. 154.1850 Section 154... cargo handling spaces. (a) The master shall ensure that the ventilation system under § 154.1200 is in operation for 30 minutes before a person enters one of the following: (1) Spaces containing cargo pumps...

  13. 46 CFR 151.25-2 - Cargo handling space.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo handling space. 151.25-2 Section 151.25-2 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Environmental Control § 151.25-2 Cargo handling space. Pump rooms, compressor rooms, refrigeration rooms, heating rooms, instrument rooms or other closed spaces...

  14. 46 CFR 151.25-2 - Cargo handling space.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Cargo handling space. 151.25-2 Section 151.25-2 Shipping... BULK LIQUID HAZARDOUS MATERIAL CARGOES Environmental Control § 151.25-2 Cargo handling space. Pump rooms, compressor rooms, refrigeration rooms, heating rooms, instrument rooms or other closed spaces...

  15. 46 CFR 69.67 - Marking of cargo spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Marking of cargo spaces. 69.67 Section 69.67 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.67 Marking of cargo spaces. Cargo spaces used in...

  16. 46 CFR 69.67 - Marking of cargo spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Marking of cargo spaces. 69.67 Section 69.67 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Convention Measurement System § 69.67 Marking of cargo spaces. Cargo spaces used in...

  17. 46 CFR 154.1850 - Entering cargo handling spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Entering cargo handling spaces. 154.1850 Section 154... cargo handling spaces. (a) The master shall ensure that the ventilation system under § 154.1200 is in operation for 30 minutes before a person enters one of the following: (1) Spaces containing cargo pumps...

  18. 46 CFR 154.310 - Cargo piping systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo piping systems. 154.310 Section 154.310 Shipping... Arrangements § 154.310 Cargo piping systems. Cargo liquid or vapor piping must: (a) Be separated from other piping systems, except where an interconnection to inert gas or purge piping is required by §...

  19. 46 CFR 153.953 - Signals during cargo transfer.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Signals during cargo transfer. 153.953 Section 153.953... red flag in the day and a red light at night when transferring cargo while fast to a dock; (b) The tankship displays a red flag when transferring cargo while at anchor; and (c) The red flag or the red light...

  20. 46 CFR 153.935a - Storage of cargo samples.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Storage of cargo samples. 153.935a Section 153.935a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Commandant (CG-522) or the tankship's flag administration for the stowage of cargo samples. (b) The master...

  1. 33 CFR 157.132 - Cargo tanks: Hydrocarbon vapor emissions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Cargo tanks: Hydrocarbon vapor... § 157.132 Cargo tanks: Hydrocarbon vapor emissions. Each tank vessel having a COW system under § 157.10a... must have— (a) A means to discharge hydrocarbon vapors from each cargo tank that is ballasted to a...

  2. 33 CFR 157.132 - Cargo tanks: Hydrocarbon vapor emissions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Cargo tanks: Hydrocarbon vapor... § 157.132 Cargo tanks: Hydrocarbon vapor emissions. Each tank vessel having a COW system under § 157.10a... must have— (a) A means to discharge hydrocarbon vapors from each cargo tank that is ballasted to a...

  3. 33 CFR 157.132 - Cargo tanks: Hydrocarbon vapor emissions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Cargo tanks: Hydrocarbon vapor... § 157.132 Cargo tanks: Hydrocarbon vapor emissions. Each tank vessel having a COW system under § 157.10a... must have— (a) A means to discharge hydrocarbon vapors from each cargo tank that is ballasted to a...

  4. 33 CFR 157.132 - Cargo tanks: Hydrocarbon vapor emissions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Cargo tanks: Hydrocarbon vapor... § 157.132 Cargo tanks: Hydrocarbon vapor emissions. Each tank vessel having a COW system under § 157.10a... must have— (a) A means to discharge hydrocarbon vapors from each cargo tank that is ballasted to a...

  5. 33 CFR 157.132 - Cargo tanks: Hydrocarbon vapor emissions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Cargo tanks: Hydrocarbon vapor... § 157.132 Cargo tanks: Hydrocarbon vapor emissions. Each tank vessel having a COW system under § 157.10a... must have— (a) A means to discharge hydrocarbon vapors from each cargo tank that is ballasted to a...

  6. 46 CFR 154.1842 - Cargo system: Controls and alarms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Cargo system: Controls and alarms. 154.1842 Section 154.1842 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES... system: Controls and alarms. The master shall ensure that the cargo emergency shut-down system and...

  7. 46 CFR 98.25-55 - Cargo piping.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Cargo piping. 98.25-55 Section 98.25-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-55...

  8. 46 CFR 98.25-55 - Cargo piping.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Cargo piping. 98.25-55 Section 98.25-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-55...

  9. 46 CFR 98.25-55 - Cargo piping.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Cargo piping. 98.25-55 Section 98.25-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-55...

  10. 46 CFR 98.25-80 - Cargo hose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Cargo hose. 98.25-80 Section 98.25-80 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-80...

  11. 46 CFR 98.25-55 - Cargo piping.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Cargo piping. 98.25-55 Section 98.25-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-55...

  12. 46 CFR 98.25-55 - Cargo piping.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Cargo piping. 98.25-55 Section 98.25-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-55...

  13. 46 CFR 98.25-80 - Cargo hose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Cargo hose. 98.25-80 Section 98.25-80 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-80...

  14. 46 CFR 98.25-80 - Cargo hose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 false Cargo hose. 98.25-80 Section 98.25-80 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-80...

  15. 46 CFR 98.25-80 - Cargo hose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 false Cargo hose. 98.25-80 Section 98.25-80 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-80...

  16. 46 CFR 98.25-80 - Cargo hose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Cargo hose. 98.25-80 Section 98.25-80 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL CONSTRUCTION, ARRANGEMENT, AND OTHER PROVISIONS FOR CERTAIN DANGEROUS CARGOES IN BULK Anhydrous Ammonia in Bulk § 98.25-80...

  17. 14 CFR 296.3 - Indirect cargo air carrier.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Indirect cargo air carrier. 296.3 Section... PROCEEDINGS) ECONOMIC REGULATIONS INDIRECT AIR TRANSPORTATION OF PROPERTY General § 296.3 Indirect cargo air carrier. An indirect cargo air carrier is any U.S. citizen who undertakes to engage indirectly in...

  18. 14 CFR 296.3 - Indirect cargo air carrier.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Indirect cargo air carrier. 296.3 Section... PROCEEDINGS) ECONOMIC REGULATIONS INDIRECT AIR TRANSPORTATION OF PROPERTY General § 296.3 Indirect cargo air carrier. An indirect cargo air carrier is any U.S. citizen who undertakes to engage indirectly in...

  19. 14 CFR 296.3 - Indirect cargo air carrier.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Indirect cargo air carrier. 296.3 Section... PROCEEDINGS) ECONOMIC REGULATIONS INDIRECT AIR TRANSPORTATION OF PROPERTY General § 296.3 Indirect cargo air carrier. An indirect cargo air carrier is any U.S. citizen who undertakes to engage indirectly in...

  20. 14 CFR 296.3 - Indirect cargo air carrier.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Indirect cargo air carrier. 296.3 Section... PROCEEDINGS) ECONOMIC REGULATIONS INDIRECT AIR TRANSPORTATION OF PROPERTY General § 296.3 Indirect cargo air carrier. An indirect cargo air carrier is any U.S. citizen who undertakes to engage indirectly in...

  1. 46 CFR 151.45-6 - Maximum amount of cargo.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... insulated, or 115 °F if uninsulated. If specific filling densities are designated in Subpart 151.50 of this...=Maximum volume to which tank may be loaded. V =Volume of tank. d r=Density of cargo at the temperature required for a cargo vapor pressure equal to the relief valve setting. d L=Density of cargo at the loading...

  2. 46 CFR 153.968 - Cargo transfer conference.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Cargo transfer conference. 153.968 Section 153.968... Procedures § 153.968 Cargo transfer conference. (a) Before he may begin making connections for cargo transfer... procedure for shutdown of shore pumps, shore valves, and ship's valves that prevents piping system...

  3. 46 CFR 153.955 - Warning signs during cargo transfer.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign...

  4. 46 CFR 153.955 - Warning signs during cargo transfer.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign...

  5. 46 CFR 153.955 - Warning signs during cargo transfer.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Warning signs during cargo transfer. 153.955 Section 153... Transfer Procedures § 153.955 Warning signs during cargo transfer. (a) When transferring cargo while fast to a dock or at anchor in port, the master shall ensure that the tankship displays a warning sign...

  6. 48 CFR 52.228-9 - Cargo Insurance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Cargo Insurance. 52.228-9... Insurance. As prescribed in 28.313(a), insert the following clause: Cargo Insurance (MAY 1999) (a) The..., cargo insurance of $_____ per vehicle to cover the value of property on each vehicle and of $_____...

  7. 48 CFR 52.228-9 - Cargo Insurance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Cargo Insurance. 52.228-9... Insurance. As prescribed in 28.313(a), insert the following clause: Cargo Insurance (MAY 1999) (a) The..., cargo insurance of $_____ per vehicle to cover the value of property on each vehicle and of $_____...

  8. 48 CFR 52.228-9 - Cargo Insurance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Cargo Insurance. 52.228-9... Insurance. As prescribed in 28.313(a), insert the following clause: Cargo Insurance (MAY 1999) (a) The..., cargo insurance of $_____ per vehicle to cover the value of property on each vehicle and of $_____...

  9. 46 CFR 151.45-6 - Maximum amount of cargo.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... temperature corresponding to the vapor pressure of the cargo at the safety relief valve setting. A reduction... required for a cargo vapor pressure equal to the relief valve setting. d L=Density of cargo at the loading temperature and pressure....

  10. 46 CFR 151.45-6 - Maximum amount of cargo.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... temperature corresponding to the vapor pressure of the cargo at the safety relief valve setting. A reduction... required for a cargo vapor pressure equal to the relief valve setting. d L=Density of cargo at the loading temperature and pressure....

  11. 46 CFR 151.45-6 - Maximum amount of cargo.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... temperature corresponding to the vapor pressure of the cargo at the safety relief valve setting. A reduction... required for a cargo vapor pressure equal to the relief valve setting. d L=Density of cargo at the loading temperature and pressure....

  12. 14 CFR 296.3 - Indirect cargo air carrier.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Indirect cargo air carrier. 296.3 Section... PROCEEDINGS) ECONOMIC REGULATIONS INDIRECT AIR TRANSPORTATION OF PROPERTY General § 296.3 Indirect cargo air carrier. An indirect cargo air carrier is any U.S. citizen who undertakes to engage indirectly in air...

  13. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Segregation of cargo from surrounding waters (Line 1 of Table 151.05). i = Skin of vessel (single skin) only required. Cargo tank wall can be vessel's hull. ii = Double skin required. Cargo tank wall cannot be vessel... segregation purposes and a secondary barrier is required for low temperature protection by § 151.15-3(d)(4...

  14. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Segregation of cargo from surrounding waters (Line 1 of Table 151.05). i=Skin of vessel (single skin) only required. Cargo tank wall can be vessel's hull. ii=Double skin required. Cargo tank wall cannot be vessel's... purposes and a secondary barrier is required for low temperature protection by § 151.15-3(d)(4), the void...

  15. 46 CFR 151.15-10 - Cargo gauging devices.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... continuous reading tape gauges. However such glasses shall be made of high strength material, suitable for... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Tanks § 151.15-10 Cargo gauging devices. This section... related fixtures which form a part of the cargo containment barrier shall be of suitable material...

  16. 46 CFR 151.15-10 - Cargo gauging devices.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... continuous reading tape gauges. However such glasses shall be made of high strength material, suitable for... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Tanks § 151.15-10 Cargo gauging devices. This section... related fixtures which form a part of the cargo containment barrier shall be of suitable material...

  17. 46 CFR 151.15-10 - Cargo gauging devices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... continuous reading tape gauges. However such glasses shall be made of high strength material, suitable for... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Tanks § 151.15-10 Cargo gauging devices. This section... related fixtures which form a part of the cargo containment barrier shall be of suitable material...

  18. 46 CFR 98.33-13 - Cargo-handling systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Cargo-handling systems. 98.33-13 Section 98.33-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS SPECIAL... Certain Grade E Combustible Liquids and Other Regulated Materials § 98.33-13 Cargo-handling systems. A...

  19. 46 CFR 98.33-3 - Cargoes authorized.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Cargoes authorized. 98.33-3 Section 98.33-3 Shipping... Certain Grade E Combustible Liquids and Other Regulated Materials § 98.33-3 Cargoes authorized. The following cargoes are authorized for transfer to and from portable tanks authorized by § 98.33-5: (a) Grade...

  20. 46 CFR 153.953 - Signals during cargo transfer.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Signals during cargo transfer. 153.953 Section 153.953 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SHIPS... Procedures § 153.953 Signals during cargo transfer. The master shall ensure that: (a) The tankship displays a...