TMBM: Tethered Micro-Balloons on Mars

Science.gov (United States)

Sims, M. H.; Greeley, R.; Cutts, J. A.; Yavrouian, A. H.; Murbach, M.

2000-01-01

The use of balloons/aerobots on Mars has been under consideration for many years. Concepts include deployment during entry into the atmosphere from a carrier spacecraft, deployment from a lander, use of super-pressurized systems for long duration flights, 'hot-air' systems, etc. Principal advantages include the ability to obtain high-resolution data of the surface because balloons provide a low-altitude platform which moves relatively slowly. Work conducted within the last few years has removed many of the technical difficulties encountered in deployment and operation of balloons/aerobots on Mars. The concept proposed here (a tethered balloon released from a lander) uses a relatively simple approach which would enable aspects of Martian balloons to be tested while providing useful and potentially unique science results. Tethered Micro-Balloons on Mars (TMBM) would be carried to Mars on board a future lander as a stand-alone experiment having a total mass of one to two kilograms. It would consist of a helium balloon of up to 50 cubic meters that is inflated after landing and initially tethered to the lander. Its primary instrumentation would be a camera that would be carried to an altitude of up to tens of meters above the surface. Imaging data would be transmitted to the lander for inclusion in the mission data stream. The tether would be released in stages allowing different resolutions and coverage. In addition during this staged release a lander camera system may observe the motion of the balloon at various heights above he lander. Under some scenarios upon completion of the primary phase of TMBM operations, the tether would be cut, allowing TMBM to drift away from the landing site, during which images would be taken along the ground.

Tethered Pyrotechnic Apparatus for Acquiring a Ground Sample

Science.gov (United States)

Jones, Jack; Zimmerman, Wayne; Wu, Jiunn Jenq; Badescu, Mircea; Sherrit, Stewart

2009-01-01

A proposed alternative design for the balloon-borne ground-sampling system described in the immediately preceding article would not rely on free fall to drive a harpoonlike sample-collecting device into the ground. Instead, the harpoon-like sample-collecting device would be a pyrotechnically driven, tethered projectile. The apparatus would include a tripod that would be tethered to the gondola. A gun for shooting the projectile into the ground would be mounted at the apex of the tripod. The gun would include an electronic trigger circuit, a chamber at the breech end containing a pyrotechnic charge, and a barrel. A sabot would be placed in the barrel just below the pyrotechnic charge, and the tethered projectile would be placed in the barrel just below the sabot. The tripod feet would be equipped with contact sensors connected to the trigger circuit. In operation, the tripod would be lowered to the ground on its tether. Once contact with the ground was detected by the sensors on all three tripod feet, the trigger circuit would fire the pyrotechnic charge to drive the projectile into the ground. (Requiring contact among all three tripod feet and the ground would ensure that the projectile would be fired into the ground, rather than up toward the gondola or the balloon.) The tethered projectile would then be reeled back up to the gondola for analysis of the sample.

Assessing tether anchor labeling and usability in pickup trucks.

Science.gov (United States)

Klinich, Kathleen D; Manary, Miriam A; Malik, Laura A; Flannagan, Carol A; Jermakian, Jessica S

2018-04-03

The objective of this study was to investigate vehicle factors associated with child restraint tether use and misuse in pickup trucks and evaluate 4 labeling interventions designed to educate consumers on proper tether use. Volunteer testing was performed with 24 subjects and 4 different pickup trucks. Each subject performed 8 child restraint installations among the 4 pickups using 2 forward-facing restraints: a Britax Marathon G4.1 and an Evenflo Triumph. Vehicles were selected to represent 4 different implementations of tether anchors among pickups: plastic loop routers (Chevrolet Silverado), webbing routers (Ram), back wall anchors (Nissan Frontier), and webbing routers plus metal anchors (Toyota Tundra). Interventions included a diagram label, Quick Response (QR) Code linked to video instruction, coordinating text label, and contrasting text tag. Subjects used the child restraint tether in 93% of trials. However, tether use was completely correct in only 9% of trials. An installation was considered functional if the subject attached the tether to a tether anchor and had a tight installation (ignoring routing and head restraint position); 28% of subjects achieved a functional installation. The most common installation error was attaching the tether hook to the anchor/router directly behind the child restraint (near the top of the seatback) rather than placing the tether through the router and attaching it to the anchor in the adjacent seating position. The Nissan Frontier, with the anchor located on the back wall of the cab, had the highest rate of correct installations but also had the highest rate of attaching the tether to components other than the tether anchor (seat adjustor, child restraint storage hook, around head restraint). None of the labeling interventions had a significant effect on correct installation; not a single subject scanned the QR Code to access the video instruction. Subjects with the most successful installations spent extensive time

Coat/Tether Interactions—Exception or Rule?

Science.gov (United States)

Schröter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

2016-01-01

Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers. PMID:27243008

Coat/Tether Interactions-Exception or Rule?

Science.gov (United States)

Schroeter, Saskia; Beckmann, Sabrina; Schmitt, Hans Dieter

2016-01-01

Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

Two Tethered Balloon Systems

Science.gov (United States)

Youngbluth, Otto; Owens, Thomas L.; Storey, Richard W.

1990-01-01

Systems take meteorological measurements for variety of research projects. Report describes work done by NASA Langley Research Center in atmospheric research using tethered balloon systems composed of commercially available equipment. Two separate tethered balloon systems described in report have payloads and configurations tailored to requirements of specific projects. Each system capable of measuring atmospheric parameter or species in situ and then telemetering this data in real time to ground station. Meteorological data and concentration of ozone typically measured. Indicates instrumented tethered balloon systems have distinct advantages over other systems for gathering data on troposphere.

Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

Science.gov (United States)

Lorenzini, Enrico C.; Gullahorn, Gordon E.; Cosmo, Mario L.; Estes, Robert D.; Grossi, Mario D.

1994-01-01

This final report covers nine years of research on future tether applications and on the actual flights of the Small Expendable Deployment System (SEDS). Topics covered include: (1) a description of numerical codes used to simulate the orbital and attitude dynamics of tethered systems during station keeping and deployment maneuvers; (2) a comparison of various tethered system simulators; (3) dynamics analysis, conceptual design, potential applications and propagation of disturbances and isolation from noise of a variable gravity/microgravity laboratory tethered to the Space Station; (4) stability of a tethered space centrifuge; (5) various proposed two-dimensional tethered structures for low Earth orbit for use as planar array antennas; (6) tethered high gain antennas; (7) numerical calculation of the electromagnetic wave field on the Earth's surface on an electrodynamically tethered satellite; (8) reentry of tethered capsules; (9) deployment dynamics of SEDS-1; (10) analysis of SEDS-1 flight data; and (11) dynamics and control of SEDS-2.

Learning characteristics of a space-time neural network as a tether skiprope observer

Science.gov (United States)

Lea, Robert N.; Villarreal, James A.; Jani, Yashvant; Copeland, Charles

1993-01-01

The Software Technology Laboratory at the Johnson Space Center is testing a Space Time Neural Network (STNN) for observing tether oscillations present during retrieval of a tethered satellite. Proper identification of tether oscillations, known as 'skiprope' motion, is vital to safe retrieval of the tethered satellite. Our studies indicate that STNN has certain learning characteristics that must be understood properly to utilize this type of neural network for the tethered satellite problem. We present our findings on the learning characteristics including a learning rate versus momentum performance table.

The Science and Applications Tethered Platform (SATP) project

Science.gov (United States)

Merlina, P.

1986-01-01

The capabilities of tether systems in orbit are going to be demonstrated by the first planned flights of the Tethered Satellite System (TSS). These test flights will investigate the properties of tether systems as low altitude atmospheric research facilities and as electric power generators. Studies are being conducted with the purpose of testing a variety of concepts and approaches. A comparative analysis of results will allow the choosing of the most promising ideas for further development. The broad range of applications presently under study include applications in electrodynamics, transportation, microgravity in addition to basic research. The SATP project definition study is now about midway through its first phase. The analyses conducted have led to an appraisal of users interest in the project and to a deeper understanding of the problems associated with large, long-lived tether systems in space. In addition, two specialized platform designs, devoted to microgravity and precise pointing applications, are being studied because of their potential usefulness and the promise of technical feasibility.

Use of top tethers with forward-facing child restraints: observations and driver interviews.

Science.gov (United States)

Eichelberger, Angela H; Decina, Lawrence E; Jermakian, Jessica S; McCartt, Anne T

2014-02-01

Despite the safety benefits, many parents do not use top tethers with forward-facing child restraints. Detailed information was collected about why parents are not using tethers. The sample included 479 drivers who had forward-facing child restraints installed in passenger vehicles equipped with tether anchors. The survey was conducted primarily at shopping centers, recreation facilities, child care facilities, car seat check events, and health care facilities in mostly suburban areas surrounding Philadelphia, Washington, DC, Fredericksburg (VA), and Seattle. Drivers were surveyed about their knowledge and use of tethers and experience with child restraints. Tether use was observed to verify whether tethers were being used correctly. Fifty-six percent of forward-facing child restraints were installed with the tether; 39% were installed with the tether used correctly. The tether was used with 71% of LATCH lower anchor installations and 33% of seat belt installations. Drivers who installed child restraints without tethers most often said they did not know about the tether or how to use it. Although the tether use rate was slightly higher in the current research than in previous studies, many parents and caregivers still use forward-facing child restraints without attaching the tether. Because the main problem is lack of awareness of the tether or how to use it, public education should focus specifically on the safety benefits of tethers and how to use them. Information about why caregivers fail to use top tethers is potentially useful to child restraint manufacturers, child passenger safety technicians, and others who work with parents to improve motor vehicle safety. Copyright © 2013 Elsevier Ltd and National Safety Council. All rights reserved.

Space tether dynamics: an introduction

Science.gov (United States)

Denny, Mark

2018-05-01

The dynamics of orbiting tethers (space elevators and skyhooks) is developed from an unusual direction: Lagrangian rather than Newtonian mechanics. These basic results are derived among others: space elevator required length with and without counterweight, location and magnitude of maximum tether tension, skyhook orbital parameters and tether tension. These conceptual devices are being increasingly discussed as technologically feasible; here they make an interesting pedagogical application of Lagrangian mechanics suitable for undergraduate physics students.

Coat/tether interactions – exceptions or rule?

Directory of Open Access Journals (Sweden)

Saskia eSchroeter

2016-05-01

Full Text Available Coat complexes are important for cargo selection and vesicle formation. Recent evidence suggests that they may also be involved in vesicle targeting. Tethering factors, which form an initial bridge between vesicles and the target membrane, may bind to coat complexes. In this review, we ask whether these coat/tether interactions share some common mechanisms, or whether they are special adaptations to the needs of very specific transport steps. We compare recent findings in two multisubunit tethering complexes, the Dsl1 complex and the HOPS complex, and put them into context with the TRAPP I complex as a prominent example for coat/tether interactions. We explore where coat/tether interactions are found, compare their function and structure, and comment on a possible evolution from a common ancestor of coats and tethers.

Novel roaming and stationary tethered aerial robots for continuous mobile missions in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Gu, Beom W.; Choi, Su Y.; Rim, Chun T. [Dept. of Nuclear and Quantum Engineering, KAIST, Daejeon (Korea, Republic of); Choi, Young Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cai, Guowei; Seneviratne, Lakmal [Dept. of Aerospace Engineering, Khalifa University, Abu Dhabi (United Arab Emirates)

2016-08-15

In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs) for radioactive material sampling and stationary tethered aerial robots (STARs) for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

Novel Roaming and Stationary Tethered Aerial Robots for Continuous Mobile Missions in Nuclear Power Plants

Directory of Open Access Journals (Sweden)

Beom W. Gu

2016-08-01

Full Text Available In this paper, new tethered aerial robots including roaming tethered aerial robots (RTARs for radioactive material sampling and stationary tethered aerial robots (STARs for environment monitoring are proposed to meet extremely-long-endurance missions of nuclear power plants. The flight of the proposed tethered aerial robots may last for a few days or even a few months as long as the tethered cable provides continuous power. A high voltage AC or DC power system was newly adopted to reduce the mass of the tethered cable. The RTAR uses a tethered cable spooled from the aerial robot and an aerial tension control system. The aerial tension control system provides the appropriate tension to the tethered cable, which is accordingly laid down on the ground as the RTAR roams. The STAR includes a tethered cable spooled from the ground and a ground tension control system, which enables the STAR to reach high altitudes. Prototypes of the RTAR and STAR were designed and successfully demonstrated in outdoor environments, where the load power, power type, operating frequency, and flight attitude of the RTAR and STAR were: 180 W, AC 100 kHz, and 20 m; and 300 W, AC or DC 100 kHz, and 80 m, respectively.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

Energy Technology Data Exchange (ETDEWEB)

Kosheverova, Vera V., E-mail: kosheverova_vera@incras.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kamentseva, Rimma S., E-mail: rkamentseva@yandex.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Gonchar, Ilya V., E-mail: ample@mail.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kharchenko, Marianna V., E-mail: mariannakharchenko@gmail.com [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); Kornilova, Elena S., E-mail: lenkor@mail.cytspb.rssi.ru [Institute of Cytology of RAS, 4, Tikhoretsky Ave, St. Petersburg, 194064 (Russian Federation); St. Petersburg State University, 7-9, Universitetskaya nab, St. Petersburg, 199034 (Russian Federation); Department of Medical Physics, Peter the Great St. Petersburg Polytechnic University, 29, Polytechnicheskaya, St.Petersburg, 195251 (Russian Federation)

2016-04-22

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Mobility of tethering factor EEA1 on endosomes is decreased upon stimulation of EGF receptor endocytosis in HeLa cells

International Nuclear Information System (INIS)

Kosheverova, Vera V.; Kamentseva, Rimma S.; Gonchar, Ilya V.; Kharchenko, Marianna V.; Kornilova, Elena S.

2016-01-01

Tethering factor EEA1, mediating homotypic fusion of early endosomes, was shown to be localized in membrane-bound state both in serum-deprived and stimulated for EGF receptor endocytosis cells. However, it is not known whether dynamics behavior of EEA1 is affected by EGF stimulation. We investigated EEA1 cytosol-to-membrane exchange rate in interphase HeLa cells by FRAP analysis. The data obtained fitted two-states binding model, with the bulk of membrane-associated EEA1 protein represented by the mobile fraction both in serum-starved and EGF-stimulated cells. Fast recovery state had similar half-times in the two cases: about 1.6 s and 2.8 s, respectively. However, the recovery half-time of slowly cycled EEA1 fraction significantly increased in EGF-stimulated comparing to serum-starved cells (from 21 to 99 s). We suppose that the retardation of EEA1 fluorescence recovery upon EGF-stimulation may be due to the increase of activated Rab5 on endosomal membranes, the growth of the number of tethering events between EEA1-positive vesicles and their clustering. - Highlights: • EEA1 mobility was compared in serum-starved and EGF-stimulated interphase HeLa cells. • FRAP analysis revealed fast and slow components of EEA1 recovery in both cases. • Stimulation of EGFR endocytosis did not affect fast EEA1 turnover. • EGF stimulation significantly increased half-time of slowly exchanged EEA1 fraction.

Tether Elevator Crawler Systems (TECS)

Science.gov (United States)

Swenson, Frank R.

1987-01-01

One of the needs of the experimenters on the space station is access to steady and controlled-variation microgravity environments. A method of providing these environments is to place the experiment on a tether attached to the space station. This provides a high degree of isolation from structural oscillations and vibrations. Crawlers can move these experiments along the tethers to preferred locations, much like an elevator. This report describes the motion control laws developed for these crawlers and the testing of laboratory models of these tether elevator crawlers.

Molecular Structure of Membrane Tethers

NARCIS (Netherlands)

Baoukina, Svetlana; Marrink, Siewert J.; Tieleman, D. Peter

2012-01-01

Membrane tethers are nanotubes formed by a lipid bilayer. They play important functional roles in cell biology and provide an experimental window on lipid properties. Tethers have been studied extensively in experiments and described by theoretical models, but their molecular structure remains

Space Environmental Effects on Coated Tether Materials

Science.gov (United States)

Gittemeier, Keith A.; Hawk, Clark W.; Finckenor, Miria M.; Watts, Ed

2005-01-01

The University of Alabama in Huntsville s Propulsion Research Center has teamed with NASA's Marshall Space Flight Center (MSFC) to research the effects of atomic oxygen (AO) bombardment on coated tether materials. Tethers Unlimited Inc. has provided several candidate tether materials with various coatings for AO exposure in MSFC s Atomic Oxygen Beam Facility. Additional samples were exposed to ultraviolet (UV) radiation at MSFC. AO erodes most organic materials, and ultraviolet radiation embrittles polymers. This test series was performed to determine the effect of AO and UV on the mechanical integrity of tether materials that were treated with AO-protective coatings, such as polyhedral oligomeric silsesquioxane (POSS) or metallization. Both TUI's Multi-Application Survivable Tether (MAST) Experiment and Marshall Space Flight Center s Momentum Exchange Electrodynamic Reboost (MXER) programs will benefit from this research by helping to determine tether materials and coatings that give the longest life with the lowest mass penalty.

Membrane tethering complexes in the endosomal system

Directory of Open Access Journals (Sweden)

Anne eSpang

2016-05-01

Full Text Available Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the CORVET complex, while fusion of late endosomes with lysosomes depends on the HOPS complex. Recycling through the TGN and to the plasma membrane is facilitated by the GARP and EARP complexes, respectively. However, there are other tethering functions in the endosomal system as there are multiple pathways through which proteins can be delivered from endosomes to either the TGN or the plasma membrane. Furthermore, complexes that may be part of novel tethering complexes have been recently identified. Thus it is likely that more tethering factors exist. In this review, I will provide an overview of different tethering complexes of the endosomal system and discuss how they may provide specificity in membrane traffic.

Heterobifunctional crosslinkers for tethering single ligand molecules to scanning probes

International Nuclear Information System (INIS)

Riener, Christian K.; Kienberger, Ferry; Hahn, Christoph D.; Buchinger, Gerhard M.; Egwim, Innocent O.C.; Haselgruebler, Thomas; Ebner, Andreas; Romanin, Christoph; Klampfl, Christian; Lackner, Bernd; Prinz, Heino; Blaas, Dieter; Hinterdorfer, Peter; Gruber, Hermann J.

2003-01-01

Single molecule recognition force microscopy (SMRFM) is a versatile atomic force microscopy (AFM) method to probe specific interactions of cognitive molecules on the single molecule level. It allows insights to be gained into interaction potentials and kinetic barriers and is capable of mapping interaction sites with nm positional accuracy. These applications require a ligand to be attached to the AFM tip, preferably by a distensible poly(ethylene glycol) (PEG) chain between the measuring tip and the ligand molecule. The PEG chain greatly facilitates specific binding of the ligand to immobile receptor sites on the sample surface. The present study contributes to tip-PEG-ligand tethering in three ways: (i) a convenient synthetic route was found to prepare NH 2 -PEG-COOH which is the key intermediate for long heterobifunctional crosslinkers; (ii) a variety of heterobifunctional PEG derivatives for tip-PEG-ligand linking were prepared from NH 2 -PEG-COOH; (iii) in particular, a new PEG crosslinker with one thiol-reactive end and one terminal nitrilotriacetic acid (NTA) group was synthesized and successfully used to tether His 6 -tagged protein molecules to AFM tips via noncovalent NTA-Ni 2+ -His 6 bridges. The new crosslinker was applied to link a recombinant His 6 -tagged fragment of the very-low density lipoprotein receptor to the AFM tip whereupon specific docking to the capsid of human rhinovirus particles was observed by force microscopy. In a parallel study, the specific interaction of the small GTPase Ran with the nuclear import receptor importin β1 was studied in detail by SMRFM, using the new crosslinker to link His 6 -tagged Ran to the measuring tip [Nat. Struct. Biol. (2003), 10, 553-557

Tethering factors as organizers of intracellular vesicular traffic.

Science.gov (United States)

Yu, I-Mei; Hughson, Frederick M

2010-01-01

Intracellular trafficking entails the budding, transport, tethering, and fusion of transport vesicles and other membrane carriers. Here we review recent progress toward a mechanistic understanding of vesicle tethering. The known tethering factors are large complexes important for one or more intracellular trafficking pathways and are capable of interacting directly with many of the other principal components of the cellular trafficking machinery. Our review emphasizes recent developments in the in vitro reconstitution of vesicle tethering and the structural characterization of multisubunit tethering factors. The combination of these and other approaches has led to exciting progress toward understanding how these essential nanomachines work.

T-Rex: A Japanese Space Tether Experiment

Science.gov (United States)

Johnson, Les

2009-01-01

Electrodynamic tether (EDT) thrusters work by virtue of the force a magnetic field exerts on a wire carrying an electrical current. The force, which acts on any charged particle moving through a magnetic field (including the electrons moving in a current-carrying wire), were concisely expressed by Lorentz in 1895 in an equation that now bears his name. The force acts in a direction perpendicular to both the direction of current flow and the magnetic field vector. Electric motors make use of this force: a wire loop in a magnetic field is made to rotate by the torque the Lorentz Force exerts on it due to an alternating current in the loop times so as to keep the torque acting in the same sense. The motion of the loop is transmitted to a shaft, thus providing work. Although the working principle of EDT thrusters is not new, its application to space transportation may be significant. In essence, an EDT thruster is just a clever way of getting an electrical current to flow in a long orbiting wire (the tether) so that the Earth s magnetic field will accelerate the wire and, consequently the payload attached to the wire. The direction of current flow in the tether, either toward or away from the Earth along the local vertical, determines whether the magnetic force will raise or lower the orbit. The bias voltage of a vertically deployed metal tether, which results just from its orbital motion (assumed eastward) through Earth s magnetic field, is positive with respect to the ambient plasma at the top and negative at the bottom. This polarization is due to the action of the Lorentz force on the electrons in the tether. Thus, the natural current flow is the result of negative electrons being attracted to the upper end and then returned to the plasma at the lower end. The magnetic force in this case has a component opposite to the direction of motion, and thus leads to a lowering of the orbit and eventually to re-entry. In this generator mode of operation the Lorentz Force

Atmospheric Electricity and Tethered Aerostats, Volume 1

Science.gov (United States)

1976-05-11

CATALOG NUMBER AFETR -TR-76-07 __ 4. TITLE (and Subtitle) -. TYPE OF REPORT & PERIOD COVERED ATMOSPHERIC ELECTRICITY AND TETHERED AEROSTATS, FINAL. 1...Electricity Faraday Capes Balloons Lightning Effects , Protection, Warning Systems Conducting and Non-Conducting ’Tethers Potential Geadient Anomalies...and identifying feasible protective systems. After a brief introductory section math models of effects of tethered balloons on surrounding

Tether Deployer And Brake

Science.gov (United States)

Carroll, Joseph A.; Alexander, Charles M.

1993-01-01

Design concept promises speed, control, and reliability. Scheme for deploying tether provides for fast, free, and snagless payout and fast, dependable braking. Developed for small, expendable tethers in outer space, scheme also useful in laying transoceanic cables, deploying guidance wires to torpedoes and missiles, paying out rescue lines from ship to ship via rockets, deploying antenna wires, releasing communication and power cables to sonobuoys and expendable bathythermographs, and in reeling out lines from fishing rods.

Review of deployment technology for tethered satellite systems

Science.gov (United States)

Yu, B. S.; Wen, H.; Jin, D. P.

2018-03-01

Tethered satellite systems (TSSs) have attracted significant attention due to their potential and valuable applications for scientific research. With the development of various launched on-orbit missions, the deployment of tethers is considered a crucial technology for operation of a TSS. Both past orbiting experiments and numerical results have shown that oscillations of the deployed tether due to the Coriolis force and environmental perturbations are inevitable and that the impact between the space tether and end-body at the end of the deployment process leads to complicated nonlinear phenomena. Hence, a set of suitable control methods plays a fundamental role in tether deployment. This review article summarizes previous work on aspects of the dynamics, control, and ground-based experiments of tether deployment. The relevant basic principles, analytical expressions, simulation cases, and experimental results are presented as well.

Investigation of electrodynamic stabilization and control of long orbiting tethers. [space shuttle payloads

Science.gov (United States)

Arnold, D. A.; Dobrowolny, M.

1981-01-01

An algorithm for using electric currents to control pendular oscillations induced by various perturbing forces on the Skyhook wire is considered. Transverse and vertical forces on the tether; tether instability modes and causes during retrieval by space shuttle; simple and spherical pendulum motion and vector damping; and current generation and control are discussed. A computer program for numerical integration of the in-plane and out-of-plane displacements of the tether vs time was developed for heuristic study. Some techniques for controlling instabilities during payload retrieval and methods for employing the tether for launching satellites from the space shuttle are considered. Derivations and analyses of a general nature used in all of the areas studied are included.

GRASP: A multitasking tether

Directory of Open Access Journals (Sweden)

Catherine eRabouille

2016-01-01

Full Text Available Originally identified as Golgi stacking factors in vitro, the Golgi reassembly stacking protein (GRASP family has been shown to act as membrane tethers with multiple cellular roles. As an update to previous comprehensive reviews of the GRASP family (Vinke et al., 2011 (Giuliani et al., 2011;Jarvela and Linstedt, 2012, we outline here the latest findings concerning their diverse roles. New insights into the mechanics of GRASP-mediated tethering come from recent crystal structures. The models of how GRASP65 and GRASP55 tether membranes relate directly to their role in Golgi ribbon formation in mammalian cells and the unlinking of the ribbon at the onset of mitosis. However, it is also clear that GRASPs act outside the Golgi with roles at the ER and ER exit sites (ERES. Furthermore, the proteins of this family display other roles upon cellular stress, especially in mediating unconventional secretion of both transmembrane proteins (Golgi bypass and cytoplasmic proteins (through secretory autophagosomes.

Forces, energetics, and dynamics of conjugated-carbon ring tethers adhered to CNTs: a computational investigation.

Science.gov (United States)

Filla, Nicholas; Ramasamy, Ramaraja; Wang, Xianqiao

2018-04-25

The strength and nature of the interactions between carbon nanotubes (CNTs) and molecular tethers plays a vital role in technology such as CNT-enzyme sensors. Tethers that attach noncovalently to CNTs are ideal for retaining the electrical properties of the CNTs since they do not degrade the CNT surface and effect its electrical conductivity. However, leaching due to weak CNT-tether attachment is very common when using noncovalent tethers, and this has limited their use in commercial products including biosensors. Thus, understanding the fundamental mechanics governing the strength of CNT-tether adhesion is crucial for the design of highly sensitive, viable sensors. Here, we computationally investigate the adhesion strength of CNT-tether complexes with 8 different tethering molecules designed to adhere noncovalently to the CNT surface. We study the effects of CNT diameter, CNT chirality, and the size/geometry of the tethering molecule on the adhesion energy and force. Our results show an asymptotic relationship between adhesion strength and CNT diameter. Calculations show that noncovalent tethers tested here can reach adhesion forces and energies that are up to 21% and 54% of the strength of the carbon-carbon single bond force and bond energy respectively. We anticipate our results will help guide CNT-enzyme sensor design to produce sensors with high sensitivity and minimal leaching.

Passivity-Based Control of a Rigid Electrodynamic Tether

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2011-01-01

Electrodynamic tethers provide actuation for performing orbit correction of spacecrafts. When an electrodynamic tether system is orbiting the Earth in an inclined orbit, periodic changes in the magnetic field result in a family of unstable periodic solutions in the attitude motion. This paper shows...... how these periodic solutions can be stabilized by controlling only the current through the tether. A port-controlled Hamiltonian formulation is employed to describe the tethered satellite system and a passive input-output connection is utilized in the control design. The control law consists of two...

Mobile tethering: Overview, perspectives and challengess

NARCIS (Netherlands)

Constantinescu, M.; Onur, E.; Durmus, Y.; Nikou, S.; Reuver, M. de; Bouwman, H.; Djurica, M.; Glatz, P.M.

2014-01-01

Purpose: The purpose of this paper is to analyze mobile tethering from technological and social perspectives. Mobile tethering allows us to share cellular data connection with others over WiFi, Bluetooth or USB. Although the technology is ready and has promising outcomes, service providers and the

Membrane Tethering Complexes in the Endosomal System

OpenAIRE

Spang, Anne

2016-01-01

Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the class C core vacuole/endosome tethering (CORVET) complex, while fusion of late endosomes with lysosomes depends on the homotypic fusion and vacuole protein sorting (HOPS) complex. Recycling through the trans-Golgi network (TGN) and to the plasma membrane is...

Enabling Tethered Exploration on Mars, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Strong science motivations exist for exploring hard to reach terrain on Mars and the leading systems proposed to do so require tethers. While tethers are used...

Tether applications for space station

Science.gov (United States)

Nobles, W.

1986-01-01

A wide variety of space station applications for tethers were reviewed. Many will affect the operation of the station itself while others are in the category of research or scientific platforms. One of the most expensive aspects of operating the space station will be the continuing shuttle traffic to transport logistic supplies and payloads to the space station. If a means can be found to use tethers to improve the efficiency of that transportation operation, it will increase the operating efficiency of the system and reduce the overall cost of the space station. The concept studied consists of using a tether to lower the shuttle from the space station. This results in a transfer of angular momentum and energy from the orbiter to the space station. The consequences of this transfer is studied and how beneficial use can be made of it.

Modeling and Simulation of a Tethered Harpoon for Comet Sampling

Science.gov (United States)

Quadrelli, Marco B.

2014-01-01

This paper describes the development of a dynamic model and simulation results of a tethered harpoon for comet sampling. This model and simulation was done in order to carry out an initial sensitivity analysis for key design parameters of the tethered system. The harpoon would contain a canister which would collect a sample of soil from a cometary surface. Both a spring ejected canister and a tethered canister are considered. To arrive in close proximity of the spacecraft at the end of its trajectory so it could be captured, the free-flying canister would need to be ejected at the right time and with the proper impulse, while the tethered canister must be recovered by properly retrieving the tether at a rate that would avoid an excessive amplitude of oscillatory behavior during the retrieval. The paper describes the model of the tether dynamics and harpoon penetration physics. The simulations indicate that, without the tether, the canister would still reach the spacecraft for collection, that the tether retrieval of the canister would be achievable with reasonable fuel consumption, and that the canister amplitude upon retrieval would be insensitive to variations in vertical velocity dispersion.

Tension waves in tethered satellite cables

Science.gov (United States)

Lallman, F. J.

1984-01-01

A one-degree-of-freedom simulation of the Tethered Satellite System (TSS) was programmed using a distributed system model of the tether based on the one-dimensional wave equation. This model represents the time varying tension profile along the tether as the sum of two traveling waves of tension moving in opposite directions. A control loop was devised which combines a deployment rate command with the measured tension at the deployer to produce a smooth, stable rate of deployment of the subsatellite. Simulation results show a buildup of periodic bursts of high frequency oscillation in tension. This report covers the mathematical modelling and simulation results and explains the reason for the observed oscillations. The design of a possible vibration damping device is discussed.

The stochastic dynamics of tethered microcantilevers in a viscous fluid

Energy Technology Data Exchange (ETDEWEB)

Robbins, Brian A.; Paul, Mark R. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Radiom, Milad; Ducker, William A. [Department of Chemical Engineering, Virginia Tech, Blacksburg, Virginia 24061 (United States); Walz, John Y. [Department of Chemical Engineering, University of Kentucky, Lexington, Kentucky 40506 (United States)

2014-10-28

We explore and quantify the coupled dynamics of a pair of micron scale cantilevers immersed in a viscous fluid that are also directly tethered to one another at their tips by a spring force. The spring force, for example, could represent the molecular stiffness or elasticity of a biomolecule or material tethered between the cantilevers. We use deterministic numerical simulations with the fluctuation-dissipation theorem to compute the stochastic dynamics of the cantilever pair for the conditions of experiment when driven only by Brownian motion. We validate our approach by comparing directly with experimental measurements in the absence of the tether which shows excellent agreement. Using numerical simulations, we quantify the correlated dynamics of the cantilever pair over a range of tether stiffness. Our results quantify the sensitivity of the auto- and cross-correlations of equilibrium fluctuations in cantilever displacement to the stiffness of the tether. We show that the tether affects the magnitude of the correlations which can be used in a measurement to probe the properties of an attached tethering substance. For the configurations of current interest using micron scale cantilevers in water, we show that the magnitude of the fluid coupling between the cantilevers is sufficiently small such that the influence of the tether can be significant. Our results show that the cross-correlation is more sensitive to tether stiffness than the auto-correlation indicating that a two-cantilever measurement has improved sensitivity when compared with a measurement using a single cantilever.

Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

Science.gov (United States)

Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

2016-09-01

We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

Lyapunov Orbits in the Jupiter System Using Electrodynamic Tethers

Science.gov (United States)

Bokelmann, Kevin; Russell, Ryan P.; Lantoine, Gregory

2013-01-01

Various researchers have proposed the use of electrodynamic tethers for power generation and capture from interplanetary transfers. The effect of tether forces on periodic orbits in Jupiter-satellite systems are investigated. A perturbation force is added to the restricted three-body problem model and a series of simplifications allows development of a conservative system that retains the Jacobi integral. Expressions are developed to find modified locations of equilibrium positions. Modified families of Lyapunov orbits are generated as functions of tether size and Jacobi integral. Zero velocity curves and stability analyses are used to evaluate the dynamical properties of tether-modified orbits.

The PROPEL Electrodynamic Tether Demonstration Mission

Science.gov (United States)

Bilen, Sven G.; Johnson, C. Les; Wiegmann, Bruce M.; Alexander, Leslie; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael

2012-01-01

The PROPEL ("Propulsion using Electrodynamics") mission will demonstrate the operation of an electrodynamic tether propulsion system in low Earth orbit and advance its technology readiness level for multiple applications. The PROPEL mission has two primary objectives: first, to demonstrate the capability of electrodynamic tether technology to provide robust and safe, near-propellantless propulsion for orbit-raising, de-orbit, plane change, and station keeping, as well as to perform orbital power harvesting and formation flight; and, second, to fully characterize and validate the performance of an integrated electrodynamic tether propulsion system, qualifying it for infusion into future multiple satellite platforms and missions with minimal modification. This paper provides an overview of the PROPEL system and design reference missions; mission goals and required measurements; and ongoing PROPEL mission design efforts.

Two-Stage Winch for Kites and Tethered Balloons or Blimps

Science.gov (United States)

Miles, Ted; Bland, Geoff

2011-01-01

A winch system provides a method for launch and recovery capabilities for kites and tethered blimps or balloons. Low power consumption is a key objective, as well as low weight for portability. This is accomplished by decoupling the tether-line storage and wind ing/ unwinding functions, and providing tailored and efficient mechanisms for each. The components of this system include rotational power input devices such as electric motors or other apparatus, line winding/unwinding reel(s), line storage reel(s), and independent drive trains. Power is applied to the wind/unwind reels to transport the tether line. Power is also applied to a line storage reel, from either the wind/unwind power source, the wind/unwind reel itself, or separate power source. The speeds of the two reels are synchronized, but not dependent on each other. This is accomplished via clutch mechanisms, variable transmissions, or independent motor controls. The speed of the storage reel is modulated as the effective diameter of the reel changes with line accumulation.

Calculating Payload for a Tethered Balloon System

Science.gov (United States)

Charles D. Tangren

1980-01-01

A graph method to calculate payload for a tethered balloon system, with the supporting helium lift and payload equations. is described. The balloon system is designed to collect emissions data during the convective-lift and no-convective-lift phases of a forest fire. A description of the balloon system and a list of factors affecting balloon selection are included....

Numerical modelling of elastic space tethers

DEFF Research Database (Denmark)

Kristiansen, Kristian Uldall; Palmer, P. L.; Roberts, R. M.

2012-01-01

In this paper the importance of the ill-posedness of the classical, non-dissipative massive tether model on an orbiting tether system is studied numerically. The computations document that via the regularisation of bending resistance a more reliable numerical integrator can be produced. Furthermo....... It is also shown that on the slow manifold the dynamics of the satellites are well-approximated by the finite dimensional slack-spring model....

ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor

Energy Technology Data Exchange (ETDEWEB)

Alvarado, Diego; Klein, Daryl E.; Lemmon, Mark A.; (UPENN-MED)

2009-09-25

The orphan receptor tyrosine kinase ErbB2 (also known as HER2 or Neu) transforms cells when overexpressed, and it is an important therapeutic target in human cancer. Structural studies have suggested that the oncogenic (and ligand-independent) signalling properties of ErbB2 result from the absence of a key intramolecular 'tether' in the extracellular region that autoinhibits other human ErbB receptors, including the epidermal growth factor (EGF) receptor. Although ErbB2 is unique among the four human ErbB receptors, here we show that it is the closest structural relative of the single EGF receptor family member in Drosophila melanogaster (dEGFR). Genetic and biochemical data show that dEGFR is tightly regulated by growth factor ligands, yet a crystal structure shows that it, too, lacks the intramolecular tether seen in human EGFR, ErbB3 and ErbB4. Instead, a distinct set of autoinhibitory interdomain interactions hold unliganded dEGFR in an inactive state. All of these interactions are maintained (and even extended) in ErbB2, arguing against the suggestion that ErbB2 lacks autoinhibition. We therefore suggest that normal and pathogenic ErbB2 signalling may be regulated by ligands in the same way as dEGFR. Our findings have important implications for ErbB2 regulation in human cancer, and for developing therapeutic approaches that target novel aspects of this orphan receptor.

Modeling and Control of Electrodynamic Tethers - an Energy and Topology Approach

DEFF Research Database (Denmark)

Larsen, Martin Birkelund

A space tether is a cable used to connect spacecrafts in an orbiting structure. If an electrical current is lead through the tether, it can be utilized to provide propulsion for the spacecraft. In this case the cable is referred to as an electrodynamic tether. The system utilizes the magnetic field...... of the Earth for creating a Lorentz force along the tether which occur when a current carrying wire operates in a magnetic field. The use of electrodynamic tethers are interesting since they operate solely on electrical energy, which can be provided by solar panels of the spacecrafts. In this way the amount...... when using electrodynamic tethers is that the force created along the tether is based on an external uncontrollable condition, namely the magnetic field. Even whit a known model of the magnetic field, limitations to the creation of the Lorentz force still exists, since the force can only be generated...

One kilometer (1 km) electric solar wind sail tether produced automatically.

Science.gov (United States)

Seppänen, Henri; Rauhala, Timo; Kiprich, Sergiy; Ukkonen, Jukka; Simonsson, Martin; Kurppa, Risto; Janhunen, Pekka; Hæggström, Edward

2013-09-01

We produced a 1 km continuous piece of multifilament electric solar wind sail tether of μm-diameter aluminum wires using a custom made automatic tether factory. The tether comprising 90,704 bonds between 25 and 50 μm diameter wires is reeled onto a metal reel. The total mass of 1 km tether is 10 g. We reached a production rate of 70 m/24 h and a quality level of 1‰ loose bonds and 2‰ rebonded ones. We thus demonstrated that production of long electric solar wind sail tethers is possible and practical.

Selected Tether Applications Cost Model

Science.gov (United States)

Keeley, Michael G.

1988-01-01

Diverse cost-estimating techniques and data combined into single program. Selected Tether Applications Cost Model (STACOM 1.0) is interactive accounting software tool providing means for combining several independent cost-estimating programs into fully-integrated mathematical model capable of assessing costs, analyzing benefits, providing file-handling utilities, and putting out information in text and graphical forms to screen, printer, or plotter. Program based on Lotus 1-2-3, version 2.0. Developed to provide clear, concise traceability and visibility into methodology and rationale for estimating costs and benefits of operations of Space Station tether deployer system.

Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

KAUST Repository

Srivastava, Samanvaya

2012-04-17

Phase behavior of poly(ethylene glycol) (PEG) tethered silica nanoparticles dispersed in PEG hosts is investigated using small-angle X-ray scattering. Phase separation in dispersions of densely grafted nanoparticles is found to display strikingly different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer composites incorporating results from this as well as various other contemporary studies is presented. We show that in the range of moderate to high grafting densities the dispersion state of nanoparticles in composites is largely insensitive to the grafting density of the tethered chains and chemistry of the polymer host. Instead, the ratio of the particle diameter to the size of the tethered chain and the ratio of the molecular weights of the host and tethered polymer chains (P/N) are shown to play a dominant role. Additionally, we find that well-functionalized nanoparticles form stable dispersions in their polymer host beyond the P/N limit that demarcates the wetting/dewetting transition in polymer brushes on flat substrates interacting with polymer melts. A general strategy for achieving uniform nanoparticle dispersion in polymers is proposed. © 2012 American Chemical Society.

Stability analysis and trend study of a balloon tethered in a wind, with experimental comparisons

Science.gov (United States)

Redd, L. T.; Bland, S. R.; Bennett, R. M.

1973-01-01

A stability analysis and trend study for a balloon tethered in a steady wind are presented. The linearized, stability-derivative type analysis includes balloon aerodynamics, buoyancy, mass (including apparent mass), and static forces resulting from the tether cable. The analysis has been applied to a balloon 7.64 m in length, and the results are compared with those from tow tests of this balloon. This comparison shows that the analysis gives reasonable predictions for the damping, frequencies, modes of motion, and stability boundaries exhibited by the balloon. A trend study for the 7.64-m balloon was made to illustrate how the stability boundaries are affected by changes in individual stability parameters. The trends indicated in this study may also be applicable to many other tethered-balloon systems.

Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

KAUST Repository

Kim, Sung A

2015-09-08

© 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2 nanoparticles to form self-suspended suspensions facilitates detailed studies of slow global chain and fast segmental mode dynamics under surface and geometrical confinement-from experiments performed in bulk materials. We report that unentangled polymer molecules tethered to nanoparticles relax far more slowly than their tethered entangled counterparts. Specifically, at fixed grafting density we find, counterintuitively, that increasing the tethered polymer molecular weight up to values close to the entanglement molecular weight speeds up chain relaxation dynamics. Decreasing the polymer grafting density for a fixed molecular weight has the opposite effect: it dramatically slows down chain relaxation, increases interchain coupling, and leads to a transition in rheological response from simple fluid behavior to viscoelastic fluid behavior for tethered PI chains that are unentangled by conventional measures. Increasing the measurement temperature produces an even stronger elastic response and speeds up molecular relaxation at a rate that decreases with grafting density and molecular weight. These observations are discussed in terms of chain confinement driven by crowding between particles and by the existence of an entropic attractive force produced by the space-filling constraint on individual chains in a self-suspended material. Our results indicate that the entropic force between densely grafted polymer molecules couples motions of individual chains in an analogous manner to reversible cross-links in associating polymers.

Climber Motion Optimization for the Tethered Space Elevator

NARCIS (Netherlands)

Williams, P.; Ockels, W.J.

The tethered space elevator could provide a revolutionary means for enabling cheap transportation to geostationary altitude and beyond. Assuming that such a system can be built, one of the dynamic design problems is determining a means of moving the elevator along the tether so as to minimize the

The effects of tether placement on antibody stability on surfaces

Science.gov (United States)

Grawe, Rebecca W.; Knotts, Thomas A.

2017-06-01

Despite their potential benefits, antibody microarrays have fallen short of performing reliably and have not found widespread use outside of the research setting. Experimental techniques have been unable to determine what is occurring on the surface of an atomic level, so molecular simulation has emerged as the primary method of investigating protein/surface interactions. Simulations of small proteins have indicated that the stability of the protein is a function of the residue on the protein where a tether is placed. The purpose of this research is to see whether these findings also apply to antibodies, with their greater size and complexity. To determine this, 24 tethering locations were selected on the antibody Protein Data Bank (PDB) ID: 1IGT. Replica exchange simulations were run on two different surfaces, one hydrophobic and one hydrophilic, to determine the degree to which these tethering sites stabilize or destabilize the antibody. Results showed that antibodies tethered to hydrophobic surfaces were in general less stable than antibodies tethered to hydrophilic surfaces. Moreover, the stability of the antibody was a function of the tether location on hydrophobic surfaces but not hydrophilic surfaces.

Operator's Manual for SHEBA Powered Tether Balloon System

Science.gov (United States)

Lappen, Cara-Lyn; Randall, David A.

1998-01-01

The Surface Heat and Energy Budget of the Arctic (SHEBA) was an intensive field project which took place in the Arctic Ocean from October 1997 through October 1998. Its purpose was to measure as many facets of the Arctic environment as possible so that we would be able to better understand the interaction between the ice, atmosphere, and ocean and their interactions with global climate. One aspect of the atmospheric field component was launching tethered balloons to monitor the profiles of temperature, wind, pressure, and humidity, as well as examine the vertical structure of cloud droplet sizes and distributions. The tethered balloon that we used was one specially designed for use in freezing climates by SPEC Corporation in Boulder, Colorado. A special winch that was able to withstand Arctic temperature and weather became necessary when the testing of simple winch systems used in warmer climates failed under these extreme conditions. The purpose of this manual is to acquaint any new user to the powered tethered balloon system deployed at the The Surface Heat and Energy Budget of the Arctic (SHEBA ice camp. It includes a description of the preparations necessary to get ready for a launch, the mechanics of the actual launch, and an account of the proper procedure for taking down the equipment when finished. It will also include tips on how to minimize potential equipment failures, some trouble shooting, and some safety ideas. This manual is designed so that new operators can use the system with minimal previous training. At the end of this manual, the reader will find a quick checklist.

Fluid-membrane tethers: minimal surfaces and elastic boundary layers.

Science.gov (United States)

Powers, Thomas R; Huber, Greg; Goldstein, Raymond E

2002-04-01

Thin cylindrical tethers are common lipid bilayer membrane structures, arising in situations ranging from micromanipulation experiments on artificial vesicles to the dynamic structure of the Golgi apparatus. We study the shape and formation of a tether in terms of the classical soap-film problem, which is applied to the case of a membrane disk under tension subject to a point force. A tether forms from the elastic boundary layer near the point of application of the force, for sufficiently large displacement. Analytic results for various aspects of the membrane shape are given.

Autonomous Vision-Based Tethered-Assisted Rover Docking

Science.gov (United States)

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

2013-01-01

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

Dynamics and stability of a tethered centrifuge in low earth orbit

Science.gov (United States)

Quadrelli, B. M.; Lorenzini, E. C.

1992-01-01

The three-dimensional attitude dynamics of a spaceborne tethered centrifuge for artificial gravity experiments in low earth orbit is analyzed using two different methods. First, the tethered centrifuge is modeled as a dumbbell with a straight viscoelastic tether, point tip-masses, and sophisticated environmental models such as nonspherical gravity, thermal perturbations, and a dynamic atmospheric model. The motion of the centrifuge during spin-up, de-spin, and steady-rotation is then simulated. Second, a continuum model of the tether is developed for analyzing the stability of lateral tether oscillations. Results indicate that the maximum fluctuation about the 1-g radial acceleration level is less than 0.001 g; the time required for spin-up and de-spin is less than one orbit; and lateral oscillations are stable for any practical values of the system parameters.

Tethered Forth system for FPGA applications

Science.gov (United States)

Goździkowski, Paweł; Zabołotny, Wojciech M.

2013-10-01

This paper presents the tethered Forth system dedicated for testing and debugging of FPGA based electronic systems. Use of the Forth language allows to interactively develop and run complex testing or debugging routines. The solution is based on a small, 16-bit soft core CPU, used to implement the Forth Virtual Machine. Thanks to the use of the tethered Forth model it is possible to minimize usage of the internal RAM memory in the FPGA. The function of the intelligent terminal, which is an essential part of the tethered Forth system, may be fulfilled by the standard PC computer or by the smartphone. System is implemented in Python (the software for intelligent terminal), and in VHDL (the IP core for FPGA), so it can be easily ported to different hardware platforms. The connection between the terminal and FPGA may be established and disconnected many times without disturbing the state of the FPGA based system. The presented system has been verified in the hardware, and may be used as a tool for debugging, testing and even implementing of control algorithms for FPGA based systems.

Trace gas measurements from tethered balloon platforms

Science.gov (United States)

Bandy, Alan R.; Bandy, Terese L.; Youngbluth, Otto; Owens, Thomas L.

1987-01-01

Instrumentation and chemical sampling and analysis procedures are described for making measurements of atmospheric carbon disulfide in the concentration range 1-1000 pptv from tethered balloon platforms. Results of a study on the CS2 composition of air downward of a saltwater marsh are reported. A method for obtaining the necessary data for solving the budget equations for surface fluxes, chemical formation rates and chemical destruction rates using data acquired from tethered balloon platforms is presented.

Transitions of tethered chain molecules under tension.

Science.gov (United States)

Luettmer-Strathmann, Jutta; Binder, Kurt

2014-09-21

An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

Dynamic analysis of the tether transportation system using absolute nodal coordinate formulation

Science.gov (United States)

Sun, Xin; Xu, Ming; Zhong, Rui

2017-10-01

Long space tethers are becoming a rising concern as an alternate way for transportation in space. It benefits from fuel economizing. This paper focuses on the dynamics of the tether transportation system, which consists of two end satellites connected by a flexible tether, and a movable vehicle driven by the actuator carried by itself. The Absolute Nodal Coordinate Formulation is applied to the establishment of the equation of motion, so that the influence caused by the distributed mass and elasticity of the tether is introduced. Moreover, an approximated method for accelerating the calculation of the generalized gravitational forces on the tether is proposed by substituting the volume integral every step into summation of finite terms. Afterwards, dynamic evolutions of such a system in different configurations are illustrated using numerical simulations. The deflection of the tether and the trajectory of the crawler during the transportation is investigated. Finally, the effect on the orbit of the system due to the crawler is revealed.

Thrust Control During Towing of Space Debris using an Elastic Tether

Directory of Open Access Journals (Sweden)

A. D. Ledkov

2014-01-01

Full Text Available The paper considers a maneuver for deorbiting the large space debris using an active spacecraft connected with the debris by an elastic tether. Tether slacking during the maneuver can lead to the tether rupture, kinking, and winding on the descending object. Therefore it is important to prevent slacking. The objective of this work is to find the law of thrust force control of the active spacecraft to ensure a continuously strained tether during the maneuver.Using Lagrange formalism a mathematical model to describe the system plane motion is developed. This model considers the active spacecraft as a mass point, the space debris as a rigid body, and the tether as a weightless elastic rod. A thrust force is directed along the local horizon of the spacecraft. Linearization of nonlinear differential equation describing longitudinal oscillations of the tether length is performed. Its phase portrait is analyzed. An approximate expression describing the position of the center on the phase portrait is obtained. A time-optimal control with full feedback to ensure that the tether is in the strained state is found by solving the Bellman equation. To use the obtained optimal law it is necessary to set the measuring equipment on the spacecraft, which is capable of accurate measuring a distance to the space debris and its relative velocity. An alternative control law, which is simpler in terms of the practical implementation, is proposed. As an example, the descent from an orbit of nonfunctioning Soviet satellite Meteor-2 is considered. It is shown that both proposed laws provide continuous strain of the tether during deorbiting of the satellite. Moreover, slack does not occur even at the first period of oscillation of the tether length. It is shown that the use of the proposed control laws leads to slight increase of deorbiting time as compared to the case of using the constant thrust.The results can be used to develop the control systems of small spacecrafts

Sonography compared with MR imaging in the evaluation of card tethering following myelomeningocele repair

International Nuclear Information System (INIS)

Newman, B.; Bowen, A.; Albright, L.

1989-01-01

This paper reports on MR imaging and videotaped US spine examinations to evaluate cord tethering were retrospectively compared in 12 children with prior myelomeningocele repair and correlated with clinical and surgical findings. Although US did not delineate normal or abnormal anatomy as well as MR imaging, both types of studies confirmed the presence of tethering in 10 patients. One child with a normal US examination and abnormal MR images had tethering confirmed surgically. A second child had a US study suggestive of tethering with equivocal MR images. Postoperative studies in eight patients correlated less well; US suggested persistent tethering in five patients and MR imaging indicated tethering in two

Ligand binding to G protein-coupled receptors in tethered cell membranes

DEFF Research Database (Denmark)

Martinez, Karen L.; Meyer, Bruno H.; Hovius, Ruud

2003-01-01

for the surface immobilization of membrane proteins was developed using the prototypic seven transmembrane neurokinin-1 receptor. The receptor was expressed as a biotinylated protein in mammalian cells. Membranes from cell homogenates were selectively immobilized on glass surfaces covered with streptavidin. TIRF...... measurements showed that a fluorescent agonist binds to the receptor on the sensor surface with similar affinity as to the receptor in live cells. This approach offers the possibility to investigate minute amounts of membrane protein in an active form and in its native environment without purification....

High-field MR imaging of tethered cord

International Nuclear Information System (INIS)

Sigal, R.; Bicetre, L.; Blass, C.; Doyon, D.; Pariente, D.

1986-01-01

MR imaging examinations of 12 patients with tethered cord syndrome have been performed on a 1.5-T MR imaging unit. Patients ranged in age from 3 to 60 years. MR findings were compared with those of myelography and metrizamide CT in all cases. Five patients underwent surgical control and postoperative MR imaging. Sagittal and axial sections were obtained using a spin-echo multisection, multiecho technique. T1-axial weighted images (SE 600/25) were sufficient to locate the position of the tip of the conus. They also allowed identification of extraspinal and intraspinal lipomas and clear-cut demarcation form associated tethered cord. Drawbacks of MR imaging were lack of precise depiction of the bone structures and the fact that clear identification of abnormal roots was problematic. The craniovertebral junction was always checked; two asymptomatic Chiari malformations were visualized. This study leads the authors to conclude that MR imaging should be used as the examination of first choice in the management of tethered cord syndrome

The investigation of tethered satellite system dynamics

Science.gov (United States)

Lorenzini, E. C.

1986-01-01

The analysis of the rotational dynamics of the satellite was focused on the rotational amplitude increase of the satellite, with respect to the tether, during retrieval. The dependence of the rotational amplitude upon the tether tension variation to the power 1/4 was thoroughly investigated. The damping of rotational oscillations achievable by reel control was also quantified while an alternative solution that makes use of a lever arm attached with a universal joint to the satellite was proposed. Comparison simulations between the Smithsonian Astrophysical Observatory and the Martin Marietta (MMA) computer code of reteival maneuvers were also carried out. The agreement between the two, completely independent, codes was extremely close, demonstrating the reliability of the models. The slack tether dynamics during reel jams was analytically investigated in order to identify the limits of applicability of the SLACK3 computer code to this particular case. Test runs with SLACK3 were also carried out.

Application of the NASCAP Spacecraft Simulation Tool to Investigate Electrodynamic Tether Current Collection in LEO

Science.gov (United States)

Adams, Mitzi; HabashKrause, Linda

2012-01-01

Recent interest in using electrodynamic tethers (EDTs) for orbital maneuvering in Low Earth Orbit (LEO) has prompted the development of the Marshall ElectroDynamic Tether Orbit Propagator (MEDTOP) model. The model is comprised of several modules which address various aspects of EDT propulsion, including calculation of state vectors using a standard orbit propagator (e.g., J2), an atmospheric drag model, realistic ionospheric and magnetic field models, space weather effects, and tether librations. The natural electromotive force (EMF) attained during a radially-aligned conductive tether results in electrons flowing down the tether and accumulating on the lower-altitude spacecraft. The energy that drives this EMF is sourced from the orbital energy of the system; thus, EDTs are often proposed as de-orbiting systems. However, when the current is reversed using satellite charged particle sources, then propulsion is possible. One of the most difficult challenges of the modeling effort is to ascertain the equivalent circuit between the spacecraft and the ionospheric plasma. The present study investigates the use of the NASA Charging Analyzer Program (NASCAP) to calculate currents to and from the tethered satellites and the ionospheric plasma. NASCAP is a sophisticated set of computational tools to model the surface charging of three-dimensional (3D) spacecraft surfaces in a time-varying space environment. The model's surface is tessellated into a collection of facets, and NASCAP calculates currents and potentials for each one. Additionally, NASCAP provides for the construction of one or more nested grids to calculate space potential and time-varying electric fields. This provides for the capability to track individual particles orbits, to model charged particle wakes, and to incorporate external charged particle sources. With this study, we have developed a model of calculating currents incident onto an electrodynamic tethered satellite system, and first results are shown

Vesicle fusion observed by content transfer across a tethered lipid bilayer.

Science.gov (United States)

Rawle, Robert J; van Lengerich, Bettina; Chung, Minsub; Bendix, Poul Martin; Boxer, Steven G

2011-10-19

Synaptic transmission is achieved by exocytosis of small, synaptic vesicles containing neurotransmitters across the plasma membrane. Here, we use a DNA-tethered freestanding bilayer as a target architecture that allows observation of content transfer of individual vesicles across the tethered planar bilayer. Tethering and fusion are mediated by hybridization of complementary DNA-lipid conjugates inserted into the two membranes, and content transfer is monitored by the dequenching of an aqueous content dye. By analyzing the diffusion profile of the aqueous dye after vesicle fusion, we are able to distinguish content transfer across the tethered bilayer patch from vesicle leakage above the patch. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Tethered by Self-Generated Flow: Mucus String Augmented Feeding Current Generation in Larval Oysters

Science.gov (United States)

Jiang, H.; Wheeler, J.; Anderson, E.

2016-02-01

Marine zooplankton live in a nutritionally dilute environment. To survive, they must process an enormous volume of water relative to their own body volume for food. To achieve this, many zooplankters including copepods, invertebrate larvae, and protists create a feeding current to concentrate and transport food items to their food gathering structures. To enhance the efficiency of the feeding current, these zooplankters often rely on certain "tethering" mechanisms to retard their translational motion for producing a strong feeding current. The tethering force may include excess weight due to gravity, force from attachment to solid surfaces, and drag experienced by strategically placed morphological structures. Larval oysters are known from previous studies to release mucus strings during feeding, presumably for supplying a tethering force to enhance their feeding-current efficiency. But the underlying mechanism is unclear. In this study, we used a high-speed microscale imaging system (HSMIS) to observe the behavior of freely swimming and feeding larval oysters. We also used HSMIS to measure larval imposed feeding currents via a micro-particle image velocimetry (µPIV) technique. HSMIS allows observations along a vertically oriented focal plane in a relatively large water vessel with unprecedented spatial and temporal resolutions. Our high-speed videos show that a feeding larval oyster continuously released a long mucus string into its feeding current that flows downward; the feeding current subsequently dragged the mucus string downward. Analysis of our µPIV data combined with a hydrodynamic model further suggests that the drag force experienced by the mucus string in the feeding current contributes significantly to the tethering force required to generate the feeding current. Thus, mucus strings in larval oysters act as "anchors" in larval self-generated flow to actively tether the feeding larvae.

Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

KAUST Repository

Kim, Sung A

2014-01-28

We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly(ethylene glycol) (PEG) chains densely grafted to SiO2 nanoparticles. The approach used for synthesizing these hybrid particles leads to homogeneous SiO2-PEG composites with polymer grafting densities as high as 1.5 chains/nm2, which allows the hybrid materials to exist as self-suspended suspensions with distinct hierarchical structure and thermal properties. On angstrom and nanometer length scales, the tethered PEG chains exhibit more dominant TTG conformations and helix unit cell structure, in comparison to the untethered polymer. The nanoparticle tethered PEG chains are also reported to form extended crystallites on tens of nanometers length scales and to exhibit more stable crystalline structure on small dimensions. On length scales comparable to the size of each hybrid SiO 2-PEG unit, the materials are amorphous presumably as a result of the difficulty fitting the nanoparticle anchors into the PEG crystal lattice. This structural change produces large effects on the thermal transitions of PEG molecules tethered to nanoparticles. © 2014 American Chemical Society.

Distinct conformational changes in activated agonist-bound and agonist-free glycine receptor subunits

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Lynch, Joseph W

2009-01-01

Ligand binding to Cys-loop receptors produces either global conformational changes that lead to activation or local conformational changes that do not. We found that the fluorescence of a fluorophore tethered to R271C in the extracellular M2 region of the alpha1 glycine receptor increases during ...

Tethered catalysts for the hydration of carbon dioxide

Science.gov (United States)

Valdez, Carlos A; Satcher, Jr., Joe H; Aines, Roger D; Wong, Sergio E; Baker, Sarah E; Lightstone, Felice C; Stolaroff, Joshuah K

2014-11-04

A system is provided that substantially increases the efficiency of CO.sub.2 capture and removal by positioning a catalyst within an optimal distance from the air-liquid interface. The catalyst is positioned within the layer determined to be the highest concentration of carbon dioxide. A hydrophobic tether is attached to the catalyst and the hydrophobic tether modulates the position of the catalyst within the liquid layer containing the highest concentration of carbon dioxide.

Numerical Simulation of Tethered Underwater Kites for Power Generation

Science.gov (United States)

Ghasemi, Amirmahdi; Olinger, David; Tryggvason, Gretar

2015-11-01

An emerging renewable energy technology, tethered undersea kites (TUSK), which is used to extract hydrokinetic energy from ocean and tidal currents, is studied. TUSK systems consist of a rigid-winged ``kite,'' or glider, moving in an ocean current which is connected by tethers to a floating buoy on the ocean surface. The TUSK kite is a current speed enhancement device since the kite can move in high-speed, cross-current motion at 4-6 times the current velocity, thus producing more power than conventional marine turbines. A computational simulation is developed to simulate the dynamic motion of an underwater kite and extendable tether. A two-step projection method within a finite volume formulation, along with an Open MP acceleration method, is employed to solve the Navier-Stokes equations. An immersed boundary method is incorporated to model the fluid-structure interaction of the rigid kite (with NACA 0012 airfoil shape in 2D and NACA 0021 airfoil shape in 3D simulations) and the fluid flow. PID control methods are used to adjust the kite angle of attack during power (tether reel-out) and retraction (reel-in) phases. Two baseline simulations (for kite motions in two and three dimensions) are studied, and system power output, flow field vorticity, tether tension, and hydrodynamic coefficients (lift and drag) for the kite are determined. The simulated power output shows good agreement with established theoretical results for a kite moving in two-dimensions.

Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

Directory of Open Access Journals (Sweden)

Chinatsu Mukai

Full Text Available Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase. We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.

Science.gov (United States)

Mukai, Chinatsu; Gao, Lizeng; Bergkvist, Magnus; Nelson, Jacquelyn L; Hinchman, Meleana M; Travis, Alexander J

2013-01-01

Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.

Tethered Ozonesonde Measurements During FRAPPE July-August 2014

Science.gov (United States)

Oltmans, S. J.; Johnson, B.; Sterling, C. W.; Cullis, P.; Hall, E. G.; Jordan, A. F.; Wendell, J.; Schnell, R. C.; McClure-Begley, A.; Thompson, A. M.

2015-12-01

O3 and temperature profiles were measured from tethered ozonesondes from surface to 400 m above ground level on 9 days during the summer of 2014 Colorado Front Range Air Pollution and Photochemistry Experiment (FRAPPE). The portable tethered ozonesonde system was set up at one of 3 sites located next to a Colorado Department of Public Health and Environment surface monitoring station. The day and site chosen were based on the previous day O3 and weather forecast. Measurements typically began at 8:30 AM and ended at 4:30 PM, averaging 40 profiles in one day. The ozonesonde when sampling at the surface consistently read within 0-3 ppbv of the surface monitor at each of the sites with a typical daytime range of 20-90 ppbv. The hourly values were averaged at 50 meter intervals showing O3 production rates were consistently around 8 ppbv per hour from 50 to 300 meters above ground level. On sunny, light wind days the O3 mixing ratio reached a maximum of 80-90 ppbv between 14:00 and 15:00 local time. The generally constant mixing ratio with height and highest mixing ratios above the surface indicate that photochemical O3 production was taking place throughout the profile. Continuous O3 profiles from a tall tower (5 and 300 m) and daily ozonesondes tracked O3 variability through the experiment. High O3 at each site was associated with different local wind directions. At Ft. Collins winds were generally out of the southeast, at Chatfield from the northeast, and at City Park Golf Course more variable. The tether system was developed at NOAA/ESRL to provide a cost effective method to measure O3 profiles on a continuous basis. The tether system consisted of a deep sea fishing pole, electric motor driving the reel with light-weight fishing line attached to the balloon ozonesonde, a tether control box, and laptop. The in house software package monitored data and controlled the tether speed and turn-around point based on real time GPS altitude from the transmitting radiosonde.

Isothermal pumping analysis for high-altitude tethered balloons.

Science.gov (United States)

Kuo, Kirsty A; Hunt, Hugh E M

2015-06-01

High-altitude tethered balloons have potential applications in communications, surveillance, meteorological observations and climate engineering. To maintain balloon buoyancy, power fuel cells and perturb atmospheric conditions, fluids could be pumped from ground level to altitude using the tether as a hose. This paper examines the pumping requirements of such a delivery system. Cases considered include delivery of hydrogen, sulfur dioxide (SO2) and powders as fluid-based slurries. Isothermal analysis is used to determine the variation of pressures and velocities along the pipe length. Results show that transport of small quantities of hydrogen to power fuel cells and maintain balloon buoyancy can be achieved at pressures and temperatures that are tolerable in terms of both the pipe strength and the current state of pumping technologies. To avoid solidification, transport of SO2 would require elevated temperatures that cannot be tolerated by the strength fibres in the pipe. While the use of particle-based slurries rather than SO2 for climate engineering can reduce the pipe size significantly, the pumping pressures are close to the maximum bursting pressure of the pipe.

An Effective Approach Control Scheme for the Tethered Space Robot System

Directory of Open Access Journals (Sweden)

Zhongjie Meng

2014-09-01

Full Text Available The tethered space robot system (TSR, which is composed of a platform, a gripper and a space tether, has great potential in future space missions. Given the relative motion among the platform, tether, gripper and the target, an integrated approach model is derived. Then, a novel coordinated approach control scheme is presented, in which the tether tension, thrusters and the reaction wheel are all utilized. It contains the open-loop trajectory optimization, the feedback trajectory control and attitude control. The numerical simulation results show that the rendezvous between TSR and the target can be realized by the proposed coordinated control scheme, and the propellant consumption is efficiently reduced. Moreover, the control scheme performs well in the presence of the initial state's perturbations, actuator characteristics and sensor errors.

Modelling a tethered mammalian sperm cell undergoing hyperactivation

KAUST Repository

Curtis, M.P.

2012-09-01

The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

Modelling a tethered mammalian sperm cell undergoing hyperactivation

KAUST Repository

Curtis, M.P.; Kirkman-Brown, J.C.; Connolly, T.J.; Gaffney, E.A.

2012-01-01

The beat patterns of mammalian sperm flagella can be categorised into two different types. The first involves symmetric waves propagating down the flagellum with a net linear propulsion of the sperm cell. The second, hyperactive, waveform is classified by vigorous asymmetric waves of higher amplitude, lower wavenumber and frequency propagating down the flagellum resulting in highly curved trajectories. The latter beat pattern is part of the capacitation process whereby sperm prepare for the prospective penetration of the zona pellucida and fusion with the egg. Hyperactivation is often observed to initiate as sperm escape from epithelial and ciliary bindings formed within the isthmic regions of the female oviducts, leading to a conjecture in the literature that this waveform is mechanically important for sperm escape. Hence, we explore the mechanical effects of hyperactivation on a tethered sperm, focussing on a Newtonian fluid. Using a resistive force theory model we demonstrate that hyperactivation can indeed generate forces that pull the sperm away from a tethering point and consequently a hyperactivated sperm cell bound to an epithelial surface need not always be pushed by its flagellum. More generally, directions of the forces generated by tethered flagella are insensitive to reductions in beat frequency and the detailed flagellar responses depend on the nature of the binding at the tethering point. Furthermore, waveform asymmetry and amplitude increases enhance the tendency for a tethered flagellum to start tugging on its binding. The same is generally predicted to be true for reductions in the wavenumber of the flagellum beat, but not universally so, emphasising the dynamical complexity of flagellar force generation. Finally, qualitative observations drawn from experimental data of human sperm bound to excised female reproductive tract are also presented and are found to be consistent with the theoretical predictions. © 2012 Elsevier Ltd.

Tethered elevator and platforms as space station facilities: Systems studies and demonstrative experiments

Science.gov (United States)

1986-01-01

Several key concepts of the science and applications tethered platforms were studied. Some conclusions reached are herein listed. Tether elevator and platform could improve the space station scientific and applicative capabilities. The space elevator presents unique characteristics as microgravity facility and as a tethered platform servicing vehicle. Pointing platforms could represent a new kind of observation facility for large class of payloads. The dynamical, control and technological complexity of these concepts advised demonstrative experiments. The on-going tethered satellite system offers the opportunity to perform such experiments. And feasibility studies are in progress.

Phase coupling of a circadian neuropeptide with rest/activity rhythms detected using a membrane-tethered spider toxin.

Directory of Open Access Journals (Sweden)

Ying Wu

2008-11-01

Full Text Available Drosophila clock neurons are self-sustaining cellular oscillators that rely on negative transcriptional feedback to keep circadian time. Proper regulation of organismal rhythms of physiology and behavior requires coordination of the oscillations of individual clock neurons within the circadian control network. Over the last decade, it has become clear that a key mechanism for intercellular communication in the circadian network is signaling between a subset of clock neurons that secrete the neuropeptide pigment dispersing factor (PDF and clock neurons that possess its G protein-coupled receptor (PDFR. Furthermore, the specific hypothesis has been proposed that PDF-secreting clock neurons entrain the phase of organismal rhythms, and the cellular oscillations of other clock neurons, via the temporal patterning of secreted PDF signals. In order to test this hypothesis, we have devised a novel technique for altering the phase relationship between circadian transcriptional feedback oscillation and PDF secretion by using an ion channel-directed spider toxin to modify voltage-gated Na(+ channel inactivation in vivo. This technique relies on the previously reported "tethered-toxin" technology for cell-autonomous modulation of ionic conductances via heterologous expression of subtype-specific peptide ion channel toxins as chimeric fusion proteins tethered to the plasma membrane with a glycosylphosphatidylinositol (GPI anchor. We demonstrate for the first time, to our knowledge, the utility of the tethered-toxin technology in a transgenic animal, validating four different tethered spider toxin ion channel modifiers for use in Drosophila. Focusing on one of these toxins, we show that GPI-tethered Australian funnel-web spider toxin delta-ACTX-Hv1a inhibits Drosophila para voltage-gated Na(+ channel inactivation when coexpressed in Xenopus oocytes. Transgenic expression of membrane-tethered delta-ACTX-Hv1a in vivo in the PDF-secreting subset of clock neurons

Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype

DEFF Research Database (Denmark)

Jorgensen, Rasmus; Martini, Lene; Schwartz, Thue W

2005-01-01

To dissect the interaction between beta-arrestin ((beta)arr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and (beta)arr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting...... that (beta)arr2 interaction locks the receptor in a high-affinity conformation, which can be explored by some, but not all, ligands. The fusion constructs adopted a signaling phenotype governed by the tethered (beta)arr2 with an attenuated G protein-mediated cAMP signal and a higher maximal internalization...... of that which has previously been characterized for family A G protein-coupled receptors, suggesting similarities in the effect of (beta)arr interaction between family A and B receptors also at the molecular level....

Fullerenic structures and such structures tethered to carbon materials

Science.gov (United States)

Goel, Anish; Howard, Jack B.; Vander Sande, John B.

2010-01-05

The fullerenic structures include fullerenes having molecular weights less than that of C.sub.60 with the exception of C.sub.36 and fullerenes having molecular weights greater than C.sub.60. Examples include fullerenes C.sub.50, C.sub.58, C.sub.130, and C.sub.176. Fullerenic structure chemically bonded to a carbon surface is also disclosed along with a method for tethering fullerenes to a carbon material. The method includes adding functionalized fullerene to a liquid suspension containing carbon material, drying the suspension to produce a powder, and heat treating the powder.

Electron Emitter for small-size Electrodynamic Space Tether using MEMS Technology

DEFF Research Database (Denmark)

Fleron, René A. W.; Blanke, Mogens

2004-01-01

Adjustment of the orbit of a spacecraft using the forces created by an electro-dynamic space-tether has been shown as a theoretic possibility in recent literature. Practical implementation is being pursued for larger scale missions where a hot filament device controls electron emission...... and the current flowing in the electrodynamic space tether. Applications to small spacecraft, or space debris in the 1–10 kg range, possess difficulties with electron emission technology, as low power emitting devices are needed. This paper addresses the system concepts of a small spacecraft electrodynamic tether...... system with focus on electron emitter design and manufacture using micro-electro-mechanical- system (MEMS) technology. The paper addresses the system concepts of a small size electrodynamic tether mission and shows a novel electron emitter for the 1-2 mA range where altitude can be effectively affected...

Rheumatic Disease: Protease-Activated Receptor-2 in Synovial Joint Pathobiology

Directory of Open Access Journals (Sweden)

Kendal McCulloch

2018-05-01

Full Text Available Protease-activated receptor-2 (PAR2 is one member of a small family of transmembrane, G-protein-coupled receptors. These receptors are activated via cleavage of their N terminus by serine proteases (e.g., tryptase, unveiling an N terminus tethered ligand which binds to the second extracellular loop of the receptor. Increasing evidence has emerged identifying key pathophysiological roles for PAR2 in both rheumatoid arthritis (RA and osteoarthritis (OA. Importantly, this includes both pro-inflammatory and destructive roles. For example, in murine models of RA, the associated synovitis, cartilage degradation, and subsequent bone erosion are all significantly reduced in the absence of PAR2. Similarly, in experimental models of OA, PAR2 disruption confers protection against cartilage degradation, subchondral bone osteosclerosis, and osteophyte formation. This review focuses on the role of PAR2 in rheumatic disease and its potential as an important therapeutic target for treating pain and joint degradation.

Results from a tethered rocket experiment (Charge-2)

Science.gov (United States)

Kawashima, N.; Sasaki, S.; Oyama, K. I.; Hirao, K.; Obayashi, T.; Raitt, W. J.; White, A. B.; Williamson, P. R.; Banks, P. M.; Sharp, W. F.

A tethered payload experiment (Charge-2) was carried out as an international program between Japan and the USA using a NASA sounding rocket at White Sands Missile Range. The objective of the experiment was to perform a new type of active experiment in space by injecting an electron beam from a mother-daughter rocket system connected with a long tether wire. The electron beam with voltage and current up to 1 kV and 80 mA (nominal) was injected from the mother payload. An insulated conductive wire of 426 m length connected the two payloads, the longest tether system flown so far. The electron gun system and diagnostic instruments (plasma, optical, particle and wave) functioned correctly throughout the flight. The potential rise of the mother payload during the electron beam emission was measured with respect to the daughter payload. The beam trajectory was detected by a camera onboard the mother rocket. Wave generation and current induction in the wire during the beam emission were also studied.

Implementation Options for the PROPEL Electrodynamic Tether Demonstration Mission

Science.gov (United States)

Bilen, Sven G.; Johnson, C. Les; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael; Stone, Nobie

2014-01-01

The PROPEL ("Propulsion using Electrodynamics") flight demonstration mission concept will demonstrate the use of an electrodynamic tether (EDT) for generating thrust, which will allow the propulsion system to overcome the limitations of the rocket equation. The mission concept has been developed by a team of government, industry, and academia partners led by NASA Marshall Space Flight Center (MSFC). PROPEL is being designed for versatility of the EDT system with multiple end users in mind and to be flexible with respect to platform. Previously, we reported on a comprehensive mission design for PROPEL with a mission duration of six months or longer with multiple mission goals including demonstration of significant boost, deboost, inclination change, and drag make-up activities. To explore a range of possible configurations, primarily driven by cost considerations, other mission concept designs have been pursued. In partnership with the NASA's Office of Chief Technologist (OCT) Game Changing Program, NASA MSFC Leadership, and the MSFC Advanced Concepts Office, a mission concept design was developed for a near-term EDT propulsion flight validation mission. The Electrodynamic Tether Propulsion Study (ETPS) defined an EDT propulsion system capable of very large delta-V for use on future missions developed by NASA, DoD, and commercial customers. To demonstrate the feasibility of an ETPS, the study focused on a space demonstration mission concept design with configuration of a pair of tethered satellite busses, one of which is the Japanese H-II Transfer Vehicle (HTV). The HTV would fly its standard ISS resupply mission. When resupply mission is complete, the ISS reconfigures and releases the HTV to perform the EDT experiment at safe orbital altitudes below the ISS. Though the focus of this particular mission concept design addresses a scenario involving the HTV or a similar vehicle, the propulsion system's capability is relevant to a number of applications, as noted above

Self-consistent field theory of tethered polymers: one dimensional, three dimensional, strong stretching theories and the effects of excluded-volume-only interactions.

Science.gov (United States)

Suo, Tongchuan; Whitmore, Mark D

2014-11-28

We examine end-tethered polymers in good solvents, using one- and three-dimensional self-consistent field theory, and strong stretching theories. We also discuss different tethering scenarios, namely, mobile tethers, fixed but random ones, and fixed but ordered ones, and the effects and important limitations of including only binary interactions (excluded volume terms). We find that there is a "mushroom" regime in which the layer thickness is independent of the tethering density, σ, for systems with ordered tethers, but we argue that there is no such plateau for mobile or disordered anchors, nor is there one in the 1D theory. In the other limit of brushes, all approaches predict that the layer thickness scales linearly with N. However, the σ(1/3) scaling is a result of keeping only excluded volume interactions: when the full potential is included, the dependence is faster and more complicated than σ(1/3). In fact, there does not appear to be any regime in which the layer thickness scales in the combination Nσ(1/3). We also compare the results for two different solvents with each other, and with earlier Θ solvent results.

Self-consistent field theory of tethered polymers: One dimensional, three dimensional, strong stretching theories and the effects of excluded-volume-only interactions

International Nuclear Information System (INIS)

Suo, Tongchuan; Whitmore, Mark D.

2014-01-01

We examine end-tethered polymers in good solvents, using one- and three-dimensional self-consistent field theory, and strong stretching theories. We also discuss different tethering scenarios, namely, mobile tethers, fixed but random ones, and fixed but ordered ones, and the effects and important limitations of including only binary interactions (excluded volume terms). We find that there is a “mushroom” regime in which the layer thickness is independent of the tethering density, σ, for systems with ordered tethers, but we argue that there is no such plateau for mobile or disordered anchors, nor is there one in the 1D theory. In the other limit of brushes, all approaches predict that the layer thickness scales linearly with N. However, the σ 1/3 scaling is a result of keeping only excluded volume interactions: when the full potential is included, the dependence is faster and more complicated than σ 1/3 . In fact, there does not appear to be any regime in which the layer thickness scales in the combination Nσ 1/3 . We also compare the results for two different solvents with each other, and with earlier Θ solvent results

Long-term evaluation of intraoperative neurophysiological monitoring-assisted tethered cord surgery

NARCIS (Netherlands)

Dulfer, S E; Drost, G; Lange, F; Journee, H L; Wapstra, F H; Hoving, E W

2017-01-01

PURPOSE: Patients with tethered spinal cord have been investigated for short-term effects after tethered spinal cord surgery in the past. However, little is known about the long-term effects in this patient group. In this retrospective, longitudinal, observational study, a patient sample of a

Two-Way Tether Gun

Science.gov (United States)

Sanger, George F.

1994-01-01

Safety-tether device enables crewmembers on spacecraft to retrieve crewmember drifting away from spacecraft. Alternatively, drifting crewmember who carries device uses it to grasp and return to spacecraft. Also used on Earth. For example, rescuer on vessel or pier uses it to retrieve and haul drowning or unconscious person to safety; drifting person or rescuer in water uses it to grasp and hold onto support.

Lifting options for stratospheric aerosol geoengineering: advantages of tethered balloon systems.

Science.gov (United States)

Davidson, Peter; Burgoyne, Chris; Hunt, Hugh; Causier, Matt

2012-09-13

The Royal Society report 'Geoengineering the Climate' identified solar radiation management using albedo-enhancing aerosols injected into the stratosphere as the most affordable and effective option for geoengineering, but did not consider in any detail the options for delivery. This paper provides outline engineering analyses of the options, both for batch-delivery processes, following up on previous work for artillery shells, missiles, aircraft and free-flying balloons, as well as a more lengthy analysis of continuous-delivery systems that require a pipe connected to the ground and supported at a height of 20 km, either by a tower or by a tethered balloon. Towers are shown not to be practical, but a tethered balloon delivery system, with high-pressure pumping, appears to have much lower operating and capital costs than all other delivery options. Instead of transporting sulphuric acid mist precursors, such a system could also be used to transport slurries of high refractive index particles such as coated titanium dioxide. The use of such particles would allow useful experiments on opacity, coagulation and atmospheric chemistry at modest rates so as not to perturb regional or global climatic conditions, thus reducing scale-up risks. Criteria for particle choice are discussed, including the need to minimize or prevent ozone destruction. The paper estimates the time scales and relatively modest costs required if a tethered balloon system were to be introduced in a measured way with testing and development work proceeding over three decades, rather than in an emergency. The manufacture of a tether capable of sustaining the high tensions and internal pressures needed, as well as strong winds, is a significant challenge, as is the development of the necessary pumping and dispersion technologies. The greatest challenge may be the manufacture and launch of very large balloons, but means have been identified to significantly reduce the size of such balloons or aerostats.

Position Control of an X4-Flyer Using a Tether

Directory of Open Access Journals (Sweden)

, Keigo Watanabe

2014-10-01

Full Text Available In Japan, aging of infrastructures, such as roads, bridges, and water and sewer services, etc. poses a problem, and it is required to extend the life-span of such infrastructures by maintenance. Among infrastructures, especially bridges are periodically inspected by short range visual observations, which check the damage and deterioration of the surface. However, since there are some cases where the short range visual observation is difficult, an alternative method is required so as to replace the short range visual observation with it. So, "X4-Flyer" is very attractive because of realizing a movement at high altitude easily. The objective of this study is to develop a tethered X4- Flyer, so that the conventional short range visual observation of bridges is replaced by it. In this paper, a method for the measurement and control of the position is described by using a tether for controlling the position of the X4-Flyer. In addition, it is checked whether the tethered X4-Flyer can control the position using the proposed method or not, letting it fly in a state in which a tether is being attached.

Synthesis and insertion chemistry of mixed tether uranium metallocene complexes

Energy Technology Data Exchange (ETDEWEB)

Siladke, Nathan A.; LeDuc, Jennifer; Ziller, Joseph W.; Evans, William J. [Department of Chemistry, University of California, Irvine, CA (United States)

2012-11-12

The synthesis of mixed tethered alkyl uranium metallocenes has been investigated by examining the reactivity of the bis(tethered alkyl) metallocene [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sub 2}U] (1) with substrates that react with only one of the U-C linkages. The effect of these mixed tether coordination environments on the reactivity of the remaining U-C bond has been studied by using CO insertion chemistry. One equivalent of azidoadamantane (AdN{sub 3}) reacts with 1 to yield the mixed tethered alkyl triazenido complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}-CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})]. Similarly, a single equivalent of CS{sub 2} reacts with 1 to form the mixed tethered alkyl dithiocarboxylate complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}- CH{sub 2}C(S){sub 2}-κ{sup 2}S,S{sup '})], a reaction that constitutes the first example of CS{sub 2} insertion into a U{sup 4+}-C bond. Complex 1 reacts with one equivalent of pyridine N-oxide by C-H bond activation of the pyridine ring to form a mixed tethered alkyl cyclometalated pyridine N-oxide complex [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 6}H{sub 4}NO-κ{sup 2} C,O)]. The remaining (η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}-κC){sup 2-} ligand in each of these mixed tethered species show reactivity towards CO and tethered enolate ligands form by insertion. Subsequent rearrangement have been identified in [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 3})U(C{sub 5}H{sub 4}NO-κ{sup 2}C,O)(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O- κO)] and [(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}CH{sub 2}NNN-Ad-κ{sup 2}N{sup 1,3})U(η{sup 5}-C{sub 5}Me{sub 4}SiMe{sub 2}C(=CH{sub 2})O-κO)]. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Computer Programs for Calculating and Plotting the Stability Characteristics of a Balloon Tethered in a Wind

Science.gov (United States)

Bennett, R. M.; Bland, S. R.; Redd, L. T.

1973-01-01

Computer programs for calculating the stability characteristics of a balloon tethered in a steady wind are presented. Equilibrium conditions, characteristic roots, and modal ratios are calculated for a range of discrete values of velocity for a fixed tether-line length. Separate programs are used: (1) to calculate longitudinal stability characteristics, (2) to calculate lateral stability characteristics, (3) to plot the characteristic roots versus velocity, (4) to plot the characteristic roots in root-locus form, (5) to plot the longitudinal modes of motion, and (6) to plot the lateral modes for motion. The basic equations, program listings, and the input and output data for sample cases are presented, with a brief discussion of the overall operation and limitations. The programs are based on a linearized, stability-derivative type of analysis, including balloon aerodynamics, apparent mass, buoyancy effects, and static forces which result from the tether line.

Simulations of momentum transfer process between solar wind plasma and bias voltage tethers of electric sail thruster

Science.gov (United States)

Xia, Guangqing; Han, Yajie; Chen, Liuwei; Wei, Yanming; Yu, Yang; Chen, Maolin

2018-06-01

The interaction between the solar wind plasma and the bias voltage of long tethers is the basic mechanism of the electric sail thruster. The momentum transfer process between the solar wind plasma and electric tethers was investigated using a 2D full particle PIC method. The coupled electric field distribution and deflected ion trajectory under different bias voltages were compared, and the influence of bias voltage on momentum transfer process was analyzed. The results show that the high potential of the bias voltage of long tethers will slow down, stagnate, reflect and deflect a large number of ions, so that ion cavities are formed in the vicinity of the tether, and the ions will transmit the axial momentum to the sail tethers to produce the thrust. Compared to the singe tether, double tethers show a better thrust performance.

Low Earth Orbit Environmental Effects on Space Tether Materials

Science.gov (United States)

Finckernor, Miria M.; Gitlemeier, Keith A.; Hawk, Clark W.; Watts, Ed

2005-01-01

Atomic oxygen (AO) and ultraviolet (UV) radiation erode and embrittle most polymeric materials. This research was designed to test several different materials and coatings under consideration for their application to space tethers, for resistance to these effects. The samples were vacuum dehydrated, weighed and then exposed to various levels of AO or UV radiation at the NASA Marshall Space Flight Center. They were then re-weighed to determine mass loss due to atomic oxygen erosion, inspected for damage and tensile tested to determine strength loss. The experiments determined that the Photosil coating process, while affording some protection, damaged the tether materials worse than the AO exposure. TOR-LM also failed to fully protect the materials, especially from UV radiation. The POSS and nickel coatings did provide some protection to the tethers, which survived the entire test regime. M5 was tested, uncoated, and survived AO exposure, though its brittleness prevented any tensile testing.

The motion and control of a complex three-body space tethered system

Science.gov (United States)

Shi, Gefei; Zhu, Zhanxia; Chen, Shiyu; Yuan, Jianping; Tang, Biwei

2017-11-01

This paper is mainly devoted to investigating the dynamics and stability control of a three body-tethered satellite system which contains a main satellite and two subsatellites connected by two straight, massless and inextensible tethers. Firstly, a detailed mathematical model is established in the central gravitational field. Then, the dynamic characteristics of the established system are investigated and analyzed. Based on the dynamic analysis, a novel sliding mode prediction model (SMPM) control strategy is proposed to suppress the motion of the built tethered system. The numerical results show that the proposed underactuated control law is highly effective in suppressing the attitude/libration motion of the underactuated three-body tethered system. Furthermore, cases of different target angles are also examined and analyzed. The simulation results reveal that even if the final equilibrium states differ from different selections of the target angles, the whole system can still be maintained in acceptable areas.

Emerging insights into the roles of membrane tethers from analysis of whole organisms: The tip of an iceberg?

Directory of Open Access Journals (Sweden)

Wei Hong eToh

2016-02-01

Full Text Available Membrane tethers have been identified throughout different compartments of the endomembrane system. It is now well established that a number of membrane tethers mediate docking of membrane carriers in anterograde and retrograde transport and in regulating the organization of membrane compartments. Much of our information on membrane tethers have been obtained from the analysis of individual membrane tethers in cultured cells. In the future it will be important to better appreciate the network of interactions mediated by tethers and the potential co-ordination of their collective functions in vivo. There are now a number of studies which have analyzed membrane tethers in tissues and organisms which are providing new insights into the role of this class of membrane protein at the physiological level. Here we review recent advances in the understanding of the function of membrane tethers from knock outs (or knock downs in whole organisms and from mutations in tethers associated with disease.

Experiments and simulation of a net closing mechanism for tether-net capture of space debris

Science.gov (United States)

Sharf, Inna; Thomsen, Benjamin; Botta, Eleonora M.; Misra, Arun K.

2017-10-01

This research addresses the design and testing of a debris containment system for use in a tether-net approach to space debris removal. The tether-net active debris removal involves the ejection of a net from a spacecraft by applying impulses to masses on the net, subsequent expansion of the net, the envelopment and capture of the debris target, and the de-orbiting of the debris via a tether to the chaser spacecraft. To ensure a debris removal mission's success, it is important that the debris be successfully captured and then, secured within the net. To this end, we present a concept for a net closing mechanism, which we believe will permit consistently successful debris capture via a simple and unobtrusive design. This net closing system functions by extending the main tether connecting the chaser spacecraft and the net vertex to the perimeter and around the perimeter of the net, allowing the tether to actuate closure of the net in a manner similar to a cinch cord. A particular embodiment of the design in a laboratory test-bed is described: the test-bed itself is comprised of a scaled-down tether-net, a supporting frame and a mock-up debris. Experiments conducted with the facility demonstrate the practicality of the net closing system. A model of the net closure concept has been integrated into the previously developed dynamics simulator of the chaser/tether-net/debris system. Simulations under tether tensioning conditions demonstrate the effectiveness of the closure concept for debris containment, in the gravity-free environment of space, for a realistic debris target. The on-ground experimental test-bed is also used to showcase its utility for validating the dynamics simulation of the net deployment, and a full-scale automated setup would make possible a range of validation studies of other aspects of a tether-net debris capture mission.

Cooperative networks : The mobile tethering game

NARCIS (Netherlands)

Constantinescu, M.; Bouwman, H.; Djurica, M.; Durmus, Y.; Onur, E.; Reuver, M. de

2012-01-01

We propose an analysis of cooperation for data sharing and the behavioral aspects involved in the process of decision making. Starting with the tethering capabilities of recent devices we apply game theoretical principles and models, inquire what makes the cooperation work, and what are the

ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology.

Science.gov (United States)

Manford, Andrew G; Stefan, Christopher J; Yuan, Helen L; Macgurn, Jason A; Emr, Scott D

2012-12-11

Endoplasmic reticulum-plasma membrane (ER-PM) junctions are conserved structures defined as regions of the ER that tightly associate with the plasma membrane. However, little is known about the mechanisms that tether these organelles together and why such connections are maintained. Using a quantitative proteomic approach, we identified three families of ER-PM tethering proteins in yeast: Ist2 (related to mammalian TMEM16 ion channels), the tricalbins (Tcb1/2/3, orthologs of the extended synaptotagmins), and Scs2 and Scs22 (vesicle-associated membrane protein-associated proteins). Loss of all six tethering proteins results in the separation of the ER from the PM and the accumulation of cytoplasmic ER. Importantly, we find that phosphoinositide signaling is misregulated at the PM, and the unfolded protein response is constitutively activated in the ER in cells lacking ER-PM tether proteins. These results reveal critical roles for ER-PM contacts in cell signaling, organelle morphology, and ER function. Copyright © 2012 Elsevier Inc. All rights reserved.

Tethered balloon-based measurements of meteorological variables and aerosols

Science.gov (United States)

Sentell, R. J.; Storey, R. W.; Chang, J. J. C.; Jacobsen, S. J.

1976-01-01

Tethered balloon based measurements of the vertical distributions of temperature, humidity, wind speed, and aerosol concentrations were taken over a 4-hour period beginning at sunrise on June 29, 1976, at Wallops Island, Virginia. Twelve consecutive profiles of each variable were obtained from ground to about 500 meters. These measurements were in conjuction with a noise propagation study on remotely arrayed acoustic range (ROMAAR) at Wallops Flight Center. An organized listing of these vertical soundings is presented. The tethered balloon system configuration utilized for these measurements is described.

Observing Formation of Flux Rope by Tether-cutting Reconnection in the Sun

Energy Technology Data Exchange (ETDEWEB)

Xue, Zhike; Yan, Xiaoli; Yang, Liheng; Wang, Jincheng; Zhao, Li, E-mail: zkxue@ynao.ac.cn [Yunnan Observatories, Chinese Academy of Sciences, Kunming Yunnan 650216 (China)

2017-05-10

Tether-cutting reconnection is considered as one mechanism for the formation of a flux rope. It has been proposed for more than 30 years; however, so far, direct observations of it are very rare. In this Letter, we present observations of the formation of a flux rope via tether-cutting reconnection in NOAA AR 11967 on 2014 February 2 by combining observations with the New Vacuum Solar Telescope and the Solar Dynamic Observatory . The tether-cutting reconnection occurs between two sets of highly sheared magnetic arcades. Comprehensive observational evidence of the reconnection is as follows: changes of the connections between the arcades, brightenings at the reconnection site, hot outflows, formation of a flux rope, slow-rise motion of the flux rope, and flux cancelation. The outflows are along three directions from the reconnection site to the footpoints with the velocities from 24 ± 1 km s{sup −1} to 69 ± 5 km s{sup −1}. Additionally, it is found that the newly formed flux rope connects far footpoints and has a left-handed twisted structure with many fine threads and a concave-up-shape structure in the middle. All the observations are in agreement with the tether-cutting model and provide evidence that tether-cutting reconnection leads to the formation of the flux rope associated with flux shear flow and cancelation.

Nano- to microscale dynamics of P-selectin detachment from leukocyte interfaces. II. Tether flow terminated by P-selectin dissociation from PSGL-1.

Science.gov (United States)

Heinrich, Volkmar; Leung, Andrew; Evans, Evan

2005-03-01

We have used a biomembrane force probe decorated with P-selectin to form point attachments with PSGL-1 receptors on a human neutrophil (PMN) in a calcium-containing medium and then to quantify the forces experienced by the attachment during retraction of the PMN at fixed speed. From first touch to final detachment, the typical force history exhibited the following sequence of events: i), an initial linear-elastic displacement of the PMN surface, ii), an abrupt crossover to viscoplastic flow that signaled membrane separation from the interior cytoskeleton and the beginning of a membrane tether, and iii), the final detachment from the probe tip most often by one precipitous step of P-selectin:PSGL-1 dissociation. Analyzing the initial elastic response and membrane unbinding from the cytoskeleton in our companion article I, we focus in this article on the regime of tether extrusion that nearly always occurred before release of the extracellular adhesion bond at pulling speeds > or =1 microm/s. The force during tether growth appeared to approach a plateau at long times. Examined over a large range of pulling speeds up to 150 microm/s, the plateau force exhibited a significant shear thinning as indicated by a weak power-law dependence on pulling speed, f(infinity) = 60 pN(nu(pull)/microm/s)(0.25). Using this shear-thinning response to describe the viscous element in a nonlinear Maxwell-like fluid model, we show that a weak serial-elastic component with a stiffness of approximately 0.07 pN/nm provides good agreement with the time course of the tether force approach to the plateau under constant pulling speed.

Relaxation Dynamics of Nanoparticle-Tethered Polymer Chains

KAUST Repository

Kim, Sung A; Mangal, Rahul; Archer, Lynden A.

2015-01-01

© 2015 American Chemical Society. Relaxation dynamics of nanoparticle-tethered cis-1,4-polyisoprene (PI) are investigated using dielectric spectroscopy and rheometry. A model system composed of polymer chains densely grafted to spherical SiO2

Phobos L1 Operational Tether Experiment (PHLOTE)

Data.gov (United States)

National Aeronautics and Space Administration — A sensor package that “floats” just above the surface of Phobos, suspended by a tether from a small spacecraft operating at the Mars/Phobos Lagrange 1 (L1) Point...

Lumbosacral arachnoid cyst with tethered cord: A rare case report

Directory of Open Access Journals (Sweden)

S K Jain

2012-01-01

Full Text Available Arachnoid cysts are cerebrospinal fluid collections in the spine that can present with neurological symptoms or be discovered accidentally. Intradural location of such cysts especially in the lumbosacral region is relatively rare. The association of such cysts with other congenital anomalies such as tethered cord lends evidence to the developmental origin of arachnoid cysts. We report a case of lumbosacral arachnoid cyst with tethered cord in a 6-year-old male child and discuss the etiopathogenesis and management options.

Design and Synthesis of a Series of L-trans-4-Substituted Prolines as Selective Antagonists for the Ionotropic Glutamate Receptors Including Functional and X-ray Crystallographic Studies of New Subtype Selective Kainic Acid Receptor Subtype 1 (GluK1) Antagonist (2S,4R)-4-(2-Carboxyphenoxy)pyrrolidine

DEFF Research Database (Denmark)

Krogsgaard-Larsen, Niels; Delgar, Claudia; Koch, Karina

2017-01-01

Ionotropic glutamate receptor antagonists are valuable tool compounds for studies of neurological pathways in the central nervous system. On the basis of rational ligand design, a new class of selective antagonists, represented by (2S,4R)-4-(2-carboxy-phenoxy)pyrrolidine-2-carboxylic acid (1b...... to the structure with glutamate, consistent with 1b being an antagonist. A structure-activity relationship study showed that the chemical nature of the tethering atom (C,O, or S) linking the pyrrolidine ring and the phenyl ring plays a key role in the receptor selectivity profile and that substituents......), for cloned homomeric kainic acid receptor subtype 1 (GluK1) was attained (Ki = 4 µM). In a functional assay, 1b displayed full antagonist activity with IC50 = 6 ± 2 µM. A crystal structure was obtained of 1b when bound in the ligand binding domain of GluK1. A domain opening of 13-14° was seen compared...

Unilateral pedicle screws asymmetric tethering: an innovative method to create idiopathic deformity

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Zhang Xuesong

2007-10-01

Full Text Available Abstract Objective To evaluate the feasibility of the method that unilateral pedicle screws asymmetric tethering in concave side in combination with convex rib resection for creating idiopathic deformity. Summary of background data Various methods are performed to create idiopathic deformity. Among these methods, posterior asmmetric tethering of the spine shows satisfying result, but some drawbacks related to the current posterior asymmetric tether were still evident. Materials and methods Unilateral pedicle screws asymmetric tethering was performed to 14 female goats (age: 5–8 week-old, weight: 6–8 kg in concave side in combination with convex rib resection. Dorsoventral and lateral plain radiographs were taken of each thoracic spine in the frontal and sagittal planes right after the surgery and later every 4 weeks. Results All animals ambulated freely after surgery. For technical reasons, 2 goats were excluded (one animal died for anesthetic during the surgery, and one animal was lost for instrumental fail due to postoperative infection. Radiography showed that 11 goats exhibited scoliosis with convex toward to the right side, and as the curve increased with time, only 1 goat showed nonprogressive. The initial scoliosis generated in the progressors after the procedures measured 29.0° on average (range 23.0°–38.5° and increased to 43.0° on average (range 36.0°–58.0° over 8 to 10 weeks. The average progression of 14.0° was measured. The curvature immediately after tethering surgery (the initial Cobb angle did have a highly significant correlation with the final curvature (p Conclusion Unilateral pedicle screws asymmetric tethering is a practical method to create experimental scoliosis, especially for those who would like to study the correction of this deformity.

Titanium-tethered vancomycin prevents resistance to rifampicin in Staphylococcus aureus in vitro.

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Martin Rottman

Full Text Available Rifampicin is currently recognized as the most potent drug against Gram positive implant related infections. The use of rifampicin is limited by the emergence of bacterial resistance, which is often managed by coadministration of a second antibiotic. The purpose of this study was to determine the effectiveness of soluble rifampicin in combination with vancomycin tethered to titanium metal as a means to control bacterial growth and resistance in vitro. Bacterial growth was inhibited when the vancomycin-tethered titanium discs were treated with Staphylococcus aureus inocula of ≤2×10⁶ CFU, however inocula greater than 2×10⁶ CFU/disc adhered and survived. The combination of surface-tethered vancomycin with soluble rifampicin enhanced the inhibitory effect of rifampicin for an inoculum of 10⁶ CFU/cm² by one dilution (combination MIC of 0.008 mg/L versus 0.015 mg/L for rifampicin alone. Moreover, surface tethered vancomycin prevented the emergence of a rifampicin resistant population in an inoculum of 2×10⁸ CFU.

FCAPD Protective Coating for Space Tethers, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Alameda Applied Sciences Corporation (AASC) proposes to demonstrate extended service lifetime of space tethers in the Low Earth Orbit (LEO) environment by using...

The ATPases of cohesin interface with regulators to modulate cohesin-mediated DNA tethering

Science.gov (United States)

Çamdere, Gamze; Guacci, Vincent; Stricklin, Jeremiah; Koshland, Douglas

2015-01-01

Cohesin tethers together regions of DNA, thereby mediating higher order chromatin organization that is critical for sister chromatid cohesion, DNA repair and transcriptional regulation. Cohesin contains a heterodimeric ATP-binding Cassette (ABC) ATPase comprised of Smc1 and Smc3 ATPase active sites. These ATPases are required for cohesin to bind DNA. Cohesin’s DNA binding activity is also promoted by the Eco1 acetyltransferase and inhibited by Wpl1. Recently we showed that after cohesin stably binds DNA, a second step is required for DNA tethering. This second step is also controlled by Eco1 acetylation. Here, we use genetic and biochemical analyses to show that this second DNA tethering step is regulated by cohesin ATPase. Furthermore, our results also suggest that Eco1 promotes cohesion by modulating the ATPase cycle of DNA-bound cohesin in a state that is permissive for DNA tethering and refractory to Wpl1 inhibition. DOI: http://dx.doi.org/10.7554/eLife.11315.001 PMID:26583750

The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

Energy Technology Data Exchange (ETDEWEB)

Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A. [Department of Mechanical Engineering, University of Sheffield, Mappin St., Sheffield, S1 3JD, England (United Kingdom)

2014-12-10

The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design.

The mechanics of motorised momentum exchange tethers when applied to active debris removal from LEO

International Nuclear Information System (INIS)

Caldecott, Ralph; Kamarulzaman, Dayangku N. S.; Kirrane, James P.; Cartmell, Matthew P.; Ganilova, Olga A.

2014-01-01

The concept of momentum exchange when applied to space tethers for propulsion is well established, and a considerable body of literature now exists on the on-orbit modelling, the dynamics, and also the control of a large range of tether system applications. The authors consider here a new application for the Motorised Momentum Exchange Tether by highlighting three key stages of development leading to a conceptualisation that can subsequently be developed into a technology for Active Debris Removal. The paper starts with a study of the on-orbit mechanics of a full sized motorised tether in which it is shown that a laden and therefore highly massasymmetrical tether can still be forced to spin, and certainly to librate, thereby confirming its possible usefulness for active debris removal (ADR). The second part of the paper concentrates on the modelling of the centripetal deployment of a symmetrical MMET in order to get it initialized for debris removal operations, and the third and final part of the paper provides an entry into scale modelling for low cost mission design and testing. It is shown that the motorised momentum exchange tether offers a potential solution to the removal of large pieces of orbital debris, and that dynamic methodologies can be implemented to in order to optimise the emergent design

Electrodynamic Tethers and E-Sails as Active Experiment Testbeds and Technologies in Space

Science.gov (United States)

Gilchrist, B. E.; Wiegmann, B.; Johnson, L.; Bilen, S. G.; Habash Krause, L.; Miars, G.; Leon, O.

2017-12-01

The use of small-to-large flexible structures in space such as tethers continues to be studied for scientific and technology applications. Here we will consider tether electrodynamic and electrostatic interactions with magneto-plasmas in ionospheres, magnetospheres, and interplanetary space. These systems are enabling fundamental studies of basic plasma physics phenomena, allowing direct studies of the space environment, and generating technological applications beneficial for science missions. Electrodynamic tethers can drive current through the tether based on the Lorenz force adding or extracting energy from its orbit allowing for the study of charged bodies or plasma plumes moving through meso-sonic magnetoplasmas [1]. Technologically, this also generates propulsive forces requiring no propellant and little or no consumables in any planetary system with a magnetic field and ionosphere, e.g., Jupiter [2]. Further, so called electric sails (E-sails) are being studied to provide thrust through momentum exchange with the hypersonic solar wind. The E-sail uses multiple, very long (10s of km) charged, mostly bare rotating conducting tethers to deflect solar wind protons. It is estimated that a spacecraft could achieve a velocity over 100 km/s with time [3,4]. 1. Banks, P.M., "Review of electrodynamic tethers for space plasma science," J. Spacecraft and Rockets, vol. 26, no. 4, pp. 234-239, 1989. 2. Talley, C., J. Moore, D. Gallagher, and L. Johnson, "Propulsion and power from a rotating electrodynamic tether at Jupiter," 38th AIAA Aerospace Sciences Meeting and Exhibit, January 2000. 3. Janhunen, P., "The electric sail—A new propulsion method which may enable fast missions to the outer solar system," J. British Interpl. Soc., vol. 61, no. 8, pp. 322-325, 2008. 4. Wiegman, B., T. Scheider, A. Heaton, J. Vaughn, N. Stone, and K. Wright, "The Heliopause Electrostatic Rapid Transit System (HERTS)—Design, trades, and analyses performed in a two-year NASA investigation

Tethered Aerostat Effects on Nearby Seismometers

Energy Technology Data Exchange (ETDEWEB)

Bowman, Daniel [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-12-01

This report assesses seismic interference generated by a tethered aerostat. The study was motivated by a planned aerostat deployment within the footprint of the Dry Alluvium Geology seismic network. No evidence was found for seismic interference generated by the aerostat, and thus the e ects on the Dry Alluvium Geology sensors will be negligible.

Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.

Directory of Open Access Journals (Sweden)

David G Nickens

Full Text Available BACKGROUND: In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. METHODOLOGY/PRINCIPAL FINDINGS: This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxyribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A(2>A(1>A(3>A(4>A(0>A(6>A(8>A(10 and T(2>T(3>T(4>T(6 approximately T(1>T(8>T(10. Bridging T's generally gave higher yield of ligated product than bridging A's. ATP concentrations above 33 microM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (>90% joined a correctly paired, or TratioG wobble-paired, substrate on the 3' side of the ligation junction while discriminating approximately 100-fold against most mispaired substrates. Tethered dC and dG gave the highest ligation rates and yields, followed by tethered deoxyinosine (dI and dT, with the slowest reactions for tethered dA. The same kinetic trends were observed in ligase-mediated capture in complex reaction mixtures with multiple substrates. The "universal" analog 5-nitroindole (dNI did not support ligation when

STICS: surface-tethered iterative carbohydrate synthesis.

Science.gov (United States)

Pornsuriyasak, Papapida; Ranade, Sneha C; Li, Aixiao; Parlato, M Cristina; Sims, Charles R; Shulga, Olga V; Stine, Keith J; Demchenko, Alexei V

2009-04-14

A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized 'stick' made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.

Hierarchical Structure in Semicrystalline Polymers Tethered to Nanospheres

KAUST Repository

Kim, Sung A; Archer, Lynden A.

2014-01-01

We report on structural and dynamic transitions of polymers tethered to nanoparticles. In particular, we use X-ray diffraction, vibrational spectroscopy, and thermal measurements to investigate multiscale structure and dynamic transitions of poly

Biomechanical simulations of costo-vertebral and anterior vertebral body tethers for the fusionless treatment of pediatric scoliosis.

Science.gov (United States)

Aubin, Carl-Éric; Clin, Julien; Rawlinson, Jeremy

2018-01-01

Compression-based fusionless tethers are an alternative to conventional surgical treatments of pediatric scoliosis. Anterior approaches place an anterior (ANT) tether on the anterolateral convexity of the deformed spine to modify growth. Posterior, or costo-vertebral (CV), approaches have not been assessed for biomechanical and corrective effectiveness. The objective was to biomechanically assess CV and ANT tethers using six patient-specific, finite element models of adolescent scoliotic patients (11.9 ± 0.7 years, Cobb 34° ± 10°). A validated algorithm simulated the growth and Hueter-Volkmann growth modulation over a period of 2 years with the CV and ANT tethers at two initial tensions (100, 200 N). The models without tethering also simulated deformity progression with Cobb angle increasing from 34° to 56°, axial rotation 11° to 13°, and kyphosis 28° to 32° (mean values). With the CV tether, the Cobb angle was reduced to 27° and 20° for tensions of 100 and 200 N, respectively, kyphosis to 21° and 19°, and no change in axial rotation. With the ANT tether, Cobb was reduced to 32° and 9° for 100 and 200 N, respectively, kyphosis unchanged, and axial rotation to 3° and 0°. While the CV tether mildly corrected the coronal curve over a 2-year growth period, it had sagittal lordosing effect, particularly with increasing initial axial rotation (>15°). The ANT tether achieved coronal correction, maintained kyphosis, and reduced the axial rotation, but over-correction was simulated at higher initial tensions. This biomechanical study captured the differences between a CV and ANT tether and indicated the variability arising from the patient-specific characteristics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:254-264, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Position Control of an X4-Flyer Using a Tether

Directory of Open Access Journals (Sweden)

Yusuke Ouchi

2016-05-01

Full Text Available In Japan, aging of infrastructures, such as roads,bridges, and water and sewer services, etc. poses a problem, andit is required to extend the life-span of such infrastructures bymaintenance. Among infrastructures, especially bridges areperiodically inspected by short range visual observations, whichcheck the damage and deterioration of the surface. However,since there are some cases where the short range visualobservation is difficult, an alternative method is required so as toreplace the short range visual observation with it. So, "X4-Flyer"is very attractive because of realizing a movement at high altitudeeasily. The objective of this study is to develop a tethered X4-Flyer, so that the conventional short range visual observation ofbridges is replaced by it. In this paper, a method for themeasurement and control of the position is described by using atether for controlling the position of the X4-Flyer. In addition, itis checked whether the tethered X4-Flyer can control the positionusing the proposed method or not, letting it fly in a state in whicha tether is being attached

Tethered elevator: A unique opportunity for space processing

Science.gov (United States)

Monti, R.

1986-01-01

The latest fluid dynamic and material science experiments in the microgravity environment have emphasized the importance of the residual gravity level and of the g-jitter on fluid physics phenomena. The tethered elevator presents the possibility of providing variable g-levels (both steady and g-jitter) around a very low steady g-level (that can be realized when the elevator is near the center of mass of the space station-tether complex). When positioning a variable periodic oscillation to the payload a clean g-jitter disturbance can be obtained that would not be otherwise obtainable by other systems. These two possibilities make the elevator a facility to help resolve a number of still open questions that are preventing wider utilization of the space environment in the microgravity area.

Tethered Nanoparticle–Polymer Composites: Phase Stability and Curvature

KAUST Repository

Srivastava, Samanvaya; Agarwal, Praveen; Archer, Lynden A.

2012-01-01

different small-angle X-ray scattering signatures in comparison to phase-separated composites comprised of bare or sparsely grafted nanoparticles. A general diagram for the dispersion state and phase stability of polymer tethered nanoparticle-polymer

Dynamics Model for a Multi-Tethered Space-Based Interferometer

National Research Council Canada - National Science Library

Gates, Stephen

2000-01-01

.... Tether constitutive behavior is discussed. Prescribed motion of any system degrees of freedom is treated, and expressions for the corresponding constraint force/torque components are established.

Ionic-Liquid-Tethered Nanoparticles: Hybrid Electrolytes

KAUST Repository

Moganty, Surya S.

2010-10-22

A new class of solventless electrolytes was created by tethering ionic liquids to hard inorganic ZrO2 nanostructures (see picture; NIM=nanoscale ionic material). These hybrid fluids exhibit exceptional redox stability windows, excellent thermal stability, good lithium transference numbers, long-term interfacial stability in the presence of a lithium anode and, when doped with lithium salt, reasonable ionic conductivities.

System Dynamics and Feedforward Control for Tether-Net Space Robot System

Directory of Open Access Journals (Sweden)

Guang Zhai

2009-06-01

Full Text Available A new concept using flexible tether-net system to capture space debris is presented in this paper. With a mass point assumption the tether-net system dynamic model is established in orbital frame by applying Lagrange Equations. In order to investigate the net in-plane trajectories during after cast, the non-control R-bar and V-bar captures are simulated with ignoring the out-of-plane libration, the effect of in-plane libration on the trajectories of the capture net is demonstrated by simulation results. With an effort to damp the in-plane libration, the control scheme based on tether tension is investigated firstly, after that an integrated control scheme is proposed by introduced the thrusters into the system, the nonlinear close-loop dynamics is linearised by feedforward strategy, the simulation results show that feedforward controllor is effective for in-plane libration damping and enable the capture net to track an expected trajectory.

Spinal column shortening for tethered cord syndrome associated with myelomeningocele, lumbosacral lipoma, and lipomyelomeningocele in children and young adults.

Science.gov (United States)

Aldave, Guillermo; Hansen, Daniel; Hwang, Steven W; Moreno, Amee; Briceño, Valentina; Jea, Andrew

2017-06-01

OBJECTIVE Tethered cord syndrome is the clinical manifestation of an abnormal stretch on the spinal cord, presumably causing mechanical injury, a compromised blood supply, and altered spinal cord metabolism. Tethered cord release is the standard treatment for tethered cord syndrome. However, direct untethering of the spinal cord carries potential risks, such as new neurological deficits from spinal cord injury, a CSF leak from opening the dura, and retethering of the spinal cord from normal scar formation after surgery. To avoid these risks, the authors applied spinal column shortening to children and transitional adults with primary and secondary tethered cord syndrome and report treatment outcomes. The authors' aim with this study was to determine the safety and efficacy of spinal column shortening for tethered cord syndrome by analyzing their experience with this surgical technique. METHODS The authors retrospectively reviewed the demographic and procedural data of children and young adults who had undergone spinal column shortening for primary or secondary tethered cord syndrome. RESULTS Seven patients with tethered cord syndrome caused by myelomeningocele, lipomyelomeningocele, and transitional spinal lipoma were treated with spinal column shortening. One patient with less than 24 months of follow-up was excluded from further analysis. There were 3 males and 4 females; the average age at the time was surgery was 16 years (range 8-30 years). Clinical presentations for our patients included pain (in 5 patients), weakness (in 4 patients), and bowel/bladder dysfunction (in 4 patients). Spinal column osteotomy was most commonly performed at the L-1 level, with fusion between T-12 and L-2 using a pedicle screw-rod construct. Pedicle subtraction osteotomy was performed in 6 patients, and vertebral column resection was performed in 1 patient. The average follow-up period was 31 months (range 26-37 months). Computed tomography-based radiographic outcomes showed solid

Long distance cell communication using spherical tether balloons

Science.gov (United States)

Manchanda, R. K.; Rajagopalan, Vasudevan; Vasudevan, Rajagopalan; Mehrotra, R. K.; Sreenivasan, S.; Pawaskar, M.; Subba Rao Jonnalagadda, Venkata; Buduru, Suneelkumar; Kulkarni, P. M.

A proof-of-concept experiment was conducted for long-range cell communication for rural tele-phony and internet. We designed and fabricated a spherical tether balloon to carry the con-ventional micro base transceiver station (BTS) along with three slotted antenna to cover 2-pi radius. AC power and optical fiber were anchored along with the tether line. A special fre-quency license was obtained from Wireless Planning Commission (WPC) wing of Department of Telecommunication (DoT), India for the period of experiment so as not to affect the opera-tional networks. The experiments were carried out for different BTS heights up to 500 meter. Signal measurement both in data mode and voice quality were done in different quadrant using mobile vans. This paper describes the methodology (under patenting) and utility of technique for operational application.

Tethered "kiteplane" design for the Laddermill project

NARCIS (Netherlands)

Breukels, J.; Ockels, W.

2005-01-01

The Laddermill is an innovative concept for generating energy from wind using large kite-like wings on a tether. The wings are able to fly in both the regime of airplanes and kites. We therefore call these structures "kiteplanes". By providing a recurring motion with a large lift during ascending

Endocytosis Pathways of the Folate Tethered Star-Shaped PEG-PCL Micelles in Cancer Cell Lines

Directory of Open Access Journals (Sweden)

Yu-Lun Li

2014-03-01

Full Text Available This study reports on the cellular uptake of folate tethered micelles using a branched skeleton of poly(ethylene glycol and poly(ε-caprolactone. The chemical structures of the copolymers were characterized by proton nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. Doxorubicin (DOX was utilized as an anticancer drug. The highest drug loading efficiencies of DOX in the folate decorated micelle (DMCF and folate-free micelle (DMC were found to be 88.5% and 88.2%, respectively, depending on the segment length of the poly(ε-caprolactone in the copolymers. A comparison of fluorescent microscopic images of the endocytosis pathway in two cell lines, human breast cancer cells (MCF-7 and human oral cavity carcinoma cells (KB, revealed that the micelles were engulfed by KB and MCF-7 cells following in vitro incubation for one hour. Flow cytometric analysis revealed that free folic acid can inhibit the uptake of DOX by 48%–57% and 26%–39% in KB cells and MCF-7 cells, respectively. These results prove that KB cells are relatively sensitive to folate-tethered micelles. Upon administering methyl-β-cyclodextrin, an inhibitor of the caveolae-mediated endocytosis pathway, the uptake of DOX by KB cells was reduced by 69% and that by MCF-7 cells was reduced by 56%. This finding suggests that DMCF enters cells via multiple pathways, thus implying that the folate receptor is not the only target of tumor therapeutics.

Measurement of calcium influx in tethered rings of rabbit aorta under tension

International Nuclear Information System (INIS)

Gleason, M.M.; Ratz, P.H.; Flaim, S.F.

1985-01-01

Calcium (Ca) influx in vascular smooth muscle is routinely measured in untethered preparations not under passive stretch, and Ca influx data are correlated with data for steady-state isometric tension obtained under parallel conditions from tethered preparations under passive stretch. The validity of this method was tested by simultaneous measurement of Ca influx and tension in tethered rings of rabbit thoracic aorta. Ca influx ( 45 Ca 3-min pulse) and tension were measured at 3 and 30 min after norepinephrine (NE) or KCl and under control (no agonist) conditions. Active tension was significantly altered by variations in passive tension. Ca influx was unaffected by passive tension under control, NE, or KCl conditions, and results were similar at 3 and 30 min. The results confirm the validity of correlating Ca influx data from untethered rings with steady-state contractile response data obtained from tethered rings under similar experimental conditions

Differential Regulation of Synaptic Vesicle Tethering and Docking by UNC-18 and TOM-1.

Science.gov (United States)

Gracheva, Elena O; Maryon, Ed B; Berthelot-Grosjean, Martine; Richmond, Janet E

2010-01-01

The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18), unc-64(syntaxin) and tom-1(tomosyn). We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25 nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin.

Differential regulation of synaptic vesicle tethering and docking by UNC-18 and TOM-1

Directory of Open Access Journals (Sweden)

Elena O Gracheva

2010-10-01

Full Text Available The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18, unc-64(syntaxin and tom-1(tomosyn. We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin

Acquisition of Ice-Tethered Profilers with Velocity (ITP-V) Instruments for Future Arctic Studies

Science.gov (United States)

2016-11-15

San Diego, CA, IEEE Xplore . Toole, J. M., R. A. Krishfield, M.-L. Timmennans, and A. Proshutinsky, 2011: The Ice-Tethered Profiler: Argo ofthe Arctic, Oceanogr., 24, 126-135. 4 ...observations from Ice-Tethered Profilers, MTS/ IEEE Oceans’ 2015, Washington DC, 1-10. Krishfield, R., J. Toole, A. Proshutinsky, and M.-L. Timmennans, 2008

[Roles of protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, in modulation of exocrine gland functions].

Science.gov (United States)

Nishikawa, Hiroyuki

2006-07-01

Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal extracellular tethered ligand that presumably binds to the extracellular loop 2 of the receptor itself. PAR-2 is widely distributed in the mammalian body and plays various roles in biological events in the cardiovascular, respiratory, alimentary, and central neurons systems. PAR-2-activating peptides administered systemically to mice and rats trigger prompt salivation in vivo. In an in vitro study, PAR-2 agonists including the endogenous PAR-2 activator trypsin induce secretion of amylase and mucin from isolated rat parotid glands and sublingual glands, respectively. PAR-2-activating peptides administered systemically also modulate pancreatic exocrine secretion in vivo as well as in vitro. In the gastric mucosa, PAR-2 stimulation enhances secretion of mucus and pepsinogen and suppresses acid secretion. Tear secretion can also be caused by PAR-2-related peptides in PAR-2-dependent and -independent manners. PAR-2 thus plays a general or key role in the regulation of exocrine secretion. This review focuses on the physiologic and/or pathophysiologic roles of PAR-2 in glandular exocrine secretion. The possibility of PAR-2 as a target for drug development is also discussed.

Orbital Propagation of Momentum Exchange Tether Systems

Science.gov (United States)

Westerhoff, John

2002-01-01

An advanced concept in in-space transportation currently being studied is the Momentum-Exchange/Electrodynamic Reboost Tether System (MXER). The system acts as a large momentum wheel, imparting a Av to a payload in low earth orbit (LEO) at the expense of its own orbital energy. After throwing a payload, the system reboosts itself using an electrodynamic tether to push against Earth's magnetic field and brings itself back up to an operational orbit to prepare for the next payload. The ability to reboost itself allows for continued reuse of the system without the expenditure of propellants. Considering the cost of lifting propellant from the ,ground to LEO to do the same Av boost at $10000 per pound, the system cuts the launch cost of the payload dramatically, and subsequently, the MXER system pays for itself after a small number of missions.1 One of the technical hurdles to be overcome with the MXER concept is the rendezvous maneuver. The rendezvous window for the capture of the payload is on the order of a few seconds, as opposed to traditional docking maneuvers, which can take as long ets necessary to complete a precise docking. The payload, therefore, must be able to match its orbit to meet up with the capture device on the end of the tether at a specific time and location in the future. In order to be able to determine that location, the MXER system must be numerically propagated forward in time to predict where the capture device will be at that instant. It should be kept in mind that the propagation computation must be done faster than real-time. This study focuses on the efforts to find and/or build the tools necessary to numerically propagate the motion of the MXER system as accurately as possible.

Space webs based on rotating tethered formations

Science.gov (United States)

Palmerini, Giovanni B.; Sgubini, Silvano; Sabatini, Marco

2009-07-01

Several on-going studies indicate the interest for large, light orbiting structures, shaped as fish nets or webs: along the ropes of the web small spacecraft can move like spiders to position and re-locate, at will, pieces of hardware devoted to specific missions. The concept could be considered as an intermediate solution between the large monolithic structure, heavy and expensive to realize, but easy to control, and the formations of satellites, where all system members are completely free and should manoeuvre in order to acquire a desired configuration. Instead, the advantage of having a "hard-but-light" link among the different grids lays in the partition of the tasks among system components and in a possible overall reduction of the control system complexity and cost. Unfortunately, there is no stable configuration for an orbiting, two-dimensional web made by light, flexible tethers which cannot support compression forces. A possible solution is to make use of centrifugal forces to pull the net, with a reduced number of simple thrusters located at the tips of the tethers to initially acquire the required spin. In this paper a dynamic analysis of a simplified rotating web is performed, in order to evaluate the spinning velocity able to satisfy the requirement for the stability of the system. The model adopted overlaps simpler elements, each of them given by a tether (made up of a number of linear finite elements) connecting two extreme bodies accommodating the spinning thrusters. The combination of these "diameter-like" elements provides the web, shaped according to the specific requirements. The net is primarily considered as subjected to Keplerian attraction and J2 and drag perturbations only, but its behaviour under thermal inputs is also investigated.

The shear flow processing of controlled DNA tethering and stretching for organic molecular electronics.

Science.gov (United States)

Yu, Guihua; Kushwaha, Amit; Lee, Jungkyu K; Shaqfeh, Eric S G; Bao, Zhenan

2011-01-25

DNA has been recently explored as a powerful tool for developing molecular scaffolds for making reproducible and reliable metal contacts to single organic semiconducting molecules. A critical step in the process of exploiting DNA-organic molecule-DNA (DOD) array structures is the controlled tethering and stretching of DNA molecules. Here we report the development of reproducible surface chemistry for tethering DNA molecules at tunable density and demonstrate shear flow processing as a rationally controlled approach for stretching/aligning DNA molecules of various lengths. Through enzymatic cleavage of λ-phage DNA to yield a series of DNA chains of various lengths from 17.3 μm down to 4.2 μm, we have investigated the flow/extension behavior of these tethered DNA molecules under different flow strengths in the flow-gradient plane. We compared Brownian dynamic simulations for the flow dynamics of tethered λ-DNA in shear, and found our flow-gradient plane experimental results matched well with our bead-spring simulations. The shear flow processing demonstrated in our studies represents a controllable approach for tethering and stretching DNA molecules of various lengths. Together with further metallization of DNA chains within DOD structures, this bottom-up approach can potentially enable efficient and reliable fabrication of large-scale nanoelectronic devices based on single organic molecules, therefore opening opportunities in both fundamental understanding of charge transport at the single molecular level and many exciting applications for ever-shrinking molecular circuits.

Towing Asteroids with Gravity Tractors Enhanced by Tethers and Solar Sails

Science.gov (United States)

Shen, Haijun; Roithmayr, Carlos M.

2015-01-01

Material collected from an asteroid's surface can be used to increase gravitational attraction between the asteroid and a Gravity Tractor (GT); the spacecraft therefore operates more effectively and is referred to as an Enhanced Gravity Tractor (EGT). The use of tethers and solar sails to further improve effectiveness and simplify operations is investigated. By employing a tether, the asteroidal material can be placed close to the asteroid while the spacecraft is stationed farther away, resulting in a better safety margin and improved thruster efficiency. A solar sail on a spacecraft can naturally provide radial offset and inter-spacecraft separation required for multiple EGTs.

Stability control of a flexible maneuverable tethered space net robot

Science.gov (United States)

Zhang, Fan; Huang, Panfeng

2018-04-01

As a promising solution for active space debris capture and removal, a maneuverable Tethered Space Net Robot (TSNR) is proposed as an improved Space Tethered Net (TSN). In addition to the advantages inherit to the TSN, the TSNR's maneuverability expands the capture's potential. However, oscillations caused by the TSNR's flexibility and elasticity of make higher requests of the control scheme. Based on the dynamics model, a modified adaptive super-twisting sliding mode control scheme is proposed in this paper for TSNR stability control. The proposed continuous control force can effectively suppress oscillations. Theoretical verification and numerical simulations demonstrate that the desired trajectory can be tracked steadily and efficiently by employing the proposed control scheme.

Tethered spinal cord: the effect of neurosurgery on the lower urinary tract and male sexual function

NARCIS (Netherlands)

Boemers, T. M.; van Gool, J. D.; de Jong, T. P.

1995-01-01

To determine the effect of neurosurgical untethering on the lower urinary tract and male sexual function, in patients with tethered spinal cord. Thirty-six children with tethered spinal cord due to neurospinal dysraphism were assessed clinically and urodynamically before and after surgical

Electromechanical engineering in SnO2 nanoparticle tethered hybrid ionic liquid

Science.gov (United States)

Deb, Debalina; Bhattacharya, Subhratanu

2017-05-01

Challenge of developing electrolytes comprising synergic properties of high mechanical strength with superior electrical and electrochemical properties has so far been unmet towards the application of secondary storage devices. In this research, we have engineered the electromechanical properties of 2-(trimethylamino) ethyl methacrylate bis(trifluoromethylsulfonyl) imide [TMEM]TFSI ionic liquid by tethering silane modified SnO2 nanoparticles within it. Different percentages of tethering are employed to achieve improved ionic conductivity, better discharge/ charging ratio (40%) along with gel like mechanical properties. Our findings appear to provide an optimal solution towards the future prospects in application in a number of areas, notably in energy-related technologies.

Stationary Tether Device for Buoy Apparatus and System for Using

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — A rigid, neutrally buoyant hydrodynamicaly-faired tether and associated fastening hardware that loosely holds a bathymetric float at a predetermined distance from a...

Fiber Optic Shape Sensing for Tethered Marsupial Rovers, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — Building upon the successful proof of concept work in Phase I, Luna Innovations Incorporated is proposing to design, build, and test a sensing tether for marsupial...

75 FR 47316 - Centennial Challenges 2010 Strong Tether Challenge

Science.gov (United States)

2010-08-05

... NATIONAL AERONAUTICS AND SPACE ADMINISTRATION Centennial Challenges 2010 Strong Tether Challenge... teams that wish to compete may register. Centennial Challenges is a program of prize competitions to..., please visit: http://www.spaceward.org/elevator2010-ts . For general information on the NASA Centennial...

Clustering of tethered satellite system simulation data by an adaptive neuro-fuzzy algorithm

Science.gov (United States)

Mitra, Sunanda; Pemmaraju, Surya

1992-01-01

Recent developments in neuro-fuzzy systems indicate that the concepts of adaptive pattern recognition, when used to identify appropriate control actions corresponding to clusters of patterns representing system states in dynamic nonlinear control systems, may result in innovative designs. A modular, unsupervised neural network architecture, in which fuzzy learning rules have been embedded is used for on-line identification of similar states. The architecture and control rules involved in Adaptive Fuzzy Leader Clustering (AFLC) allow this system to be incorporated in control systems for identification of system states corresponding to specific control actions. We have used this algorithm to cluster the simulation data of Tethered Satellite System (TSS) to estimate the range of delta voltages necessary to maintain the desired length rate of the tether. The AFLC algorithm is capable of on-line estimation of the appropriate control voltages from the corresponding length error and length rate error without a priori knowledge of their membership functions and familarity with the behavior of the Tethered Satellite System.

Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

OpenAIRE

Keiichiro Hara; Kazuo Osada; Takashi Yamanouchi

2007-01-01

The 46th Japanese Antarctic Research Expedition (JARE-46) carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

Tethered balloon operation for wintering aerosol measurements in the lower troposphere at Syowa Station, Antarctica

Directory of Open Access Journals (Sweden)

Keiichiro Hara

2007-03-01

Full Text Available The 46th Japanese Antarctic Research Expedition (JARE-46 carried out twenty seven tethered-balloon-borne aerosol measurements at Syowa Station for better understanding of aerosol chemical and physical properties in the lower troposphere from 6th January 2005 until 11 December 2005. This report summarizes the plan, preparation, field activities and some troubles/problems in the tethered-balloon observations.

Stabilization of periodic solutions in a tethered satellite system by damping injection

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2009-01-01

presents a control design for stabilizing these periodic solutions. The design consists of a control law for stabilizing the open-loop equilibrium and a bias term which forces the system trajectory away from the equilibrium. The tether needs to be positioned away from open-loop equilibrium for the tether...... to affect the orbit parameters. An approximation of the periodic solutions of the closed loop system is found as a series expansion in the parameter plane spanned by the controller gain and the bias term. The stability of the solutions is investigated using linear Floquet analysis of the variational...

Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

KAUST Repository

Agarwal, Praveen; Kim, Sung A.; Archer, Lynden A.

2012-01-01

Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered

Disaster Coverage Predication for the Emerging Tethered Balloon Technology: Capability for Preparedness, Detection, Mitigation, and Response.

Science.gov (United States)

Alsamhi, Saeed H; Samar Ansari, Mohd; Rajput, Navin S

2018-04-01

A disaster is a consequence of natural hazards and terrorist acts, which have significant potential to disrupt the entire wireless communication infrastructure. Therefore, the essential rescue squads and recovery operations during a catastrophic event will be severely debilitated. To provide efficient communication services, and to reduce casualty mortality and morbidity during the catastrophic events, we proposed the Tethered Balloon technology for disaster preparedness, detection, mitigation, and recovery assessment. The proposed Tethered Balloon is applicable to any type of disaster except for storms. The Tethered Balloon is being actively researched and developed as a simple solution to improve the performance of rescues, facilities, and services of emergency medical communication in the disaster area. The most important requirement for rescue and relief teams during or after the disaster is a high quality of service of delivery communication services to save people's lives. Using our proposed technology, we report that the Tethered Balloon has a large disaster coverage area. Therefore, the rescue and research teams are given higher priority, and their performance significantly improved in the particular coverage area. Tethered Balloon features made it suitable for disaster preparedness, mitigation, and recovery. The performance of rescue and relief teams was effective and efficient before and after the disaster as well as can be continued to coordinate the relief teams until disaster recovery. (Disaster Med Public Health Preparedness. 2018;12:222-231).

Refining the tethering of American oysters (Crassostrea virginica) to measure the effects of two environmental stressors.

Science.gov (United States)

Poirier, Luke A; Gilbert, Shane T C; St-Hilaire, Sophie; Davidson, Jeff; Cox, Ruth; Quijón, Pedro A

2018-02-01

Tethering assays, or the physical restraint of test organisms, has been used in the past to measure selected organisms' response to stressors while removing the observer from the experimental setting. Although informative for monitoring and hypothesis testing, these assays often used microfilaments that have been found to be too invasive or prone to biases given their effects on test organisms' behavior. Here, we describe a new variation of tethering using American oysters (Crassostrea virginica) and illustrate its use in the study of their mortality rates as a result of two stressors: siltation and predation by a non-indigenous species. Our protocol identified a resistant (non-toxic) glue that could be used to attach oysters to stone slabs, thus partially mimicking the natural cementation of the shell to natural substrates. This variation of tethering was harmless and maintained oysters' body position and natural ability to filter feed. Using tethered oysters in separate two-week field cage experiments, we also show how siltation and predation by a non-indigenous species (the European green crab, Carcinus maenas), caused a gradual, easily measurable increase in oyster mortality rates. We argue that this variation of tethering is a cost-effective and advantageous way to monitor or test the effects of these and other stressors on oysters and similar species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Associative visual learning by tethered bees in a controlled visual environment.

Science.gov (United States)

Buatois, Alexis; Pichot, Cécile; Schultheiss, Patrick; Sandoz, Jean-Christophe; Lazzari, Claudio R; Chittka, Lars; Avarguès-Weber, Aurore; Giurfa, Martin

2017-10-10

Free-flying honeybees exhibit remarkable cognitive capacities but the neural underpinnings of these capacities cannot be studied in flying insects. Conversely, immobilized bees are accessible to neurobiological investigation but display poor visual learning. To overcome this limitation, we aimed at establishing a controlled visual environment in which tethered bees walking on a spherical treadmill learn to discriminate visual stimuli video projected in front of them. Freely flying bees trained to walk into a miniature Y-maze displaying these stimuli in a dark environment learned the visual discrimination efficiently when one of them (CS+) was paired with sucrose and the other with quinine solution (CS-). Adapting this discrimination to the treadmill paradigm with a tethered, walking bee was successful as bees exhibited robust discrimination and preferred the CS+ to the CS- after training. As learning was better in the maze, movement freedom, active vision and behavioral context might be important for visual learning. The nature of the punishment associated with the CS- also affects learning as quinine and distilled water enhanced the proportion of learners. Thus, visual learning is amenable to a controlled environment in which tethered bees learn visual stimuli, a result that is important for future neurobiological studies in virtual reality.

A Fiber-Optic Tether for the Hull Search UUV System Documentation

National Research Council Canada - National Science Library

Buescher, J. G

2006-01-01

...) conducting ship hull inspection missions, defines the required specifications that will allow the integration and installation of a FO tether system on UUVs with ship hull inspection capability...

A simplified tether model for molecular motor transporting cargo

International Nuclear Information System (INIS)

Fang-Zhen, Li; Li-Chun, Jiang

2010-01-01

Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin's work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor–cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity. (general)

Phase 3 study of selected tether applications in space. Volume 2: Study results

Science.gov (United States)

1986-01-01

Engineering designs were developed relative to a tethered launch assist from the Shuttle for payloads up to 10,000 kg mass and the tethering of a 15,000 kg science platform from the space station. These designs are used for a cost benefit analysis which assesses the feasibility of using such systems as a practical alternative to what would otherwise be accomplished by conventional means. The term conventional as related to both these applications is intended to apply to the use of some form(s) of chemical propulsion system.

DOE Geothermal Data Repository - Tethering Data to Information: Preprint

Energy Technology Data Exchange (ETDEWEB)

Weers, J.; Anderson, A.

2014-02-01

Data are not inherently information. Without context, data are just numbers, figures, names, or points on a line. By assigning context to data, we can validate ideas, form opinions, and generate knowledge. This is an important distinction to information scientists, as we recognize that the context in which we keep our data plays a big part in generating its value. The mechanisms used to assign this context often include their own data, supplemental to the data being described and defining semantic relationships, commonly referred to as metadata. This paper provides the status of the DOE Geothermal Data Repository (DOE GDR), including recent efforts to tether data submissions to information, discusses the important distinction between data and information, outlines a path to generate useful knowledge from raw data, and details the steps taken in order to become a node on the National Geothermal Data System (NGDS).

Tethered Contactless Mobile Nuclear Environment Monitoring Robot

International Nuclear Information System (INIS)

Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T.

2013-01-01

In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded

Tethered Contactless Mobile Nuclear Environment Monitoring Robot

Energy Technology Data Exchange (ETDEWEB)

Choi, S. Y.; Lee, E. S.; Lee, Kun J.; Kim, Su H.; Rim, C. T. [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2013-05-15

In fact, the nuclear environment monitoring is significantly crucial for early detection of NPP accident, radiological emergency, the estimation of radiation exposure to nearby residents as well as the long term radioactivity. In the UAE, the nuclear environment monitoring is, however, quite challenging because sampling locations are far from NPPs and the outdoor temperature and humidity are very high for NPP workers to collect soil, air, and water samples. Therefore, nuclear environment monitoring robots (Nubos) are strongly needed for the NPPs in the UAE. The Nubos can be remotely controlled to collect samples in extreme environment instead of NPP workers. Moreover, the Nubos can be unmanned ground vehicles (UGVs), unmanned aerial vehicles (UAVs) and unmanned marine vehicles (UMVs) to collect soil, air, and water samples, respectively. In this paper, the prototype development of UGV type Nubos using power cable for a long distance power delivery, called Tethered contactless mobile Nubo is introduced and validated by experiments. In this paper, the prototype development of Tethered Contactless Mobile (TeCoM) Nubo, which can be powered continuously within several km distance and avoid tangled cable, and the indoor test are finished. As further works, outdoor demonstration and a grand scale R and D proposal of practical Nubo will be proceeded.

Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve

NARCIS (Netherlands)

Dal-Bianco, Jacob P; Aikawa, Elena; Bischoff, Joyce; Guerrero, J Luis; Hjortnaes, Jesper; Beaudoin, Jonathan; Szymanski, Catherine; Bartko, Philipp E; Seybolt, Margo M; Handschumacher, Mark D; Sullivan, Suzanne; Garcia, Michael L; Mauskapf, Adam; Titus, James S; Wylie-Sears, Jill; Irvin, Whitney S; Chaput, Miguel; Messas, Emmanuel; Hagège, Albert A; Carpentier, Alain; Levine, Robert A

2016-01-01

BACKGROUND: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that

Electrostatics and N-glycan-mediated membrane tethering of SCUBE1 is critical for promoting bone morphogenetic protein signalling.

Science.gov (United States)

Liao, Wei-Ju; Tsao, Ku-Chi; Yang, Ruey-Bing

2016-03-01

SCUBE1 (S1), a secreted and membrane-bound glycoprotein, has a modular protein structure composed of an N-terminal signal peptide sequence followed by nine epidermal growth factor (EGF)-like repeats, a spacer region and three cysteine-rich (CR) motifs with multiple potential N-linked glycosylation sites, and one CUB domain at the C-terminus. Soluble S1 is a biomarker of platelet activation but an active participant of thrombosis via its adhesive EGF-like repeats, whereas its membrane-associated form acts as a bone morphogenetic protein (BMP) co-receptor in promoting BMP signal activity. However, the mechanism responsible for the membrane tethering and the biological importance of N-glycosylation of S1 remain largely unknown. In the present study, molecular mapping analysis identified a polycationic segment (amino acids 501-550) in the spacer region required for its membrane tethering via electrostatic interactions possibly with the anionic heparan sulfate proteoglycans. Furthermore, deglycosylation by peptide N-glycosidase F treatment revealed that N-glycans within the CR motif are essential for membrane recruitment through lectin-mediated surface retention. Injection of mRNA encoding zebrafish wild-type but not N-glycan-deficient scube1 restores the expression of haematopoietic and erythroid markers (scl and gata1) in scube1-knockdown embryos. We describe novel mechanisms in targeting S1 to the plasma membrane and demonstrate that N-glycans are required for S1 functions during primitive haematopoiesis in zebrafish. © 2016 Authors; published by Portland Press Limited.

Development of a Tethered Formation Flight Testbed for ISS, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The development of a testbed for the development and demonstration of technologies needed by tethered formation flying satellites is proposed. Such a testbed would...

Stabilized platform for tethered balloon soundings of broadband long- and short-wave radiation

International Nuclear Information System (INIS)

Alzheimer, J.M.; Anderson, G.A.; Whiteman, C.D.

1993-01-01

Changes in the composition of trace gases in the earth's atmosphere have been reported by many observers, and a general concern has been expressed regarding possible changes to the earth's climate that may be caused by radiatively active gases introduced into the earth's atmosphere by man's activities. Radiatively active trace gases produce temperature changes in the earth's atmosphere through changes in radiative flux divergence. Our knowledge of and means of measuring radiative flux divergence is very limited. A few observations of vertical radiative flux divergences have been reported from aircraft from radiometersondes from towers and from large tethered balloons. These measurement techniques suffers from one or more drawbacks, including shallow sounding depths (towers), high cost (aircraft), complicated logistics (large tethered balloons), and limitation to nighttime hours (radiometersondes). Changes in radiative flux divergence caused by anthropogenic trace gases are expected to be quite small, and will be difficult to measure with existing broadband radiative flux instruments. The emphasis of present research in global climate change is thus being focused on improving radiative transfer algorithms in global climate models. The radiative parameterizations in these models are at an early stage of development and information is needed regarding their performance, especially in cloudy conditions. The impetus for the research reported in this paper is the need for a device that can supplement existing means of measuring vertical profiles of long- and short-wave irradiance and radiative flux divergence. We have designed a small tethered-balloon-based system that can make radiometric soundings through the atmospheric boundary layer. This paper discusses the concept, the design considerations, and the design and construction of this sounding system. The performance of the system will be tested in a series of balloon flights scheduled for the fall and winter of 1992

Materials for advancement of MXER tether design (1000-371), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — There exist a need to develop, identify, and classify various materials that can be used in the fabrication of electrodynamic tethers for various applications. These...

Tethered capsule OCT endomicroscopy: from bench to bedside at the primary care office (Conference Presentation)

Science.gov (United States)

Gora, Michalina J.; Simmons, Leigh H.; Tiernan, Aubrey R.; Grant, Catriona N.; Soomro, Amna R.; Walker Corkery, Elizabeth S.; Rosenberg, Mireille; Metlay, Joshua P.; Tearney, Guillermo J.

2016-03-01

We have developed a swallowable tethered capsule OCT endomicroscopy (TCE) device that acquires microscopic images of the entire esophagus in unsedated subjects in a quick and comfortable procedure. To test its capabilities of TCE to become a population-based screening device, we conducted a clinical feasibility study in the primary care office. The swept-source OCT imaging system (1310nm central wavelength, 40kHz A-line rate, 10um axial resolution) together with the tethered capsule catheter (11x25mm capsule attached to a flexible tether) were transferred to the PCP office where unsedated patients scheduled for non-urgent PCP visits swallowed the capsule and microscopic OCT images of the entire esophagus were collected. After the whole length of the esophagus was imaged, the catheter was disinfected for reuse. Twenty subjects were enrolled in the study, including nine female and eleven male. All TCE procedures were performed by a nurse and lasted in average 5:42 ± 1:54 min. High-resolution images of the esophagus were obtained in all seventeen subjects that swallowed the capsule. Our clinical experience in this cohort, subject feedback, image quality, and technological adaptations for efficient utilization in this setting will be presented. The ease and simplicity of the procedure combined with high quality of the images demonstrate the potential for this technology to become a population-based screening device. Technology limitations and future development guided by findings from this initial experience will be discussed with the goal of effectively translating TCE to the outpatient primary care setting.

Folding of multidomain proteins: biophysical consequences of tethering even in apparently independent folding.

Science.gov (United States)

Arviv, Oshrit; Levy, Yaakov

2012-12-01

Most eukaryotic and a substantial fraction of prokaryotic proteins are composed of more than one domain. The tethering of these evolutionary, structural, and functional units raises, among others, questions regarding the folding process of conjugated domains. Studying the folding of multidomain proteins in silico enables one to identify and isolate the tethering-induced biophysical determinants that govern crosstalks generated between neighboring domains. For this purpose, we carried out coarse-grained and atomistic molecular dynamics simulations of two two-domain constructs from the immunoglobulin-like β-sandwich fold. Each of these was experimentally shown to behave as the "sum of its parts," that is, the thermodynamic and kinetic folding behavior of the constituent domains of these constructs seems to occur independently, with the folding of each domain uncoupled from the folding of its partner in the two-domain construct. We show that the properties of the individual domains can be significantly affected by conjugation to another domain. The tethering may be accompanied by stabilizing as well as destabilizing factors whose magnitude depends on the size of the interface, the length, and the flexibility of the linker, and the relative stability of the domains. Accordingly, the folding of a multidomain protein should not be viewed as the sum of the folding patterns of each of its parts, but rather, it involves abrogating several effects that lead to this outcome. An imbalance between these effects may result in either stabilization or destabilization owing to the tethering. Copyright © 2012 Wiley Periodicals, Inc.

Comprehensive analysis of LANA interacting proteins essential for viral genome tethering and persistence.

Directory of Open Access Journals (Sweden)

Subhash C Verma

Full Text Available Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human malignancies including Kaposi's sarcoma (KS, Primary Effusion Lymphoma (PEL and Multicentric Castleman's Disease (MCD. KSHV like other herpesviruses establishes life-long latency in the infected host by persisting as chromatin and tethering to host chromatin through the virally encoded protein Latency Associated Nuclear Antigen (LANA. LANA, a multifunctional protein, is capable of binding to a large number of cellular proteins responsible for transcriptional regulation of various cellular and viral pathways involved in blocking cell death and promoting cell proliferation. This leads to enhanced cell division and replication of the viral genome, which segregates faithfully in the dividing tumor cells. The mechanism of genome segregation is well known and the binding of LANA to nucleosomal proteins, throughout the cell cycle, suggests that these interactions play an important role in efficient segregation. Various biochemical methods have identified a large number of LANA binding proteins, including histone H2A/H2B, histone H1, MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may have various functions in tethering of the viral genome during specific phases of the viral life cycle. Therefore, we performed a comprehensive analysis of their interaction with LANA using a number of different assays. We show that LANA binds to core nucleosomal histones and also associates with other host chromatin proteins including histone H1 and high mobility group proteins (HMGs. We used various biochemical assays including co-immunoprecipitation and in-vivo localization by split GFP and fluorescence resonance energy transfer (FRET to demonstrate their association.

Biomimetic chimeric peptide-tethered hydrogels for human mesenchymal stem cell delivery.

Science.gov (United States)

Shim, Gayong; Kim, Gunwoo; Choi, Junhyeok; Yi, TacGhee; Cho, Yun Kyoung; Song, Sun Uk; Byun, Youngro; Oh, Yu-Kyoung

2015-12-01

Here, we report a chimeric peptide-tethered fibrin hydrogel scaffold for delivery of human mesenchymal stem cells (hMSC). Osteopontin-derived peptide (OP) was used as an hMSC-tethering moiety. OP showed hMSC adhesion properties and enhanced hMSC proliferation. A natural fibrin-binding protein-derived peptide (FBP) was tested for its ability to tether hMSC to the fibrin gel matrix. FBP loading on fibrin gels was 8.2-fold higher than that of a scrambled peptide (scFBP). FBP-loaded fibrin gels were retained at injection sites longer than scFBP-loaded fibrin gels, showing a 15.9-fold higher photon intensity of fluorescent FBP-grafted fibrin gels than fluorescent scFBP-loaded fibrin gels 48 h after injection. On the basis of the fibrin gel-binding properties of FBP and the hMSC-binding and proliferation-supporting properties of OP, we constructed chimeric peptides containing FBP and OP linked with a spacer (FBPsOP). Four days after transplantation, the survival of hMSC in FBPsOP-grafted fibrin gels was 3.9-fold higher than hMSC in fibrin gels alone. Our results suggest the potential of FBPsOP-grafted fibrin gels as a bioactive delivery system for enhanced survival of stem cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Acquisition of Human Operation Characteristics for Kite-based Tethered Flying Robot using Human Operation Data

OpenAIRE

Todoroki, Chiaki; Takahashi, Yasutake; Nakamura, Takayuki

2015-01-01

This paper shows human skill acquisition systems to control the kite-based tethered flying robot. The kite-based tethered flying robot has been proposed as a flying observation system with long-term activity capability[1]. It is a relatively new system and aimed to complement other information gathering systems using a balloon or an air vehicle. This paper shows some approaches of human operation characteristics acquisition based on fuzzy learning controller, knearest neighbor algorithm, and ...

Control by damping Injection of Electrodynamic Tether System in an Inclined Orbit

DEFF Research Database (Denmark)

Larsen, Martin Birkelund; Blanke, Mogens

2009-01-01

dynamical system. Based on this model, a nonlinear controller is designed that will make the system asymptotically stable around its open-loop equilibrium. The control scheme handles the time-varying nature of the system in a suitable manner resulting in a large operational region. The performance...... of the closed loop system is treated using Floquet theory, investigating the closed loop properties for their dependency of the controller gain and orbit inclination.......Control of a satellite system with an electrodynamic tether as actuator is a time-periodic and underactuated control problem. This paper considers the tethered satellite in a Hamiltonian framework and determines a port-controlled Hamiltonian formulation that adequately describes the nonlinear...

A Correlational Analysis of Tethered Swimming, Swim Sprint Performance and Dry-land Power Assessments.

Science.gov (United States)

Loturco, I; Barbosa, A C; Nocentini, R K; Pereira, L A; Kobal, R; Kitamura, K; Abad, C C C; Figueiredo, P; Nakamura, F Y

2016-03-01

Swimmers are often tested on both dry-land and in swimming exercises. The aim of this study was to test the relationships between dry-land, tethered force-time curve parameters and swimming performances in distances up to 200 m. 10 young male high-level swimmers were assessed using the maximal isometric bench-press and quarter-squat, mean propulsive power in jump-squat, squat and countermovement jumps (dry-land assessments), peak force, average force, rate of force development (RFD) and impulse (tethered swimming) and swimming times. Pearson product-moment correlations were calculated among the variables. Peak force and average force were very largely correlated with the 50- and 100-m swimming performances (r=- 0.82 and -0.74, respectively). Average force was very-largely/largely correlated with the 50- and 100-m performances (r=- 0.85 and -0.67, respectively). RFD and impulse were very-largely correlated with the 50-m time (r=- 0.72 and -0.76, respectively). Tethered swimming parameters were largely correlated (r=0.65 to 0.72) with mean propulsive power in jump-squat, squat-jump and countermovement jumps. Finally, mean propulsive power in jump-squat was largely correlated (r=- 0.70) with 50-m performance. Due to the significant correlations between dry-land assessments and tethered/actual swimming, coaches are encouraged to implement strategies able to increase leg power in sprint swimmers. © Georg Thieme Verlag KG Stuttgart · New York.

Single-Molecule Tethered Particle Motion: Stepwise Analyses of Site-Specific DNA Recombination

Directory of Open Access Journals (Sweden)

Hsiu-Fang Fan

2018-05-01

Full Text Available Tethered particle motion/microscopy (TPM is a biophysical tool used to analyze changes in the effective length of a polymer, tethered at one end, under changing conditions. The tether length is measured indirectly by recording the Brownian motion amplitude of a bead attached to the other end. In the biological realm, DNA, whose interactions with proteins are often accompanied by apparent or real changes in length, has almost exclusively been the subject of TPM studies. TPM has been employed to study DNA bending, looping and wrapping, DNA compaction, high-order DNA–protein assembly, and protein translocation along DNA. Our TPM analyses have focused on tyrosine and serine site-specific recombinases. Their pre-chemical interactions with DNA cause reversible changes in DNA length, detectable by TPM. The chemical steps of recombination, depending on the substrate and the type of recombinase, may result in a permanent length change. Single molecule TPM time traces provide thermodynamic and kinetic information on each step of the recombination pathway. They reveal how mechanistically related recombinases may differ in their early commitment to recombination, reversibility of individual steps, and in the rate-limiting step of the reaction. They shed light on the pre-chemical roles of catalytic residues, and on the mechanisms by which accessory proteins regulate recombination directionality.

Quinine-Promoted, Enantioselective Boron-Tethered Diels-Alder Reaction by Anomeric Control of Transition State Conformation.

Science.gov (United States)

Scholl, Katie; Dillashaw, John; Timpy, Evan; Lam, Yu-Hong; DeRatt, Lindsey; Benton, Tyler R; Powell, Jacqueline P; Houk, Kendall N; Morgan, Jeremy B

2018-05-01

Diels-Alder reactions of tethered vinyl-metal species offer the opportunity to fashion highly functionalized diol intermediates for synthesis. We have developed the first enantioselective boron-tethered Diels-Alder reaction using quinine as a chiral promoter. Quinine recovery, enantioselectivity enhancement, and manipulation of the cyclohexene core are also investigated. DFT modeling calculations confirm the role of quinine as a bidentate ligand enhancing reaction rates. The enantioselectivity of the cycloaddition is proposed to originate from a boron-centered anomeric effect.

UV-Curable Hybrid Nanocomposite Coating to Protect Tether Polymer Materials, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — To address the NASA need for coatings to protect and strengthen tether materials for Momentum-exchange Electrodynamic Reboost (MXER) technology, Luminit, LLC,...

Mini-open spinal column shortening for the treatment of adult tethered cord syndrome.

Science.gov (United States)

Safaee, Michael M; Winkler, Ethan A; Chou, Dean

2017-10-01

Tethered cord syndrome (TCS) is a challenging entity characterized by adhesions at the caudal spinal cord that prevent upward movement during growth and result in stretching of the cord with a concomitant constellation of neurologic symptoms. Although growth in height stops in adulthood, some patients still develop progressive symptoms; many underwent detethering as a child or adolescent, resulting in significant scar tissue and re-tethering. Recent strategies have focused on spinal column shortening to reduce tension on the spinal cord without exposing the previous de-tethering site. Mini-open and minimally invasive approaches avoid the large dissection and exposure associated with traditional approaches and are associated with reduced blood loss, shorter hospital stay, and similar outcomes when compared to conventional open approaches. We describe a technique for mini-open spinal column shortening. Using intraoperative navigation pedicle screws were placed at T10, T11, L1, and L2. A mini-open 3-column "egg shell" decancellation osteotomy of T12 was performed through a transpedicular approach with preservation of the superior and inferior endplates. This procedure was performed on a 28year old male with recurrent TCS and neurogenic bladder. Postoperative imaging showed a reduction in spinal column length of 1.5cm and evidence of decreased tension on the spinal cord. At last follow-up he was recovering well with improved urinary function. Spinal column shortening for adult TCS can be safely achieved through a mini-open approach. Future studies should compare the efficacy of this technique to both traditional de-tethering and open spinal column shortening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

International Nuclear Information System (INIS)

Hauer-Jensen, M.

2003-01-01

Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

Tuning peptide self-assembly by an in-tether chiral center

Science.gov (United States)

Hu, Kuan; Xiong, Wei; Li, Hu; Zhang, Pei-Yu; Yin, Feng; Zhang, Qianling; Jiang, Fan; Li, Zigang

2018-01-01

The self-assembly of peptides into ordered nanostructures is important for understanding both peptide molecular interactions and nanotechnological applications. However, because of the complexity and various self-assembling pathways of peptide molecules, design of self-assembling helical peptides with high controllability and tunability is challenging. We report a new self-assembling mode that uses in-tether chiral center-induced helical peptides as a platform for tunable peptide self-assembly with good controllability. It was found that self-assembling behavior was governed by in-tether substitutional groups, where chirality determined the formation of helical structures and aromaticity provided the driving force for self-assembly. Both factors were essential for peptide self-assembly to occur. Experiments and theoretical calculations indicate long-range crystal-like packing in the self-assembly, which was stabilized by a synergy of interpeptide π-π and π-sulfur interactions and hydrogen bond networks. In addition, the self-assembled peptide nanomaterials were demonstrated to be promising candidate materials for applications in biocompatible electrochemical supercapacitors.

Optodynamic simulation of β-adrenergic receptor signalling.

Science.gov (United States)

Siuda, Edward R; McCall, Jordan G; Al-Hasani, Ream; Shin, Gunchul; Il Park, Sung; Schmidt, Martin J; Anderson, Sonya L; Planer, William J; Rogers, John A; Bruchas, Michael R

2015-09-28

Optogenetics has provided a revolutionary approach to dissecting biological phenomena. However, the generation and use of optically active GPCRs in these contexts is limited and it is unclear how well an opsin-chimera GPCR might mimic endogenous receptor activity. Here we show that a chimeric rhodopsin/β2 adrenergic receptor (opto-β2AR) is similar in dynamics to endogenous β2AR in terms of: cAMP generation, MAP kinase activation and receptor internalization. In addition, we develop and characterize a novel toolset of optically active, functionally selective GPCRs that can bias intracellular signalling cascades towards either G-protein or arrestin-mediated cAMP and MAP kinase pathways. Finally, we show how photoactivation of opto-β2AR in vivo modulates neuronal activity and induces anxiety-like behavioural states in both fiber-tethered and wireless, freely moving animals when expressed in brain regions known to contain β2ARs. These new GPCR approaches enhance the utility of optogenetics and allow for discrete spatiotemporal control of GPCR signalling in vitro and in vivo.

Tethered and Polymer Supported Bilayer Lipid Membranes: Structure and Function

Directory of Open Access Journals (Sweden)

Jakob Andersson

2016-05-01

Full Text Available Solid supported bilayer lipid membranes are model systems to mimic natural cell membranes in order to understand structural and functional properties of such systems. The use of a model system allows for the use of a wide variety of analytical tools including atomic force microscopy, impedance spectroscopy, neutron reflectometry, and surface plasmon resonance spectroscopy. Among the large number of different types of model membranes polymer-supported and tethered lipid bilayers have been shown to be versatile and useful systems. Both systems consist of a lipid bilayer, which is de-coupled from an underlying support by a spacer cushion. Both systems will be reviewed, with an emphasis on the effect that the spacer moiety has on the bilayer properties.

Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

Energy Technology Data Exchange (ETDEWEB)

Sund, James B., E-mail: jim@jamessund.com [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Causey, Corey P. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Wolter, Scott D. [Department of Physics, Elon University, Elon, NC 27244 (United States); Parker, Charles B., E-mail: charles.parker@duke.edu [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Stoner, Brian R. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Research Triangle Institute (RTI) International, Research Triangle Park, NC (United States); Toone, Eric J. [Departments of Chemistry and Biochemistry, Duke University, Durham, NC (United States); Glass, Jeffrey T. [Department of Electrical and Computer Engineering, Duke University, Durham, NC (United States)

2014-05-01

Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

Diamond surface functionalization with biomimicry – Amine surface tether and thiol moiety for electrochemical sensors

International Nuclear Information System (INIS)

Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

2014-01-01

Highlights: • Diamond surfaces were functionalized with organic molecules using a novel approach. • Used biomimicry to select a molecule to bind NO, similar to the human body. • Molecular orbital theory predicted the molecule-analyte oxidation behavior. • A thiol moiety was attached to an amine surface tether on the diamond surface. • XPS analysis verified each surface functionalization step. - Abstract: The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen–oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis

Technical and economical assessment on tethered wind-energy systems (TWES)

Energy Technology Data Exchange (ETDEWEB)

Furuya, O.; Maekawa, S.

1982-06-01

The objective of the work reported was to establish the potential of tethered wind energy systems for energy conversion in the upper atmosphere. Of the concepts investigated, the Vertical Takeoff and Landing (VTOL) lift generation concept had the highest potential as compared to balloon, wind and hybrid concepts.

Diamond surface functionalization with biomimicry - Amine surface tether and thiol moiety for electrochemical sensors

Science.gov (United States)

Sund, James B.; Causey, Corey P.; Wolter, Scott D.; Parker, Charles B.; Stoner, Brian R.; Toone, Eric J.; Glass, Jeffrey T.

2014-05-01

The surface of conducting diamond was functionalized with a terminal thiol group that is capable of binding and detecting nitrogen-oxygen species. The functionalization process employed multiple steps starting with doped diamond films grown by plasma enhanced chemical vapor deposition followed by hydrogen termination and photochemical attachment of a chemically protected amine alkene. The surface tether was deprotected to reveal the amine functionality, which enabled the tether to be extended with surface chemistry to add a terminal thiol moiety for electrochemical sensing applications. Each step of the process was validated using X-ray photoelectron spectroscopy analysis.

Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection.

Directory of Open Access Journals (Sweden)

Roy Cohen

Full Text Available Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs. As proof of principle, we use oriented immobilization of pyruvate kinase (PK and luciferase (Luc on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE, a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices.We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815 with the current gold standard for biomarker detection, ELISA-with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA.Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using oriented immobilization of active

Endogenous opioids are involved in abnormal stereotyped behaviour of tethered sows

NARCIS (Netherlands)

Cronin, G.M.; Wiepkema, P.R.; Ree, van J.M.

1985-01-01

Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

Endogenous opioids are involved in abnormal stereotyped behaviours of tethered sows

NARCIS (Netherlands)

Cronin, G.M.; Wiepkema, P.R.; Ree, J.M. van

1985-01-01

Tethered sows continuously performed stereotypies during a substantial part of the day time. A single subcutaneous injection with naloxone significantly decreased the profound stereotypies, while explorative behaviours of pigs were not affected by naloxone. In addition a long-term effect of naloxone

TETHERED BALLOON MEASUREMENTS OF BIOGENIC VOCS IN THE ATMOSPHERIC BOUNDARY LAYER

Science.gov (United States)

Measurements of biogenic volatile organic compounds (BVOCs) have been made on a tethered balloon platform in eleven field deployments between 1985 and 1996. A series of balloon sampling packages have been developed for these campaigns and they have been used to describe boundary ...

Analytical investigation of the dynamics of tethered constellations in Earth orbit, phase 2

Science.gov (United States)

Lorenzini, E. C.; Arnold, D. A.; Cosmo, M.; Grossi, M. D.

1986-10-01

The following topics related to the dynamics of the 4-mass tethered system are addressed: (1) the development of damping algorithms for damping the out-of-plane libration of the system and the interaction of the out-of-plane control with the other degrees of freedom; and (2) the development of environmental models to be added to the dynamics simulation computer code. The environmental models are specifically a new drag routine based on the Jacchia's 1977 model, a J(2) model and an accurate thermal model of the wire. Regarding topic (1) a survey of various out-of-plane libration control laws was carried out. Consequently a yo-yo control law with amplitude of the tether length variation proportional to the amplitude of the out-of-game libration has been selected. This control law provides good damping when applied to a (theoretical) two-dimensional system. In the actual 3-dimensional 4-mass tethered system, however, energy is transferred to the least damped degrees of freedom (the out-of-plane lateral deflections are still undamped in the present simulations) in such a way as to decrease the effectiveness of the algorithm for out-of-plane libration control. The addition of damping algorithms for the out-of-plane lateral deflections is therefore necessary.

Compact, planar, translational piezoelectric bimorph actuator with Archimedes’ spiral actuating tethers

International Nuclear Information System (INIS)

Yang, Chenye; Liu, Sanwei; Livermore, Carol; Xie, Xin

2016-01-01

The design, analytical modelling, finite element analysis (FEA), and experimental characterization of a microelectromechanical system (MEMS) out-of-plane (vertical) translational piezoelectric lead–zirconate–titanate (PZT) bimorph actuator supported on Archimedes’ spiral tethers are presented. Three types of bimorph actuators with different electrode patterns (with spiral tethers half actuated, fully actuated with uniform polarity, or fully actuated with reversed polarity) are designed and modelled. The two actuators with the highest predicted performance (half actuated and fully actuated with uniform polarity) are implemented and characterized. Both designs are fabricated by commercial processes and are compatible with integration into more complex MEMS systems. Analytical modelling and FEA are used to analyze and predict the actuators’ displacements and blocking forces. Experimental measurements of the deflections and blocking forces of actuators with full uniform actuation and half actuation validate the design. At an applied voltage of 110 V, the out-of-plane deflections of the actuators with half actuation and full uniform actuation are measured at about 17 µ m and 29 µ m respectively, in good agreement with analytical predictions of 17.3 µ m and 34.2 µ m and FEA predictions of 17.1 µ m and 25.8 µ m. The blocking force for devices with half-actuated tethers is predicted to be 12 mN (analytical) and 10 mN (FEA), close to the experimental value of 9 mN. The blocking force for devices with full uniform actuation is predicted to be 23 mN (analytical) and 17 mN (FEA), as compared with 15 mN in experiments. (paper)

Structural mechanism of ligand activation in human calcium-sensing receptor

Energy Technology Data Exchange (ETDEWEB)

Geng, Yong; Mosyak, Lidia; Kurinov, Igor; Zuo, Hao; Sturchler, Emmanuel; Cheng, Tat Cheung; Subramanyam, Prakash; Brown, Alice P.; Brennan, Sarah C.; Mun, Hee-chang; Bush, Martin; Chen, Yan; Nguyen, Trang X.; Cao, Baohua; Chang, Donald D.; Quick, Matthias; Conigrave, Arthur D.; Colecraft, Henry M.; McDonald, Patricia; Fan, Qing R.

2016-07-19

Human calcium-sensing receptor (CaSR) is a G-protein-coupled receptor (GPCR) that maintains extracellular Ca²⁺homeostasis through the regulation of parathyroid hormone secretion. It functions as a disulfide-tethered homodimer composed of three main domains, the Venus Flytrap module, cysteine-rich domain, and seven-helix transmembrane region. Here, we present the crystal structures of the entire extracellular domain of CaSR in the resting and active conformations. We provide direct evidence that L-amino acids are agonists of the receptor. In the active structure, L-Trp occupies the orthosteric agonist-binding site at the interdomain cleft and is primarily responsible for inducing extracellular domain closure to initiate receptor activation. Our structures reveal multiple binding sites for Ca²⁺and PO₄^3-ions. Both ions are crucial for structural integrity of the receptor. While Ca²⁺ions stabilize the active state, PO₄^3-ions reinforce the inactive conformation. The activation mechanism of CaSR involves the formation of a novel dimer interface between subunits.

The secret life of tethers: the role of tethering factors in SNARE complex regulation

Directory of Open Access Journals (Sweden)

Michelle L Dubuke

2016-05-01

Full Text Available Trafficking in eukaryotic cells is a tightly regulated process to ensure correct cargo delivery to the proper destination organelle or plasma membrane. In this review, we focus on how the vesicle fusion machinery, the SNARE complex, is regulated by the interplay of the multisubunit tethering complexes (MTC with the SNAREs and Sec1/Munc18 (SM proteins. Although these factors are used in different stages of membrane trafficking, e.g. Golgi to plasma membrane transport vs vacuolar fusion, and in a variety of diverse eukaryotic cell types, many commonalities between their functions are being revealed. We explore the various protein-protein interactions and findings from functional reconstitution studies in order to highlight both their common features and the differences in their modes of regulation. These studies serve as a starting point for mechanistic explorations in other systems.

Tethered Lubricants for Small Systems

Energy Technology Data Exchange (ETDEWEB)

Lynden A. Archer

2006-01-09

The objective of this research project is two-fold. First, to fundamentally understand friction and relaxation dynamics of polymer chains near surfaces; and second, to develop novel self-lubricated substrates suitable for MEMS devices. During the three-year performance period of this study the PI and his students have shown using theory and experiments that systematic introduction of disorder into tethered lubricant coatings (e.g. by using self-assembled monolayer (SAM) mixtures or SAMs with nonlinear, branched architectures) can be used to significantly reduce the friction coefficient of a surface. They have also developed a simple procedure based on dielectric spectroscopy for quantifying the effect of surface disorder on molecular relaxation in lubricant coatings. Details of research accomplishments in each area of the project are described in the body of the report.

Theseus: tethered distributed robotics (TDR)

Science.gov (United States)

Digney, Bruce L.; Penzes, Steven G.

2003-09-01

The Defence Research and Development Canada's (DRDC) Autonomous Intelligent System's program conducts research to increase the independence and effectiveness of military vehicles and systems. DRDC-Suffield's Autonomous Land Systems (ALS) is creating new concept vehicles and autonomous control systems for use in outdoor areas, urban streets, urban interiors and urban subspaces. This paper will first give an overview of the ALS program and then give a specific description of the work being done for mobility in urban subspaces. Discussed will be the Theseus: Thethered Distributed Robotics (TDR) system, which will not only manage an unavoidable tether but exploit it for mobility and navigation. Also discussed will be the prototype robot called the Hedgehog, which uses conformal 3D mobility in ducts, sewer pipes, collapsed rubble voids and chimneys.

Real-time profiling of organic trace gases in the planetary boundary layer by PTR-MS using a tethered balloon

Directory of Open Access Journals (Sweden)

R. Schnitzhofer

2009-12-01

Full Text Available A method for real-time profiling of volatile organic compounds (VOCs was developed combining the advantages of a tethered balloon as a research platform and of proton transfer reaction mass spectrometry (PTR-MS as an analytical technique for fast and highly sensitive VOC measurements. A 200 m Teflon tube was used to draw sampling air from a tethered aerodynamic balloon to the PTR-MS instrument. Positive and negative artefacts (i.e. formation and loss of VOCs in the tube were characterised in the laboratory and in the field by a set of 11 atmospherically relevant VOCs including both pure and oxygenated hydrocarbons. The only two compounds that increased or decreased when sampled through the tube were acetone (+7% and xylene (-6%. The method was successfully deployed during a winter field campaign to determine the small scale spatial and temporal patterns of air pollutants under winter inversion conditions.

Cholesterol tethered bioresponsive polycation as a candidate for gene delivery

Energy Technology Data Exchange (ETDEWEB)

Zhu Ying [Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310009 (China); Wang Youxiang, E-mail: yx_wang@zju.edu.cn [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China); Hu Qiaoling; Shen Jiacong [Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Zhejiang University, Hangzhou 310027 (China)

2009-04-30

The efficient unpacking of viral protein shell gave the inspiration for the synthesized vectors. In this research, novel cholesterol tethered bioresponsive polyethylenimine (PEI) was specially designed via disulfide-containing cross-linker. The cholesterol lipid had proved to increase the permeability of gene vector through cell membrane. The acid-base titration indicated that the synthesized polycation possessed efficient proton sponge effect, which was suggested to increase endosomal release of pDNA complexes into the cytoplasm. The cholesterol tethered polycation could effectively induce DNA condensation and form spherical particles with diameter about 200 nm at N/P ratio of 10. At glutathione concentration of 3 mM, the polyplexes were unpacked due to the bioresponsive cleavage of the disulfide bonds. The in-vitro experiment indicated that the polyplexes showed efficient transfection efficiency to HEK293T cells. All the results indicated that the bioresponsive polycation could be served as an effective trigger to control the release of DNA at the intracellular environment. The novel bioresponsive polycation might have great potential in non-viral gene delivery research and application.

Effect of mass variation on dynamics of tethered system in orbital maneuvering

Science.gov (United States)

Sun, Liang; Zhao, Guowei; Huang, Hai

2018-05-01

In orbital maneuvering, the mass variation due to fuel consumption has an obvious impact on the dynamics of tethered system, which cannot be neglected. The contributions of the work are mainly shown in two aspects: 1) the improvement of the model; 2) the analysis of dynamics characteristics. As the mass is variable, and the derivative of the mass is directly considered in the traditional Lagrange equation, the expression of generalized force is complicated. To solve this problem, the coagulated derivative is adopted in the paper; besides, the attitude dynamics equations derived in this paper take into account the effect of mass variation and the drift of orbital trajectory at the same time. The bifurcation phenomenon, the pendular motion angular frequency, and amplitudes of tether vibration revealed in this paper can provide a reference for the parameters and controller design in practical engineering. In the article, a dumbbell model is adopted to analyze the dynamics of tethered system, in which the mass variation of base satellite is fully considered. Considering the practical application, the case of orbital transfer under a transversal thrust is mainly studied. Besides, compared with the analytical solutions of librational angles, the effects of mass variation on stability and librational characteristic are studied. Finally, in order to make an analysis of the effect on vibrational characteristic, a lumped model is introduced, which reveals a strong coupling of librational and vibrational characteristics.

Calculating the electromagnetic field on the earth due to an electrodynamic tethered system in the ionosphere

Science.gov (United States)

Estes, Robert D.

1989-01-01

A method is presented for calculating the electromagnetic wave field on the earth's surface associated with the operation of an electrodynamic tethered satellite system of constant or slowly varying current in the upper ionosphere. The wave field at the ionospheric boundary and on the earth's surface is obtained by numerical integration. The results suggest that the ionospheric waves do not propagate into the atmosphere and that the image of the Alfven wings from a steady-current tether should be greatly broadened on the earth's surface.

Elasticity of Hard-Spheres-And-Tether Systems

International Nuclear Information System (INIS)

Farago, O.; Kantor, Y.

1999-01-01

Physical properties of a large class of systems ranging from noble gases to polymers and rubber are primarily determined by entropy, while the internal energy plays a minor role. Such systems can be conveniently modeled and numerically studied using ''hard' (i.e., ''infinity-or-zero'') potentials, such as hard sphere repulsive interactions, or inextensible (''tether'') bonds which limit the distance between the bonded monomers, but have zero energy at all permitted distances. The knowledge of elastic constants is very important for understanding the behavior of entropy-dominated systems. Computational methods for determination of the elastic constants in such systems are broadly classified into ''strain'' methods and (fluctuation methods. In the former, the elastic constants are extracted from stress-strain relations, while in the latter they are determined from measurements of stress fluctuations. The fluctuation technique usually enables more accurate and well-controlled determination of the elastic constants since in this method the elastic constants are computed directly from simulations of the un strained system with no need to deform the simulation cell and perform numerical differentiations. For central forces systems, the original ''fluctuation'' formalism can be applied provided the pair potential is twice differentiable. We have extended this formalism to apply to hard-spheres-and-tether models in which this requirement is not fulfilled. We found that for such models the components of the tensor of elastic constants can be related to (two-, three- and four-point) probability densities of contacts between hard spheres and stretched bonds. We have tested our formalism on simple (phantom networks and three-dimensional hard spheres systems

Synthesis and characterization of macromolecular rhodamine tethers and their interactions with P-glycoprotein.

Science.gov (United States)

Crawford, Lindsey; Putnam, David

2014-08-20

Rhodamine dyes are well-known P-glycoprotein (P-gp) substrates that have played an important role in the detection of inhibitors and other substrates of P-gp, as well as in the understanding of P-gp function. Macromolecular conjugates of rhodamines could prove useful as tethers for further probing of P-gp structure and function. Two macromolecular derivatives of rhodamine, methoxypolyethylene glycol-rhodamine6G and methoxypolyethylene glycol-rhodamine123, were synthesized through the 2'-position of rhodamine6G and rhodamine123, thoroughly characterized, and then evaluated by inhibition with verapamil for their ability to interact with P-gp and to act as efflux substrates. To put the results into context, the P-gp interactions of the new conjugates were compared to the commercially available methoxypolyethylene glycol-rhodamineB. FACS analysis confirmed that macromolecular tethers of rhodamine6G, rhodamine123, and rhodamineB were accumulated in P-gp expressing cells 5.2 ± 0.3%, 26.2 ± 4%, and 64.2 ± 6%, respectively, compared to a sensitive cell line that does not overexpress P-gp. Along with confocal imaging, the efflux analysis confirmed that the macromolecular rhodamine tethers remain P-gp substrates. These results open potential avenues for new ways to probe the function of P-gp both in vitro and in vivo.

Cholesterol-Induced Buckling in Physisorbed Polymer-Tethered Lipid Monolayers

Directory of Open Access Journals (Sweden)

Christoph A. Naumann

2013-04-01

Full Text Available The influence of cholesterol concentration on the formation of buckling structures is studied in a physisorbed polymer-tethered lipid monolayer system using epifluorescence microscopy (EPI and atomic force microscopy (AFM. The monolayer system, built using the Langmuir-Blodgett (LB technique, consists of 3 mol % poly(ethylene glycol (PEG lipopolymers and various concentrations of the phospholipid, 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC, and cholesterol (CHOL. In the absence of CHOL, AFM micrographs show only occasional buckling structures, which is caused by the presence of the lipopolymers in the monolayer. In contrast, a gradual increase of CHOL concentration in the range of 0–40 mol % leads to fascinating film stress relaxation phenomena in the form of enhanced membrane buckling. Buckling structures are moderately deficient in CHOL, but do not cause any notable phospholipid-lipopolymer phase separation. Our experiments demonstrate that membrane buckling in physisorbed polymer-tethered membranes can be controlled through CHOL-mediated adjustment of membrane elastic properties. They further show that CHOL may have a notable impact on molecular confinement in the presence of crowding agents, such as lipopolymers. Our results are significant, because they offer an intriguing prospective on the role of CHOL on the material properties in complex membrane architecture.

Use of Tethered Enzymes as a Platform Technology for Rapid Analyte Detection

Science.gov (United States)

Cohen, Roy; Lata, James P.; Lee, Yurim; Hernández, Jean C. Cruz; Nishimura, Nozomi; Schaffer, Chris B.; Mukai, Chinatsu; Nelson, Jacquelyn L.; Brangman, Sharon A.; Agrawal, Yash; Travis, Alexander J.

2015-01-01

Background Rapid diagnosis for time-sensitive illnesses such as stroke, cardiac arrest, and septic shock is essential for successful treatment. Much attention has therefore focused on new strategies for rapid and objective diagnosis, such as Point-of-Care Tests (PoCT) for blood biomarkers. Here we use a biomimicry-based approach to demonstrate a new diagnostic platform, based on enzymes tethered to nanoparticles (NPs). As proof of principle, we use oriented immobilization of pyruvate kinase (PK) and luciferase (Luc) on silica NPs to achieve rapid and sensitive detection of neuron-specific enolase (NSE), a clinically relevant biomarker for multiple diseases ranging from acute brain injuries to lung cancer. We hypothesize that an approach capitalizing on the speed and catalytic nature of enzymatic reactions would enable fast and sensitive biomarker detection, suitable for PoCT devices. Methods and findings We performed in-vitro, animal model, and human subject studies. First, the efficiency of coupled enzyme activities when tethered to NPs versus when in solution was tested, demonstrating a highly sensitive and rapid detection of physiological and pathological concentrations of NSE. Next, in rat stroke models the enzyme-based assay was able in minutes to show a statistically significant increase in NSE levels in samples taken 1 hour before and 0, 1, 3 and 6 hours after occlusion of the distal middle cerebral artery. Finally, using the tethered enzyme assay for detection of NSE in samples from 20 geriatric human patients, we show that our data match well (r = 0.815) with the current gold standard for biomarker detection, ELISA—with a major difference being that we achieve detection in 10 minutes as opposed to the several hours required for traditional ELISA. Conclusions Oriented enzyme immobilization conferred more efficient coupled activity, and thus higher assay sensitivity, than non-tethered enzymes. Together, our findings provide proof of concept for using

On the effect of tether composition on cis/trans selectivity in intramolecular Diels-Alder reactions.

Science.gov (United States)

Paddon-Row, Michael N; Longshaw, Alistair I; Willis, Anthony C; Sherburn, Michael S

2009-01-05

Intramolecular Diels-Alder (IMDA) transition structures (TSs) and energies have been computed at the B3LYP/6-31+G(d) and CBS-QB3 levels of theory for a series of 1,3,8-nonatrienes, H(2)C=CH-CH=CH-CH(2)-X-Z-CH=CH(2) [-X-Z- = -CH(2)-CH(2)- (1); -O-C(=O)- (2); -CH(2)-C(=O)- (3); -O-CH(2)- (4); -NH-C(=O)- (5); -S-C(=O)- (6); -O-C(=S)- (7); -NH-C(=S)- (8); -S-C(=S)- (9)]. For each system studied (1-9), cis- and trans-TS isomers, corresponding, respectively, to endo- and exo-positioning of the -C-X-Z- tether with respect to the diene, have been located and their relative energies (E(rel) (TS)) employed to predict the cis/trans IMDA product ratio. Although the E(rel) (TS) values are modest (typically NH or S), the IMDA cis stereoselectivity diminishes. The predicted stereochemical reaction preferences are explained in terms of two opposing effects operating in the cis-TS, namely (1) unfavorable torsional (eclipsing) strain about the C4-C5 bond, that is caused by the -C-X-C(=Y)- group's strong tendency to maintain local planarity; and (2) attractive electrostatic and secondary orbital interactions between the endo-(thio)carbonyl group, C=Y, and the diene. The former interaction predominates when X is weakly electronegative (X=N, S), while the latter is dominant when X is more strongly electronegative (X=O), or a methylene group (X=CH(2)) which increases tether flexibility. These predictions hold up to experimental scrutiny, with synthetic IMDA reactions of 1, 2, 3, and 4 (published work) and 5, 6, and 8 (this work) delivering ratios close to those calculated. The reactions of thiolacrylate 5 and thioamide 8 represent the first examples of IMDA reactions with tethers of these types. Our results point to strategies for designing tethers, which lead to improved cis/trans-selectivities in IMDAs that are normally only weakly selective. Experimental verification of the validity of this claim comes in the form of fumaramide 14, which undergoes a more trans-selective IMDA reaction

The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes

International Nuclear Information System (INIS)

Zhang, Bo; Edwards, Brian J.

2015-01-01

A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes

The effect of particle size on the morphology and thermodynamics of diblock copolymer/tethered-particle membranes.

Science.gov (United States)

Zhang, Bo; Edwards, Brian J

2015-06-07

A combination of self-consistent field theory and density functional theory was used to examine the effect of particle size on the stable, 3-dimensional equilibrium morphologies formed by diblock copolymers with a tethered nanoparticle attached either between the two blocks or at the end of one of the blocks. Particle size was varied between one and four tenths of the radius of gyration of the diblock polymer chain for neutral particles as well as those either favoring or disfavoring segments of the copolymer blocks. Phase diagrams were constructed and analyzed in terms of thermodynamic diagrams to understand the physics associated with the molecular-level self-assembly processes. Typical morphologies were observed, such as lamellar, spheroidal, cylindrical, gyroidal, and perforated lamellar, with the primary concentration region of the tethered particles being influenced heavily by particle size and tethering location, strength of the particle-segment energetic interactions, chain length, and copolymer radius of gyration. The effect of the simulation box size on the observed morphology and system thermodynamics was also investigated, indicating possible effects of confinement upon the system self-assembly processes.

Otolith tethering in the zebrafish otic vesicle requires Otogelin and α-Tectorin.

Science.gov (United States)

Stooke-Vaughan, Georgina A; Obholzer, Nikolaus D; Baxendale, Sarah; Megason, Sean G; Whitfield, Tanya T

2015-03-15

Otoliths are biomineralised structures important for balance and hearing in fish. Their counterparts in the mammalian inner ear, otoconia, have a primarily vestibular function. Otoliths and otoconia form over sensory maculae and are attached to the otolithic membrane, a gelatinous extracellular matrix that provides a physical coupling between the otolith and the underlying sensory epithelium. In this study, we have identified two proteins required for otolith tethering in the zebrafish ear, and propose that there are at least two stages to this process: seeding and maintenance. The initial seeding step, in which otolith precursor particles tether directly to the tips of hair cell kinocilia, fails to occur in the einstein (eis) mutant. The gene disrupted in eis is otogelin (otog); mutations in the human OTOG gene have recently been identified as causative for deafness and vestibular dysfunction (DFNB18B). At later larval stages, maintenance of otolith tethering to the saccular macula is dependent on tectorin alpha (tecta) function, which is disrupted in the rolling stones (rst) mutant. α-Tectorin (Tecta) is a major constituent of the tectorial membrane in the mammalian cochlea. Mutations in the human TECTA gene can cause either dominant (DFNA8/12) or recessive (DFNB21) forms of deafness. Our findings indicate that the composition of extracellular otic membranes is highly conserved between mammals and fish, reinforcing the view that the zebrafish is an excellent model system for the study of deafness and vestibular disease. © 2015. Published by The Company of Biologists Ltd.

Tethered Balloon Operations at ARM AMF3 Site at Oliktok Point, AK

Science.gov (United States)

Dexheimer, D.; Lucero, D. A.; Helsel, F.; Hardesty, J.; Ivey, M.

2015-12-01

Oliktok Point has been the home of the Atmospheric Radiation Measurement Program's (ARM) third ARM Mobile Facility, or AMF3, since October 2013. The AMF3 is operated through Sandia National Laboratories and hosts instrumentation collecting continuous measurements of clouds, aerosols, precipitation, energy, and other meteorological variables. The Arctic region is warming more quickly than any other region due to climate change and Arctic sea ice is declining to record lows. Sparsity of atmospheric data from the Arctic leads to uncertainty in process comprehension, and atmospheric general circulation models (AGCM) are understood to underestimate low cloud presence in the Arctic. Increased vertical resolution of meteorological properties and cloud measurements will improve process understanding and help AGCMs better characterize Arctic clouds. SNL is developing a tethered balloon system capable of regular operation at AMF3 in order to provide increased vertical resolution atmospheric data. The tethered balloon can be operated within clouds at altitudes up to 7,000' AGL within DOE's R-2204 restricted area. Pressure, relative humidity, temperature, wind speed, and wind direction are recorded at multiple altitudes along the tether. These data were validated against stationary met tower data in Albuquerque, NM. The altitudes of the sensors were determined by GPS and calculated using a line counter and clinometer and compared. Wireless wetness sensors and supercooled liquid water content sensors have also been deployed and their data has been compared with other sensors. This presentation will provide an overview of the balloons, sensors, and test flights flown, and will provide a preliminary look at data from sensor validation campaigns and test flights.

Structural Determinants at the Interface of the ARC2 and LRR Domains Control the Activation of the NB-LRR Plant Immune Receptors Rx1 and Gpa2

NARCIS (Netherlands)

Slootweg, E.J.; Spiridon, L.N.; Roosien, J.; Butterbach, P.B.E.; Pomp, H.; Westerhof, L.B.; Wilbers, R.H.P.; Bakker, E.H.; Bakker, J.; Petrescu, A.J.; Smant, G.; Goverse, A.

2013-01-01

Many plant and animal immune receptors have a modular NB-LRR architecture in which a nucleotide-binding switch domain (NB-ARC) is tethered to a leucine-rich repeat sensor domain (LRR). The cooperation between the switch and sensor domains, which regulates the activation of these proteins, is poorly

The Tethered Balloon Current Generator - A space shuttle-tethered subsatellite for plasma studies and power generation

Science.gov (United States)

Williamson, P. R.; Banks, P. M.

1976-01-01

The objectives of the Tethered Balloon Current Generator experiment are to: (1) generate relatively large regions of thermalized, field-aligned currents, (2) produce controlled-amplitude Alfven waves, (3) study current-driven electrostatic plasma instabilities, and (4) generate substantial amounts of power or propulsion through the MHD interaction. A large balloon (a diameter of about 30 m) will be deployed with a conducting surface above the space shuttle at a distance of about 10 km. For a generally eastward directed orbit at an altitude near 400 km, the balloon, connected to the shuttle by a conducting wire, will be positive with respect to the shuttle, enabling it to collect electrons. At the same time, the shuttle will collect positive ions and, upon command, emit an electron beam to vary current flow in the system.

Nuclear pore complex tethers to the cytoskeleton.

Science.gov (United States)

Goldberg, Martin W

2017-08-01

The nuclear envelope is tethered to the cytoskeleton. The best known attachments of all elements of the cytoskeleton are via the so-called LINC complex. However, the nuclear pore complexes, which mediate the transport of soluble and membrane bound molecules, are also linked to the microtubule network, primarily via motor proteins (dynein and kinesins) which are linked, most importantly, to the cytoplasmic filament protein of the nuclear pore complex, Nup358, by the adaptor BicD2. The evidence for such linkages and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture are discussed. Copyright © 2017. Published by Elsevier Ltd.

Approaching control for tethered space robot based on disturbance observer using super twisting law

Science.gov (United States)

Hu, Yongxin; Huang, Panfeng; Meng, Zhongjie; Wang, Dongke; Lu, Yingbo

2018-05-01

Approaching control is a key mission for the tethered space robot to perform the task of removing space debris. But the uncertainties of the TSR such as the change of model parameter have an important effect on the approaching mission. Considering the space tether and the attitude of the gripper, the dynamic model of the TSR is derived using Lagrange method. Then a disturbance observer is designed to estimate the uncertainty based on STW control method. Using the disturbance observer, a controller is designed, and the performance is compared with the dynamic inverse controller which turns out that the proposed controller performs better. Numerical simulation validates the feasibility of the proposed controller on the position and attitude tracking of the TSR.

Arctic Atmospheric Measurements Using Manned and Unmanned Aircraft, Tethered Balloons, and Ground-Based Systems at U.S. DOE ARM Facilities on the North Slope Of Alaska

Science.gov (United States)

Ivey, M.; Dexheimer, D.; Roesler, E. L.; Hillman, B. R.; Hardesty, J. O.

2016-12-01

The U.S. Department of Energy (DOE) provides scientific infrastructure and data to the international Arctic research community via research sites located on the North Slope of Alaska and an open data archive maintained by the ARM program. In 2016, DOE continued investments in improvements to facilities and infrastructure at Oliktok Point Alaska to support operations of ground-based facilities and unmanned aerial systems for science missions in the Arctic. The Third ARM Mobile Facility, AMF3, now deployed at Oliktok Point, was further expanded in 2016. Tethered instrumented balloons were used at Oliktok to make measurements of clouds in the boundary layer including mixed-phase clouds and to compare measurements with those from the ground and from unmanned aircraft operating in the airspace above AMF3. The ARM facility at Oliktok Point includes Special Use Airspace. A Restricted Area, R-2204, is located at Oliktok Point. Roughly 4 miles in diameter, it facilitates operations of tethered balloons and unmanned aircraft. R-2204 and a new Warning Area north of Oliktok, W-220, are managed by Sandia National Laboratories for DOE Office of Science/BER. These Special Use Airspaces have been successfully used to launch and operate unmanned aircraft over the Arctic Ocean and in international airspace north of Oliktok Point.A steady progression towards routine operations of unmanned aircraft and tethered balloon systems continues at Oliktok. Small unmanned aircraft (DataHawks) and tethered balloons were successfully flown at Oliktok starting in June of 2016. This poster will discuss how principal investigators may apply for use of these Special Use Airspaces, acquire data from the Third ARM Mobile Facility, or bring their own instrumentation for deployment at Oliktok Point, Alaska.

A Quantitative Study of Tethered Chains in Various Solution Conditions Using Langmuir Diblock Copolymer Monolayers

Energy Technology Data Exchange (ETDEWEB)

Kent, Michael S.

1999-08-13

This article summarizes our investigations of tethered chain systems using Langmuir monolayer of polydimethysiloxane-poly styrene (PDMS-PS) diblock copolymers on organic liquids. In this system, the PDMS block adsorbs to the air surface while the PS block dangles into the subphase liquid. The air surface can be made either repulsive or attractive for the tethered PS chain segments by choosing a subphase liquid which has a surface tension lower or greater than that of PS, respectively. The segment profile of the PS block is determined by neutron reflection as a function of the surface density, the molecular weights of the PS and PDMS blocks, and the solution conditions. We cover the range of reduced surface density (SIGMA) characteristic of the large body of data in the literature for systems of chains tethered onto solid surfaces from dilute solution in good or theta solvent conditions (SIGMA < 12). We emphasize quantitative comparisons with analytical profile forms and scaling predictions. We find that the strong-stretching limit invoked in analytical SCF and scaling theories is not valid over this Z range. On the other hand, over a large portion of this range (SIGMA < 5) tethered layers are well described by a renormalization group theory addressing weakly interacting or noninteracting chains. Simultaneous with the study of the profile form, the free energy of the chains is examined through the surface tension. A strong increase in the surface pressure is observed with increasing surface density which determines the maximum surface density which can be achieved. This apparently nonequilibrium effect is attributed to steric interactions and limited lateral interpenetration. This effect may explain several outstanding discrepancies regarding the adsorption of end-functionalized chains and diblock copolymers onto solid surfaces.

Piperidinium tethered nanoparticle-hybrid electrolyte for lithium metal batteries

KAUST Repository

Korf, Kevin S.

2014-06-23

We report on the synthesis of novel piperidinium-based ionic liquid tethered nanoparticle hybrid electrolytes and investigate their physical and electrochemical properties. Hybrid electrolytes based on the ionic liquid 1-methyl-1-propylpiperidinium bis(trifluoromethanesulfone) imide covalently tethered to silica nanoparticles (SiO2-PP-TFSI) were blended with propylene carbonate-1 M lithium bis(trifluoromethanesulfone) imide (LiTFSI). We employed NMR analysis to confirm the successful creation of the hybrid material. Dielectric and rheological measurements show that these electrolytes exhibit exceptional room-temperature DC ionic conductivity (10-2 to 10 -3 S cm-1) as well as high shear mechanical moduli (105 to 106 Pa). Lithium transference numbers were found to increase with particle loading and to reach values as high as 0.22 at high particle loadings where the particle jam to form a soft glassy elastic medium. Analysis of lithium electrodeposits obtained in the hybrid electrolytes using SEM and EDX spectra show that the SiO2-PP-TFSI nanoparticles are able to smooth lithium deposition and inhibit lithium dendrite proliferation in Li metal batteries. LTOSiO2-PP-TFSI/PC in 1 M LiTFSILi half-cells based on the SiO2-PP-TFSI hybrid electrolytes exhibit attractive voltage profiles and trouble-free extended cycling behavior over more than 1000 cycles of charge and discharge. This journal is © the Partner Organisations 2014.

The radiation budget of stratocumulus clouds measured by tethered balloon instrumentation: Variability of flux measurements

Science.gov (United States)

Duda, David P.; Stephens, Graeme L.; Cox, Stephen K.

1990-01-01

Measurements of longwave and shortwave radiation were made using an instrument package on the NASA tethered balloon during the FIRE Marine Stratocumulus experiment. Radiation data from two pairs of pyranometers were used to obtain vertical profiles of the near-infrared and total solar fluxes through the boundary layer, while a pair of pyrgeometers supplied measurements of the longwave fluxes in the cloud layer. The radiation observations were analyzed to determine heating rates and to measure the radiative energy budget inside the stratocumulus clouds during several tethered balloon flights. The radiation fields in the cloud layer were also simulated by a two-stream radiative transfer model, which used cloud optical properties derived from microphysical measurements and Mie scattering theory.

Energy dissipation/transfer and stable attitude of spatial on-orbit tethered system

Science.gov (United States)

Hu, Weipeng; Song, Mingzhe; Deng, Zichen

2018-01-01

For the Tethered Satellite System, the coupling between the platform system and the solar panel is a challenge in the dynamic analysis. In this paper, the coupling dynamic behaviors of the Tethered Satellite System that is idealized as a planar flexible damping beam-spring-mass composite system are investigated via a structure-preserving method. Considering the coupling between the plane motion of the system, the oscillation of the spring and the transverse vibration of the beam, the dynamic model of the composite system is established based on the Hamiltonian variational principle. A symplectic dimensionality reduction method is proposed to decouple the dynamic system into two subsystems approximately. Employing the complex structure-preserving approach presented in our previous work, numerical iterations are performed between the two subsystems with weak damping to study the energy dissipation/transfer in the composite system, the effect of the spring stiffness on the energy distribution and the effect of the particle mass on the stability of the composite system. The numerical results show that: the energy transfer approach is uniquely determined by the initial attitude angle, while the energy dissipation speed is mainly depending on the initial attitude angle and the spring stiffness besides the weak damping. In addition, the mass ratio between the platform system and the solar panel determines the stable state as well as the time needed to reach the stable state of the composite system. The numerical approach presented in this paper provides a new way to deal with the coupling dynamic system and the conclusions obtained give some useful advices on the overall design of the Tethered Satellite System.

Reverse cope elimination of hydroxylamines and alkenes or alkynes: theoretical investigation of tether length and substituent effects.

Science.gov (United States)

Krenske, Elizabeth H; Davison, Edwin C; Forbes, Ian T; Warner, Jacqueline A; Smith, Adrian L; Holmes, Andrew B; Houk, K N

2012-02-01

Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes ("reverse Cope eliminations"). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations. © 2012 American Chemical Society

Relationship between anaerobic capacity estimated using a single effort and 30-s tethered running outcomes.

Directory of Open Access Journals (Sweden)

Alessandro Moura Zagatto

Full Text Available The purpose of the current study was to investigate the relationship between alternative anaerobic capacity method (MAODALT and a 30-s all-out tethered running test. Fourteen male recreational endurance runners underwent a graded exercise test, a supramaximal exhaustive effort and a 30-s all-out test on different days, interspaced by 48h. After verification of data normality (Shapiro-Wilk test, the Pearson's correlation test was used to verify the association between the anaerobic estimates from the MAODALT and the 30-s all-out tethered running outputs. Absolute MAODALT was correlated with mean power (r = 0.58; P = 0.03, total work (r = 0.57; P = 0.03, and mean force (r = 0.79; P = 0.001. In addition, energy from the glycolytic pathway (E[La-] was correlated with mean power (r = 0.58; P = 0.03. Significant correlations were also found at each 5s interval between absolute MAODALT and force values (r between 0.75 and 0.84, and between force values and E[La-] (r between 0.73 to 0.80. In conclusion, the associations between absolute MAODALT and the mechanical outputs from the 30-s all-out tethered running test evidenced the importance of the anaerobic capacity for maintaining force during the course of time in short efforts.

Overload control of artificial gravity facility using spinning tether system for high eccentricity transfer orbits

Science.gov (United States)

Gou, Xing-wang; Li, Ai-jun; Tian, Hao-chang; Wang, Chang-qing; Lu, Hong-shi

2018-06-01

As the major part of space life supporting systems, artificial gravity requires further study before it becomes mature. Spinning tether system is a good alternative solution to provide artificial gravity for the whole spacecraft other than additional devices, and its longer tether length could significantly reduce spinning velocity and thus enhance comfortability. An approximated overload-based feedback method is proposed to provide estimated spinning velocity signals for controller, so that gravity level could be accurately controlled without complicated GPS modules. System behavior in high eccentricity transfer orbits is also studied to give a complete knowledge of the spinning stabilities. The application range of the proposed method is studied in various orbit cases and spinning velocities, indicating that it is accurate and reliable for most of the mission phases especially for the final constant gravity level phase. In order to provide stable gravity level for transfer orbit missions, a sliding mode controller based on estimated angular signals is designed for closed-loop control. Numerical results indicate that the combination of overload-based feedback and sliding mode controller could satisfy most of the long-term artificial gravity missions. It is capable of forming flexible gravity environment in relatively good accuracy even in the lowest possible orbital radiuses and high eccentricity orbits of crewed space missions. The proposed scheme provides an effective tether solution for the artificial gravity construction in interstellar travel.

Advanced Electrodynamic Tether Systems: Modeling of Scattering and Unsteady Effects

Science.gov (United States)

2008-06-06

spacecraft and satellites. A high altitude nuclear detonation would likely create a new high energy electron belt and increase the radiation risk to...our tether has no reason to roll, making O=0, and thus cosO =1. The y-component of the torque is thus expressed: < = < =< = FF cossin3 222 ’ (S...ions from the integral limits to manageable levels. Our goal is to isolate the permutations of initial velocities and impact parameters such that

The Reverse Cope Elimination of Hydroxylamines and Alkenes or Alkynes: Theoretical Investigation of Tether Length and Substituent Effects

Science.gov (United States)

Krenske, Elizabeth H.; Davison, Edwin C.; Forbes, Ian T.; Warner, Jacqueline A.; Smith, Adrian L.; Holmes, Andrew B.; Houk, K. N.

2012-01-01

Quantum mechanical calculations have been used to study the intramolecular additions of hydroxylamines to alkenes and alkynes (“reverse Cope eliminations”). In intermolecular reverse Cope eliminations, alkynes are more reactive than alkenes. However, competition experiments have shown that tethering the hydroxylamine to the alkene or alkyne can reverse the reactivity order from that normally observed. The exact outcome depends on the length of the tether. In agreement with experiment, a range of density functional theory methods and CBS-QB3 calculations predict that the activation energies for intramolecular reverse Cope eliminations follow the order 6-exo-dig hydroxylamine and alkyne. Cyclization onto an alkene in the 5-exo-trig fashion incurs slightly less tether strain than a 6-exo-dig alkyne cyclization, but its activation energy is higher because the hydroxylamine fragment must distort more before the TS is reached. If the alkene terminus is substituted with two methyl groups, the barrier becomes so much higher that it is also disfavored compared to the 5- and 7-exo-dig cyclizations. PMID:22280245

Diagnosis and surgical treatment of terminal syringomyelia within spinal cord combined with tethered cord syndrome

Directory of Open Access Journals (Sweden)

Jing-cheng XIE

2016-04-01

months to 14.50 years (average 6.10 years. All patients presented neurological intactness (McCormick gradeⅠ, recovery of conus medullaris, rising of the end of spinal cord, no recurrence of syringomyelia with favorable alignment of spine during follow- up period.  Conclusions Terminal syringomyelia in the spinal cord with TCS is rarely occurred and characterized by chronic dysfunction of spinal cord and nerve. The manifestation in MRI imaging is characterized by low level of spinal cord, disappearing of conus medullaris, long T1 and long T2 signal of filum terminale and spinal cord, and no enhancement of capsule wall. The surgical treatment includes resection of filum terminale, drainage of the cerebrospinal fluid (CSF in syringomyelia, and de-tethering of the spinal cord under microscope. The outcome is satisfactory. DOI: 10.3969/j.issn.1672-6731.2016.03.006

Molecular mechanism of 7TM receptor activation--a global toggle switch model

DEFF Research Database (Denmark)

Schwartz, Thue W; Frimurer, Thomas M; Holst, Birgitte

2006-01-01

the accumulated biophysical data supporting an outward rigid-body movement of the intracellular segments, as well as the recent data derived from activating metal ion sites and tethered ligands, which suggests an opposite, inward movement of the extracellular segments of the transmembrane helices. According...... to this model, a vertical see-saw movement of TM-VI-and to some degree TM-VII-around a pivot corresponding to the highly conserved prolines will occur during receptor activation, which may involve the outer segment of TM-V in an as yet unclear fashion. Small-molecule agonists can stabilize such a proposed...

Reversibly tethering growth factors to surfaces : guiding cell function at the cell-material interface

NARCIS (Netherlands)

Cabanas Danés, Jordi

2013-01-01

Development of novel methodologies for tethering growth factors (GFs) to materials is highly desired for the generation of biomaterials with improved tissue repair properties. Progress in the development of biomaterials that incorporate GFs and the in vivo performance of such biomaterials in tissue

Elongated membrane tethers, individually anchored by high affinity α4β1/VCAM-1 complexes, are the quantal units of monocyte arrests.

Directory of Open Access Journals (Sweden)

Calvin Chu

Full Text Available The α4β1 integrin facilitates both monocyte rolling and adhesion to the vascular endothelium and is physiologically activated by monocyte chemoattractant protein (MCP-1. The current study investigated the initial events in the adhesion of THP-1 cells to immobilized Vascular Cell Adhesion Molecule 1 (VCAM-1. Using AFM force measurements, cell adhesion was shown to be mediated by two populations of α4β1/VCAM-1 complexes. A low affinity form of α4β1 was anchored to the elastic elements of the cytoskeleton, while a higher affinity conformer was coupled to the viscous elements of the cell membrane. Within 100 ms of contact, THP-1 cells, stimulated by co-immobilized MCP-1, exhibited a tremendous increase in adhesion to VCAM-1. Enhanced cell adhesion was accompanied by a local decoupling of the cell membrane from the cytoskeleton and the formation of long membrane tethers. The tethers were individually anchored by multiple α4β1/VCAM-1 complexes that prolonged the extension of the viscous tethers. In vivo, the formation of these membrane tethers may provide the quantal structural units for the arrest of rolling monocytes within the blood vessels.

Brownian motion of tethered nanowires.

Science.gov (United States)

Ota, Sadao; Li, Tongcang; Li, Yimin; Ye, Ziliang; Labno, Anna; Yin, Xiaobo; Alam, Mohammad-Reza; Zhang, Xiang

2014-05-01

Brownian motion of slender particles near a boundary is ubiquitous in biological systems and in nanomaterial assembly, but the complex hydrodynamic interaction in those systems is still poorly understood. Here, we report experimental and computational studies of the Brownian motion of silicon nanowires tethered on a substrate. An optical interference method enabled direct observation of microscopic rotations of the slender bodies in three dimensions with high angular and temporal resolutions. This quantitative observation revealed anisotropic and angle-dependent hydrodynamic wall effects: rotational diffusivity in inclined and azimuth directions follows different power laws as a function of the length, ∼ L(-2.5) and ∼ L(-3), respectively, and is more hindered for smaller inclined angles. In parallel, we developed an implicit simulation technique that takes the complex wire-wall hydrodynamic interactions into account efficiently, the result of which agreed well with the experimentally observed angle-dependent diffusion. The demonstrated techniques provide a platform for studying the microrheology of soft condensed matters, such as colloidal and biological systems near interfaces, and exploring the optimal self-assembly conditions of nanostructures.

Crowded, Confined, and Frustrated: Dynamics of Molecules Tethered to Nanoparticles

KAUST Repository

Agarwal, Praveen

2012-12-01

Above a critical chemistry-dependent molecular weight, all polymer molecules entangle and, as a result, exhibit slow dynamics, enhanced viscosity, and elasticity. Herein we report on the dynamics of low molecular weight polymers tethered to nanoparticles and find that even conventionally unentangled chains manifest dynamical features similar to entangled, long-chain molecules. Our findings are shown to imply that crowding and confinement of polymers on particles produce topological constraints analogous to those in entangled systems. © 2012 American Physical Society.

Surface Ocean Dispersion Observations from the Ship-Tethered Aerostat Remote Sensing System

DEFF Research Database (Denmark)

Carlson, Daniel Frazier; Ozgokmen, Tamay; Novelli, Guillaume

2018-01-01

Oil slicks and sheens reside at the air-sea interface, a region of the ocean that is notoriously difficult to measure and, therefore, little is known about the velocity field at the sea surface. The Ship-Tethered Aerostat Remote Sensing System (STARSS) was developed to measure Lagrangian velocities...... of experiments in the northern Gulf of Mexico in January- February 2016. STARSS was equipped with a GPS and inertial navigation system (INS) that was used to directly georectify the aerial images. A relative rectification technique was developed that translates and rotates the drift cards to minimize the total...... movement of all drift cards from one frame to the next. Rectified drift card positions were used to quantify scale-dependent dispersion by computing relative dispersion, relative diffusivity, and velocity structure functions. STARSS was part of a nested observational framework, which included deployments...

A NASBA on microgel-tethered molecular-beacon microarray for real-time microbial molecular diagnostics.

Science.gov (United States)

Ma, Y; Dai, X; Hong, T; Munk, G B; Libera, M

2016-12-19

Despite their many advantages and successes, molecular beacon (MB) hybridization probes have not been extensively used in microarray formats because of the complicating probe-substrate interactions that increase the background intensity. We have previously shown that tethering to surface-patterned microgels is an effective means for localizing MB probes to specific surface locations in a microarray format while simultaneously maintaining them in as water-like an environment as possible and minimizing probe-surface interactions. Here we extend this approach to include both real-time detection together with integrated NASBA amplification. We fabricate small (∼250 μm × 250 μm) simplex, duplex, and five-plex assays with microarray spots of controllable size (∼20 μm diameter), position, and shape to detect bacteria and fungi in a bloodstream-infection model. The targets, primers, and microgel-tethered probes can be combined in a single isothermal reaction chamber with no post-amplification labelling. We extract total RNA from clinical blood samples and differentiate between Gram-positive and Gram-negative bloodstream infection in a duplex assay to detect RNA- amplicons. The sensitivity based on our current protocols in a simplex assay to detect specific ribosomal RNA sequences within total RNA extracted from S. aureus and E. coli cultures corresponds to tens of bacteria per ml. We furthermore show that the platform can detect RNA- amplicons from synthetic target DNA with 1 fM sensitivity in sample volumes that contain about 12 000 DNA molecules. These experiments demonstrate an alternative approach that can enable rapid and real-time microarray-based molecular diagnostics.

Aberrant localization of lamin B receptor (LBR) in cellular senescence in human cells

Energy Technology Data Exchange (ETDEWEB)

Arai, Rumi; En, Atsuki; Ukekawa, Ryo [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Miki, Kensuke [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama 231-0048 (Japan); Fujii, Michihiko, E-mail: mifuji@yokohama-cu.ac.jp [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ayusawa, Dai [Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama 236-0027 (Japan); Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama 231-0048 (Japan)

2016-05-13

5-Bromodeoxyuridine (BrdU), a thymidine analogue, induces cellular senescence in mammalian cells. BrdU induces cellular senescence probably through the regulation of chromatin because BrdU destabilizes or disrupts nucleosome positioning and decondenses heterochromatin. Since heterochromatin is tethered to the nuclear periphery through the interaction with the nuclear envelope proteins, we examined the localization of the several nuclear envelope proteins such as lamins, lamin-interacting proteins, nuclear pore complex proteins, and nuclear transport proteins in senescent cells. We have shown here that lamin B receptor (LBR) showed a change in localization in both BrdU-induced and replicative senescent cells.

TFG facilitates outer coat disassembly on COPII transport carriers to promote tethering and fusion with ER-Golgi intermediate compartments.

Science.gov (United States)

Hanna, Michael G; Block, Samuel; Frankel, E B; Hou, Feng; Johnson, Adam; Yuan, Lin; Knight, Gavin; Moresco, James J; Yates, John R; Ashton, Randolph; Schekman, Randy; Tong, Yufeng; Audhya, Anjon

2017-09-12

The conserved coat protein complex II (COPII) mediates the initial steps of secretory protein trafficking by assembling onto subdomains of the endoplasmic reticulum (ER) in two layers to generate cargo-laden transport carriers that ultimately fuse with an adjacent ER-Golgi intermediate compartment (ERGIC). Here, we demonstrate that Trk-fused gene (TFG) binds directly to the inner layer of the COPII coat. Specifically, the TFG C terminus interacts with Sec23 through a shared interface with the outer COPII coat and the cargo receptor Tango1/cTAGE5. Our findings indicate that TFG binding to Sec23 outcompetes these other associations in a concentration-dependent manner and ultimately promotes outer coat dissociation. Additionally, we demonstrate that TFG tethers vesicles harboring the inner COPII coat, which contributes to their clustering between the ER and ERGIC in cells. Together, our studies define a mechanism by which COPII transport carriers are retained locally at the ER/ERGIC interface after outer coat disassembly, which is a prerequisite for fusion with ERGIC membranes.

Role of Double-Strand Break End-Tethering during Gene Conversion in Saccharomyces cerevisiae.

Directory of Open Access Journals (Sweden)

Suvi Jain

2016-04-01

Full Text Available Correct repair of DNA double-strand breaks (DSBs is critical for maintaining genome stability. Whereas gene conversion (GC-mediated repair is mostly error-free, repair by break-induced replication (BIR is associated with non-reciprocal translocations and loss of heterozygosity. We have previously shown that a Recombination Execution Checkpoint (REC mediates this competition by preventing the BIR pathway from acting on DSBs that can be repaired by GC. Here, we asked if the REC can also determine whether the ends that are engaged in a GC-compatible configuration belong to the same break, since repair involving ends from different breaks will produce potentially deleterious translocations. We report that the kinetics of repair are markedly delayed when the two DSB ends that participate in GC belong to different DSBs (termed Trans compared to the case when both DSB ends come from the same break (Cis. However, repair in Trans still occurs by GC rather than BIR, and the overall efficiency of repair is comparable. Hence, the REC is not sensitive to the "origin" of the DSB ends. When the homologous ends for GC are in Trans, the delay in repair appears to reflect their tethering to sequences on the other side of the DSB that themselves recombine with other genomic locations with which they share sequence homology. These data support previous observations that the two ends of a DSB are usually tethered to each other and that this tethering facilitates both ends encountering the same donor sequence. We also found that the presence of homeologous/repetitive sequences in the vicinity of a DSB can distract the DSB end from finding its bona fide homologous donor, and that inhibition of GC by such homeologous sequences is markedly increased upon deleting Sgs1 but not Msh6.

Tether-directed synthesis of highly substituted oxasilacycles via an intramolecular allylation employing allylsilanes

Directory of Open Access Journals (Sweden)

Cox Liam R

2007-02-01

Full Text Available Abstract Background Using a silyl tether to unite an aldehyde electrophile and allylsilane nucleophile into a single molecule allows a subsequent Lewis-acid-mediated allylation to proceed in an intramolecular sense and therefore receive all the benefits associated with such processes. However, with the ability to cleave the tether post allylation, a product that is the result of a net intermolecular reaction can be obtained. In the present study, four diastereoisomeric β-silyloxy-α-methyl aldehydes, which contain an allylsilane tethered through the β-carbinol centre, have been prepared, in order to probe how the relative configuration of the two stereogenic centres affects the efficiency and selectivity of the intramolecular allylation. Results Syn-aldehydes, syn-4a and syn-4b, both react poorly, affording all four possible diastereoisomeric oxasilacycle products. In contrast, the anti aldehydes anti-4a and anti-4b react analogously to substrates that lack substitution at the α-site, affording only two of the four possible allylation products. Conclusion The outcome of the reaction with anti-aldehydes is in accord with reaction proceeding through a chair-like transition state (T.S.. In these systems, the sense of 1,3-stereoinduction can be rationalised by the aldehyde electrophile adopting a pseudoaxial orientation, which will minimise dipole-dipole interactions in the T.S. The 1,4-stereoinduction in these substrates is modest and seems to be modulated by the R substituent in the starting material. In the case of the syn-substrates, cyclisation through a chair T.S. is unlikely as this would require the methyl substituent α to the reacting carbonyl group to adopt an unfavourable pseudoaxial position. It is therefore proposed that these substrates react through poorly-defined T.S.s and consequently exhibit essentially no stereoselectivity.

Significance of relative velocity in drag force or drag power estimation for a tethered float

Digital Repository Service at National Institute of Oceanography (India)

Vethamony, P.; Sastry, J.S.

There is difference in opinion regarding the use of relative velocity instead of particle velocity alone in the estimation of drag force or power. In the present study, a tethered spherical float which undergoes oscillatory motion in regular waves...

A magnetic tether system to investigate visual and olfactory mediated flight control in Drosophila.

Science.gov (United States)

Duistermars, Brian J; Frye, Mark

2008-11-21

It has been clear for many years that insects use visual cues to stabilize their heading in a wind stream. Many animals track odors carried in the wind. As such, visual stabilization of upwind tracking directly aids in odor tracking. But do olfactory signals directly influence visual tracking behavior independently from wind cues? Also, the recent deluge of research on the neurophysiology and neurobehavioral genetics of olfaction in Drosophila has motivated ever more technically sophisticated and quantitative behavioral assays. Here, we modified a magnetic tether system originally devised for vision experiments by equipping the arena with narrow laminar flow odor plumes. A fly is glued to a small steel pin and suspended in a magnetic field that enables it to yaw freely. Small diameter food odor plumes are directed downward over the fly's head, eliciting stable tracking by a hungry fly. Here we focus on the critical mechanics of tethering, aligning the magnets, devising the odor plume, and confirming stable odor tracking.

Tethered Balloon Technology in Design Solutions for Rescue and Relief Team Emergency Communication Services.

Science.gov (United States)

Alsamhi, Saeed Hamood; Ansari, Mohd Samar; Ma, Ou; Almalki, Faris; Gupta, Sachin Kumar

2018-05-23

The actions taken at the initial times of a disaster are critical. Catastrophe occurs because of terrorist acts or natural hazards which have the potential to disrupt the infrastructure of wireless communication networks. Therefore, essential emergency functions such as search, rescue, and recovery operations during a catastrophic event will be disabled. We propose tethered balloon technology to provide efficient emergency communication services and reduce casualty mortality and morbidity for disaster recovery. The tethered balloon is an actively developed research area and a simple solution to support the performance, facilities, and services of emergency medical communication. The most critical requirement for rescue and relief teams is having a higher quality of communication services which enables them to save people's lives. Using our proposed technology, it has been reported that the performance of rescue and relief teams significantly improved. OPNET Modeler 14.5 is used for a network simulated with the help of ad hoc tools (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

Analysis of tethered balloon data from San Nicolas Island on 8 July 1987

Science.gov (United States)

Cox, Stephen K.; Duda, David P.; Guinn, Thomas A.; Johnson-Pasqua, Christopher M.; Schubert, Wayne H.; Snider, Jack B.

1990-01-01

Analysis of the 8 July 1987 (Julian Day 189) tethered balloon flight from San Nicolas Island is summarized. The flight commenced at about 14:30 UTC (7:30 Pacific Daylight Time) and lasted six and one-half hours. The position of the Colorado State University (CSU) instrument package as a function of time is shown. For the purpose of presentation of results, researchers divided the flight into 13 legs. These legs consist of 20 minute constant level runs, with the exception of leg 1, which is a sounding from the surface to just above 930 mb. The laser ceilometer record of cloud base is also shown. The cloud base averaged around 970 mb during much of the flight but was more variable near the end. Before the tethered balloon flight commenced, a Communications Link Analysis and Simulation System (CLASS) sounding was released at 12:11 UTC (5:11 PDT). Temperature and moisture data below 927 mb for this sounding is shown. The sounding indicates a cloud top around 955 mb at this time.

Estimation of added-mass and damping coefficients of a tethered spherical float using potential flow theory

Digital Repository Service at National Institute of Oceanography (India)

Vethamony, P.; Chandramohan, P.; Sastry, J.S.; Narasimhan, S.

Added-mass (alpha) and damping coefficients (beta) of a tethered spherical float, undergoing oscillatory motion in sinusoidal waves, have been derived from the motion generated velocity potential for one degree-of-freedom (surge) using potential...

Palladium-Catalyzed Tandem Oxidative Arylation/Olefination of Aromatic Tethered Alkenes/Alkynes.

Science.gov (United States)

Gao, Yang; Gao, Yinglan; Wu, Wanqing; Jiang, Huanfeng; Yang, Xiaobo; Liu, Wenbo; Li, Chao-Jun

2017-01-18

We describe herein a palladium-catalyzed tandem oxidative arylation/olefination reaction of aromatic tethered alkenes/alkynes for the synthesis of dihydrobenzofurans and 2 H-chromene derivatives. This reaction features a 1,2-difunctionalization of C-C π-bond with two C-H bonds using O 2 as terminal oxidant at room temperature. The products obtained are valuable synthons and important scaffolds in biological agents and natural products. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stalk-dependent and Stalk-independent Signaling by the Adhesion G Protein-coupled Receptors GPR56 (ADGRG1) and BAI1 (ADGRB1).

Science.gov (United States)

Kishore, Ayush; Purcell, Ryan H; Nassiri-Toosi, Zahra; Hall, Randy A

2016-02-12

The adhesion G protein-coupled receptors (aGPCRs) are a large yet poorly understood family of seven-transmembrane proteins. A defining characteristic of the aGPCR family is the conserved GAIN domain, which has autoproteolytic activity and can cleave the receptors near the first transmembrane domain. Several aGPCRs, including ADGRB1 (BAI1 or B1) and ADGRG1 (GPR56 or G1), have been found to exhibit significantly increased constitutive activity when truncated to mimic GAIN domain cleavage (ΔNT). Recent reports have suggested that the new N-terminal stalk, which is revealed by GAIN domain cleavage, can directly activate aGPCRs as a tethered agonist. We tested this hypothesis in studies on two distinct aGPCRs, B1 and G1, by engineering mutant receptors lacking the entire NT including the stalk (B1- and G1-SL, with "SL" indicating "stalkless"). These receptors were evaluated in a battery of signaling assays and compared with full-length wild-type and cleavage-mimicking (ΔNT) forms of the two receptors. We found that B1-SL, in multiple assays, exhibited robust signaling activity, suggesting that the membrane-proximal stalk region is not necessary for its activation. For G1, however, the results were mixed, with the SL mutant exhibiting robust activity in several signaling assays (including TGFα shedding, activation of NFAT luciferase, and β-arrestin recruitment) but reduced activity relative to ΔNT in a distinct assay (activation of SRF luciferase). These data support a model in which the activation of certain pathways downstream of aGPCRs is stalk-dependent, whereas signaling to other pathways is stalk-independent. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Tethered Moon

Science.gov (United States)

Zahnle, Kevin; Lupu, Roxana Elena; Dubrovolskis, A. R.

2014-01-01

A reasonable initial condition on Earth after the Moonforming impact is that it begins as a hot global magma ocean1,2. We therefore begin our study with the mantle as a liquid ocean with a surface temperature on the order of 3000- 4000 K at a time some 100-1000 years after the impact, by which point we can hope that early transients have settled down. A 2nd initial condition is a substantial atmosphere, 100-1000 bars of H2O and CO2, supplemented by smaller amounts of CO, H2, N2, various sulfur-containing gases, and a suite of geochemical volatiles evaporated from the magma. Third, we start the Moon with its current mass at the relevant Roche limit. The 4th initial condition is the angular momentum of the Earth-Moon system. Canonical models hold this constant, whilst some recent models begin with considerably more angular momentum than is present today. Here we present a ruthlessly simplified model of Earth's cooling magmasphere based on a full-featured atmosphere and including tidal heating by the newborn Moon. Thermal blanketing by H2O-CO2 atmospheres slows cooling of a magma ocean. Geochemical volatiles - chiefly S, Na, and Cl - raise the opacity of the magma ocean's atmosphere and slow cooling still more. We assume a uniform mantle with a single internal (potential) temperature and a global viscosity. The important "freezing point" is the sharp rheological transition between a fluid carrying suspended crystals and a solid matrix through which fluids percolate. Most tidal heating takes place at this "freezing point" in a gel that is both pliable and viscous. Parameterized convection links the cooling rate to the temperature and heat generation inside the Earth. Tidal heating is a major effect. Tidal dissipation in the magma ocean is described by viscosity. The Moon is entwined with Earth by the negative feedback between thermal blanketing and tidal heating that comes from the temperature-dependent viscosity of the magma ocean. Because of this feedback, the rate

On the escape transition of a tethered Gaussian chain; exact results in two conjugate ensembles

NARCIS (Netherlands)

Skvortsov, A.M.; Klushin, L.I.; Leermakers, F.A.M.

2006-01-01

Upon compression between two pistons an end-tethered polymer chain undergoes an abrupt transition from a confined coil state to an inhomogeneous flower-like conformation that is partially escaped from the gap. In the thermodynamic limit the system demonstrates a first-order phase transition. A

Design and Operation of Automated Ice-Tethered Profilers for Real-Time Seawater Observations in the Polar Oceans

National Research Council Canada - National Science Library

Toole, J; Proshutinsky, A; Krishfield, R; Doherty, K; Frye, Daniel E; Hammar, T; Kemp, J; Peters, D; Heydt, K. von der

2006-01-01

An automated, easily-deployed Ice-Tethered Profiler (ITP) has been developed for deployment on perennial sea ice in polar oceans to measure changes in upper ocean temperature and salinity in all seasons...

An electrochemical lipopolysaccharide sensor based on an immobilized Toll-Like Receptor-4.

Science.gov (United States)

Mayall, R M; Renaud-Young, M; Chan, N W C; Birss, V I

2017-01-15

Infections affect millions of people each year and yet methods to ascertain their cause can take more than 24h to be effective. This delay between the presentation with symptoms and the ability to make an informed decision about treatment can have adverse consequences, including death in severe cases. Additionally, pathogen identification is a concern for public safety amid the growing threat of bioterrorism. Developing a detection system based on the immune system offers the advantage of broad specificity, while still remaining pertinent to human health. In this work, human Toll-Like Receptor-4 (TLR-4), a protein responsible for detecting lipopolysaccharide (LPS) of Gram-negative bacteria, was immobilized on both a large area and micro gold electrode via the tethering interaction of a modified Self-Assembled Monolayer (mSAM). In response to varying concentrations of its target, the protein-electrode combination showed a logarithmically proportional increased resistance to charge transfer from a solution-based redox probe, due to the formation of TLR-4 protein dimers. It also demonstrated excellent sensitivity to trace levels of Gram-negative bacteria, while remaining insensitive to both Gram-positive and viral challenges. Further characterization of our mSAM revealed that maintaining the appropriate receptor orientation on the electrode surface, mimicking TLR-4's role in a cellular context, was essential in producing a responsive sensor. Copyright © 2016 Elsevier B.V. All rights reserved.

The monomeric orphan nuclear receptor Schistosoma mansoni Ftz-F1 dimerizes specifically and functionally with the schistosome RXR homologue, SmRXR1

International Nuclear Information System (INIS)

Bertin, Benjamin; Caby, Stephanie; Oger, Frederik; Sasorith, Souphatta; Wurtz, Jean-Marie; Pierce, Raymond J.

2005-01-01

In an attempt to understand development and differentiation processes of the parasitic blood fluke Schistosoma mansoni, several members of the nuclear receptor superfamily were cloned, including SmFtz-F1 (S. mansoni Fushi Tarazu-factor 1). The Ftz-F1 nuclear receptor subfamily only contains orphan receptors that bind to their response element as monomers. Whereas SmFtz-F1 displays these basic functional properties, we have identified an original and specific interaction between SmFtz-F1 and the schistosome RXR homologue, SmRXR1. The mammalian two-hybrid assay showed that the D, E, and F domains of SmFtz-F1 were capable of interacting specifically with the E domain of SmRXR1 but not with that of mouse RXRα. Using three-dimensional LBD homology modelling and structure-guided mutagenesis, we were able to demonstrate the essential role of exposed residues located in the dimerization interfaces of both receptors in the maintenance of the interaction. Cotransfection experiments with constructions encoding full-length nuclear receptors show that SmRXR1 potentiates the transcriptional activity of SmFtz-F1 from various promoters. Nevertheless, the lack of identification of a dimeric response element for this SmFtz-F1/SmRXR1 heterodimer seems to indicate a 'tethering' mechanism. Thus, our results suggest for the first time that a member of the Ftz-F1 family could heterodimerize functionally with a homologue of the universal heterodimerization partner of nuclear receptors. This unique property confirms that SmFtz-F1 may be involved in the development and differentiation of schistosome-specific structures

The t-SNAREs syntaxin4 and SNAP23 but not v-SNARE VAMP2 are indispensable to tether GLUT4 vesicles at the plasma membrane in adipocyte

International Nuclear Information System (INIS)

Kawaguchi, Takayuki; Tamori, Yoshikazu; Kanda, Hajime; Yoshikawa, Mari; Tateya, Sanshiro; Nishino, Naonobu; Kasuga, Masato

2010-01-01

SNARE proteins (VAMP2, syntaxin4, and SNAP23) have been thought to play a key role in GLUT4 trafficking by mediating the tethering, docking and subsequent fusion of GLUT4-containing vesicles with the plasma membrane. The precise functions of these proteins have remained elusive, however. We have now shown that depletion of the vesicle SNARE (v-SNARE) VAMP2 by RNA interference in 3T3-L1 adipocytes inhibited the fusion of GLUT4 vesicles with the plasma membrane but did not affect tethering of the vesicles to the membrane. In contrast, depletion of the target SNAREs (t-SNAREs) syntaxin4 or SNAP23 resulted in impairment of GLUT4 vesicle tethering to the plasma membrane. Our results indicate that the t-SNAREs syntaxin4 and SNAP23 are indispensable for the tethering of GLUT4 vesicles to the plasma membrane, whereas the v-SNARE VAMP2 is not required for this step but is essential for the subsequent fusion event.

Tethered cord in patients affected by anorectal malformations: a survey from the ARM-Net Consortium

NARCIS (Netherlands)

Fanjul, M.; Samuk, I.; Bagolan, P.; Leva, E.; Sloots, C.; Gine, C.; Aminoff, D.; Midrio, P.; Blaauw, I. de; Marcelis, C.L.M.; Rooij, I.A.L.M. van; Wester, T.; Zwink, N.

2017-01-01

PURPOSE: The goal of this study was to determine the degree of consensus in the management of spinal cord tethering (TC) in patients with anorectal malformation (ARM) in a large cohort of European pediatric centers. METHODS: A survey was sent to pediatric surgeons (one per center) members of the

A tethered balloon system for observation of atmospheric temperature inversion

International Nuclear Information System (INIS)

Hayashi, Takashi; Kakuta, Michio

1979-05-01

In environmental assessment of near-shore nuclear plants, information is often required on the development of internal boundary layer (IBL) and associated fumigation condition. Single tower data is not sufficient to clarify the site-dependent IBL structure that affects the atmospheric diffusion in shoreline-stack-site boundary complex. A tethered balloon system has been developed, which comprises a fixed point kitoon and a car-borne small balloon. The system enables us to measure the detailed time-space distribution of temperature without much man-power. The system and example of field observations with it are described. (author)

Nucleoside conjugates of quantum dots for characterization of G protein-coupled receptors: strategies for immobilizing A2A adenosine receptor agonists

Directory of Open Access Journals (Sweden)

Gao Zhan-Guo

2010-05-01

Full Text Available Abstract Background Quantum dots (QDs are crystalline nanoparticles that are compatible with biological systems to provide a chemically and photochemically stable fluorescent label. New ligand probes with fluorescent reporter groups are needed for detection and characterization of G protein-coupled receptors (GPCRs. Results Synthetic strategies for coupling the A2A adenosine receptor (AR agonist CGS21680 (2-[4-(2-carboxyethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine to functionalized QDs were explored. Conjugates tethered through amide-linked chains and poly(ethyleneglycol (PEG displayed low solubility and lacked receptor affinity. The anchor to the dendron was either through two thiol groups of (R-thioctic acid or through amide formation to a commercial carboxy-derivatized QD. The most effective approach was to use polyamidoamine (PAMAM D5 dendrons as multivalent spacer groups, grafted on the QD surface through a thioctic acid moiety. In radioligand binding assays, dendron nucleoside conjugate 11 displayed a moderate affinity at the human A2AAR (Kiapp 1.02 ± 0.15 μM. The QD conjugate of increased water solubility 13, resulting from the anchoring of this dendron derivative, interacted with the receptor with Kiapp of 118 ± 54 nM. The fluorescence emission of 13 occurred at 565 nm, and the presence of the pendant nucleoside did not appreciably quench the fluorescence. Conclusions This is a feasibility study to demonstrate a means of conjugating to a QD a small molecular pharmacophore of a GPCR that is relatively hydrophobic. Further enhancement of affinity by altering the pharmacophore or the linking structures will be needed to make useful affinity probes.

Kv7 channels can function without constitutive calmodulin tethering.

Directory of Open Access Journals (Sweden)

Juan Camilo Gómez-Posada

Full Text Available M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC, a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function.

Characterization of the stability and bio-functionality of tethered proteins on bioengineered scaffolds: implications for stem cell biology and tissue repair.

Science.gov (United States)

Wang, Ting-Yi; Bruggeman, Kiara A F; Sheean, Rebecca K; Turner, Bradley J; Nisbet, David R; Parish, Clare L

2014-05-23

Various engineering applications have been utilized to deliver molecules and compounds in both innate and biological settings. In the context of biological applications, the timely delivery of molecules can be critical for cellular and organ function. As such, previous studies have demonstrated the superiority of long-term protein delivery, by way of protein tethering onto bioengineered scaffolds, compared with conventional delivery of soluble protein in vitro and in vivo. Despite such benefits little knowledge exists regarding the stability, release kinetics, longevity, activation of intracellular pathway, and functionality of these proteins over time. By way of example, here we examined the stability, degradation and functionality of a protein, glial-derived neurotrophic factor (GDNF), which is known to influence neuronal survival, differentiation, and neurite morphogenesis. Enzyme-linked immunosorbent assays (ELISA) revealed that GDNF, covalently tethered onto polycaprolactone (PCL) electrospun nanofibrous scaffolds, remained present on the scaffold surface for 120 days, with no evidence of protein leaching or degradation. The tethered GDNF protein remained functional and capable of activating downstream signaling cascades, as revealed by its capacity to phosphorylate intracellular Erk in a neural cell line. Furthermore, immobilization of GDNF protein promoted cell survival and differentiation in culture at both 3 and 7 days, further validating prolonged functionality of the protein, well beyond the minutes to hours timeframe observed for soluble proteins under the same culture conditions. This study provides important evidence of the stability and functionality kinetics of tethered molecules. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Tethered balloon-based particle number concentration, and size distribution vertical profiles within the lower troposphere of Shanghai

Science.gov (United States)

Zhang, Kun; Wang, Dongfang; Bian, Qinggen; Duan, Yusen; Zhao, Mengfei; Fei, Dongnian; Xiu, Guangli; Fu, Qingyan

2017-04-01

A tethered balloon-based measurement campaign of particle number concentration (PNC) and particle number size distribution (PNSD) in the size range of 15.7-661.2 nm was conducted within the lower troposphere of 1000 m in Shanghai, a Chinese megacity, during December of 2015. The meteorological conditions, PNC, and PNSD were synchronously measured at the ground-based station as well as by the tethered balloon. On ground level, the 88.2 nm particles were found to have the highest PNC. The Pearson correlation analysis based on the ground level data showed NO2 had a strong correlation with PNC. The synchronous measurement of PNC and PNSD at the ground station and on the tethered balloon showed that the 15.7-200 nm particles had higher PNC on ground level, but the PNC of 200-661.2 nm particles was higher at 400 m. One haze event (Dec 22nd-Dec 23rd) was selected for detailed discussion on the variation of vertical profiles of PNSD and PNC. The vertical distribution of characteristics of PNC and PNSD were observed and compared. Results indicated that the highest MaxDm (the diameter with the highest PNC) during those three launches all appeared at a high altitude, usually above 300 m. Compared to the clean days, the relatively bigger MaxDm at each height in the haze days also indicated regional transport of pollutants might contribute to more to that haze event.

Spectral mixture analyses of hyperspectral data acquired using a tethered balloon

Science.gov (United States)

Chen, Xuexia; Vierling, Lee

2006-01-01

Tethered balloon remote sensing platforms can be used to study radiometric issues in terrestrial ecosystems by effectively bridging the spatial gap between measurements made on the ground and those acquired via airplane or satellite. In this study, the Short Wave Aerostat-Mounted Imager (SWAMI) tethered balloon-mounted platform was utilized to evaluate linear and nonlinear spectral mixture analysis (SMA) for a grassland-conifer forest ecotone during the summer of 2003. Hyperspectral measurement of a 74-m diameter ground instantaneous field of view (GIFOV) attained by the SWAMI was studied. Hyperspectral spectra of four common endmembers, bare soil, grass, tree, and shadow, were collected in situ, and images captured via video camera were interpreted into accurate areal ground cover fractions for evaluating the mixture models. The comparison between the SWAMI spectrum and the spectrum derived by combining in situ spectral data with video-derived areal fractions indicated that nonlinear effects occurred in the near infrared (NIR) region, while nonlinear influences were minimal in the visible region. The evaluation of hyperspectral and multispectral mixture models indicated that nonlinear mixture model-derived areal fractions were sensitive to the model input data, while the linear mixture model performed more stably. Areal fractions of bare soil were overestimated in all models due to the increased radiance of bare soil resulting from side scattering of NIR radiation by adjacent grass and trees. Unmixing errors occurred mainly due to multiple scattering as well as close endmember spectral correlation. In addition, though an apparent endmember assemblage could be derived using linear approaches to yield low residual error, the tree and shade endmember fractions calculated using this technique were erroneous and therefore separate treatment of endmembers subject to high amounts of multiple scattering (i.e. shadows and trees) must be done with caution. Including the

Evaluation of calix[4]arene tethered Schiff bases for anion recognition

International Nuclear Information System (INIS)

Chawla, H.M.; Munjal, Priyanka

2016-01-01

Two calix[4]arene tethered Schiff base derivatives (L1 and L2) have been synthesized and their ion recognition capability has been evaluated through NMR, UV–vis and fluorescence spectroscopy. L1 interacts with cyanide ions very selectively to usher a significant change in color and fluorescence intensity. On the other hand L2 does not show selectivity for anion sensing despite having the same functional groups as those present in L1. The differential observations may be attributed to plausible stereo control of anion recognition and tautomerization in the synthesized Schiff base derivatives.

Evaluation of calix[4]arene tethered Schiff bases for anion recognition

Energy Technology Data Exchange (ETDEWEB)

Chawla, H.M., E-mail: hmchawla@chemistry.iitd.ac.in; Munjal, Priyanka

2016-11-15

Two calix[4]arene tethered Schiff base derivatives (L1 and L2) have been synthesized and their ion recognition capability has been evaluated through NMR, UV–vis and fluorescence spectroscopy. L1 interacts with cyanide ions very selectively to usher a significant change in color and fluorescence intensity. On the other hand L2 does not show selectivity for anion sensing despite having the same functional groups as those present in L1. The differential observations may be attributed to plausible stereo control of anion recognition and tautomerization in the synthesized Schiff base derivatives.

A Simple Flight Mill for the Study of Tethered Flight in Insects.

Science.gov (United States)

Attisano, Alfredo; Murphy, James T; Vickers, Andrew; Moore, Patricia J

2015-12-10

Flight in insects can be long-range migratory flights, intermediate-range dispersal flights, or short-range host-seeking flights. Previous studies have shown that flight mills are valuable tools for the experimental study of insect flight behavior, allowing researchers to examine how factors such as age, host plants, or population source can influence an insects' propensity to disperse. Flight mills allow researchers to measure components of flight such as speed and distance flown. Lack of detailed information about how to build such a device can make their construction appear to be prohibitively complex. We present a simple and relatively inexpensive flight mill for the study of tethered flight in insects. Experimental insects can be tethered with non-toxic adhesives and revolve around an axis by means of a very low friction magnetic bearing. The mill is designed for the study of flight in controlled conditions as it can be used inside an incubator or environmental chamber. The strongest points are the very simple electronic circuitry, the design that allows sixteen insects to fly simultaneously allowing the collection and analysis of a large number of samples in a short time and the potential to use the device in a very limited workspace. This design is extremely flexible, and we have adjusted the mill to accommodate different species of insects of various sizes.

Multidirectional seismo-acoustic wavefield of strombolian explosions at Yasur, Vanuatu using a broadband seismo-acoustic network, infrasound arrays, and infrasonic sensors on tethered balloons

Science.gov (United States)

Matoza, R. S.; Jolly, A. D.; Fee, D.; Johnson, R.; Kilgour, G.; Christenson, B. W.; Garaebiti, E.; Iezzi, A. M.; Austin, A.; Kennedy, B.; Fitzgerald, R.; Key, N.

2016-12-01

Seismo-acoustic wavefields at volcanoes contain rich information on shallow magma transport and subaerial eruption processes. Acoustic wavefields from eruptions are predicted to be directional, but sampling this wavefield directivity is challenging because infrasound sensors are usually deployed on the ground surface. We attempt to overcome this observational limitation using a novel deployment of infrasound sensors on tethered balloons in tandem with a suite of dense ground-based seismo-acoustic, geochemical, and eruption imaging instrumentation. We present preliminary results from a field experiment at Yasur Volcano, Vanuatu from July 26th to August 4th 2016. Our observations include data from a temporary network of 11 broadband seismometers, 6 single infrasonic microphones, 7 small-aperture 3-element infrasound arrays, 2 infrasound sensor packages on tethered balloons, an FTIR, a FLIR, 2 scanning Flyspecs, and various visual imaging data. An introduction to the dataset and preliminary analysis of the 3D seismo-acoustic wavefield and source process will be presented. This unprecedented dataset should provide a unique window into processes operating in the shallow magma plumbing system and their relation to subaerial eruption dynamics.

Multifunctional inulin tethered silver-graphene quantum dots nanotheranostic module for pancreatic cancer therapy.

Science.gov (United States)

Nigam Joshi, Preeti; Agawane, Sachin; Athalye, Meghana C; Jadhav, Vrushali; Sarkar, Dhiman; Prakash, Rajiv

2017-09-01

Cancer nanotechnology is an emerging area of cancer diagnosis and therapy. Although considerable progress has been made for targeted drug delivery systems to deliver anticancer agents to particular site of interest, new nanomaterials are frequently being developed and explored for better drug delivery efficiency. In the present work, we have explored a novel nanoformulation based on silver-graphene quantum dots (Ag-GQDs) nanocomposite for its successful implementation for pancreatic cancer specific drug delivery in wistar rats. Carboxymethyl inulin (CMI); a modified variant of natural polysaccharide inulin is tethered with the nanocomposite via carbodiimide coupling to enhance the biocompatibility of nanoformulation. Experiments are performed to investigate the cytotoxicity reduction of silver nanoparticles after inulin tethering as well as anticancer efficacy of the system using 5-Fluorouracil (5-FU) as model drug. SEM, TEM, FT-IR, UV-vis, photoluminescence and anti proliferative assays (MTT) are performed for characterisation of the nanocomposite. Hyaluronic acid (HA) is conjugated as targeting moiety for CD-44 (cancer stem cell marker) to fabricate a complete targeted drug delivery vehicle specific for pancreatic cancer. In the present work two prime objectives were achieved; mitigation the toxicity of silver nanoparticles by inulin coating and it's in vivo application for pancreatic cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of standard, prone and cine MRI in the evaluation of tethered cord

International Nuclear Information System (INIS)

Singh, Sukhjinder; Kline-Fath, Beth; Racadio, Judy M.; Bierbrauer, Karin; Salisbury, Shelia; Macaluso, Maurizio; Jackson, Elizabeth C.; Egelhoff, John C.

2012-01-01

Tethered cord syndrome (TCS) is defined by abnormal traction on the spinal cord that confines its movement. Surgical cord release usually stops neurological deterioration; therefore, early and accurate neuroradiological diagnosis is important. Supine MRI is the imaging modality of choice, but prone MRI and cine MRI can demonstrate cord movement. We compared the diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging. Children who underwent MRI for suspicion of TCS were retrospectively identified. Supine, prone and cine MRI studies were re-read by two pediatric neuroradiologists. Conus level, filum appearance and cord movement were documented. Thirteen of 49 children had tethered cord documented at surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%, specificity 94%, positive predictive value 82-83%, negative predictive value 89-92%, correct diagnosis 88-90%) and highest between-reader concordance (98%). Prone and cine MRI did not add to the accuracy of the supine imaging. Conus level provides the highest diagnostic accuracy and inter-reader reliability in TCS. Until a larger series is evaluated, it remains questionable whether prone or cine MRI provides enough additional diagnostic information to warrant routine use. (orig.)

Comparison of standard, prone and cine MRI in the evaluation of tethered cord

Energy Technology Data Exchange (ETDEWEB)

Singh, Sukhjinder [Cohen Children' s Medical Center, Department of Radiology, New Hyde Park, NY (United States); Kline-Fath, Beth; Racadio, Judy M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Bierbrauer, Karin [Cincinnati Children' s Hospital Medical Center, Department of Neurosurgery, Cincinnati, OH (United States); Salisbury, Shelia; Macaluso, Maurizio [Cincinnati Children' s Hospital Medical Center, Division of Biostatistics and Epidemiology, Cincinnati, OH (United States); Jackson, Elizabeth C. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics, Division of Nephrology, Cincinnati, OH (United States); Egelhoff, John C. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Phoenix Children' s Hospital, Department of Radiology, Phoenix, AZ (United States)

2012-06-15

Tethered cord syndrome (TCS) is defined by abnormal traction on the spinal cord that confines its movement. Surgical cord release usually stops neurological deterioration; therefore, early and accurate neuroradiological diagnosis is important. Supine MRI is the imaging modality of choice, but prone MRI and cine MRI can demonstrate cord movement. We compared the diagnostic accuracies of standard MRI, prone MRI and cine MRI in patients with clinical suspicion of TCS and evaluated inter-reader reliability for MR imaging. Children who underwent MRI for suspicion of TCS were retrospectively identified. Supine, prone and cine MRI studies were re-read by two pediatric neuroradiologists. Conus level, filum appearance and cord movement were documented. Thirteen of 49 children had tethered cord documented at surgery. Conus level had the highest diagnostic accuracy (sensitivity 69-77%, specificity 94%, positive predictive value 82-83%, negative predictive value 89-92%, correct diagnosis 88-90%) and highest between-reader concordance (98%). Prone and cine MRI did not add to the accuracy of the supine imaging. Conus level provides the highest diagnostic accuracy and inter-reader reliability in TCS. Until a larger series is evaluated, it remains questionable whether prone or cine MRI provides enough additional diagnostic information to warrant routine use. (orig.)

Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

KAUST Repository

Takanabe, Kazuhiro

2015-03-05

The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

Tethered Transition Metals Promoted Photocatalytic System for Efficient Hydrogen Evolutions

KAUST Repository

Takanabe, Kazuhiro; Isimjan, Tayirjan; Yu, Weili; Del Gobbo, Silvano; Xu, Wei

2015-01-01

The present invention is directed, at least in part, to a process for improving the efficiency of a photocatalyst (a semiconductor photocatalyst) by tethering (depositing) a metal (e.g., metal ions of a late transition metal, such as nickel) to the semiconductor (photocatalyst) surface through the use of an organic ligand. More specifically, 1,2-ethanedithiol (EDT) functions as an excellent molecular linker (organic ligand) to attach a transition metal complex (e.g., nickel (Ni.sup.2+ ions)) to the semiconductor surface, which can be in the form of a cadmium sulfide surface. The photocatalyst has particular utility in generating hydrogen from H.sub.2S.

Feasibility study of Tethered Capsule Endomicroscopy (TCE) deployment in the small intestine (Conference Presentation)

Science.gov (United States)

Otuya, David O.; Verma, Yogesh; Dong, Jing; Gora, Michalina J.; Tearney, Guillermo J.

2017-02-01

Environmental enteric dysfunction (EED) is a poorly understood disease of the small intestine that causes nutrient malabsorption in children, predominantly from low and middle income countries. The clinical importance of EED is neurological and growth stunting that remains as the child grows into adulthood. Tethered capsule endomicroscopy (TCE) has the potential to improve the understanding of EED and could be used to determine the effectiveness of EED interventions. TCE in the adult esophagus and the duodenum has been demonstrated for Barrett`s esophagus and celiac disease diagnosis, respectively. While adult subjects can independently swallow these capsules, it is likely that infants will not, and, as a result, new strategies for introducing these devices in young children aged 0.5-2 years need to be investigated. Our first approach will be to introduce the TCE devices in infants under the aid of endoscopic guidance. To determine the most effective method, we have tested endoscopic approaches for introducing TCE devices into the small intestine of living swine. These methods will be compared and contrasted to discuss the most effective means for endoscopic tethered capsule introduction into the small intestine.

Sound propagation in water containing large tethered spherical encapsulated gas bubbles with resonance frequencies in the 50 Hz to 100 Hz range.

Science.gov (United States)

Lee, Kevin M; Hinojosa, Kevin T; Wochner, Mark S; Argo, Theodore F; Wilson, Preston S; Mercier, Richard S

2011-11-01

The efficacy of large tethered encapsulated gas bubbles for the mitigation of low frequency underwater noise was investigated with an acoustic resonator technique. Tethered latex balloons were used as the bubbles, which had radii of approximately 5 cm. Phase speeds were inferred from the resonances of a water and balloon-filled waveguide approximately 1.8 m in length. The Commander and Prosperetti effective-medium model [J. Acoust. Soc. Am. 85, 732-746 (1989)] quantitatively described the observed dispersion from well below to just below the individual bubble resonance frequency, and it qualitatively predicted the frequency range of high attenuation for void fractions between 2% and 5% for collections of stationary balloons within the waveguide. A finite-element model was used to investigate the sensitivity of the waveguide resonance frequencies, and hence the inferred phase speeds, to changes in individual bubble size and position. The results indicate that large tethered encapsulated bubbles could be used mitigate low frequency underwater noise and that the Commander and Prosperetti model would be useful in the design of such a system.

Development of operational models of receptor activation including constitutive receptor activity and their use to determine the efficacy of the chemokine CCL17 at the CC chemokine receptor CCR4.

Science.gov (United States)

Slack, R J; Hall, D A

2012-07-01

BACKGROUND AND PURPOSE The operational model provides a key conceptual framework for the analysis of pharmacological data. However, this model does not include constitutive receptor activity, a frequent phenomenon in modern pharmacology, particularly in recombinant systems. Here, we developed extensions of the operational model which include constitutive activity and applied them to effects of agonists at the chemokine receptor CCR4. EXPERIMENTAL APPROACH The effects of agonists of CCR4 on [(35) S]GTPγS binding to recombinant cell membranes and on the filamentous (F-) actin content of human CD4(+) CCR4(+) T cells were determined. The basal [(35) S]GTPγS binding was changed by varying the GDP concentration whilst the basal F-actin contents of the higher expressing T cell populations were elevated, suggesting constitutive activity of CCR4. Both sets of data were analysed using the mathematical models. RESULTS The affinity of CCL17 (also known as TARC) derived from analysis of the T cell data (pK(a) = 9.61 ± 0.17) was consistent with radioligand binding experiments (9.50 ± 0.11) while that from the [(35) S]GTPγS binding experiments was lower (8.27 ± 0.09). Its intrinsic efficacy differed between the two systems (110 in T cells vs. 11). CONCLUSIONS AND IMPLICATIONS The presence of constitutive receptor activity allows the absolute intrinsic efficacy of agonists to be determined without a contribution from the signal transduction system. Intrinsic efficacy estimated in this way is consistent with Furchgott's definition of this property. CCL17 may have a higher intrinsic efficacy at CCR4 in human T cells than that expressed recombinantly in CHO cells. © 2012 GSK Services Unlimited. British Journal of Pharmacology © 2012 The British Pharmacological Society.

DNA Electrochemistry with Tethered Methylene Blue

Science.gov (United States)

Pheeney, Catrina G.

2012-01-01

Methylene blue (MB′), covalently attached to DNA through a flexible C12 alkyl linker, provides a sensitive redox reporter in DNA electrochemistry measurements. Tethered, intercalated MB′ is reduced through DNA-mediated charge transport; the incorporation of a single base mismatch at position 3, 10, or 14 of a 17-mer causes an attenuation of the signal to 62 ± 3% of the well-matched DNA, irrespective of position in the duplex. The redox signal intensity for MB′–DNA is found to be least 3-fold larger than that of Nile blue (NB)–DNA, indicating that MB′ is even more strongly coupled to the π-stack. The signal attenuation due to an intervening mismatch does, however, depend on DNA film density and the backfilling agent used to passivate the surface. These results highlight two mechanisms for reduction of MB′ on the DNA-modified electrode: reduction mediated by the DNA base pair stack and direct surface reduction of MB′ at the electrode. These two mechanisms are distinguished by their rates of electron transfer that differ by 20-fold. The extent of direct reduction at the surface can be controlled by assembly and buffer conditions. PMID:22512327

DIRECT OBSERVATIONS OF TETHER-CUTTING RECONNECTION DURING A MAJOR SOLAR EVENT FROM 2014 FEBRUARY 24 TO 25

Energy Technology Data Exchange (ETDEWEB)

Chen, Huadong; Zhang, Jun; Yang, Shuhong; Li, Ting [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China); Cheng, Xin [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China); Ma, Suli, E-mail: hdchen@nao.cas.cn [College of Science, China University of Petroleum, Qingdao 266580 (China)

2014-12-20

Using multi-wavelength data from the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory, we investigated two successive solar flares, a C5.1 confined flare and an X4.9 ejective flare with a halo coronal mass ejection, in NOAA active region 11990 from 2014 February 24 to 25. Before the confined flare onset, EUV brightening beneath the filament was detected. As the flare began, a twisted helical flux rope (FR) wrapping around the filament moved upward and then stopped, and in the meantime an obvious X-ray source below it was observed. Prior to the ejective X4.9 flare, some pre-existing loop structures in the active region interacted with each other, which produced a brightening region beneath the filament. Meanwhile, a small flaring loop appeared below the interaction region and some new helical lines connecting the far ends of the loop structures were gradually formed and continually added into the former twisted FR. Then, due to the resulting imbalance between the magnetic pressure and tension, the new FR, together with the filament, erupted outward. Our observations coincide well with a tether-cutting model, suggesting that the two flares probably have the same triggering mechanism, i.e., tether-cutting reconnection. To our knowledge, this is the first direct observation of tether-cutting reconnection occurring between pre-existing loops in an active region. In the ejective flare case, the erupting filament exhibited an Ω-like kinked structure and underwent an exponential rise after a slow-rise phase, indicating that the kink instability might be also responsible for the eruption initiation.

Minimally invasive tethered cord release in children: A technical note

Directory of Open Access Journals (Sweden)

S. Kağan Başarslan

2014-03-01

Full Text Available Tethered cord release is commonly performed in pediatric neurosurgery. Nowadays, minimally invasive procedures are created growing interest due to its highly tolerable nature for surgery. It has been main purpose a minimal damaging on access route and maximum protection of normal structures in surgery. We present a surgical treatment of tethered cord syndrome, by which is provided the cord releasing unlike the many methods being applied with tissue removal. The main advantage of performing this surgery through 2 cm hole is to avoid removing ligamentum flavum and bony structure like lamina in addition to reduce the length of the incision and the related scar tissue. J Clin Exp Invest 2014; 5 (1: 115-117 Technical note: the patient was taken on the operating table in the sitting-prone position, and L5-S1 distance was determined by fluoroscopy. The skin and subcutaneous tissues was passed via a 2 cm vertical incision settled in 0.5 cm laterally from midline. L5-S1 distance and its covering ligamentum flavum are displayed by the guidance of L5 lamina. Williams’s retractor was placed in the distance after fetching microscope. The foregoing procedures are the same with microdiscectomic surgery. By a vertical incision made on the flavum, its both layer was lifted up and hanged with simple suture on the back tissue for a comfortable exposure of the Dura. Thecal sac was opened by 0.5 cm long vertical incision on the Dura after obtaining secure CSF drainage with the help of yellow-tipped syringe needle. With finding by a nerve hook, the phylum was burned and released securely. Then the Dura was sutured primarily for the closure by means of microsurgery instruments, and flavum was laid on it again.

An Unusual Presentation of Adult Tethered Cord Syndrome Associated with Severe Chest and Upper Back Pain

Directory of Open Access Journals (Sweden)

Shotaro Kanda

2015-01-01

Full Text Available Adult tethered cord syndrome (ATCS is a rare entity that usually presents with multiple neurological symptoms, including lower extremity pain, backache, lower extremity muscle weakness, and bowel/bladder disturbances. Prompt surgical treatment is often necessary to avoid permanent sequelae. We report a 63-year-old man with sudden-onset severe right chest and upper back pain, followed by urinary retention. His initial workup included computed tomography of the abdomen and pelvis, which showed a presacral mass. His symptom-driven neurological workup focused on the cervical and thoracic spine, the results of which were normal. Pelvic radiographs and magnetic resonance imaging of the lumbosacral spine showed spina bifida occulta, meningocele, and presacral masses consistent with a teratomatous tumor. His symptoms, except for urinary retention, improved dramatically with surgical treatment. The excised specimen contained a teratomatous lesion plus an organized hematoma. Hematoma formation was suspected as the trigger of his sudden-onset right chest and upper back pain.

Phosphate Tether-Mediated Ring-Closing Metathesis for the Generation of P-Stereogenic, Z-Configured Bicyclo[7.3.1]- and Bicyclo[8.3.1]phosphates.

Science.gov (United States)

Markley, Jana L; Maitra, Soma; Hanson, Paul R

2016-02-05

A phosphate tether-mediated ring-closing metathesis (RCM) study to the synthesis of Z-configured, P-stereogenic bicyclo[7.3.1]- and bicyclo[8.3.1]phosphates is reported. Investigations suggest that C3-substitution, olefin substitution, and proximity of the forming olefin to the bridgehead carbon of the bicyclic affect the efficiency and stereochemical outcome of the RCM event. This study demonstrates the utility of phosphate tether-mediated desymmetrization of C2-symmetric, 1,3-anti-diol-containing dienes in the generation of macrocyclic phosphates with potential synthetic and biological utility.

ARM Tethered Balloon System & AALCO Activities at AMF3 Site at Oliktok Point, AK

Science.gov (United States)

Hardesty, J.; Dexheimer, D.; Mei, F.; Roesler, E. L.; Longbottom, C.; Hillman, B. R.

2017-12-01

Sandia National Laboratories (SNL) has operated the Atmospheric Radiation Measurement program's (ARM) third ARM Mobile Facility (AMF3) and the restricted airspace associated with it at Oliktok Point, Alaska, since October 2013. The site hosts ground-based instrumentation which collects a variety of continuous atmospheric measurements as well as user-conducted unmanned aircraft and tethered balloon campaigns. SNL has operated ARM's tethered balloon system (TBS) as part of the Inaugural Campaigns for ARM Research using Unmanned Systems (ICARUS) since 2016. AALCO (Aerial Assessment of Liquid in Clouds at Oliktok), is an ARM Intensive Operations Period conducted by SNL at the AMF3 since 2016. The operation of the TBS during ICARUS and AALCO to altitudes above 4,000' AGL in a variety of seasons and conditions is addressed. A Distributed Temperature Sensing (DTS) system and supercooled liquid water content (SLWC) sensors have been deployed under both campaigns. The performance of these sensors is discussed and results are presented. DTS measurements and their relationship to concurrent temperature measurements from unmanned aircraft and radiosondes are shown. SLWC sensor in situ measurements are compared with microwave radiometer and radiosonde-derived measurements. Preliminary analysis of using Large Eddy Simulations to compare with the SLWC measurements reveals three-dimensional properties of the observed clouds.

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

International Nuclear Information System (INIS)

Abu-Hamdah, Rania; Cho, Won Jin; Hoerber, J.K.H.; Jena, Bhanu P.

2006-01-01

It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 μm in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles

Secretory vesicles in live cells are not free-floating but tethered to filamentous structures: A study using photonic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Abu-Hamdah, Rania [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Cho, Won Jin [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States); Hoerber, J.K.H. [Department of Physics, University of Bristol, Bristol BS8 1TD (United Kingdom); Jena, Bhanu P. [Department of Physiology, Wayne State University School of Medicine, 5245 Scott Hall, 540 E. Canfield, Detroit, MI 48201 (United States)]. E-mail: bjena@med.wayne.edu

2006-06-15

It is well established that actin and microtubule cytoskeletal systems are involved in organelle transport and membrane trafficking in cells. This is also true for the transport of secretory vesicles in neuroendocrine cells and neurons. It was however unclear whether secretory vesicles remain free-floating, only to associate with such cytoskeletal systems when needing transport. This hypothesis was tested using live pancreatic acinar cells in physiological buffer solutions, using the photonic force microscope (PFM). When membrane-bound secretory vesicles (0.2-1.2 {mu}m in diameter) in live pancreatic acinar cells were trapped at the laser focus of the PFM and pulled, they were all found tethered to filamentous structures. Mild exposure of cells to nocodazole and cytochalasin B, disrupts the tether. Immunoblot analysis of isolated secretory vesicles, further demonstrated the association of actin, myosin V, and kinesin. These studies demonstrate for the first time that secretory vesicles in live pancreatic acinar cells are tethered and not free-floating, suggesting that following vesicle biogenesis, they are placed on their own railroad track, ready to be transported to their final destination within the cell when required. This makes sense, since precision and regulation are the hallmarks of all cellular process, and therefore would hold true for the transport and localization of subcellular organelles such as secretory vesicles.

Turbulence fluxes and variances measured with a sonic anemometer mounted on a tethered balloon

OpenAIRE

Canut, Guylaine; Couvreux, Fleur; Lothon, Marie; Legain, Dominique; Piguet, Bruno; Lampert, Astrid; Maurel, William; Moulin, Eric

2016-01-01

This study presents the first deployment in field campaigns of a balloon-borne turbulence probe, developed with a sonic anemometer and an inertial motion sensor suspended below a tethered balloon. This system measures temperature and horizontal and vertical wind at high frequency and allows the estimation of heat and momentum fluxes as well as turbulent kinetic energy in the lower part of the boundary layer. The system was validated during three field experiments with differ...

Ozone profiles from tethered balloon measurements in an urban plume experiment

Science.gov (United States)

Youngbluth, O., Jr.; Storey, R. W.; Clendenin, C. G.; Jones, S.; Leighty, B.

1981-01-01

NASA Langley Research Center used two tethered balloon systems to measure ozone in the general area of Norfolk, Va. The large balloon system which has an altitude range of 1,500 meters was located at Wallops Island, Va., and the smaller balloon which has an altitude range of 900 meters was located at Chesapeake, Va. Each balloon system measured ozone, temperature, humidity, wind speed, and wind direction from ground to its maximum altitude. From these measurements and from the location of the balloon sites, areas of ozone generation and ozone transport may be inferred. The measurements which were taken during August 1979 are discussed as well as the measurement techniques.

Observer enhanced control for spin-stabilized tethered formation in earth orbit

Science.gov (United States)

Guang, Zhai; Yuyang, Li; Liang, Bin

2018-04-01

This paper addresses the issues relevant to control of spin-stabilized tethered formation in circular orbit. Due to the dynamic complexities and nonlinear perturbations, it is challenging to promote the control precision for the formation deployment and maintenance. In this work, the formation dynamics are derived with considering the spinning rate of the central body, then major attention is dedicated to develop the nonlinear disturbance observer. To achieve better control performance, the observer-enhanced controller is designed by incorporating the disturbance observer into the control loop, benefits from the disturbance compensation are demonstrated, and also, the dependences of the disturbance observer performance on some important parameters are theoretically and numerically analyzed.

Physisorbed Polymer-Tethered Lipid Bilayer with Lipopolymer Gradient

Directory of Open Access Journals (Sweden)

Christoph A. Naumann

2012-11-01

Full Text Available Physisorbed polymer-tethered lipid bilayers consisting of phospholipids and lipopolymers represent an attractive planar model membrane platform, in which bilayer fluidity and membrane elastic properties can be regulated through lipopolymer molar concentration. Herein we report a method for the fabrication of such a planar model membrane system with a lateral gradient of lipopolymer density. In addition, a procedure is described, which leads to a sharp boundary between regions of low and high lipopolymer molar concentrations. Resulting gradients and sharp boundaries are visualized on the basis of membrane buckling structures at elevated lipopolymer concentrations using epifluorescence microscopy and atomic force microscopy. Furthermore, results from spot photobleaching experiments are presented, which provide insight into the lipid lateral fluidity in these model membrane architectures. The presented experimental data highlight a planar, solid-supported membrane characterized by fascinating length scale-dependent dynamics and elastic properties with remarkable parallels to those observed in cellular membranes.

Development of Tethered Hsp90 Inhibitors Carrying Radioiodinated Probes to Specifically Discriminate and Kill Malignant Breast Tumor Cells

Science.gov (United States)

2017-05-01

ligand localization . These molecules will be tested as imaging agents in mouse models of breast cancer. 15. SUBJECT TERMS Radiodination, tethered...annually leading to the diagnosis and surgical resection of breast cancer or breast carcinoma in situ in over 250,000 women respectively. Unfortunately

Polyamidoamine (PAMAM) Dendrimer Conjugates of Clickable Agonists of the A3 Adenosine Receptor and Coactivation of the P2Y14 Receptor by a Tethered Nucleotide

Energy Technology Data Exchange (ETDEWEB)

Tosh, Dilip, K. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Yoo, Lena S. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Chinn, Moshe [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Hong, Kunlun [ORNL; Kilbey, II, S Michael [ORNL; Barrett, Matthew O. [University of North Carolina School of Medicine; Fricks, Ingrid P. [University of North Carolina School of Medicine; Harden, T. Kendall [University of North Carolina School of Medicine; Jacobson, Kenneth A. [National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health

2010-01-01

We previously synthesized a series of potent and selective A{sub 3} adenosine receptor (AR) agonists (North-methanocarba nucleoside 5{prime}-uronamides) containing dialkyne groups on extended adenine C2 substituents. We coupled the distal alkyne of a 2-octadiynyl nucleoside by Cu(I)-catalyzed 'click' chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. A{sub 3}AR activation was preserved in these multivalent conjugates, which bound with apparent Ki of 0.1-0.3 nM. They were substituted with nucleoside moieties, solely or in combination with water-solubilizing carboxylic acid groups derived from hexynoic acid. A comparison with various amide-linked dendrimers showed that triazole-linked conjugates displayed selectivity and enhanced A{sub 3}AR affinity. We prepared a PAMAM dendrimer containing equiproportioned peripheral azido and amino groups for conjugation of multiple ligands. A bifunctional conjugate activated both A{sub 3} and P2Y{sub 14} receptors (via amide-linked uridine-5{prime}-diphosphoglucuronic acid), with selectivity in comparison to other ARs and P2Y receptors. This is the first example of targeting two different GPCRs with the same dendrimer conjugate, which is intended for activation of heteromeric GPCR aggregates. Synergistic effects of activating multiple GPCRs with a single dendrimer conjugate might be useful in disease treatment.

International survey on the management of skin stigmata and suspected tethered cord.

Science.gov (United States)

Ponger, Penina; Ben-Sira, Liat; Beni-Adani, Liana; Steinbok, Paul; Constantini, Shlomi

2010-12-01

We designed a survey to investigate current international management trends of neonates with lumbar midline skin stigmata suspicious of tethered cord, among pediatric neurosurgeons, focusing on the lower risk stigmata, simple dimples, deviated gluteal folds, and discolorations. Our findings will enable physicians to assess their current diagnosis routine and aid in clarifying management controversies. A questionnaire on the proposed diagnostic evaluation of seven case reports, each accompanied by relevant imaging, was distributed by e-mail to members of the International Society for Pediatric Neurosurgery, the European Society for Pediatric Neurosurgery, and via the PEDS server list between March and August 2008. Sixty-two questionnaires, completed by experienced professionals with a rather uniform distribution of experience levels, were analyzed. Forty-eight percent do not recommend any imaging of simple dimples, 30% recommend US screening and 22% recommend MR. Seventy-nine percent recommend imaging of deviated gluteal fold with 30% recommending MR. Ninety-two percent recommend imaging infants with hemangiomas with 74% recommending MR. MR for sinus tracts is recommended by 90% if sacral and by 98% if lumber. Eighty-four percent recommend MR for filar cyst. Our survey demonstrates that management of low-risk skin stigmata, simple dimple, deviated gluteal fold, and discolorations lacks consensus. In addition, a significant sector of the professional community proposes a work-up of simple dimples, sacral tracts, and filar cysts that contradicts established recommendations. A simple classification system is needed to attain a better approach, enabling correct diagnosis of tethered cord without exposing neonates to unnecessary examinations.

Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation

Directory of Open Access Journals (Sweden)

Papa Maria

2011-01-01

Full Text Available Abstract Background Estrogen receptors alpha (ERα and beta (ERβ are transcription factors (TFs that mediate estrogen signaling and define the hormone-responsive phenotype of breast cancer (BC. The two receptors can be found co-expressed and play specific, often opposite, roles, with ERβ being able to modulate the effects of ERα on gene transcription and cell proliferation. ERβ is frequently lost in BC, where its presence generally correlates with a better prognosis of the disease. The identification of the genomic targets of ERβ in hormone-responsive BC cells is thus a critical step to elucidate the roles of this receptor in estrogen signaling and tumor cell biology. Results Expression of full-length ERβ in hormone-responsive, ERα-positive MCF-7 cells resulted in a marked reduction in cell proliferation in response to estrogen and marked effects on the cell transcriptome. By ChIP-Seq we identified 9702 ERβ and 6024 ERα binding sites in estrogen-stimulated cells, comprising sites occupied by either ERβ, ERα or both ER subtypes. A search for TF binding matrices revealed that the majority of the binding sites identified comprise one or more Estrogen Response Element and the remaining show binding matrixes for other TFs known to mediate ER interaction with chromatin by tethering, including AP2, E2F and SP1. Of 921 genes differentially regulated by estrogen in ERβ+ vs ERβ- cells, 424 showed one or more ERβ site within 10 kb. These putative primary ERβ target genes control cell proliferation, death, differentiation, motility and adhesion, signal transduction and transcription, key cellular processes that might explain the biological and clinical phenotype of tumors expressing this ER subtype. ERβ binding in close proximity of several miRNA genes and in the mitochondrial genome, suggests the possible involvement of this receptor in small non-coding RNA biogenesis and mitochondrial genome functions. Conclusions Results indicate that the

Scientific Infrastructure To Support Manned And Unmanned Aircraft, Tethered Balloons, And Related Aerial Activities At Doe Arm Facilities On The North Slope Of Alaska

Science.gov (United States)

Ivey, M.; Dexheimer, D.; Hardesty, J.; Lucero, D. A.; Helsel, F.

2015-12-01

The U.S. Department of Energy (DOE), through its scientific user facility, the Atmospheric Radiation Measurement (ARM) facilities, provides scientific infrastructure and data to the international Arctic research community via its research sites located on the North Slope of Alaska. DOE has recently invested in improvements to facilities and infrastructure to support operations of unmanned aerial systems for science missions in the Arctic and North Slope of Alaska. A new ground facility, the Third ARM Mobile Facility, was installed at Oliktok Point Alaska in 2013. Tethered instrumented balloons were used to make measurements of clouds in the boundary layer including mixed-phase clouds. A new Special Use Airspace was granted to DOE in 2015 to support science missions in international airspace in the Arctic. Warning Area W-220 is managed by Sandia National Laboratories for DOE Office of Science/BER. W-220 was successfully used for the first time in July 2015 in conjunction with Restricted Area R-2204 and a connecting Altitude Reservation Corridor (ALTRV) to permit unmanned aircraft to operate north of Oliktok Point. Small unmanned aircraft (DataHawks) and tethered balloons were flown at Oliktok during the summer and fall of 2015. This poster will discuss how principal investigators may apply for use of these Special Use Airspaces, acquire data from the Third ARM Mobile Facility, or bring their own instrumentation for deployment at Oliktok Point, Alaska. The printed poster will include the standard DOE funding statement.

Low work-function thermionic emission and orbital-motion-limited ion collection at bare-tether cathodic contact

Energy Technology Data Exchange (ETDEWEB)

Chen, Xin, E-mail: xin.chen@upm.es; Sanmartín, J. R., E-mail: juanr.sanmartin@upm.es [Departamento de Física Aplicada, Escuela Técnica Superior de Ingeniería Aeronáutica y del Espacio, Universidad Politécnica de Madrid, Plaza Cardenal Cisneros, 3, 28040 Madrid (Spain)

2015-05-15

With a thin coating of low-work-function material, thermionic emission in the cathodic segment of bare tethers might be much greater than orbital-motion-limited (OML) ion collection current. The space charge of the emitted electrons decreases the electric field that accelerates them outwards, and could even reverse it for high enough emission, producing a potential hollow. In this work, at the conditions of high bias and relatively low emission that make the potential monotonic, an asymptotic analysis is carried out, extending the OML ion-collection analysis to investigate the probe response due to electrons emitted by the negatively biased cylindrical probe. At given emission, the space charge effect from emitted electrons increases with decreasing magnitude of negative probe bias. Although emitted electrons present negligible space charge far away from the probe, their effect cannot be neglected in the global analysis for the sheath structure and two thin layers in between sheath and the quasineutral region. The space-charge-limited condition is located. It is found that thermionic emission increases the range of probe radius for OML validity and is greatly more effective than ion collection for cathodic contact of tethers.

Macrophage receptor with collagenous structure (MARCO) is a dynamic adhesive molecule that enhances uptake of carbon nanotubes by CHO-K1 Cells

Energy Technology Data Exchange (ETDEWEB)

Hirano, Seishiro, E-mail: seishiro@nies.go.jp [Environmental Nanotoxicology Project, RCER, National Institute for Environmental Studies (Japan); Fujitani, Yuji; Furuyama, Akiko [Environmental Nanotoxicology Project, RCER, National Institute for Environmental Studies (Japan); Kanno, Sanae [Department of Legal Medicine, St. Marianna School of Medicine (Japan)

2012-02-15

The toxicity of carbon nanotubes (CNTs), a highly promising nanomaterial, is similar to that of asbestos because both types of particles have a fibrous shape and are biopersistent. Here, we investigated the characteristics of macrophage receptor with collagenous structure (MARCO), a membrane receptor expressed on macrophages that recognizes environmental or unopsonized particles, and we assessed whether and how MARCO was involved in cellular uptake of multi-walled CNTs (MWCNTs). MARCO-transfected Chinese hamster ovary (CHO-K1) cells took up polystyrene beads irrespective of the particle size (20 nm–1 μm). In the culture of MARCO-transfected CHO-K1 cells dendritic structures were observed on the bottom of culture dishes, and the edges of these dendritic structures were continually renewed as the cell body migrated along the dendritic structures. MWCNTs were first tethered to the dendritic structures and then taken up by the cell body. MWCNTs appeared to be taken up via membrane ruffling like macropinocytosis, rather than phagocytosis. The cytotoxic EC{sub 50} value of MWCNTs in MARCO-transfected CHO-K1 cells was calculated to be 6.1 μg/mL and transmission electron microscopic observation indicated that the toxicity of MWCNTs may be due to the incomplete inclusion of MWCNTs by the membrane structure. -- Highlights: ►Carbon nanotubes (CNTs) were tethered to MARCO in vitro. ►CNTs were taken up rapidly into the cell body via MARCO by membrane ruffling. ►The incomplete inclusion of CNTs by membranes caused cytotoxicity.

Circular Orbit Target Capture Using Space Tether-Net System

Directory of Open Access Journals (Sweden)

Guang Zhai

2013-01-01

Full Text Available The space tether-net system for on-orbit capture is proposed in this paper. In order to research the dynamic behaviors during system deployment, both free and nonfree deployment dynamics in circular orbit are developed; the system motion with respect to Local Vertical and Local Horizontal frame is also researched with analysis and simulation. The results show that in the case of free deployment, the capture net follows curve trajectories due to the relative orbit dynamic perturbation, and the initial deployment velocities are planned by state transformation equations for static and floating target captures; in the case of non-free deployment, the system undergoes an altitude libration along the Local Vertical, and the analytical solutions that describe the attitude libration are obtained by using variable separation and integration. Finally, the dynamics of postdeployment system is also proved marginally stable if the critical initial conditions are satisfied.

Fluorosilicone multi-block copolymers tethering quaternary ammonium salt groups for antimicrobial purpose

Energy Technology Data Exchange (ETDEWEB)

Zhou, Fang; Qin, Xiaoshuai; Li, Yancai; Ren, Lixia; Zhao, Yunhui, E-mail: zhaoyunhui@tju.edu.cn; Yuan, Xiaoyan

2015-08-30

Highlights: • QAS-containing fluorosilicone multi-block copolymers were synthesized. • The block length of PHFBMA in the copolymers was tailored via RAFT polymerization. • Surface roughness of the copolymers decreased with the increased PHFBMA content. • A certain length of PHFBMA block enhanced C−N{sup +} percentage on the surface. - Abstract: Symmetrically structured fluorosilicone multi-block copolymers containing poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(hexafluorobutyl methacrylate) (PHFBMA) were sequentially synthesized via reversible addition–fragmentation chain transfer polymerization, using a polydimethylsiloxane (PDMS) chain transfer agent with dithiocarbonate groups at both ends. Then, the CBABC-type block copolymers were quaternized with n-octyliodide to tether quaternary ammonium salt (QAS) groups in the PDMAEMA blocks for the antimicrobial use. The obtained fluorosilicone copolymers showed clear variations in the C-N{sup +} composition and surface morphology on their films depending on the content of the PHFBMA blocks, which were characterized by X-ray photoelectron spectroscopy and atomic force microscopy, respectively. The results indicated that the symmetrical CBABC structure favored PDMS and QAS tethered blocks migrating to the film surface. With the mass percentage of the PHFBMA increased from 0 to 32.5%, the surface roughness of the copolymer film decreased gradually with a tendency to form a smooth surface. Owing to the surface properties, fluorosilicone multi-block copolymers containing a certain amount of PHFBMA with higher C-N{sup +} content and relatively smooth morphology demonstrated obvious antimicrobial activity against Gram-positive bacteria, Bacillus subtilis and Gram-negative bacteria, Escherichia coli. The functionalized multi-block copolymers based on fluorosilicone and QAS groups would have potential applications in antimicrobial coatings.

Fluorosilicone multi-block copolymers tethering quaternary ammonium salt groups for antimicrobial purpose

International Nuclear Information System (INIS)

Zhou, Fang; Qin, Xiaoshuai; Li, Yancai; Ren, Lixia; Zhao, Yunhui; Yuan, Xiaoyan

2015-01-01

Highlights: • QAS-containing fluorosilicone multi-block copolymers were synthesized. • The block length of PHFBMA in the copolymers was tailored via RAFT polymerization. • Surface roughness of the copolymers decreased with the increased PHFBMA content. • A certain length of PHFBMA block enhanced C−N + percentage on the surface. - Abstract: Symmetrically structured fluorosilicone multi-block copolymers containing poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(hexafluorobutyl methacrylate) (PHFBMA) were sequentially synthesized via reversible addition–fragmentation chain transfer polymerization, using a polydimethylsiloxane (PDMS) chain transfer agent with dithiocarbonate groups at both ends. Then, the CBABC-type block copolymers were quaternized with n-octyliodide to tether quaternary ammonium salt (QAS) groups in the PDMAEMA blocks for the antimicrobial use. The obtained fluorosilicone copolymers showed clear variations in the C-N + composition and surface morphology on their films depending on the content of the PHFBMA blocks, which were characterized by X-ray photoelectron spectroscopy and atomic force microscopy, respectively. The results indicated that the symmetrical CBABC structure favored PDMS and QAS tethered blocks migrating to the film surface. With the mass percentage of the PHFBMA increased from 0 to 32.5%, the surface roughness of the copolymer film decreased gradually with a tendency to form a smooth surface. Owing to the surface properties, fluorosilicone multi-block copolymers containing a certain amount of PHFBMA with higher C-N + content and relatively smooth morphology demonstrated obvious antimicrobial activity against Gram-positive bacteria, Bacillus subtilis and Gram-negative bacteria, Escherichia coli. The functionalized multi-block copolymers based on fluorosilicone and QAS groups would have potential applications in antimicrobial coatings

Inhibition of Wnt/β-catenin signaling by a soluble collagen-derived frizzled domain interacting with Wnt3a and the receptors frizzled 1 and 8.

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Ismaïl Hendaoui

Full Text Available The Wnt/β-catenin pathway controls cell proliferation, death and differentiation. Several families of extracellular proteins can antagonize Wnt/β-catenin signaling, including the decoy receptors known as secreted frizzled related proteins (SFRPs, which have a cysteine-rich domain (CRD structurally similar to the extracellular Wnt-binding domain of the frizzled receptors. SFRPs inhibit Wnt signaling by sequestering Wnts through the CRD or by forming inactive complexes with the frizzled receptors. Other endogenous molecules carrying frizzled CRDs inhibit Wnt signaling, such as V3Nter, which is proteolytically derived from the cell surface component collagen XVIII and contains a biologically active frizzled domain (FZC18 inhibiting in vivo cell proliferation and tumor growth in mice. We recently showed that FZC18 expressing cells deliver short-range signals to neighboring cells, decreasing their proliferation in vitro and in vivo through the Wnt/β-catenin signaling pathway. Here, using low concentrations of soluble FZC18 and Wnt3a, we show that they physically interact in a cell-free system. In addition, soluble FZC18 binds the frizzled 1 and 8 receptors' CRDs, reducing cell sensitivity to Wnt3a. Conversely, inhibition of Wnt/β-catenin signaling was partially rescued by the expression of full-length frizzled 1 and 8 receptors, but enhanced by the expression of a chimeric cell-membrane-tethered frizzled 8 CRD. Moreover, soluble, partially purified recombinant FZC18_CRD inhibited Wnt3a-induced β-catenin activation. Taken together, the data indicate that collagen XVIII-derived frizzled CRD shifts Wnt sensitivity of normal cells to a lower pitch and controls their growth.

Multiple Hydrogen Bond Tethers for Grazing Formic Acid in Its Complexes with Phenylacetylene.

Science.gov (United States)

Karir, Ginny; Kumar, Gaurav; Kar, Bishnu Prasad; Viswanathan, K S

2018-03-01

Complexes of phenylacetylene (PhAc) and formic acid (FA) present an interesting picture, where the two submolecules are tethered, sometimes multiply, by hydrogen bonds. The multiple tentacles adopted by PhAc-FA complexes stem from the fact that both submolecules can, in the same complex, serve as proton acceptors and/or proton donors. The acetylenic and phenyl π systems of PhAc can serve as proton acceptors, while the ≡C-H or -C-H of the phenyl ring can act as a proton donor. Likewise, FA also is amphiprotic. Hence, more than 10 hydrogen-bonded structures, involving O-H···π, C-H···π, and C-H···O contacts, were indicated by our computations, some with multiple tentacles. Interestingly, despite the multiple contacts in the complexes, the barrier between some of the structures is small, and hence, FA grazes around PhAc, even while being tethered to it, with hydrogen bonds. We used matrix isolation infrared spectroscopy to experimentally study the PhAc-FA complexes, with which we located global and a few local minima, involving primarily an O-H···π interaction. Experiments were corroborated by ab initio computations, which were performed using MP2 and M06-2X methods, with 6-311++G (d,p) and aug-cc-pVDZ basis sets. Single-point energy calculations were also done at MP2/CBS and CCSD(T)/CBS levels. The nature, strength, and origin of these noncovalent interactions were studied using AIM, NBO, and LMO-EDA analysis.

Optimizing fluorescently tethered Hsp90 inhibitor dose for maximal specific uptake by breast tumors

Science.gov (United States)

Crouch, Brian T.; Duer, Joy; Wang, Roujia; Gallagher, Jennifer; Hall, Allison; Soo, Mary Scott; Hughes, Philip; Haystead, Timothy A. J.; Ramanujam, Nirmala

2018-03-01

Despite improvements in surgical resection, 20-40% of patients undergoing breast conserving surgery require at least one additional re-excision. Leveraging the unique surface expression of heat shock protein 90 (Hsp90), a chaperone protein involved in several key hallmarks of cancer, in breast cancer provides an exciting opportunity to identify residual disease during surgery. We developed a completely non-destructive strategy using HS-27, a fluorescently-tethered Hsp90 inhibitor, to assay surface Hsp90 expression on intact tissue specimens using a fluorescence microendoscope with a field of view of 750 μm and subcellular resolution of 4 μm. HS-27 consists of an FDA approved Hsp90 inhibitor tethered to fluorescein isothiocyanate (EX 488nm, EM 525nm). Here, we optimized ex vivo HS-27 administration in pre-clinical breast cancer models and validated our approach on 21 patients undergoing standard of care ultrasound guided core needle biopsy. HS-27 administration time was fixed at 1- minute to minimize imaging impact on clinical workflow. HS-27 and HS-217 (non-specific control) doses were modulated from 1 μM up to 100 μM to identify the dose maximizing the ratio of specific uptake (HS-27 fluorescence) to non-specific uptake (HS-217 fluorescence). The specificity ratio was maximized at 100 μM and was significantly greater than all other doses (pcancer makes this technology attractive for assessing tumor margins, as one agent can be used for all subtypes.

Characterization of a sol-gel-entrapped artificial receptor

Science.gov (United States)

Dunbar, Richard A.; Narang, Upvan; Prasad, Paras N.; Bright, Frank V.

1993-04-01

We report on the development, characterization, and photophysics of a new fiber-optic-based sensor which uses a sol-gel entrapped recognition element. The recognition element is modified (beta) -cyclodextrin to which we have added a short tether (glycine) and a fluorophore (dansyl). This recognition element forms an intramolecular complex, and the dansyl group can include within the cyclodextrin cavity. Non-fluorescent analytes, that bind to the cyclodextrin cavity, can effectively displace the included dansyl group and result in a measurable change in signal. We report on the detection limits, dynamic range, and photophysics (i.e., transduction mechanism) of this new sensor.

Relative Contribution of Arms and Legs in 30 s Fully Tethered Front Crawl Swimming

Directory of Open Access Journals (Sweden)

Pedro G. Morouço

2015-01-01

Full Text Available The relative contribution of arm stroke and leg kicking to maximal fully tethered front crawl swimming performance remains to be solved. Twenty-three national level young swimmers (12 male and 11 female randomly performed 3 bouts of 30 s fully tethered swimming (using the whole body, only the arm stroke, and only the leg kicking. A load-cell system permitted the continuous measurement of the exerted forces, and swimming velocity was calculated from the time taken to complete a 50 m front crawl swim. As expected, with no restrictions swimmers were able to exert higher forces than that using only their arm stroke or leg kicking. Estimated relative contributions of arm stroke and leg kicking were 70.3% versus 29.7% for males and 66.6% versus 33.4% for females, with 15.6% and 13.1% force deficits, respectively. To obtain higher velocities, male swimmers are highly dependent on the maximum forces they can exert with the arm stroke (r=0.77, P<0.01, whereas female swimmers swimming velocity is more related to whole-body mean forces (r=0.81, P<0.01. The obtained results point that leg kicking plays an important role over short duration high intensity bouts and that the used methodology may be useful to identify strength and/or coordination flaws.

Experimental and analytical determination of stability parameters for a balloon tethered in a wind

Science.gov (United States)

Redd, L. T.; Bennett, R. M.; Bland, S. R.

1973-01-01

Experimental and analytical techniques for determining stability parameters for a balloon tethered in a steady wind are described. These techniques are applied to a particular 7.64-meter-long balloon, and the results are presented. The stability parameters of interest appear as coefficients in linearized stability equations and are derived from the various forces and moments acting on the balloon. In several cases the results from the experimental and analytical techniques are compared and suggestions are given as to which techniques are the most practical means of determining values for the stability parameters.

Turbulence fluxes and variances measured with a sonic anemometer mounted on a tethered balloon

Science.gov (United States)

Canut, Guylaine; Couvreux, Fleur; Lothon, Marie; Legain, Dominique; Piguet, Bruno; Lampert, Astrid; Maurel, William; Moulin, Eric

2016-09-01

This study presents the first deployment in field campaigns of a balloon-borne turbulence probe, developed with a sonic anemometer and an inertial motion sensor suspended below a tethered balloon. This system measures temperature and horizontal and vertical wind at high frequency and allows the estimation of heat and momentum fluxes as well as turbulent kinetic energy in the lower part of the boundary layer. The system was validated during three field experiments with different convective boundary-layer conditions, based on turbulent measurements from instrumented towers and aircraft.

Optimization of motion control laws for tether crawler or elevator systems

Science.gov (United States)

Swenson, Frank R.; Von Tiesenhausen, Georg

1988-01-01

Based on the proposal of a motion control law by Lorenzini (1987), a method is developed for optimizing motion control laws for tether crawler or elevator systems in terms of the performance measures of travel time, the smoothness of acceleration and deceleration, and the maximum values of velocity and acceleration. The Lorenzini motion control law, based on powers of the hyperbolic tangent function, is modified by the addition of a constant-velocity section, and this modified function is then optimized by parameter selections to minimize the peak acceleration value for a selected travel time or to minimize travel time for the selected peak values of velocity and acceleration. It is shown that the addition of a constant-velocity segment permits further optimization of the motion control law performance.

Sponges with covalently tethered amines for high-efficiency carbon capture

KAUST Repository

Qi, Genggeng

2014-12-12

© 2014 Macmillan Publishers Limited. All rights reserved. Adsorption using solid amine sorbents is an attractive emerging technology for energy-efficient carbon capture. Current syntheses for solid amine sorbents mainly based on physical impregnation or grafting-to methods (for example, aminosilane-grafting) lead to limited sorbent performance in terms of stability and working capacity, respectively. Here we report a family of solid amine sorbents using a grafting-from synthesis approach and synthesized by cationic polymerization of oxazolines on mesoporous silica. The sorbent with high amount of covalently tethered amines shows fast adsorption rate, high amine efficiency and sorbent capacity well exceeding the highest value reported to date for lowerature carbon dioxide sorbents under simulated flue gas conditions. The demonstrated efficiency of the new amine-immobilization chemistry may open up new avenues in the development of advanced carbon dioxide sorbents, as well as other nitrogen-functionalized systems.

Purification and crystallization of mono-ubiquitylated ubiquitin receptor Rpn10

International Nuclear Information System (INIS)

Keren-Kaplan, Tal; Prag, Gali

2012-01-01

A novel reconstitution system for the modification and purification of ubiquitylated proteins yielded the first diffracting crystals of a ubiquitylated substrate, namely Rpn10. Protein ubiquitylation controls nearly all cellular pathways in eukaryotes. A repertoire of proteins named ubiquitin (Ub) receptors harbouring ubiquitin-binding domains (UBDs) recognize ubiquitylated proteins. These Ub receptors decode the Ub signal by tethering a UBD or UBDs to a functional domain or domains, thus linking the ubiquitylated target to a specific function. The rapid dynamics of ubiquitylation/deubiquitylation has impeded the characterization of ubiquitylated proteins. To bypass this obstacle, a recently developed synthetic system that reconstructs the entire eukaryotic ubiquitylation cascade in Escherichia coli was used to purify the mono-ubiquitylated form of the regulatory proteasomal non-ATPase subunit (Ub-Rpn10) from Saccharomyces cerevisiae. Here, the first crystallization and data collection of Ub-Rpn10 is reported. Purified Ub-Rpn10 was crystallized in 12%(w/v) PEG 20 000, 0.1 M MES pH 6.5 and yielded thin rhombus-shaped crystals. X-ray analysis revealed that these crystals belonged to the monoclinic system C2, with unit-cell parameters a = 107.3, b = 49.7, c = 81.3 Å, α = γ = 90.0, β = 130.5°. A full synchrotron data set has been collected, merged and scaled with a diffraction limit of 3.14 Å

Density functional study of a typical thiol tethered on a gold surface: ruptures under normal or parallel stretch

International Nuclear Information System (INIS)

Wang, Guan M; Sandberg, William C; Kenny, Steven D

2006-01-01

The mechanical and dynamical properties of a model Au(111)/thiol surface system were investigated by using localized atomic-type orbital density functional theory in the local density approximation. Relaxing the system gives a configuration where the sulfur atom forms covalent bonds to two adjacent gold atoms as the lowest energy structure. Investigations based on ab initio molecular dynamics simulations at 300, 350 and 370 K show that this tethering system is stable. The rupture behaviour between the thiol and the surface was studied by displacing the free end of the thiol. Calculated energy profiles show a process of multiple successive ruptures that account for experimental observations. The process features successive ruptures of the two Au-S bonds followed by the extraction of one S-bonded Au atom from the surface. The force required to rupture the thiol from the surface was found to be dependent on the direction in which the thiol was displaced, with values comparable with AFM measurements. These results aid the understanding of failure dynamics of Au(111)-thiol-tethered biosurfaces in microfluidic devices where fluidic shear and normal forces are of concern

Proposed tethered unmanned aerial system for the detection of pollution entering the Chesapeake Bay area

Science.gov (United States)

Goodman, J.; McKay, J.; Evans, W.; Gadsden, S. Andrew

2016-05-01

This paper is based on a proposed unmanned aerial system platform that is to be outfitted with high-resolution sensors. The proposed system is to be tethered to a moveable ground station, which may be a research vessel or some form of ground vehicle (e.g., car, truck, or rover). The sensors include, at a minimum: camera, infrared sensor, thermal, normalized difference vegetation index (NDVI) camera, global positioning system (GPS), and a light-based radar (LIDAR). The purpose of this paper is to provide an overview of existing methods for pollution detection of failing septic systems, and to introduce the proposed system. Future work will look at the high-resolution data from the sensors and integrating the data through a process called information fusion. Typically, this process is done using the popular and well-published Kalman filter (or its nonlinear formulations, such as the extended Kalman filter). However, future work will look at using a new type of strategy based on variable structure estimation for the information fusion portion of the data processing. It is hypothesized that fusing data from the thermal and NDVI sensors will be more accurate and reliable for a multitude of applications, including the detection of pollution entering the Chesapeake Bay area.

3-D acoustic waveform simulation and inversion supplemented by infrasound sensors on a tethered weather balloon at Yasur Volcano, Vanuatu

Science.gov (United States)

Iezzi, A. M.; Fee, D.; Matoza, R. S.; Jolly, A. D.; Kim, K.; Christenson, B. W.; Johnson, R.; Kilgour, G.; Garaebiti, E.; Austin, A.; Kennedy, B.; Fitzgerald, R.; Gomez, C.; Key, N.

2017-12-01

Well-constrained acoustic waveform inversion can provide robust estimates of erupted volume and mass flux, increasing our ability to monitor volcanic emissions (potentially in real-time). Previous studies have made assumptions about the multipole source mechanism, which can be represented as the combination of pressure fluctuations from a volume change, directionality, and turbulence. The vertical dipole has not been addressed due to ground-based recording limitations. In this study we deployed a high-density seismo-acoustic network around Yasur Volcano, Vanuatu, including multiple acoustic sensors along a tethered balloon that was moved every 15-60 minutes. Yasur has frequent strombolian eruptions every 1-4 minutes from any one of three active vents within a 400 m diameter crater. Our experiment captured several explosions from each vent at 38 tether locations covering 200 in azimuth and a take-off range of 50 (Jolly et. al., in review). Additionally, FLIR, FTIR, and a variety of visual imagery were collected during the deployment to aid in the seismo-acoustic interpretations. The third dimension (vertical) of pressure sensor coverage allows us to more completely constrain the acoustic source. Our analysis employs Finite-Difference Time-Domain (FDTD) modeling to obtain the full 3-D Green's functions for each propagation path. This method, following Kim et al. (2015), takes into account realistic topographic scattering based on a high-resolution digital elevation model created using structure-from-motion techniques. We then invert for the source location and multipole source-time function using a grid-search approach. We perform this inversion for multiple events from vents A and C to examine the source characteristics of the vents, including an infrasound-derived volume flux as a function of time. These volumes fluxes are then compared to those derived independently from geochemical and seismic inversion techniques. Jolly, A., Matoza, R., Fee, D., Kennedy, B

Exploration of Two Training Paradigms Using Forced Induced Weight Shifting With the Tethered Pelvic Assist Device to Reduce Asymmetry in Individuals After Stroke: Case Reports.

Science.gov (United States)

Bishop, Lauri; Khan, Moiz; Martelli, Dario; Quinn, Lori; Stein, Joel; Agrawal, Sunil

2017-10-01

Many robotic devices in rehabilitation incorporate an assist-as-needed haptic guidance paradigm to promote training. This error reduction model, while beneficial for skill acquisition, could be detrimental for long-term retention. Error augmentation (EA) models have been explored as alternatives. A robotic Tethered Pelvic Assist Device has been developed to study force application to the pelvis on gait and was used here to induce weight shift onto the paretic (error reduction) or nonparetic (error augmentation) limb during treadmill training. The purpose of these case reports is to examine effects of training with these two paradigms to reduce load force asymmetry during gait in two individuals after stroke (>6 mos). Participants presented with baseline gait asymmetry, although independent community ambulators. Participants underwent 1-hr trainings for 3 days using either the error reduction or error augmentation model. Outcomes included the Borg rating of perceived exertion scale for treatment tolerance and measures of force and stance symmetry. Both participants tolerated training. Force symmetry (measured on treadmill) improved from pretraining to posttraining (36.58% and 14.64% gains), however, with limited transfer to overground gait measures (stance symmetry gains of 9.74% and 16.21%). Training with the Tethered Pelvic Assist Device device proved feasible to improve force symmetry on the treadmill irrespective of training model. Future work should consider methods to increase transfer to overground gait.

Ionic Liquid-Tethered Nanoparticle Suspensions: A Novel Class of Ionogels

KAUST Repository

Moganty, Surya S.

2012-04-10

We report a novel class of silica ionogels created by dispersing silica nanoparticles densely grafted with the ionic liquid (IL) 1-trimethoxysilyl propyl-3-methyl-imidazolium bis- (trifluoromethylsulfonyl) imide (SpmImTSFI) in a 1-butyl-3- methyl-pyrrolidinium bis(trifluoromethylsulfonyl) imide (BmpyrTFSI) IL host. We find that over the entire range of nanoparticle volume fractions studied the systems exist as stable suspensions of SiO 2-SpmImTFSI in the BmpyrTFSI host. Remarkably, we also find that addition of even minute quantities of SiO 2-SpmImTFSI to the BmpyrTFSI IL suppresses crystallization of the host. The resulting disordered hybrid fluids exhibit liquid-like transport properties over a vastly extended temperature range; they open the way for facile synthesis of ILs with extended operating temperature windows. These observations are explained in terms of ionic coupling of the nanoparticle-tethered and free TFSI anions, which is thought to suppress crystallization of BmpyrTFSI. © 2012 American Chemical Society.

Attitude Control Tradeoff Study Between the Use of a Flexible Beam and a Tether Configuration for the Connection of Two Bodies in Orbit

Science.gov (United States)

Graff, S. H.

1985-01-01

Sometimes it is necessary to mount a payload remotely from the main body of a spacecraft or space station. The reasons for this vary from vibration isolation to avoidance of measurement contamination. For example the SP-100 project, which grew out of the increased interest in nuclear power in space for space stations and for deep space explorations, requires separation of the nuclear reactor from the user because of vibration, heat and radiation. The different attitude control problems for beam and tether configurations are discussed. The beam configuration uses a conservative design approach. The vibration, beam flexibility and deployment concerns are analyzed. The tether configuration offers some very attractive design features, but not without several thorny problems. These problems are analyzed. One configuration will be recommended for the main thrust of the SP-100 design effort based on attitude control considerations.

Corrigendum to "Dynamics of a flexible tethered satellite system utilising various materials for coplanar and non-coplanar models" [Adv. Space Res. 56 (2015) 648-663

Science.gov (United States)

Hong, Aaron Aw Teik; Varatharajoo, Renuganth

2015-12-01

The authors would like to thank Dr. N.A. Ismail for some of the discussions found in her thesis as these discussions have facilitated to achieve some of the results published in this article. Therefore, Ismail, N.A., "The Dynamics of a Flexible Motorised Momentum Exchange Tether (MMET)", PhD. thesis, University of Glasgow, UK, pp. 26-41, 2012 is cited accordingly herein. The thesis was missed out from the reference list in the original version of this article due to an oversight with no other intention. Similarly the thesis by Stevens, R.E., "Optimal Control of Electrodynamic Tether Satellites", PhD. thesis, Air Force Institute of Technology, USA, pp. 87-96, 2008 is referred for a further readership completeness.

SATB1 tethers multiple gene loci to reprogram expression profiledriving breast cancer metastasis

Energy Technology Data Exchange (ETDEWEB)

Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

2006-07-13

Global changes in gene expression occur during tumor progression, as indicated by expression profiling of metastatic tumors. How this occurs is poorly understood. SATB1 functions as a genome organizer by folding chromatin via tethering multiple genomic loci and recruiting chromatin remodeling enzymes to regulate chromatin structure and expression of a large number of genes. Here we show that SATB1 is expressed at high levels in aggressive breast cancer cells, and is undetectable in non-malignant breast epithelial cells. Importantly, RNAi-mediated removal of SATB1 from highly-aggressive MDA-MB-231 cells altered the expression levels of over 1200 genes, restored breast-like acinar polarity in three-dimensional cultures, and prevented the metastastic phenotype in vivo. Conversely, overexpression of SATB1 in the less-aggressive breast cancer cell line Hs578T altered the gene expression profile and increased metastasis dramatically in vivo. Thus, SATB1 is a global regulator of gene expression in breast cancer cells, directly regulating crucial metastasis-associated genes, including ERRB2 (HER2/NEU), TGF-{beta}1, matrix metalloproteinase 3, and metastasin. The identification of SATB1 as a protein that re-programs chromatin organization and transcription profiles to promote breast cancer metastasis suggests a new model for metastasis and may provide means of therapeutic intervention.

Single molecular switch based on thiol tethered iron(II)clathrochelate on gold

Energy Technology Data Exchange (ETDEWEB)

Viswanathan, Subramanian [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland); Voloshin, Yan Z. [Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, 119991 Moscow (Russian Federation); Radecka, Hanna [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland); Radecki, Jerzy [Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-747 Olsztyn (Poland)], E-mail: radecki@pan.olsztyn.pl

2009-09-30

Molecular electronics has been associated with high density nano-electronic devices. Developments of molecular electronic devices were based on reversible switching of molecules between the two conductive states. In this paper, self-assembled monolayers of dodecanethiol (DDT) and thiol tethered iron(II)clathrochelate (IC) have been prepared on gold film. The electrochemical and electronic properties of IC molecules inserted into the dodecanethiol monolayer (IC-DDT SAM) were investigated using voltammetric, electrochemical impedance spectroscopy (EIS), scanning tunneling microscopy (STM) and cross-wire tunneling measurements. The voltage triggered switching behaviour of IC molecules on mixed SAM was demonstrated. Deposition of polyaniline on the redox sites of IC-DDT SAM using electrochemical polymerization of aniline was performed in order to confirm that this monolayer acts as nano-patterned semiconducting electrode surface.

BST2/CD317 counteracts human coronavirus 229E productive infection by tethering virions at the cell surface

Energy Technology Data Exchange (ETDEWEB)

Wang, Shiu-Mei [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Huang, Kuo-Jung [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Wang, Chin-Tien, E-mail: chintien@ym.edu.tw [Department of Medical Research and Education, Taipei Veterans General Hospital and Institute of Clinical Medicine, Taipei 11217, Taiwan (China); Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

2014-01-20

Bone marrow stromal antigen 2 (BST2), an interferon-inducible antiviral factor, has been shown to block the release of various enveloped viruses from cells. It has also been identified as an innate immune system component. Most enveloped viruses subject to BST2 restriction bud at the plasma membrane. Here we report our findings that (a) the production of human coronavirus 229E (HCoV-229E) progeny viruses, whose budding occurs at the ER-Golgi intermediate compartment (ERGIC), markedly decreases in the presence of BST2; and (b) BST2 knockdown expression results in enhanced HCoV-229E virion production. Electron microscopy analyses indicate that HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. Our results suggest that BST2 exerts a broad blocking effect against enveloped virus release, regardless of whether budding occurs at the plasma membrane or intracellular compartments. - Highlights: • BST2 knockdown expression results in enhanced HCoV-229E egress. • HCoV-229E virions are tethered to cell surfaces or intracellular membranes by BST2. • HCoV-229E infection at high MOI can significantly downregulate HeLa BST2 and rescue HIV-1 egress.

Application of tethered balloon for studying vertical distribution of air pollutants within lower tropsphere of Shanghai

Science.gov (United States)

Zhang, K.; Wang, D.; Fu, Q.; Xiu, G.; Duan, Y.

2016-12-01

Tethered balloon-based measurement campaign of particle number concentration (PNC) and particle number size distribution (PNSD) in the range of 15.7-661.2 nm was conducted within the lower troposphere of 1000 m in Shanghai, a Chinses megacity, in December 2015. The meteorological condition, PNC, and PNSD were synchronous measured at ground-based station as well as on the tethered balloon. Overall, the mixing layer height (MLH) showed a peak at about LST 14:00-15:00. On ground level, the 88.2 nm particles had the highest number concentration. The Pearson correlation analysis based on the ground level data shows the Pearson correlation coefficient between PNC and NO2was 0.774. The synchronous measurement of PNC and PNSD on ground level and on the tethered balloon showed the 15.7-200 nm particles had higher PNC on ground level, but the PNC of 200-661.2 nm particles are higher at 400 m. And the wind condition showed a strong influence on PNC.The vertical profiles of meteorological parameters and air pollutants was observed. The particle mass concentration, ozone concentration, temperature, and humidity all showed a quick change when the balloon across the atmosphere boundary layer. One episodic haze event (Dec 22nd-Dec 23rd) was selected with specific focus on the variation of PNSD and PNC vertical profiles. Before the haze, the PNC at ground was 9281 cm-3. The MaxDm (the particle diameter with the highest number concentration) was 53.3 nm at that time. Due to the shallow MLH, the MaxDm changed rapidly to 126.3 nm at 321 m. During the haze, the MaxDm and the PNC on ground level was 126.3 nm and 18515 cm-3 respectively. And a quick drop of PNC was observed at 553 m. This may due to the change of wind direction, temperature, and relative humidity. At the end of haze, the MaxDm and the PNC on ground level was 126.3 nm and 10711 cm-3 respectively. The highest MaxDm during those three launches all appeared at a high altitude, usually above 300 m. This result is consisted

Cytoplasmic tethering of a RING protein RBCK1 by its splice variant lacking the RING domain

International Nuclear Information System (INIS)

Yoshimoto, Nobuo; Tatematsu, Kenji; Koyanagi, Tomoyoshi; Okajima, Toshihide; Tanizawa, Katsuyuki; Kuroda, Shun'ichi

2005-01-01

RBCC protein interacting with PKC 1 (RBCK1) is a transcription factor belonging to the RING-IBR protein family and has been shown to shuttle between the nucleus and cytoplasm, possessing both the nuclear export and localization signals within its amino acid sequence. RBCK2, lacking the C-terminal half of RBCK1 including the RING-IBR domain, has also been identified as an alternative splice variant of RBCK1. RBCK2 shows no transcriptional activity and instead it represses the transcriptional activity of RBCK1. Here, we show that RBCK2 is present usually in the cytoplasm containing two Leu-rich regions that presumably serve as a nuclear export signal (NES). Moreover, an NES-disrupted RBCK1 that is mostly localized within the nucleus is translocated to the cytoplasm when coexpressed with RBCK2, suggesting that RBCK2 serves as a cytoplasmic tethering protein for RBCK1. We propose a novel and general function of RING-lacking splice variants of RING proteins to control the intracellular localization and functions of the parental RING proteins by forming a hetero-oligomeric complex

The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

DEFF Research Database (Denmark)

Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

2015-01-01

We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

A practical concept for powered or tethered weight-lifting LTA vehicles

Science.gov (United States)

Balleyguier, M. A.

1975-01-01

A concept for a multi-hull weightlifting airship is presented. The concept is based upon experience in the design and handling of gas-filled balloons for commercial purposes, it was first tested in April, 1972. In the flight test, two barrage balloons were joined side-by-side, with an intermediate frame, and launched in captive flight. The success of this flight test led to plans for a development program calling for a powered, piloted prototype, a follow-on 40 ton model, and a 400 ton transport model. All of these airships utilize a tetrehedric three-line tethering method for loading and unloading phases of flight, which bypasses many of the difficulties inherent in the handling of a conventional airship near the ground. Both initial and operating costs per ton of lift capability are significantly less for the subject design than for either helicopters or airships of conventional mono-hull design.

Optical properties of mixed phase boundary layer clouds observed from a tethered balloon platform in the Arctic

International Nuclear Information System (INIS)

Sikand, M.; Koskulics, J.; Stamnes, K.; Hamre, B.; Stamnes, J.J.; Lawson, R.P.

2010-01-01

A tethered balloon system was used to collect data on radiometric and cloud microphysical properties for mixed phase boundary layer clouds, consisting of ice crystals and liquid water droplets during a May-June 2008 experimental campaign in Ny-Alesund, Norway, located high in the Arctic at 78.9 o N, 11.9 o E. The balloon instrumentation was controlled and powered from the ground making it possible to fly for long durations and to profile clouds vertically in a systematic manner. We use a radiative transfer model to analyze the radiometric measurements and estimate the optical properties of mixed-phase clouds. The results demonstrate the ability of instruments deployed on a tethered balloon to provide information about optical properties of mixed-phase clouds in the Arctic. Our radiative transfer simulations show that cloud layering has little impact on the total downward irradiance measured at the ground as long as the total optical depth remains unchanged. In contrast, the mean intensity measured by an instrument deployed on a balloon depends on the vertical cloud structure and is thus sensitive to the altitude of the balloon. We use the total downward irradiance measured by a ground-based radiometer to estimate the total optical depth and the mean intensity measured at the balloon to estimate the vertical structure of the cloud optical depth.

Dissimilar kinetic behavior of electrically manipulated single- and double-stranded DNA tethered to a gold surface.

Science.gov (United States)

Rant, Ulrich; Arinaga, Kenji; Tornow, Marc; Kim, Yong Woon; Netz, Roland R; Fujita, Shozo; Yokoyama, Naoki; Abstreiter, Gerhard

2006-05-15

We report on the electrical manipulation of single- and double-stranded oligodeoxynucleotides that are end tethered to gold surfaces in electrolyte solution. The response to alternating repulsive and attractive electric surface fields is studied by time-resolved fluorescence measurements, revealing markedly distinct dynamics for the flexible single-stranded and stiff double-stranded DNA, respectively. Hydrodynamic simulations rationalize this finding and disclose two different kinetic mechanisms: stiff polymers undergo rotation around the anchoring pivot point; flexible polymers, on the other hand, are pulled onto the attracting surface segment by segment.

Flow structures around a beetle in a tethered flight

Science.gov (United States)

Lee, Boogeon; Oh, Sehyeong; Park, Hyungmin; Choi, Haecheon

2017-11-01

In the present study, through a wind-tunnel experiment, we visualize the flow in a tethered flight of a rhinoceros beetle using a smoke-wire visualization technique. Measurements are done at five side planes along the wind span while varying the body angle (angle between the horizontal and the body axis) to investigate the influence of the stroke plane angle that was observed to change depending on the flight mode such as hovering, forward and takeoff flights so on. Observing that a large attached leading-edge vortex is only found on the hindwing, it is inferred that most of the aerodynamic forces would be generated by hindwings (flexible inner wings) compared to the elytra (hard outer wings). In addition, it is observed to use unsteady lift-generating mechanisms such as clap-and-fling, wing-wing interaction and wake capture. Finally, we discuss the relation between the advance ratio and Strouhal number by adjusting free-stream velocity and the body angle (i.e., angle of wake-induced flow). Supported by a Grant to Bio-Mimetic Robot Research Center Funded by Defense Acquisition Program Administration, and by ADD, Korea (UD130070ID).

Coarse-grained molecular simulation of epidermal growth factor receptor protein tyrosine kinase multi-site self-phosphorylation.

Directory of Open Access Journals (Sweden)

John G Koland

2014-01-01

Full Text Available Upon the ligand-dependent dimerization of the epidermal growth factor receptor (EGFR, the intrinsic protein tyrosine kinase (PTK activity of one receptor monomer is activated, and the dimeric receptor undergoes self-phosphorylation at any of eight candidate phosphorylation sites (P-sites in either of the two C-terminal (CT domains. While the structures of the extracellular ligand binding and intracellular PTK domains are known, that of the ∼225-amino acid CT domain is not, presumably because it is disordered. Receptor phosphorylation on CT domain P-sites is critical in signaling because of the binding of specific signaling effector molecules to individual phosphorylated P-sites. To investigate how the combination of conventional substrate recognition and the unique topological factors involved in the CT domain self-phosphorylation reaction lead to selectivity in P-site phosphorylation, we performed coarse-grained molecular simulations of the P-site/catalytic site binding reactions that precede EGFR self-phosphorylation events. Our results indicate that self-phosphorylation of the dimeric EGFR, although generally believed to occur in trans, may well occur with a similar efficiency in cis, with the P-sites of both receptor monomers being phosphorylated to a similar extent. An exception was the case of the most kinase-proximal P-site-992, the catalytic site binding of which occurred exclusively in cis via an intramolecular reaction. We discovered that the in cis interaction of P-site-992 with the catalytic site was facilitated by a cleft between the N-terminal and C-terminal lobes of the PTK domain that allows the short CT domain sequence tethering P-site-992 to the PTK core to reach the catalytic site. Our work provides several new mechanistic insights into the EGFR self-phosphorylation reaction, and demonstrates the potential of coarse-grained molecular simulation approaches for investigating the complexities of self-phosphorylation in

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

1998-01-01

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Monitoring ligand-receptor interactions by photonic force microscopy

Energy Technology Data Exchange (ETDEWEB)

Jeney, Sylvia [M E Mueller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, Basel, 4056 (Switzerland); Mor, Flavio; Forro, Laszlo [Laboratory of Complex Matter Physics (LPMC), Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland); Koszali, Roland [Institute for Information and Communication Technologies (IICT), University of Applied Sciences of Western Switzerland (HEIG-VD), Rue Galilee 15, CH 1401 Yverdon-les-bains (Switzerland); Moy, Vincent T, E-mail: sylvia.jeney@unibas.ch, E-mail: vmoy@miami.edu [Department of Physiology and Biophysics, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136 (United States)

2010-06-25

We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

Monitoring ligand-receptor interactions by photonic force microscopy

International Nuclear Information System (INIS)

Jeney, Sylvia; Mor, Flavio; Forro, Laszlo; Koszali, Roland; Moy, Vincent T

2010-01-01

We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

Science.gov (United States)

Jain, Anupriya; Jain, Keerti; Mehra, Neelesh Kumar; Jain, N. K.

2013-10-01

In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

Lipoproteins tethered dendrimeric nanoconstructs for effective targeting to cancer cells

Energy Technology Data Exchange (ETDEWEB)

Jain, Anupriya; Jain, Keerti, E-mail: keertijain02@gmail.com; Mehra, Neelesh Kumar, E-mail: neelesh81mph@gmail.com; Jain, N. K., E-mail: dr.jnarendr@gmail.com [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

2013-10-15

In the present investigation, poly (propylene imine) dendrimers up to fifth generation (PPI G5.0) were synthesized using ethylene diamine and acrylonitrile. Lipoproteins (high-density lipoprotein; HDL and low-density lipoprotein; LDL) were isolated from human plasma by discontinuous density gradient ultracentrifugation, characterized and tethered to G5.0 PPI dendrimers to construct LDL- and HDL-conjugated dendrimeric nanoconstructs for tumor-specific delivery of docetaxel. Developed formulations showed sustained release characteristics in in vitro drug release and in vivo pharmacokinetic studies. The cancer targeting potential of lipoprotein coupled dendrimers was investigated by ex vivo cytotoxicity and cell uptake studies using human hepatocellular carcinoma cell lines (HepG2 cells) and biodistribution studies in albino rats of Sprague-Dawley strain. Lipoprotein anchored dendrimeric nanoconstructs showed significant uptake by cancer cells as well as higher biodistribution of docetaxel to liver and spleen. It is concluded that these precisely synthesized engineered dendrimeric nanoconstructs could serve as promising drug carrier for fighting with the fatal disease, i.e., cancer, attributed to their defined targeting and therapeutic potential.

Paraplegia como manifestação inicial de medula presa: relato de caso Paraplegia as initial manifestation of tethered spinal cord: case report

Directory of Open Access Journals (Sweden)

ANA GUARDIOLA

1999-03-01

Full Text Available A medula presa (MP é entidade pouco frequente que ocorre quando há restrição da migração normal do cone medular por cistos, lipomas ou disrafismos espinhais. Esta patologia pode levar a paraplegia, distúrbios sensoriais e esficterianos. Relatamos o caso de uma menina de 22 meses que consultou com quadro de paraplegia. O diagnóstico de medula presa foi confirmado pela mielotomografia e a paciente foi submetida à cirurgia para liberação do filo terminal.Tethered spinal cord (TSC is a rare disorder; it occurs when the conus medularis is anchored to the base of the vertebral canal by thickened filum terminale cysts, lipoma and spinal dysraphia. This disorder may cause paraplegia, sensory and sphincter disturbance. We report a twenty-two months-old girl presenting with paraplegia. TSC diagnostic was confirmed by myelotomography. The patient was submitted to surgical relief of tethered filum terminale.

Tethered particle analysis of supercoiled circular DNA using peptide nucleic acid handles

DEFF Research Database (Denmark)

Norregaard, Kamilla; Andersson, Magnus; Nielsen, Peter Eigil

2014-01-01

This protocol describes how to monitor individual naturally supercoiled circular DNA plasmids bound via peptide nucleic acid (PNA) handles between a bead and a surface. The protocol was developed for single-molecule investigation of the dynamics of supercoiled DNA, and it allows the investigation...... of both the dynamics of the molecule itself and of its interactions with a regulatory protein. Two bis-PNA clamps designed to bind with extremely high affinity to predetermined homopurine sequence sites in supercoiled DNA are prepared: one conjugated with digoxigenin for attachment to an anti......-digoxigenin-coated glass cover slide, and one conjugated with biotin for attachment to a submicron-sized streptavidin-coated polystyrene bead. Plasmids are constructed, purified and incubated with the PNA handles. The dynamics of the construct is analyzed by tracking the tethered bead using video microscopy: less...

Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

Science.gov (United States)

Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

2008-08-01

Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

Science.gov (United States)

Keegan, A D; Pierce, J H

1994-02-01

Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

Performance of a Tethered Point Wave-Energy Absorber in Regular and Irregular Waves

KAUST Repository

Bachynski, Erin E.; Young, Yin Lu; Yeung, Ronald W.

2010-01-01

The importance of the mooring system on the dynamic response of a point-absorber type ocean-wave energy converter (WEC) is investigated using a frequency-domain approach. In order to ensure the safety of WECs, careful consideration of the response and resonance frequencies in all motions must be evaluated, including the effects of the mooring system. In this study, a WEC floater with a closed, flat bottom is modeled as a rigid vertical cylinder tethered by elastic mooring lines. The WEC hydrodynamic added mass and damping are obtained using established potential-flow methods, with additional damping provided by the energy-extraction system. The results show that the response of the WEC, and the corresponding power takeoff, varies with the diameter-to-draft (D=T) ratio, mooring system stiffness, and mass distribution. For a given wave climate in Northern California, near San Francisco, the heave energy extraction is found to be best for a shallow WEC with a soft mooring system, compared to other systems that were examined. This result assumes a physical limit (cap) on the motion which is related to the significant wave height to draft ratio. Shallow draft designs, however, may experience excessive pitch motions and relatively larger viscous damping. In order to mitigate the pitch response, the pitch radius of gyration should be small and the center of mass should be low. Copyright © 2010 by ASME.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

Protein tethering enables rapid and label-free SERS platform for screening drugs of abuse (Conference Presentation)

Science.gov (United States)

Siddhanta, Soumik; Wróbel, Maciej S.; Barman, Ishan

2017-02-01

A quick, cost-effective method for detection of drugs of abuse in biological fluids would be of great value in healthcare, law enforcement, and home testing applications. The alarming rise in narcotics abuse has led to considerable focus on developing potent and versatile analytical tools that can address this societal problem. While laboratory testing plays a key role in the current detection of drug misuse and the evaluation of patients with drug induced intoxication, these typically require expensive reagents and trained personnel, and may take hours to complete. Thus, a significant unmet need is to engineer a facile method that can rapidly detect drugs with little sample preparation, especially the bound fraction that is typically dominant in the blood stream. Here we report an approach that combines the exquisite sensitivity of surface enhanced Raman spectroscopy (SERS) and a facile protein tethering mechanism to reliably detect four different classes of drugs, barbiturate, benzodiazepine, amphetamine and benzoylecgonine. The proposed approach harnesses the reliable and specific attachment of proteins to both drugs and nanoparticle to facilitate the enhancement of spectral markers that are sensitive to the presence of the drugs. In conjunction with chemometric tools, we have shown the ability to quantify these drugs lower than levels achievable by existing clinical immunoassays. Through molecular docking simulations, we also probe the mechanistic underpinnings of the protein tethering approach, opening the door to detection of a broad class of narcotics in biological fluids within a few minutes as well as for groundwater analysis and toxin detection.

Preliminary Results from the First Deployment of a Tethered-Balloon Cloud Particle Imager Instrument Package in Arctic Stratus Clouds at Ny-Alesund

Science.gov (United States)

Lawson, P.; Stamnes, K.; Stamnes, J.; Zmarzly, P.; O'Connor, D.; Koskulics, J.; Hamre, B.

2008-12-01

A tethered balloon system specifically designed to collect microphysical data in mixed-phase clouds was deployed in Arctic stratus clouds during May 2008 near Ny-Alesund, Svalbard, at 79 degrees North Latitude. This is the first time a tethered balloon system with a cloud particle imager (CPI) that records high-resolution digital images of cloud drops and ice particles has been operated in cloud. The custom tether supplies electrical power to the instrument package, which in addition to the CPI houses a 4-pi short-wavelength radiometer and a met package that measures temperature, humidity, pressure, GPS position, wind speed and direction. The instrument package was profiled vertically through cloud up to altitudes of 1.6 km. Since power was supplied to the instrument package from the ground, it was possible to keep the balloon package aloft for extended periods of time, up to 9 hours at Ny- Ålesund, which was limited only by crew fatigue. CPI images of cloud drops and the sizes, shapes and degree of riming of ice particles are shown throughout vertical profiles of Arctic stratus clouds. The images show large regions of mixed-phase cloud from -8 to -2 C. The predominant ice crystal habits in these regions are needles and aggregates of needles. The amount of ice in the mixed-phase clouds varied considerably and did not appear to be a function of temperature. On some occasions, ice was observed near cloud base at -2 C with supercooled cloud above to - 8 C that was devoid of ice. Measurements of shortwave radiation are also presented. Correlations between particle distributions and radiative measurements will be analyzed to determine the effect of these Arctic stratus clouds on radiative forcing.

Lamin B Receptor: Interplay between Structure, Function and Localization

Directory of Open Access Journals (Sweden)

Eleni Nikolakaki

2017-08-01

Full Text Available Lamin B receptor (LBR is an integral protein of the inner nuclear membrane, containing a hydrophilic N-terminal end protruding into the nucleoplasm, eight hydrophobic segments that span the membrane and a short, nucleoplasmic C-terminal tail. Two seemingly unrelated functions have been attributed to LBR. Its N-terminal domain tethers heterochromatin to the nuclear periphery, thus contributing to the shape of interphase nuclear architecture, while its transmembrane domains exhibit sterol reductase activity. Mutations within the transmembrane segments result in defects in cholesterol synthesis and are associated with diseases such as the Pelger–Huët anomaly and Greenberg skeletal dysplasia, whereas no such harmful mutations related to the anchoring properties of LBR have been reported so far. Recent evidence suggests a dynamic regulation of LBR expression levels, structural organization, localization and function, in response to various signals. The molecular mechanisms underlying this dynamic behavior have not yet been fully unraveled. Here, we provide an overview of the current knowledge of the interplay between the structure, function and localization of LBR, and hint at the interconnection of the two distinct functions of LBR.

Critical force during tethered swimming for the evaluation of aerobic capacity and prediction of performances in freestyle swimming

OpenAIRE

Marcelo Papoti; Ricardo Vitório; Gustavo Gomes Araújo; Luiz Eduardo Barreto Martins; Sérgio Augusto Cunha; Claudio Alexandre Gobatto

2010-01-01

The present study investigated the relationship of critical force (Fcrit) with lactate threshold (LLNA) and the intensity corresponding to VO2max (iVO2max) in tethered swimming (TS), and their correlation with maximal performance in 400-m (V400) and 30-min (VT30) freestyle swimming (FS). Seven swimmers were submitted to a TS incremental test for the determination of LLNA and iVO2max. For the determination of Fcrit, the swimmers performed four exercises to exhaustion at intensities (F) corresp...

Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.

Science.gov (United States)

Weekes, Michael P; Antrobus, Robin; Talbot, Suzanne; Hör, Simon; Simecek, Nikol; Smith, Duncan L; Bloor, Stuart; Randow, Felix; Lehner, Paul J

2012-03-02

The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.

A central region in the minor capsid protein of papillomaviruses facilitates viral genome tethering and membrane penetration for mitotic nuclear entry.

Directory of Open Access Journals (Sweden)

Inci Aydin

2017-05-01

Full Text Available Incoming papillomaviruses (PVs depend on mitotic nuclear envelope breakdown to gain initial access to the nucleus for viral transcription and replication. In our previous work, we hypothesized that the minor capsid protein L2 of PVs tethers the incoming vDNA to mitotic chromosomes to direct them into the nascent nuclei. To re-evaluate how dynamic L2 recruitment to cellular chromosomes occurs specifically during prometaphase, we developed a quantitative, microscopy-based assay for measuring the degree of chromosome recruitment of L2-EGFP. Analyzing various HPV16 L2 truncation-mutants revealed a central chromosome-binding region (CBR of 147 amino acids that confers binding to mitotic chromosomes. Specific mutations of conserved motifs (IVAL286AAAA, RR302/5AA, and RTR313EEE within the CBR interfered with chromosomal binding. Moreover, assembly-competent HPV16 containing the chromosome-binding deficient L2(RTR313EEE or L2(IVAL286AAAA were inhibited for infection despite their ability to be transported to intracellular compartments. Since vDNA and L2 were not associated with mitotic chromosomes either, the infectivity was likely impaired by a defect in tethering of the vDNA to mitotic chromosomes. However, L2 mutations that abrogated chromatin association also compromised translocation of L2 across membranes of intracellular organelles. Thus, chromatin recruitment of L2 may in itself be a requirement for successful penetration of the limiting membrane thereby linking both processes mechanistically. Furthermore, we demonstrate that the association of L2 with mitotic chromosomes is conserved among the alpha, beta, gamma, and iota genera of Papillomaviridae. However, different binding patterns point to a certain variance amongst the different genera. Overall, our data suggest a common strategy among various PVs, in which a central region of L2 mediates tethering of vDNA to mitotic chromosomes during cell division thereby coordinating membrane

No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene

DEFF Research Database (Denmark)

Haagerup, A; Bjerke, T; Schiøtz, P O

2001-01-01

BACKGROUND: Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type ...

Linear Viscoelasticity of Spherical SiO 2 Nanoparticle-Tethered Poly(butyl acrylate) Hybrids

KAUST Repository

Goel, Vivek; Pietrasik, Joanna; Matyjaszewski, Krzysztof; Krishnamoorti, Ramanan

2010-01-01

The melt state linear viscoelastic properties of spherical silica nanoparticles with grafted poly(n-butyl acrylate) chains of varying molecular weight were probed using linear small amplitude dynamic oscillatory measurements and complementary linear stress relaxation measurements. While the pure silica-tethered-polymer hybrids with no added homopolymer exhibit solid-like response, addition of matched molecular weight free matrix homopolymer chains to this hybrid, at low concentrations of added homopolymer, maintains the solid-like response with a lowered modulus that can be factored into a silica concentration dependence and a molecular weight dependence. While the silica concentration dependence of the modulus is strong, the dependence on molecular weight is weak. On the other hand, increasing the amount of added homopolymer changes the viscoelastic response to that of a liquid with a relaxation time that scales exponentially with hybrid concentration. © 2010 American Chemical Society.

Linear Viscoelasticity of Spherical SiO 2 Nanoparticle-Tethered Poly(butyl acrylate) Hybrids

KAUST Repository

Goel, Vivek

2010-12-01

The melt state linear viscoelastic properties of spherical silica nanoparticles with grafted poly(n-butyl acrylate) chains of varying molecular weight were probed using linear small amplitude dynamic oscillatory measurements and complementary linear stress relaxation measurements. While the pure silica-tethered-polymer hybrids with no added homopolymer exhibit solid-like response, addition of matched molecular weight free matrix homopolymer chains to this hybrid, at low concentrations of added homopolymer, maintains the solid-like response with a lowered modulus that can be factored into a silica concentration dependence and a molecular weight dependence. While the silica concentration dependence of the modulus is strong, the dependence on molecular weight is weak. On the other hand, increasing the amount of added homopolymer changes the viscoelastic response to that of a liquid with a relaxation time that scales exponentially with hybrid concentration. © 2010 American Chemical Society.

Fast and facile fabrication of antifouling and hemocompatible PVDF membrane tethered with amino-acid modified PEG film

Science.gov (United States)

Zhang, Shuyou; Cao, Jingjing; Ma, Na; You, Meng; Wang, Xushan; Meng, Jianqiang

2018-01-01

A fast and facile protocol is reported aiming at improving the antifouling property and hemocompatibility of poly(vinylidene fluoride) (PVDF) membranes by tethering PEG hydrogel and zwitterion immobilization. The coated PEG hydrogel was first prepared by interfacial polymerization and tethered on an alkali treated PVDF membrane (PVDFA) surface via a simultaneous thio-ene and thiol-epoxy reaction. Then, the thiol groups of cysteine reacted with the epoxy groups in PEG hydrogel to fabricate the PVDFA-g-Cys membrane. The membrane fabrication was complete within less than 20 min and was conducted in mild conditions. The successful preparation of PVDFA-g-Cys membrane was confirmed by ATR-FTIR and XPS. Raman spectroscopy showed that the hydrogels covalently bonded to the PVDF membrane surface. The membrane retained its mechanical strength after modification. The SEM measurements suggested that the membrane became denser after hydrogel coating, meanwhile, the EDX test verified that the functional species uniformly distributed in the membrane matrix. Water contact angle (WCA), protein adsorption and protein filtration tests showed significant improvements in hydrophilicity and antifouling properties for the modified membrane. The negativity of the membrane surface measured by the streaming potential method provides a basis for protein resistance and hemocompatibility. Moreover, the suppressed platelet adhesion and prolonged plasma coagulant time show that the PVDFA-g-Cys membrane has ultralow thrombotic potential and better hemocompatibility. The reported surface modification method combing thio-ene and thio-epoxy chemistry not only facilitates fabrication of hemocompatible PVDF membrane but also provide an universal chemical platform for multifunctionalization of porous membranes.

Quinone methides tethered to naphthalene diimides as selective G-quadruplex alkylating agents.

Science.gov (United States)

Di Antonio, Marco; Doria, Filippo; Richter, Sara N; Bertipaglia, Carolina; Mella, Mariella; Sissi, Claudia; Palumbo, Manlio; Freccero, Mauro

2009-09-16

We have developed novel G-quadruplex (G-4) ligand/alkylating hybrid structures, tethering the naphthalene diimide moiety to quaternary ammonium salts of Mannich bases, as quinone-methide precursors, activatable by mild thermal digestion (40 degrees C). The bis-substituted naphthalene diimides were efficiently synthesized, and their reactivity as activatable bis-alkylating agents was investigated in the presence of thiols and amines in aqueous buffered solutions. The electrophilic intermediate, quinone-methide, involved in the alkylation process was trapped, in the presence of ethyl vinyl ether, in a hetero Diels-Alder [4 + 2] cycloaddition reaction, yielding a substituted 2-ethoxychroman. The DNA recognition and alkylation properties of these new derivatives were investigated by gel electrophoresis, circular dichroism, and enzymatic assays. The alkylation process occurred preferentially on the G-4 structure in comparison to other DNA conformations. By dissecting reversible recognition and alkylation events, we found that the reversible process is a prerequisite to DNA alkylation, which in turn reinforces the G-quadruplex structural rearrangement.

The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins

DEFF Research Database (Denmark)

Madsen, Louise; Kriegenburg, Franziska; Lages Lino Vala, Andrea

2011-01-01

is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p......The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded...... protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8...

Nuclear receptors and nonalcoholic fatty liver disease1

Science.gov (United States)

Cave, Matthew C.; Clair, Heather B.; Hardesty, Josiah E.; Falkner, K. Cameron; Feng, Wenke; Clark, Barbara J.; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A.; McClain, Craig J.; Prough, Russell A.

2016-01-01

Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

Which Users Should Be the Focus of Mobile Personal Health Records? Analysis of User Characteristics Influencing Usage of a Tethered Mobile Personal Health Record.

Science.gov (United States)

Lee, Guna; Park, Joong Yeol; Shin, Soo-Yong; Hwang, Jong Su; Ryu, Hyeon Jeong; Lee, Jae Ho; Bates, David W

2016-05-01

This study was conducted to analyze the usage pattern of a hospital-tethered mobile personal health records (m-PHRs) application named My Chart in My Hand (MCMH) and to identify user characteristics that influence m-PHR usage. Access logs to MCMH and its menus were collected for a total of 18 months, from August 2011 to January 2013. Usage patterns between users without a patient identification number (ID) and users with a patient ID were compared. Users with a patient ID were divided into light and heavy user groups by the median number of monthly access. Multiple linear regression models were used to assess MCMH usage pattern by characteristics of MCMH user with a patient ID. The total number of MCMH logins was 105,603, and the median number of accesses was 15 times. Users (n = 7,096) mostly accessed the "My Chart" menu, but "OPD [outpatient department] Service Support" and "Health Management" menus were also frequently used. Patients with chronic diseases, experience of hospital visits including emergency room and OPD, and age group of 0-19 years were more frequently found among users with a patient ID (n = 2,186) (p < 0.001). A similar trend was found in the heavy user group (n = 1,123). Submenus of laboratory result, online appointment, and medication lists that were accessed mostly by users with a patient ID were associated with OPD visit and chronic diseases. This study showed that focuses on patients with chronic disease and more hospital visits and empowerment functions in a tethered m-PHR would be helpful to pursue the extensive use.

Confinement of β1- and β2-adrenergic receptors in the plasma membrane of cardiomyocyte-like H9c2 cells is mediated by selective interactions with PDZ domain and A-kinase anchoring proteins but not caveolae

Science.gov (United States)

Valentine, Cathleen D.; Haggie, Peter M.

2011-01-01

The sympathetic nervous system regulates cardiac output by activating adrenergic receptors (ARs) in cardiac myocytes. The predominant cardiac ARs, β1- and β2AR, are structurally similar but mediate distinct signaling responses. Scaffold protein–mediated compartmentalization of ARs into discrete, multiprotein complexes has been proposed to dictate differential signaling responses. To test the hypothesis that βARs integrate into complexes in live cells, we measured receptor diffusion and interactions by single-particle tracking. Unstimulated β1- and β2AR were highly confined in the membrane of H9c2 cardiomyocyte-like cells, indicating that receptors are tethered and presumably integrated into protein complexes. Selective disruption of interactions with postsynaptic density protein 95/disks large/zonula occludens-1 (PDZ)–domain proteins and A-kinase anchoring proteins (AKAPs) increased receptor diffusion, indicating that these scaffold proteins participate in receptor confinement. In contrast, modulation of interactions between the putative scaffold caveolae and β2AR did not alter receptor dynamics, suggesting that these membrane domains are not involved in β2AR confinement. For both β1- and β2AR, the receptor carboxy-terminus was uniquely responsible for scaffold interactions. Our data formally demonstrate that distinct and stable protein complexes containing β1- or β2AR are formed in the plasma membrane of cardiomyocyte-like cells and that selective PDZ and AKAP interactions are responsible for the integration of receptors into complexes. PMID:21680711

Confinement of β(1)- and β(2)-adrenergic receptors in the plasma membrane of cardiomyocyte-like H9c2 cells is mediated by selective interactions with PDZ domain and A-kinase anchoring proteins but not caveolae.

Science.gov (United States)

Valentine, Cathleen D; Haggie, Peter M

2011-08-15

The sympathetic nervous system regulates cardiac output by activating adrenergic receptors (ARs) in cardiac myocytes. The predominant cardiac ARs, β(1)- and β(2)AR, are structurally similar but mediate distinct signaling responses. Scaffold protein-mediated compartmentalization of ARs into discrete, multiprotein complexes has been proposed to dictate differential signaling responses. To test the hypothesis that βARs integrate into complexes in live cells, we measured receptor diffusion and interactions by single-particle tracking. Unstimulated β(1)- and β(2)AR were highly confined in the membrane of H9c2 cardiomyocyte-like cells, indicating that receptors are tethered and presumably integrated into protein complexes. Selective disruption of interactions with postsynaptic density protein 95/disks large/zonula occludens-1 (PDZ)-domain proteins and A-kinase anchoring proteins (AKAPs) increased receptor diffusion, indicating that these scaffold proteins participate in receptor confinement. In contrast, modulation of interactions between the putative scaffold caveolae and β(2)AR did not alter receptor dynamics, suggesting that these membrane domains are not involved in β(2)AR confinement. For both β(1)- and β(2)AR, the receptor carboxy-terminus was uniquely responsible for scaffold interactions. Our data formally demonstrate that distinct and stable protein complexes containing β(1)- or β(2)AR are formed in the plasma membrane of cardiomyocyte-like cells and that selective PDZ and AKAP interactions are responsible for the integration of receptors into complexes.

Structural studies of the 5'-phenazinium-tethered matched and G-A-mismatched DNA duplexes by NMR spectroscopy.

Science.gov (United States)

Maltseva, T; Sandström, A; Ivanova, I M; Sergeyev, D S; Zarytova, V F; Chattopadhyaya, J

1993-05-01

The mechanism through which modified oligo-DNA analogues act as antisense repressors at the transcriptional and translational level of gene expression is based on the information content in the nucleotide sequence which is determined by the specific base pairing. The efficiency of such action is largely determined by the stability of the duplex formed between the oligonucleotide reagent and the target sequence and also by the mismatched base pairing, such as G-A, that occurs during replication or recombination. We herein report that the phenazinium (Pzn)-tethered matched duplex p(d(TGTTTGGC)):(Pzn)-p(d(CCAAACA)) (III) (Tm = 50 degrees C) has a much larger stability than the parent matched duplex p(d(TGTTTGGC)):p(d(CCAAACA)) (I) (Tm = 30 degrees C). On the other hand, the Pzn-tethered G-A-mismatched duplex p(d(TGTTTGGC)):(Pzn)-p(d(ACAAACA)) (IV) (Tm = 34 degrees C) is only slightly more stable than its parent mismatched duplex p(d(TGTTTGGC)):p(d(ACAAACA)) (Tm = 25 degrees C). A detailed 500 MHz NMR study and constrained MD refinements of NMR-derived structures have been undertaken for the DNA duplexes (I), (II), (III) and (IV) in order to understand the structural basis of stabilization of Pzn-tethered matched DNA duplex (delta Tm = 20 degrees C) compared to mismatched duplex (delta Tm = 9 degrees C). Assignment of the 1H-NMR (500 MHz) spectra of the duplexes has been carried out by 2D NOESY, HOHAHA and DQF-COSY experiments. The torsion angles have been extracted from the J-coupling constants obtained by simulation of most of the DQF-COSY cross-peaks using program SMART. The solution structure of the duplexes were assessed by an iterative hybride relaxation matrix method (MORASS) combined with NOESY distances and torsion angles restrained molecular dynamics (MD) using program Amber 4.0. The standard Amber 4.0 force-field parameters were used for the oligonucleotide in conjunction with the new parameters for Pzn residue which was obtained by full geometry

Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

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Hiroki Ide

2015-01-01

Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

Towards routine measurements of meteorological and aerosol parameters using small unmanned aerial and tethered balloon systems

Science.gov (United States)

Mei, F.; Dexheimer, D.; Hubbe, J. M.; deBoer, G.; Schmid, B.; Ivey, M.; Longbottom, C.; Carroll, P.

2017-12-01

The Inaugural Campaigns for ARM Research using Unmanned Systems (ICARUS) had been launched in 2016 and then the effort has been continued in 2017. ICARUS centered on Oliktok Point, Alaska focusses on developing routine operations of Unmanned Aerial Systems (UAS) and Tethered Balloon Systems (TBS). The operation routine practiced during ICARUS 2016 provided valuable guidance for the ICARUS 2017 deployment. During two intensive operation periods in 2017, a small DataHawk II UAS has been deployed to collect data for two weeks each in May and August. Coordinated with DataHawk flights, the TBS has been launched with meteorology sensors such as iMet and Tethersondes, therefore vertical profiles of the basic atmospheric state (temperature, humidity, and horizontal wind) were observed simultaneously by UAS and TBS. In addition, an aerosol payload was attached and launched with 2 TBS flights in April and 7 TBS flights in May, which include a condensation particle counter (CPC, TSI 3007) and two printed optical particle spectrometers (POPS, Handix TBS version). The two POPS were operated at different inlet temperatures. This approach provided potential measurements for aerosol optical closure in future. Measured aerosol properties include total particle number concentrations, particle size distribution, at different ambient temperature and relative humidity. Vertical profiles of atmospheric state and aerosol properties will be discussed based on the coordinated flights. Monthly variation will be assessed with data from the upcoming August flights.

Covalent growth factor tethering to direct neural stem cell differentiation and self-organization.

Science.gov (United States)

Ham, Trevor R; Farrag, Mahmoud; Leipzig, Nic D

2017-04-15

Tethered growth factors offer exciting new possibilities for guiding stem cell behavior. However, many of the current methods present substantial drawbacks which can limit their application and confound results. In this work, we developed a new method for the site-specific covalent immobilization of azide-tagged growth factors and investigated its utility in a model system for guiding neural stem cell (NSC) behavior. An engineered interferon-γ (IFN-γ) fusion protein was tagged with an N-terminal azide group, and immobilized to two different dibenzocyclooctyne-functionalized biomimetic polysaccharides (chitosan and hyaluronan). We successfully immobilized azide-tagged IFN-γ under a wide variety of reaction conditions, both in solution and to bulk hydrogels. To understand the interplay between surface chemistry and protein immobilization, we cultured primary rat NSCs on both materials and showed pronounced biological effects. Expectedly, immobilized IFN-γ increased neuronal differentiation on both materials. Expression of other lineage markers varied depending on the material, suggesting that the interplay of surface chemistry and protein immobilization plays a large role in nuanced cell behavior. We also investigated the bioactivity of immobilized IFN-γ in a 3D environment in vivo and found that it sparked the robust formation of neural tube-like structures from encapsulated NSCs. These findings support a wide range of potential uses for this approach and provide further evidence that adult NSCs are capable of self-organization when exposed to the proper microenvironment. For stem cells to be used effectively in regenerative medicine applications, they must be provided with the appropriate cues and microenvironment so that they integrate with existing tissue. This study explores a new method for guiding stem cell behavior: covalent growth factor tethering. We found that adding an N-terminal azide-tag to interferon-γ enabled stable and robust Cu-free 'click

Validated simulator for space debris removal with nets and other flexible tethers applications

Science.gov (United States)

Gołębiowski, Wojciech; Michalczyk, Rafał; Dyrek, Michał; Battista, Umberto; Wormnes, Kjetil

2016-12-01

In the context of active debris removal technologies and preparation activities for the e.Deorbit mission, a simulator for net-shaped elastic bodies dynamics and their interactions with rigid bodies, has been developed. Its main application is to aid net design and test scenarios for space debris deorbitation. The simulator can model all the phases of the debris capturing process: net launch, flight and wrapping around the target. It handles coupled simulation of rigid and flexible bodies dynamics. Flexible bodies were implemented using Cosserat rods model. It allows to simulate flexible threads or wires with elasticity and damping for stretching, bending and torsion. Threads may be combined into structures of any topology, so the software is able to simulate nets, pure tethers, tether bundles, cages, trusses, etc. Full contact dynamics was implemented. Programmatic interaction with simulation is possible - i.e. for control implementation. The underlying model has been experimentally validated and due to significant gravity influence, experiment had to be performed in microgravity conditions. Validation experiment for parabolic flight was a downscaled process of Envisat capturing. The prepacked net was launched towards the satellite model, it expanded, hit the model and wrapped around it. The whole process was recorded with 2 fast stereographic camera sets for full 3D trajectory reconstruction. The trajectories were used to compare net dynamics to respective simulations and then to validate the simulation tool. The experiments were performed on board of a Falcon-20 aircraft, operated by National Research Council in Ottawa, Canada. Validation results show that model reflects phenomenon physics accurately enough, so it may be used for scenario evaluation and mission design purposes. The functionalities of the simulator are described in detail in the paper, as well as its underlying model, sample cases and methodology behind validation. Results are presented and

Autonomous Rendezvous and Docking with Nonfull Field of View for Tethered Space Robot

Directory of Open Access Journals (Sweden)

Panfeng Huang

2017-01-01

Full Text Available In the ultra-close approaching phase of tethered space robot, a highly stable self-attitude control is essential. However, due to the field of view limitation of cameras, typical point features are difficult to extract, where commonly adopted position-based visual servoing cannot be valid anymore. To provide robot’s relative position and attitude with the target, we propose a monocular visual servoing control method using only the edge lines of satellite brackets. Firstly, real time detection of edge lines is achieved based on image gradient and region growing. Then, we build an edge line based model to estimate the relative position and attitude between the robot and the target. Finally, we design a visual servoing controller combined with PD controller. Experimental results demonstrate that our algorithm can extract edge lines stably and adjust the robot’s attitude to satisfy the grasping requirements.

Tethered balloons for radio detection of ultra high energy cosmic neutrinos in Antarctica

Energy Technology Data Exchange (ETDEWEB)

Besson, D. [Department of Physics and Astronomy, University of Kansas, Lawrence 66045, KS (United States); Dagkesamanskii, R.; Kravchenko, E. [Radio Astronomy Observatory LPI RAS, Pushchino 142290, Moscow Region (Russian Federation); Kravchenko, I., E-mail: ikrav@cern.ch [Department of Physics and Astronomy, University of Nebraska, Lincoln, 68588, NE (United States); Zheleznykh, I. [Institute for Nuclear Research RAS, Moscow 117312 (Russian Federation)

2012-01-11

We present a brief overview of experimental efforts in Antarctica to search for radio pulses from electron-hadron cascades produced by cosmic ultrahigh-energy neutrinos in Antarctic ice. Thus far, the essential features (energy thresholds, effective recording volumes, etc.) of Antarctic neutrino radio experiments can be classified according to the deployment scheme employed: either (1) on the surface of the glacier - RAMAND-type, (2) in holes in the ice at depths of several hundred meters - RICE-type or (3) on board of a stratospheric balloon at an altitude of 40 km - ANITA-type. We herein propose an alternative possibility, namely to use tethered balloons for placing the radio antennas at modest (compared to ANITA) altitudes above the ice surface (1-2 km). This configuration of antennas will reduce (as compared to ANITA) the energy threshold for detection of neutrinos and increase the observation time.

Tethered balloons for radio detection of ultra high energy cosmic neutrinos in Antarctica

International Nuclear Information System (INIS)

Besson, D.; Dagkesamanskii, R.; Kravchenko, E.; Kravchenko, I.; Zheleznykh, I.

2012-01-01

We present a brief overview of experimental efforts in Antarctica to search for radio pulses from electron-hadron cascades produced by cosmic ultrahigh-energy neutrinos in Antarctic ice. Thus far, the essential features (energy thresholds, effective recording volumes, etc.) of Antarctic neutrino radio experiments can be classified according to the deployment scheme employed: either (1) on the surface of the glacier - RAMAND-type, (2) in holes in the ice at depths of several hundred meters - RICE-type or (3) on board of a stratospheric balloon at an altitude of 40 km - ANITA-type. We herein propose an alternative possibility, namely to use tethered balloons for placing the radio antennas at modest (compared to ANITA) altitudes above the ice surface (1-2 km). This configuration of antennas will reduce (as compared to ANITA) the energy threshold for detection of neutrinos and increase the observation time.

Subunit Organisation of In Vitro Reconstituted HOPS and CORVET Multisubunit Membrane Tethering Complexes

Science.gov (United States)

Guo, Zhong; Johnston, Wayne; Kovtun, Oleksiy; Mureev, Sergey; Bröcker, Cornelia; Ungermann, Christian; Alexandrov, Kirill

2013-01-01

Biochemical and structural analysis of macromolecular protein assemblies remains challenging due to technical difficulties in recombinant expression, engineering and reconstitution of multisubunit complexes. Here we use a recently developed cell-free protein expression system based on the protozoan Leishmania tarentolae to produce in vitro all six subunits of the 600 kDa HOPS and CORVET membrane tethering complexes. We demonstrate that both subcomplexes and the entire HOPS complex can be reconstituted in vitro resulting in a comprehensive subunit interaction map. To our knowledge this is the largest eukaryotic protein complex in vitro reconstituted to date. Using the truncation and interaction analysis, we demonstrate that the complex is assembled through short hydrophobic sequences located in the C-terminus of the individual Vps subunits. Based on this data we propose a model of the HOPS and CORVET complex assembly that reconciles the available biochemical and structural data. PMID:24312556

XMRV: usage of receptors and potential co-receptors

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Gaddam Durga

2011-09-01

Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

Quantifying the Role of Atmospheric Forcing in Ice Edge Retreat and Advance Including Wind-Wave Coupling

Science.gov (United States)

2015-09-30

Low-Level Profiles, Pressure, Temperature, Humidity Rawinsonde (Kite, Tethered Balloon , Unmanned Aerial vehicle) Wave Characteristics, Wind wave and...Thermistor, Ship intake, Manual Bucket Tropospheric Profiles, 4/day – Pressure, Temperature, Humidity, Wind Vector Rawinsonde (Weather Balloon

The N-terminal domains of Vps3 and Vps8 are critical for localization and function of the CORVET tethering complex on endosomes.

Directory of Open Access Journals (Sweden)

Nadine Epp

Full Text Available Endosomal biogenesis depends on multiple fusion and fission events. For fusion, the heterohexameric CORVET complex as an effector of the endosomal Rab5/Vps21 GTPase has a central function in the initial tethering event. Here, we show that the CORVET-specific Vps3 and Vps8 subunits, which interact with Rab5/Vps21, require their N-terminal domains for localization and function. Surprisingly, CORVET may lack either one of the two N-terminal domains, but not both, to promote protein sorting via the endosome. The dually truncated complex mislocalizes to the cytosol and is impaired in endocytic protein sorting, but not in assembly. Furthermore, the endosomal localization can be rescued by overexpression of Vps21 or one of the truncated CORVET subunits, even though CORVET assembly is not impaired by loss of the N-terminal domains or in strains lacking all endosomal Rab5s and Ypt7. We thus conclude that CORVET requires only its C-terminal domains for assembly and has beyond its putative β-propeller domains additional binding sites for endosomes, which could be important to bind Vps21 and other endosome-specific factors for efficient endosome tethering.

Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor

DEFF Research Database (Denmark)

Gårdsvoll, Henrik; Kjærgaard, Magnus; Jacobsen, Benedikte

2011-01-01

The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed that the ......The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed...... that the adhesive function of uPAR is allosterically regulated via a "tightening" of its three-domain structure elicited by uPA binding. To challenge this proposition, we redesigned the uPAR structure to limit its inherent conformational flexibility by covalently tethering domains DI and DIII via a non...... adhering to vitronectin. In this respect, the engineered constraint in uPAR(H47C-N259C) thus bypasses the regulatory role of uPA binding, resulting in a constitutively active uPAR. In conclusion, our data argue for a biological relevance of the interdomain dynamics of the glycolipid-anchored u...

How calcium makes endocytic receptors attractive

DEFF Research Database (Denmark)

Andersen, Christian B F; Moestrup, Søren K

2014-01-01

of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

Prostaglandin Receptor Signaling in Disease

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Toshiyuki Matsuoka

2007-01-01

Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

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Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Angiotensin type 2 receptors

DEFF Research Database (Denmark)

Sumners, Colin; de Kloet, Annette D; Krause, Eric G

2015-01-01

In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

Localization of mineralocorticoid receptors at mammalian synapses.

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Eric M Prager

Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

Synthesis and Properties of Chiral Thioureas Bearing an Additional Function at a Remote Position Tethered by a 1,5-Disubstituted Triazole

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Yoshiji Takemoto

2010-11-01

Full Text Available The synthesis and properties of multifunctional thioureas bearing a variety of functional groups at a position remote from the thiourea moiety are described. A 1,5-disubstituted triazole tether connected with a thiourea and another functional group was synthesized via ruthenium catalyzed Huisgen cycloaddition. We demonstrate the utility of the synthetic thioureas as asymmetric catalysts and probes for the mechanistic elucidation of the course of the Michael reaction of an α,β-unsaturated imide

A new class of tunable hypersonic phononic crystals based on polymer-tethered colloids.

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Alonso-Redondo, E; Schmitt, M; Urbach, Z; Hui, C M; Sainidou, R; Rembert, P; Matyjaszewski, K; Bockstaller, M R; Fytas, G

2015-09-22

The design and engineering of hybrid materials exhibiting tailored phononic band gaps are fundamentally relevant to innovative material technologies in areas ranging from acoustics to thermo-optic devices. Phononic hybridization gaps, originating from the anti-crossing between local resonant and propagating modes, have attracted particular interest because of their relative robustness to structural disorder and the associated benefit to 'manufacturability'. Although hybridization gap materials are well known, their economic fabrication and efficient control of the gap frequency have remained elusive because of the limited property variability and expensive fabrication methodologies. Here we report a new strategy to realize hybridization gap materials by harnessing the 'anisotropic elasticity' across the particle-polymer interface in densely polymer-tethered colloidal particles. Theoretical and Brillouin scattering analysis confirm both the robustness to disorder and the tunability of the resulting hybridization gap and provide guidelines for the economic synthesis of new materials with deliberately controlled gap position and width frequencies.

A new class of tunable hypersonic phononic crystals based on polymer-tethered colloids

Science.gov (United States)

Alonso-Redondo, E.; Schmitt, M.; Urbach, Z.; Hui, C. M.; Sainidou, R.; Rembert, P.; Matyjaszewski, K.; Bockstaller, M. R.; Fytas, G.

2015-09-01

The design and engineering of hybrid materials exhibiting tailored phononic band gaps are fundamentally relevant to innovative material technologies in areas ranging from acoustics to thermo-optic devices. Phononic hybridization gaps, originating from the anti-crossing between local resonant and propagating modes, have attracted particular interest because of their relative robustness to structural disorder and the associated benefit to `manufacturability'. Although hybridization gap materials are well known, their economic fabrication and efficient control of the gap frequency have remained elusive because of the limited property variability and expensive fabrication methodologies. Here we report a new strategy to realize hybridization gap materials by harnessing the `anisotropic elasticity' across the particle-polymer interface in densely polymer-tethered colloidal particles. Theoretical and Brillouin scattering analysis confirm both the robustness to disorder and the tunability of the resulting hybridization gap and provide guidelines for the economic synthesis of new materials with deliberately controlled gap position and width frequencies.

Sigma-2 receptor ligands QSAR model dataset

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Antonio Rescifina

2017-08-01

Full Text Available The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2 receptor ligands selective over Sigma-1 (σ1 receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together. Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included.

The novel 2Fe–2S outer mitochondrial protein mitoNEET displays conformational flexibility in its N-terminal cytoplasmic tethering domain

International Nuclear Information System (INIS)

Conlan, Andrea R.; Paddock, Mark L.; Axelrod, Herbert L.; Cohen, Aina E.; Abresch, Edward C.; Wiley, Sandra; Roy, Melinda; Nechushtai, Rachel; Jennings, Patricia A.

2009-01-01

The crystal structure of the anti-diabetic drug target mitoNEET obtained from a GFP fusion construct (1.4 Å resolution, R factor = 20.2%) shows that the CDGSH 2Fe–2S binding domains are superimposable with previously determined non-fused constructs. However, there is considerable flexibility in the position of the outer mitochondrial tethering arms resulting in two different conformations in the crystal structure. A primary role for mitochondrial dysfunction is indicated in the pathogenesis of insulin resistance. A widely used drug for the treatment of type 2 diabetes is pioglitazone, a member of the thiazolidinedione class of molecules. MitoNEET, a 2Fe–2S outer mitochondrial membrane protein, binds pioglitazone [Colca et al. (2004 ▶), Am. J. Physiol. Endocrinol. Metab.286, E252–E260]. The soluble domain of the human mitoNEET protein has been expressed C-terminal to the superfolder green fluorescent protein and the mitoNEET protein has been isolated. Comparison of the crystal structure of mitoNEET isolated from cleavage of the fusion protein (1.4 Å resolution, R factor = 20.2%) with other solved structures shows that the CDGSH domains are superimposable, indicating proper assembly of mitoNEET. Furthermore, there is considerable flexibility in the position of the cytoplasmic tethering arms, resulting in two different conformations in the crystal structure. This flexibility affords multiple orientations on the outer mitochondrial membrane

Osseointegration of titanium implants functionalised with phosphoserine-tethered poly(epsilon-lysine) dendrons: a comparative study with traditional surface treatments in sheep.

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Stübinger, Stefan; Nuss, Katja; Bürki, Alexander; Mosch, Isabel; le Sidler, Miché; Meikle, Steve T; von Rechenberg, Brigitte; Santin, Matteo

2015-02-01

The aim of this study was to analyse the osseointegrative potential of phosphoserine-tethered dendrons when applied as surface functionalisation molecules on titanium implants in a sheep model after 2 and 8 weeks of implantation. Uncoated and dendron-coated implants were implanted in six sheep. Sandblasted and etched (SE) or porous additive manufactured (AM) implants with and without additional dendron functionalisation (SE-PSD; AM-PSD) were placed in the pelvic bone. Three implants per group were examined histologically and six implants were tested biomechanically. After 2 and 8 weeks the bone-to-implant contact (BIC) total values of SE implants (43.7±12.2; 53.3±9.0%) and SE-PSD (46.7±4.5; 61.7±4.9%) as well as AM implants (20.49±5.1; 43.9±9.7%) and AM-PSD implants (19.7±3.5; 48.3±15.6%) showed no statistically significant differences. For SE-PSD and AM-PSD a separate analysis of only the cancellous BIC demonstrated a statistically significant difference after 2 and 8 weeks. Biomechanical findings proved the overall increased stability of the porous implants after 8 weeks. Overall, the great effect of implant macro design on osseointegration was further supported by additional phosphoserine-tethered dendrons for SE and AM implants.

Seventh Symposium on Subtypes of Musccarinic Receptors.

Science.gov (United States)

1997-01-01

nociceptive pain, are less than ideal. For mild to moderate pain, the first line of therapy includes aspirin, acetaminophen/ paracetamol , and nonsteroidal...due to receptor degradation triggered by prolonged carbachol occupancy. This down-regulation was accompanied by uncoupling of the M2-receptors after 24...be under control by the m3 mAChR, suggesting a complex receptor regulation of phosphoinositide metabolism, including degradation and synthesis. Future

Targeting the TAM Receptors in Leukemia.

Science.gov (United States)

Huey, Madeline G; Minson, Katherine A; Earp, H Shelton; DeRyckere, Deborah; Graham, Douglas K

2016-11-08

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

Targeting the TAM Receptors in Leukemia

Directory of Open Access Journals (Sweden)

Madeline G. Huey

2016-11-01

Full Text Available Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

Serotonin Receptors in Hippocampus

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Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

2012-01-01

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

Science.gov (United States)

Khan, Muhammad Zahid; He, Ling

2017-04-01

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

Restricted processing of CD16a/Fc γ receptor IIIa N-glycans from primary human NK cells impacts structure and function.

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Patel, Kashyap R; Roberts, Jacob T; Subedi, Ganesh P; Barb, Adam W

2018-03-09

CD16a/Fc γ receptor IIIa is the most abundant antibody Fc receptor expressed on human natural killer (NK) cells and activates a protective cytotoxic response following engagement with antibody clustered on the surface of a pathogen or diseased tissue. Therapeutic monoclonal antibodies (mAbs) with greater Fc-mediated affinity for CD16a show superior therapeutic outcome; however, one significant factor that promotes antibody-CD16a interactions, the asparagine-linked carbohydrates ( N -glycans), remains undefined. Here, we purified CD16a from the primary NK cells of three donors and identified a large proportion of hybrid (22%) and oligomannose N -glycans (23%). These proportions indicated restricted N -glycan processing and were unlike those of the recombinant CD16a forms, which have predominantly complex-type N -glycans (82%). Tethering recombinant CD16a to the membrane by including the transmembrane and intracellular domains and via coexpression with the Fc ϵ receptor γ-chain in HEK293F cells was expected to produce N -glycoforms similar to NK cell-derived CD16a but yielded N -glycoforms different from NK cell-derived CD16a and recombinant soluble CD16a. Of note, these differences in CD16a N -glycan composition affected antibody binding: CD16a with oligomannose N -glycans bound IgG1 Fc with 12-fold greater affinity than did CD16a having primarily complex-type and highly branched N -glycans. The changes in binding activity mirrored changes in NMR spectra of the two CD16a glycoforms, indicating that CD16a glycan composition also affects the glycoprotein's structure. These results indicated that CD16a from primary human NK cells is compositionally, and likely also functionally, distinct from commonly used recombinant forms. Furthermore, our study provides critical evidence that cell lineage determines CD16a N -glycan composition and antibody-binding affinity. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

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Petri, Doris; Schlicker, Eberhard

2016-07-01

The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

NRL tethered balloon measurements at San Nicolas Island during FIRE IFO 1987

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Gerber, Hermann; Gathman, Stuart; James, Jeffrey; Smith, Mike; Consterdine, Ian; Brandeki, Scott

1990-01-01

An overview is given of the tethered balloon measurements made during the First ISCCP Regional Experiment (FIRE) marine stratocumulus intensive field observations (IFO) at San Nicolas Island in 1987. The instrument utilized on the balloon flights, the 17 flights over a 10 day period, the state of the data analysis, and some preliminary results are described. A goal of the measurements with the Naval Research Laboratory (NRL) balloon was to give a unique and greatly improved look at the microphysics of the clear and cloud-topped boundary layer. For this goal, collocated measurements were made of turbulence, aerosol, cloud particles, and meteorology. Two new instruments which were expected to make significant contributions to this effort were the saturation hygrometer, capable of measuring 95 percent less than RH 105 percent (with an accuracy of 0.05 percent near 100 percent) and used for the first time in clouds; and the forward scatter meter which gives in situ LWC measurements at more than 10 Hz. The data set, while unfortunately only partially simultaneous with the bulk of the FIRE stratocumulus observations, is unique and worthwhile in its own right. For the first time accurate RH measurements near 100 percent have been made in-cloud; although, the use of the saturation hygrometer reflected a learning experience which will result is substantially better performance the next time. These measurements were made in conjunction with other microphysical measurements such as aerosol and cloud droplet spectra, and perhaps most important of all, they were all collocated with bivane turbulence measurements thus permitting flux calculations. Thus the analysis of this data set, which consisted of about 50 percent stratocumulus cases including increasing and decreasing partial cloud cover, should lead to new insights on the physical mechanisms which drive the boundary-layer/cloud/turbulence system.

The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

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Ngai John

2006-12-01

Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

Receptor conversion in distant breast cancer metastases

NARCIS (Netherlands)

Hoefnagel, L.D.C.

2013-01-01

The routine pathological work-up of breast cancer includes the evaluation of the estrogen receptor (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) which reveals biological information about the tumour as well as provides predictive biomarkers regarding hormonal

Scavenger receptors in homeostasis and immunity.

Science.gov (United States)

Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

2013-09-01

Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

The Medicago truncatula lysine motif-receptor-like kinase gene family includes NFP and new nodule-expressed genes

NARCIS (Netherlands)

Arrighi, J.F.; Barre, A.; Amor, Ben B.; Bersoult, A.; Campos Soriano, L.; Mirabella, R.; Carvalho-Niebel, de F.; Journet, E.P.; Ghérardi, M.; Huguet, T.; Geurts, R.; Dénarié, J.; Rougé, P.; Gough, C.

2006-01-01

Rhizobial Nod factors are key symbiotic signals responsible for starting the nodulation process in host legume plants. Of the six Medicago truncatula genes controlling a Nod factor signaling pathway, Nod Factor Perception (NFP) was reported as a candidate Nod factor receptor gene. Here, we provide

Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

DEFF Research Database (Denmark)

Sivertsen, B; Holliday, N; Madsen, A N

2013-01-01

UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

Turbulence measurements using tethered balloon instrumentation during FIRE 1987

Science.gov (United States)

Hignett, Phillip

1990-01-01

As part of the surface-based observations conducted on San Nicolas Island, the U.K. Meteorological Office operated a set of turbulence probes attached to a balloon tether cable. Typically six probes were used, each capable of measuring momentum, heat, and humidity fluxes. Two probes were fitted with net radiometers, one positioned above cloud and the other below; a third probe carried a Lyman-alpha hygrometer fitted with a pre-heater for the measurement of total water content. Some preliminary results are presented from the 14th July describing the variation in structure of the cloudy boundary layer during the daytime. This day was characterized by a complete cloud cover, an inversion height of approximately 600 m. and north-westerly winds of approximately 6 m.s(-1). As an illustration the equivalent potential temperature derived from a profile ascent made between approximately 0830 and 0930 (PDT) is shown. The data has been smoothed to a height resolution of about 4 metres. At this time the cloud base was approximately 200 m. and very light drizzle was reaching the surface. The vertical velocity variance and potential temperature flux for two periods are shown; the first (shown by full lines) immediately follows the profile and the second (shown by dashed lines) is central around 1400 (PDT). The data have been normalized by their maximum values in the first period. Cloud base has now risen to approximately 300 m. There is a marked variation during the morning, particularly in sigma w. The net radiative flux above cloud top has by now reached its maximum value.

Biogenic nonmethane hydrocarbon emissions estimated from tethered balloon observations

Science.gov (United States)

Davis, K. J.; Lenschow, D. H.; Zimmerman, P. R.

1994-01-01

A new technique for estimating surface fluxes of trace gases, the mixed-layer gradient technique, is used to calculate isoprene and terpene emissions from forests. The technique is applied to tethered balloon measurements made over the Amazon forest and a pine-oak forest in Alabama at altitudes up to 300 m. The observations were made during the dry season Amazon Boundary Layer Experiment (ABLE 2A) and the Rural Oxidants in the Southern Environment 1990 experiment (ROSE I). Results from large eddy simulations of scalar transport in the clear convective boundary layer are used to infer fluxes from the balloon profiles. Profiles from the Amazon give a mean daytime emission of 3630 +/- 1400 micrograms isoprene sq m/h, where the uncertainty represents the standard deviation of the mean of eight flux estimates. Twenty profiles from Alabama give emissions of 4470 +/- 3300 micrograms isoprene sq m/h, 1740 +/- 1060 micrograms alpha-pinene sq m/h, and 790 +/- 560 micrograms beta-pinene sq m/h, respectively. These results are in agreement with emissions derived from chemical budgets. The emissions may be overestimated because of uncertainty about how to incorporate the effects of the canopy on the mixed-layer gradients. The large variability in these emission estimates is probably due to the relatively short sampling times of the balloon profiles, though spatially heterogeneous emissions may also play a role. Fluxes derived using this technique are representative of an upwind footprint of several kilometers and are independent of hydrocarbon oxidation rate and mean advection.

Low-Cost Propellant Launch From a Tethered Balloon

Science.gov (United States)

Wilcox, Brian

2006-01-01

A document presents a concept for relatively inexpensive delivery of propellant to a large fuel depot in low orbit around the Earth, for use in rockets destined for higher orbits, the Moon, and for remote planets. The propellant is expected to be at least 85 percent of the mass needed in low Earth orbit to support the NASA Exploration Vision. The concept calls for the use of many small ( 10 ton) spin-stabilized, multistage, solid-fuel rockets to each deliver 250 kg of propellant. Each rocket would be winched up to a balloon tethered above most of the atmospheric mass (optimal altitude 26 2 km). There, the rocket would be aimed slightly above the horizon, spun, dropped, and fired at a time chosen so that the rocket would arrive in orbit near the depot. Small thrusters on the payload (powered, for example, by boil-off gases from cryogenic propellants that make up the payload) would precess the spinning rocket, using data from a low-cost inertial sensor to correct for small aerodynamic and solid rocket nozzle misalignment torques on the spinning rocket; would manage the angle of attack and the final orbit insertion burn; and would be fired on command from the depot in response to observations of the trajectory of the payload so as to make small corrections to bring the payload into a rendezvous orbit and despin it for capture by the depot. The system is low-cost because the small rockets can be mass-produced using the same techniques as those to produce automobiles and low-cost munitions, and one or more can be launched from a U.S. territory on the equator (Baker or Jarvis Islands in the mid-Pacific) to the fuel depot on each orbit (every 90 minutes, e.g., any multiple of 6,000 per year).

Accurate and rapid modeling of iron–bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis

OpenAIRE

Harsch, Andreas; Marzilli, Lisa A.; Bunt, Richard C.; Stubbe, Joanne; Vouros, Paul

2000-01-01

Bleomycin B2 (BLM) in the presence of iron [Fe(II)] and O2 catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands were used in this investigation, allowing facile monitoring of all ss and ds cleavage events. A sequence for site-specific binding and cleavage by Fe–BLM was incorporated into each an...

Human dopamine receptor and its uses

Energy Technology Data Exchange (ETDEWEB)

Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

1999-01-01

The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

Ror receptor tyrosine kinases: orphans no more

OpenAIRE

Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

2008-01-01

Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

Synthesis of Cyclohexane-Fused Isocoumarins via Cationic Palladium(II)-Catalyzed Cascade Cyclization Reaction of Alkyne-Tethered Carbonyl Compounds Initiated by Intramolecular Oxypalladation of Ester-Substituted Aryl Alkynes.

Science.gov (United States)

Zhang, Jianbo; Han, Xiuling; Lu, Xiyan

2016-04-15

A cationic Pd(II)-catalyzed cascade cyclization reaction of alkyne-tethered carbonyl compounds was developed. This reaction is initiated by intramolecular oxypalladation of alkynes with an ester group followed by 1,2-addition of the formed C-Pd(II) bond to the carbonyl group, providing a highly efficient method for the synthesis of cyclohexane-fused isocoumarins.

Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-05-05

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-06-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Science.gov (United States)

Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

2008-01-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

Some theoretical aspects of hormone receptor determination

International Nuclear Information System (INIS)

Sluiter, W.J.

1981-01-01

Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

Labeled receptor ligands for spect

International Nuclear Information System (INIS)

Kung, H.F.

1989-01-01

Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

Identification of the receptor scavenging hemopexin-heme complexes

DEFF Research Database (Denmark)

Hvidberg, Vibeke; Maniecki, Maciej B; Jacobsen, Christian

2005-01-01

and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons......, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin......-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation....

Adenosine receptor desensitization and trafficking.

Science.gov (United States)

Mundell, Stuart; Kelly, Eamonn

2011-05-01

As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

Quantifying parenchymal tethering in a finite element simulation of a human lung slice under bronchoconstriction.

Science.gov (United States)

Breen, Barbara J; Donovan, Graham M; Sneyd, James; Tawhai, Merryn H

2012-08-15

Airway hyper-responsiveness (AHR), a hallmark of asthma, is a highly complex phenomenon characterised by multiple processes manifesting over a large range of length and time scales. Multiscale computational models have been derived to embody the experimental understanding of AHR. While current models differ in their derivation, a common assumption is that the increase in parenchymal tethering pressure P(teth) during airway constriction can be described using the model proposed by Lai-Fook (1979), which is based on intact lung experimental data for elastic moduli over a range of inflation pressures. Here we reexamine this relationship for consistency with a nonlinear elastic material law that has been parameterised to the pressure-volume behaviour of the intact lung. We show that the nonlinear law and Lai-Fook's relationship are consistent for small constrictions, but diverge when the constriction becomes large. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmacological significance of the interplay between angiotensin receptors: MAS receptors as putative final mediators of the effects elicited by angiotensin AT1 receptors antagonists.

Science.gov (United States)

Pernomian, Larissa; Pernomian, Laena; Gomes, Mayara S; da Silva, Carlos H T P

2015-12-15

The interplay between angiotensin AT1 receptors and MAS receptors relies on several inward regulatory mechanisms from renin-angiotensin system (RAS) including the functional crosstalk between angiotensin II and angiotensin-(1-7), the competitive AT1 antagonism exhibited by angiotensin-(1-7), the antagonist feature assigned to AT1/MAS heterodimerization on AT1 signaling and the AT1-mediated downregulation of angiotensin-converting enzyme 2 (ACE2). Recently, such interplay has acquired an important significance to RAS Pharmacology since a few studies have supporting strong evidences that MAS receptors mediate the effects elicited by AT1 antagonists. The present Perspective provides an overview of the regulatory mechanisms involving AT1 and MAS receptors, their significance to RAS Pharmacology and the future directions on the interplay between angiotensin receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

A candidate pheromone receptor and two odorant receptors of the hawkmoth Manduca sexta.

Science.gov (United States)

Patch, Harland M; Velarde, Rodrigo A; Walden, Kimberly K O; Robertson, Hugh M

2009-05-01

In this study, we cloned and characterized three Manduca sexta odorant receptors (ORs). One receptor is a putative pheromone receptor expressed exclusively in a cell associated with male-specific type-I trichoid sensilla. We describe the results of real-time PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) experiments that show MsextaOR1 is expressed only in male antennae. In situ hybridization labels a single cell associated with type-1 trichoid sensilla, which houses two neurons that have been previously determined to respond to the major components of the pheromone blend. The second receptor, MsextaOR2, was discovered using degenerate primers designed to conserved motifs of a unique group ORs that share as much as 88% identity. Comparison of RT-PCR, qRT-PCR, and in situ hybridization results with those of ORs in the Drosophila melanogaster Or83b subfamily shows a strong sequence and expression pattern similarity. The third receptor, MsextaOR3, was found by 5'-end sequencing of a normalized and subtracted cDNA library from male M. sexta antennae. RT-PCR and qRT-PCR show that this receptor is expressed only in male and female antennae. These are the first ORs, including a putative pheromone receptor, to be described from M. sexta.

Synthesis and characterization of tethered lipid assemblies for membrane protein reconstitution (Review).

Science.gov (United States)

Veneziano, Rémi; Rossi, Claire; Chenal, Alexandre; Brenner, Catherine; Ladant, Daniel; Chopineau, Joël

2017-09-28

Biological membranes and their related molecular mechanisms are essential for all living organisms. Membranes host numerous proteins and are responsible for the exchange of molecules and ions, cell signaling, and cell compartmentation. Indeed, the plasma membrane delimits the intracellular compartment from the extracellular environment and intracellular membranes. Biological membranes also play a major role in metabolism regulation and cellular physiology (e.g., mitochondrial membranes). The elaboration of membrane based biomimetic systems allows us to reconstitute and investigate, in controlled conditions, biological events occurring at the membrane interface. A whole variety of model membrane systems have been developed in the last few decades. Among these models, supported membranes were developed on various hydrophilic supports. The use of solid supports enables the direct use of surface sensitive techniques (e.g., surface plasmon resonance, quartz crystal microbalance, and atomic force microscopy) to monitor and quantify events occurring at the membrane surface. Tethered bilayer membranes (tBLMs) could be considered as an achievement of the first solid supported membranes described by the McConnell group. Tethered bilayers on solid supports were designed to delimit an inside compartment from an outside one. They were used for measuring interactions with ligands or incorporating large membrane proteins or complexes without interference with the support. In this context, the authors developed an easy concept of versatile tBLMs assembled on amino coated substrates that are formed upon the vesicle fusion rupture process applicable to protein-free vesicles as well as proteoliposomes. The phospholipid bilayer (natural or synthetic lipids) incorporated 5% of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-N-hydroxy succinimide to ensure the anchorage of the bilayer to the amino coated surface. The conditions for the formation of tBLMs on amino

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

Science.gov (United States)

Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

2015-08-19

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

Xenobiotics and the Glucocorticoid Receptor

International Nuclear Information System (INIS)

Gulliver, Linda S M

2017-01-01

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

Xenobiotics and the Glucocorticoid Receptor

Energy Technology Data Exchange (ETDEWEB)

Gulliver, Linda S M, E-mail: linda.gulliver@otago.ac.nz

2017-03-15

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

Overview of receptor-based source apportionment studies for speciated atmospheric mercury

OpenAIRE

Cheng, I.; Xu, X.; Zhang, L.

2015-01-01

Receptor-based source apportionment studies of speciated atmospheric mercury are not only concerned with source contributions but also with the influence of transport, transformation, and deposition processes on speciated atmospheric mercury concentrations at receptor locations. Previous studies applied multivariate receptor models including principal components analysis and positive matrix factorization, and back trajectory receptor models including potential source contri...

Multiple kisspeptin receptors in early Osteichthyans provide new insights into the evolution of this receptor family

DEFF Research Database (Denmark)

Pasquier, J.; Lafont, A._G.; Jeng, S.-R.

2012-01-01

Deorphanization of GPR54 receptor a decade ago led to the characterization of the kisspeptin receptor (Kissr) in mammals and the discovery of its major role in the brain control of reproduction. While a single gene encodes for Kissr in eutherian mammals including human, other vertebrates present ...

Development programme update for a socket solution offering a highly efficient termination of polyester mooring tethers

International Nuclear Information System (INIS)

Firth, Kevin M.; Calverley, Steve; Quintas, Manuel Pedro

2000-01-01

Bridon have previously developed a patented 'Socket and Spike' design for polyester tethers comprising a parallel array of seven sub-ropes. This phase of the development was successfully completed, subsequently Bridon have embarked on a new phase which aims to increase the efficiency of the socket and address the assembly problems that have been identified. The development has continued with the 'Socket and Spike' principle but a unique termination method has been devised such that each sub-rope is terminated in it is own mini-socket and pre-loaded prior to fitting into the main socket ensuring zero slippage and equal transfer of the mooring load. The sub-ropes are nested into the main socket body resulting in a socket termination that lighter, more efficient and easier to handle than the current method of spliced eye incorporating a steel spool and shackle. (author)

Lipid raft integrity affects GABAA receptor, but not NMDA receptor modulation by psychopharmacological compounds.

Science.gov (United States)

Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Uhr, Manfred; Wagner, Eva-Maria; Gilling, Kate E; Parsons, Chris G; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer; Rammes, Gerhard

2013-07-01

Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.

Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

Science.gov (United States)

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Multi-Sensor RSS Spatial Sensing-Based Robust Stochastic Optimization Algorithm for Enhanced Wireless Tethering

CERN Document Server

Parasuraman, Ramviyas; Molinari, Luca; Kershaw, Keith; Di Castro, Mario; Masi, Alessandro; Ferre, Manuel

2014-01-01

The reliability of wireless communication in a network of mobile wireless robot nodes depends on the received radio signal strength (RSS). When the robot nodes are deployed in hostile environments with ionizing radiations (such as in some scientific facilities), there is a possibility that some electronic components may fail randomly (due to radiation effects), which causes problems in wireless connectivity. The objective of this paper is to maximize robot mission capabilities by maximizing the wireless network capacity and to reduce the risk of communication failure. Thus, in this paper, we consider a multi-node wireless tethering structure called the “server-relay-client” framework that uses (multiple) relay nodes in between a server and a client node. We propose a robust stochastic optimization (RSO) algorithm using a multi-sensor-based RSS sampling method at the relay nodes to efficiently improve and balance the RSS between the source and client nodes to improve the network capacity and to provide red...

Trapping or tethering stones (TS: A multifunctional device in the Pastoral Neolithic of the Sahara.

Directory of Open Access Journals (Sweden)

Marina Gallinaro

Full Text Available The Pierres de Ben Barour, also known as trapping or tethering stones (TS, are stone artefacts with notches or grooves usually interpreted as hunting devices on the basis of rock art engravings. Though their presence is a peculiar feature of desert landscapes from the Sahara to the Arabian Peninsula, we know little about their age, context and function. Here we present a new approach to the study of these artefacts based on a large dataset (837 items recorded in the Messak plateau (SW Libya. A statistically-based geoarchaeological survey carried out between 2007 and 2011 in Libya, alongside landscape and intra-site analyses of specific archaeological features (such as rock art, settlement and ceremonial contexts, reveal that these artefacts were used for a prolonged period, probably from the early Holocene. This was followed by a multifunctional use of these devices, particularly during the Pastoral Neolithic phase (ca. 6400-3000 cal BC, with the highest concentrations being found near ceremonial contexts related to cattle burials.

NRSAS: Nuclear Receptor Structure Analysis Servers.

NARCIS (Netherlands)

Bettler, E.J.M.; Krause, R.; Horn, F.; Vriend, G.

2003-01-01

We present a coherent series of servers that can perform a large number of structure analyses on nuclear hormone receptors. These servers are part of the NucleaRDB project, which provides a powerful information system for nuclear hormone receptors. The computations performed by the servers include

Analysis of tethered balloon, ceilometer and class sounding data taken on San Nicolas Island during the FIRE project

Science.gov (United States)

Schubert, Wayne H.; Ciesielski, Paul E.; Guinn, Thomas A.; Cox, Stephen K.; Mckee, Thomas B.

1990-01-01

During the FIRE Marine Stratocumulus Program on San Nicolas Island, Colorado State University (CSU) and the British Meteorological Office (BMO) operated separate instrument packages on the NASA tethered balloon. The CSU package contained instrumentation for the measurement of temperature, pressure, humidity, cloud droplet concentration, and long and short wave radiation. Eight research flights, performed between July 7 and July 14, are summarized. An analysis priority to the July 7, 8 and 11 flights was assigned for the purposes of comparing the CSU and BMO data. Results are presented. In addition, CSU operated a laser ceilometer for the determination of cloud base, and a CLASS radiosonde site which launched 69 sondes. Data from all of the above systems are being analyzed.

Flexural Stiffness of Myosin Va Subdomains as Measured from Tethered Particle Motion

Science.gov (United States)

Michalek, Arthur J.; Kennedy, Guy G.; Warshaw, David M.; Ali, M. Yusuf

2015-01-01

Myosin Va (MyoVa) is a processive molecular motor involved in intracellular cargo transport on the actin cytoskeleton. The motor's processivity and ability to navigate actin intersections are believed to be governed by the stiffness of various parts of the motor's structure. Specifically, changes in calcium may regulate motor processivity by altering the motor's lever arm stiffness and thus its interhead communication. In order to measure the flexural stiffness of MyoVa subdomains, we use tethered particle microscopy, which relates the Brownian motion of fluorescent quantum dots, which are attached to various single- and double-headed MyoVa constructs bound to actin in rigor, to the motor's flexural stiffness. Based on these measurements, the MyoVa lever arm and coiled-coil rod domain have comparable flexural stiffness (0.034 pN/nm). Upon addition of calcium, the lever arm stiffness is reduced 40% as a result of calmodulins potentially dissociating from the lever arm. In addition, the flexural stiffness of the full-length MyoVa construct is an order of magnitude less stiff than both a single lever arm and the coiled-coil rod. This suggests that the MyoVa lever arm-rod junction provides a flexible hinge that would allow the motor to maneuver cargo through the complex intracellular actin network. PMID:26770194

Tethered particle analysis of supercoiled circular DNA using peptide nucleic acid handles.

Science.gov (United States)

Norregaard, Kamilla; Andersson, Magnus; Nielsen, Peter Eigil; Brown, Stanley; Oddershede, Lene B

2014-09-01

This protocol describes how to monitor individual naturally supercoiled circular DNA plasmids bound via peptide nucleic acid (PNA) handles between a bead and a surface. The protocol was developed for single-molecule investigation of the dynamics of supercoiled DNA, and it allows the investigation of both the dynamics of the molecule itself and of its interactions with a regulatory protein. Two bis-PNA clamps designed to bind with extremely high affinity to predetermined homopurine sequence sites in supercoiled DNA are prepared: one conjugated with digoxigenin for attachment to an anti-digoxigenin-coated glass cover slide, and one conjugated with biotin for attachment to a submicron-sized streptavidin-coated polystyrene bead. Plasmids are constructed, purified and incubated with the PNA handles. The dynamics of the construct is analyzed by tracking the tethered bead using video microscopy: less supercoiling results in more movement, and more supercoiling results in less movement. In contrast to other single-molecule methodologies, the current methodology allows for studying DNA in its naturally supercoiled state with constant linking number and constant writhe. The protocol has potential for use in studying the influence of supercoils on the dynamics of DNA and its associated proteins, e.g., topoisomerase. The procedure takes ~4 weeks.

Quencher-free molecular beacon tethering 7-hydroxycoumarin detects targets through protonation/deprotonation.

Science.gov (United States)

Kashida, Hiromu; Yamaguchi, Kyohei; Hara, Yuichi; Asanuma, Hiroyuki

2012-07-15

In this study, we synthesized a simple but efficient quencher-free molecular beacon tethering 7-hydroxycoumarin on D-threoninol based on its pK(a) change. The pK(a) of 7-hydroxycoumarin in a single strand was determined as 8.8, whereas that intercalated in the duplex was over 10. This large pK(a) shift (more than 1.2) upon hybridization could be attributed to the anionic and hydrophobic microenvironment inside the DNA duplex. Because 7-hydroxycoumarin quenches its fluorescence upon protonation, the emission intensity of the duplex at pH 8.5 was 1/15 that of the single strand. We applied this quenching mechanism to the preparation of a quencher-free molecular beacon by introducing the dye into the middle of the stem part. In the absence of the target, the stem region formed a duplex and fluorescence was quenched. However, when the target was added, the molecular beacon opened and the dye was deprotonated. As a result, the emission intensity of the molecular beacon with the target was 10 times higher than that without the target. Accordingly, a quencher-free molecular beacon utilizing the pK(a) change was successfully developed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

Science.gov (United States)

Mizejewski, G J

2015-01-01

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

Real-time single-molecule tethered particle motion experiments reveal the kinetics and mechanisms of Cre-mediated site-specific recombination

Science.gov (United States)

Fan, Hsiu-Fang

2012-01-01

Tyrosine family recombinases (YRs) are widely utilized in genome engineering systems because they can easily direct DNA rearrangement. Cre recombinases, one of the most commonly used types of YRs, catalyze site-specific recombination between two loxP sites without the need for high-energy cofactors, other accessory proteins or a specific DNA target sequence between the loxP sites. Previous structural, analytical ultracentrifuge and electrophoretic analyses have provided details of the reaction kinetics and mechanisms of Cre recombinase activity; whether there are reaction intermediates or side pathways involved has been left unaddressed. Using tethered particle motion (TPM), the Cre-mediated site-specific recombination process has been delineated, from beginning to end, at the single-molecule level, including the formation of abortive complexes and wayward complexes blocking inactive nucleoprotein complexes from entering the recombination process. Reversibility in the strand-cleavage/-ligation process and the formation of a thermally stable Holliday junction intermediate were observed within the Cre-mediated site-specific recombination process. Rate constants for each elementary step, which explain the overall reaction outcomes under various conditions, were determined. Taking the findings of this study together, they demonstrate the potential of single-molecule methodology as an alternative approach for exploring reaction mechanisms in detail. PMID:22467208

Quantitative analysis of receptor imaging

International Nuclear Information System (INIS)

Fu Zhanli; Wang Rongfu

2004-01-01

Model-based methods for quantitative analysis of receptor imaging, including kinetic, graphical and equilibrium methods, are introduced in detail. Some technical problem facing quantitative analysis of receptor imaging, such as the correction for in vivo metabolism of the tracer and the radioactivity contribution from blood volume within ROI, and the estimation of the nondisplaceable ligand concentration, is also reviewed briefly

Effects of topology on the adsorption of singly tethered ring polymers to attractive surfaces.

Science.gov (United States)

Li, Bing; Sun, Zhao-Yan; An, Li-Jia

2015-07-14

We investigate the effect of topology on the equilibrium behavior of singly tethered ring polymers adsorbed on an attractive surface. We focus on the change of square radius of gyration Rg(2), the perpendicular component Rg⊥(2) and the parallel component Rg‖(2) to the adsorbing surface, the mean contacting number of monomers with the surface , and the monomer distribution along z-direction during transition from desorption to adsorption. We find that both of the critical point of adsorption εc and the crossover exponent ϕ depend on the knot type when the chain length of ring ranges from 48 to 400. The behaviors of Rg(2), Rg⊥(2), and Rg‖(2) are found to be dependent on the topology and the monomer-surface attractive strength. At weak adsorption, the polymer chains with more complex topology are more adsorbable than those with simple topology. However, at strong adsorption, the polymer chains with complex topology are less adsorbable. By analyzing the distribution of monomer along z-direction, we give a possible mechanism for the effect of topology on the adsorption behavior.

Posttranslational Modification Biology of Glutamate Receptors and Drug Addiction

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Li-Min eMao

2011-03-01

Full Text Available Posttranslational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues on their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling and protein-protein interactions, subcellular redistribution (trafficking, endocytosis, synaptic delivery and clustering, and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamines. Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction.

Expression and function of nicotinic acetylcholine receptors in stem cells

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Herman S. Cheung

2016-07-01

Full Text Available Nicotinic acetylcholine receptors are prototypical ligand gated ion channels typically found in muscular and neuronal tissues. Functional nicotinic acetylcholine receptors, however, have also recently been identified on other cell types, including stem cells. Activation of these receptors by the binding of agonists like choline, acetylcholine, or nicotine has been implicated in many cellular changes. In regards to stem cell function, nicotinic acetylcholine receptor activation leads to changes in stem cell proliferation, migration and differentiation potential. In this review we summarize the expression and function of known nicotinic acetylcholine receptors in different classes of stem cells including: pluripotent stem cells, mesenchymal stem cells, periodontal ligament derived stem cells, and neural progenitor cells and discuss the potential downstream effects of receptor activation on stem cell function.

Revisiting the tethered ureteral stents in children: a novel modification.

Science.gov (United States)

Kajbafzadeh, Abdol-Mohammad; Nabavizadeh, Behnam; Keihani, Sorena; Hosseini Sharifi, Seyed Hossein

2015-06-01

To propose a simple noninvasive method for ureteral stent retrieval using an extraction string sutured to the skin in children. A retrospective chart review was performed to gather relevant data from December 2005 to February 2013. After the surgeries, if indicated, a tethered double-J stent was placed in the ureter. A 5-0 non-absorbable Prolene stitch was used as an extraction string passing through the urethra and was sutured to subcoronal skin in boys or inner surface of labia majora in girls. For stent removal, a small amount of 2 % lidocaine jelly was pushed into the urethra 5 min before the procedure. The string was then pulled by continuous and gentle force until the entire stent was out. The suture was then cut to release the stent. No sedation or anesthesia was needed. A total of 378 double-J stents with extraction strings were inserted for a total of 325 patients (61.2 % male). Of the 53 patients with bilateral ureteral stents, one male patient (1.88 %) experienced early stent protrusion from urethral meatus. Two of 272 patients (0.73 %) with unilateral ureteral stent (one male and one female) encountered the same problem. All other stents were extracted successfully using the extraction string without any complications. No upward stent migration or suture site reaction was encountered. This method is a safe, easy-to-use, feasible and noninvasive alternative for cystoscopic stent removal with high success rate and minimal complications. This can lead to considerable saving in time and costs for patients, families and healthcare system.

Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self-Assembly of Distinct Amyloid Structures.

Science.gov (United States)

Ruiz, Jérémy; Boehringer, Régis; Grogg, Marcel; Raya, Jésus; Schirer, Alicia; Crucifix, Corinne; Hellwig, Petra; Schultz, Patrick; Torbeev, Vladimir

2016-12-02

Polymorphism is a common property of amyloid fibers that complicates their detailed structural and functional studies. Here we report experiments illustrating the chemical principles that enable the formation of amyloid polymorphs with distinct stoichiometric composition. Using appropriate covalent tethering we programmed self-assembly of a model peptide corresponding to the [20-41] fragment of human β2-microglobulin into fibers with either trimeric or dimeric amyloid cores. Using a set of biophysical and biochemical methods we demonstrated their distinct structural, morphological, and templating properties. Furthermore, we showed that supramolecular approaches in which the peptide is modified with bulky substituents can also be applied to modulate the formation of different fiber polymorphs. Such strategies, when applied to disease-related peptides and proteins, will greatly help in the evaluation of the biological properties of structurally distinct amyloids. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Bridging Water Anchors the Tethered 5-(3-Aminopropyl)-2′-deoxyuridine Amine in the DNA Major Groove Proximate to the N+2 C·G Base Pair: Implications for Formation of Interstrand 5′-GNC-3′ Cross-Links by Nitrogen Mustards‡

Science.gov (United States)

Wang, Feng; Li, Feng; Ganguly, Manjori; Marky, Luis A.; Gold, Barry; Egli, Martin; Stone, Michael P.

2009-01-01

Site-specific insertion of 5-(3-aminopropyl)-2′-deoxyuridine (Z3dU) and 7-deaza-dG into the Dickerson-Drew dodecamers 5′-d(C1G2C3G4A5A6T7T8C9Z10C11G12)-3′ · 5′-d(C13G14C15G16A17A18T19T20-C21Z22C23G24)-3′ (named DDDZ10) and 5′-d(C1G2C3G4A5A6T7X8C9Z10C11G12)-3′ · 5′-d(C13G14C15G16A17A18-T19X20C21Z22C23G24)-3′ (named DDD2+Z10)(X = Z3dU; Z = 7-deaza-dG) suggests a mechanism underlying the formation of interstrand N+2 DNA cross-links by nitrogen mustards, e.g., melphalan and mechlorethamine. Analysis of the DDD2+Z10 duplex reveals that the tethered cations at base pairs A5 · X20 and X8 · A17 extend within the major groove in the 3′-direction, toward conserved Mg2+ binding sites located adjacent to N+2 base pairs C3 · Z22 and Z10 · C15. Bridging waters located between the tethered amines and either Z10 or Z22 O6 stabilize the tethered cations and allow interactions with the N + 2 base pairs without DNA bending. Incorporation of 7-deaza-dG into the DDD2+Z10 duplex weakens but does not eliminate electrostatic interactions between tethered amines and Z10 O6 and Z22 O6. The results suggest a mechanism by which tethered N7-dG aziridinium ions, the active species involved in formation of interstrand 5′-GNC-3′ cross-links by nitrogen mustards, modify the electrostatics of the major groove and position the aziridinium ions proximate to the major groove edge of the N+2 C · G base pair, facilitating interstrand cross-linking. PMID:18549246

Comparison of acoustic properties of tethered flight sounds for wild, mass-reared, and irradiated melon flies, Dacus cucurbitae COQUILLETT (Diptera: Tephritidae)

International Nuclear Information System (INIS)

Kanmiya, Kenkichi; Nakagawa, Kohjin; Tanaka, Akira; Kamiwada, Hidemi.

1987-01-01

Acoustic properties of tethered flight sounds produced by the male melon fly, Dacus cucurbitae COQUILLETT in wild (W-), mass-reared (M-), and irradiated (I-) strains were analyzed. Properties included fundamental frequency (FFQ), peak power density of FFQ (PPD), overall root mean square value (ORMS), total harmonic RMS (THRMS), total harmonic distortion (THDIST), bandwidth of FFQ (BWFF), and the number of harmonics and wing-strokes. M- and I-strains developed FFQ 3 days earlier than the W-strain. The W-strain had a greater variance in the mean, and overall lower values for FFQ, PPD, and ORMS than M- and I-strains. The fluctuation of acoustic properties of wild strain with aging was markedly different from that of the laboratory strains. The fact that values of these parameters for laboratory strains developed at earlier adult age and continued relatively high may by due to selection effects. No significant differences were observed between laboratory strains resulting from effect of irradiation. There were, however, significant differences among the 6 parameters in 8 age groups which were recognized for 12 cases between W- and I-, 8 between W- and M-, and 4 between M- and I-strains. (author)

Involvement of Activating NK Cell Receptors and Their Modulation in Pathogen Immunity

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Francesco Marras

2011-01-01

Full Text Available Natural Killer (NK cells are endowed with cell-structure-sensing receptors providing inhibitory protection from self-destruction (inhibitory NK receptors, iNKRs, including killer inhibitory receptors and other molecules and rapid triggering potential leading to functional cell activation by Toll-like receptors (TLRs, cytokine receptors, and activating NK cell receptors including natural cytotoxicity receptors (NCRs, i.e., NKp46, NKp46, and NKp44. NCR and NKG2D recognize ligands on infected cells which may be endogenous or may directly bind to some structures derived from invading pathogens. In this paper, we address the known direct or indirect interactions between activating receptors and pathogens and their expression during chronic HIV and HCV infections.

Identification of Human P2X1 Receptor-interacting Proteins Reveals a Role of the Cytoskeleton in Receptor Regulation*

Science.gov (United States)

Lalo, Ulyana; Roberts, Jonathan A.; Evans, Richard J.

2011-01-01

P2X1 receptors are ATP-gated ion channels expressed by smooth muscle and blood cells. Carboxyl-terminally His-FLAG-tagged human P2X1 receptors were stably expressed in HEK293 cells and co-purified with cytoskeletal proteins including actin. Disruption of the actin cytoskeleton with cytochalasin D inhibited P2X1 receptor currents with no effect on the time course of the response or surface expression of the receptor. Stabilization of the cytoskeleton with jasplakinolide had no effect on P2X1 receptor currents but decreased receptor mobility. P2X2 receptor currents were unaffected by cytochalasin, and P2X1/2 receptor chimeras were used to identify the molecular basis of actin sensitivity. These studies showed that the intracellular amino terminus accounts for the inhibitory effects of cytoskeletal disruption similar to that shown for lipid raft/cholesterol sensitivity. Stabilization of the cytoskeleton with jasplakinolide abolished the inhibitory effects of cholesterol depletion on P2X1 receptor currents, suggesting that lipid rafts may regulate the receptor through stabilization of the cytoskeleton. These studies show that the cytoskeleton plays an important role in P2X1 receptor regulation. PMID:21757694

Action mechanisms of Liver X Receptors

Energy Technology Data Exchange (ETDEWEB)

Gabbi, Chiara; Warner, Margaret [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Gustafsson, Jan-Åke, E-mail: jgustafs@central.uh.edu [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Department of Biosciences and Nutrition, Karolinska Institutet, Novum S-141 86 (Sweden)

2014-04-11

Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors.

Action mechanisms of Liver X Receptors

International Nuclear Information System (INIS)

Gabbi, Chiara; Warner, Margaret; Gustafsson, Jan-Åke

2014-01-01

Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors

Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

Science.gov (United States)

Nishikawa, H; Hashino, A; Kume, T; Katsuki, H; Kaneko, S; Akaike, A

2000-09-15

This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.

Mediator and p300/CBP-Steroid Receptor Coactivator Complexes Have Distinct Roles, but Function Synergistically, during Estrogen Receptor α-Dependent Transcription with Chromatin Templates

OpenAIRE

Acevedo, Mari Luz; Kraus, W. Lee

2003-01-01

Ligand-dependent transcriptional activation by nuclear receptors involves the recruitment of various coactivators to the promoters of hormone-regulated genes assembled into chromatin. Nuclear receptor coactivators include histone acetyltransferase complexes, such as p300/CBP-steroid receptor coactivator (SRC), as well as the multisubunit mediator complexes (“Mediator”), which may help recruit RNA polymerase II to the promoter. We have used a biochemical approach, including an in vitro chromat...

Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

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Luigi F. Agnati

2007-01-01

Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

BOU: Development of a low-cost tethered balloon sensing system for monitoring the lower atmosphere

Science.gov (United States)

Picos, Rodrigo; Lopez-Grifol, Alvaro; Martinez-Villagrassa, Daniel; Simó, Gemma; Wenger, Burkhard; Dünnermann, Jens; Jiménez, Maria Antonia; Cuxart, Joan

2016-04-01

The study of the atmospheric boundary layer, the lowest part of the atmosphere, and the processes that occur therein often requires the observation of vertical profiles of the main meteorological variables, i.e. air temperature and humidity, wind vector and barometric pressure. In particular, when the interest is focused on the air-surface interactions, a high vertical resolution over the first 500 m is required for the observations to describe the physical processes that occur immediately above the surface. Typically, these needs are covered with the use of captive balloons, which are helium-filled balloons tethered to a winch on the ground and a sensor package suspended a short distance below the balloon. Since the commercial version of such instrumental platforms are scarce and expensive, a new low-cost device has been developed in the last years: BOU (tethered Balloon sonde OWL-UIB). In this paper, we focus on the sensor package and data acquisition system part, that is able to fulfill the low-cost requirements. The system uses a low-cost Arduino Mega board as the processor, and stores all the data in a SD card, though an RF connection is also possible but more unreliable. The system has been configured to sample temperature, humidity, air pressure, wind speed, having also a magnetometer and an accelerometer. Sampling time was 1 second, though it was possible to set it faster. It is worth mentioning that the system is easily reconfigurable, and more sensors can be added. The system is powered by a Polymer battery of 1800mA , allowing the system to run continously for more than 6 hours. The temperature is acquired using three different sensors (a HYT 271 calibrated sensor with an accuracy of ±0.2 °C, plus the internal temperature sensors of the wind and pressure sensors, with accuracies around ±0.5 °C). The humidity is also sensed using the calibrated HYT 271 sensor, which features an accuracy of ±1.8%. Air pressure is sensed using a BMP080 sensor, which

Crosslinked Aspartic Acids as Helix-Nucleating Templates.

Science.gov (United States)

Zhao, Hui; Liu, Qi-Song; Geng, Hao; Tian, Yuan; Cheng, Min; Jiang, Yan-Hong; Xie, Ming-Sheng; Niu, Xiao-Gang; Jiang, Fan; Zhang, Ya-Ou; Lao, Yuan-Zhi; Wu, Yun-Dong; Xu, Nai-Han; Li, Zi-Gang

2016-09-19

Described is a facile helix-nucleating template based on a tethered aspartic acid at the N-terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side-chain-end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N-terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix-stabilizing methods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

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Yasuko Kitagishi

2013-10-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Satoru, E-mail: smatsuda@cc.nara-wu.ac.jp; Kitagishi, Yasuko [Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506 (Japan)

2013-10-21

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

International Nuclear Information System (INIS)

Matsuda, Satoru; Kitagishi, Yasuko

2013-01-01

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer

Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

International Nuclear Information System (INIS)

Levy, J.R.; Olefsky, J.M.

1988-01-01

The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 0 C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 0 C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation

Low-Cost Propellant Launch to Earth Orbit from a Tethered Balloon

Science.gov (United States)

Wilcox, Brian H.

2006-01-01

Propellant will be more than 85% of the mass that needs to be lofted into Low Earth Orbit (LEO) in the planned program of Exploration of the Moon, Mars, and beyond. This paper describes a possible means for launching thousands of tons of propellant per year into LEO at a cost 15 to 30 times less than the current launch cost per kilogram. The basic idea is to mass-produce very simple, small and relatively low-performance rockets at a cost per kilogram comparable to automobiles, instead of the 25X greater cost that is customary for current launch vehicles that are produced in small quantities and which are manufactured with performance near the limits of what is possible. These small, simple rockets can reach orbit because they are launched above 95% of the atmosphere, where the drag losses even on a small rocket are acceptable, and because they can be launched nearly horizontally with very simple guidance based primarily on spin-stabilization. Launching above most of the atmosphere is accomplished by winching the rocket up a tether to a balloon. A fuel depot in equatorial orbit passes over the launch site on every orbit (approximately every 90 minutes). One or more rockets can be launched each time the fuel depot passes overhead, so the launch rate can be any multiple of 6000 small rockets per year, a number that is sufficient to reap the benefits of mass production.

Palmitoylation as a Functional Regulator of Neurotransmitter Receptors

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Vladimir S. Naumenko

2018-01-01

Full Text Available The majority of neuronal proteins involved in cellular signaling undergo different posttranslational modifications significantly affecting their functions. One of these modifications is a covalent attachment of a 16-C palmitic acid to one or more cysteine residues (S-palmitoylation within the target protein. Palmitoylation is a reversible modification, and repeated cycles of palmitoylation/depalmitoylation might be critically involved in the regulation of multiple signaling processes. Palmitoylation also represents a common posttranslational modification of the neurotransmitter receptors, including G protein-coupled receptors (GPCRs and ligand-gated ion channels (LICs. From the functional point of view, palmitoylation affects a wide span of neurotransmitter receptors activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, recycling, and synaptic clustering. This review summarizes the current knowledge on the palmitoylation of neurotransmitter receptors and its role in the regulation of receptors functions as well as in the control of different kinds of physiological and pathological behavior.

Back to Future Health Blueprint: The Effects of a Brief Bioenergy Economy Program on a Patient with Tethered Cord Syndrome

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Farzad Goli

2016-12-01

Full Text Available Background: The spinal cord congenital abnormalities may prevent normal cephalad movement of the conusmedullaris such as tethered cord. A child or even an adult with these abnormalities may develop progressiveneurological dysfunction due to traction on the cord or nerve roots. As the most problematic technicalconsideration in surgery for the release of the tethered cord is how to preserve functions of neural elementsand rebuild the dural sac to maintain normal cerebrospinal fluid (CSF circulation; the priority is to treat thecondition through less invasive methods. Bioenergy economy (BEE is an integrative healing model which triesto abstract healing modalities and integrate them into a psychosomatic health system. In contrast toreductionistic and pathology-based approach of biomedical treatment, bioenergy healing is a salutogenic,holistic and metadiagnostic approach which creates healing responses from a blueprint of healthy body.Case Report: We report the process of a bioenergy economy intervention in a 10-year-old boy withclinical signs of drop foot, urinary incontinence, urinary reflux, and low back pain who was candidate forsurgeries by neurosurgical and urological criteria. The clinical results indicated that after about two yearsof 12 healing sessions in a brief bioenergy economy package of biofield scanning, biofield attunement,and hand-on self-healing, the patient’s clinical signs remarkably improved to the extent that he returned tonormal activities of his age and followed an athletic lifestyle.Conclusion: From a biosemiotic viewpoint, it can be discussed that bioenergy economy, by focusing onenhancing the pathways of salutogenesis was effective to evoke healing response in the patient’s body.The effect of the bioenergy economy practice may be due to the healing images and intentions flowedthrough patient’s body and healer-healee biofields’ coupling and interactions.

Evolution of endothelin receptors in vertebrates.

Science.gov (United States)

Braasch, Ingo; Schartl, Manfred

2014-12-01

Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

G protein-coupled receptor mutations and human genetic disease.

Science.gov (United States)

Thompson, Miles D; Hendy, Geoffrey N; Percy, Maire E; Bichet, Daniel G; Cole, David E C

2014-01-01

Genetic variations in G protein-coupled receptor genes (GPCRs) disrupt GPCR function in a wide variety of human genetic diseases. In vitro strategies and animal models have been used to identify the molecular pathologies underlying naturally occurring GPCR mutations. Inactive, overactive, or constitutively active receptors have been identified that result in pathology. These receptor variants may alter ligand binding, G protein coupling, receptor desensitization and receptor recycling. Receptor systems discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone (FSH), luteinizing hormone, gonadotropin-releasing hormone (GNRHR), adrenocorticotropic hormone, vasopressin, endothelin-β, purinergic, and the G protein associated with asthma (GPRA or neuropeptide S receptor 1 (NPSR1)). The role of activating and inactivating calcium-sensing receptor (CaSR) mutations is discussed in detail with respect to familial hypocalciuric hypercalcemia (FHH) and autosomal dominant hypocalemia (ADH). The CASR mutations have been associated with epilepsy. Diseases caused by the genetic disruption of GPCR functions are discussed in the context of their potential to be selectively targeted by drugs that rescue altered receptors. Examples of drugs developed as a result of targeting GPCRs mutated in disease include: calcimimetics and calcilytics, therapeutics targeting melanocortin receptors in obesity, interventions that alter GNRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor congenital bleeding phenotype. De-orphanization projects have identified novel disease-associated receptors, such as NPSR1 and GPR35. The identification of variants in these receptors provides genetic reagents useful in drug screens. Discussion of the variety of GPCRs that are disrupted in monogenic Mendelian disorders provides the basis for examining the significance of common

Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

International Nuclear Information System (INIS)

Magno, Aaron L.; Ingley, Evan; Brown, Suzanne J.; Conigrave, Arthur D.; Ratajczak, Thomas; Ward, Bryan K.

2011-01-01

Highlights: → A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. → The second zinc finger of LIM domain 1 of testin is critical for interaction. → Testin bound to a region of the receptor tail important for cell signalling. → Testin and receptor interaction was confirmed in mammalian (HEK293) cells. → Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

Differences between tethered polyelectrolyte chains adsorbed onto bare mica and hydrophobically modified mica, comparison with theory.

Science.gov (United States)

Balastre, Marc; Tamashiro, Mario N.; Hernandez, Ernesto; Pincus, Philip; Tirrell, Matthew

2001-03-01

End-grafted polymers generated from the adsorption of asymmetric diblock copolymers on solid surface play an important role in many areas of science and technology. While the small insoluble block acts as an anchor, the charged soluble block confers useful properties to the surface. This study looks at tethered layers of poly(styrene sulfonate)/poly(t-butyl styrene) (PtBS-PSS) adsorbed on both mica (hydrophilic) and octadecyltriethoxysilane (OTE) modified mica (hydrophobic). Normal compressing forces at two different constant grafting densities (bare and modified mica) were measured with the surface force apparatus and compared with theoretical prediction. The effect of salt concentration (Cs) upon the thickness of the self-assembled layers (Lo) was measured in each case. For adsorption of diblock copolymers onto OTE the resulting scaling relationship is much closer to the brush theory, Lo Cs-1/3. This result suggests that the adsorbed amount on mica is not high enough to form a brush.

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.

Science.gov (United States)

Keedy, Daniel A; Hill, Zachary B; Biel, Justin T; Kang, Emily; Rettenmaier, T Justin; Brandao-Neto, Jose; Pearce, Nicholas M; von Delft, Frank; Wells, James A; Fraser, James S

2018-06-07

Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function. © 2018, Keedy et al.

Membrane Trafficking of Death Receptors: Implications on Signalling

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Wulf Schneider-Brachert

2013-07-01

Full Text Available Death receptors were initially recognised as potent inducers of apoptotic cell death and soon ambitious attempts were made to exploit selective ignition of controlled cellular suicide as therapeutic strategy in malignant diseases. However, the complexity of death receptor signalling has increased substantially during recent years. Beyond activation of the apoptotic cascade, involvement in a variety of cellular processes including inflammation, proliferation and immune response was recognised. Mechanistically, these findings raised the question how multipurpose receptors can ensure selective activation of a particular pathway. A growing body of evidence points to an elegant spatiotemporal regulation of composition and assembly of the receptor-associated signalling complex. Upon ligand binding, receptor recruitment in specialized membrane compartments, formation of receptor-ligand clusters and internalisation processes constitute key regulatory elements. In this review, we will summarise the current concepts of death receptor trafficking and its implications on receptor-associated signalling events.

Ror receptor tyrosine kinases: orphans no more.

Science.gov (United States)

Green, Jennifer L; Kuntz, Steven G; Sternberg, Paul W

2008-11-01

Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these mysterious proteins and, in particular, we focus on their function as Wnt receptors.

The cellular receptors of exogenous RNA

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Patryk Reniewicz

2016-04-01

Full Text Available One of the key determinants of survival for organisms is proper recognition of exogenous and endogenous nucleic acids. Therefore, high eukaryotes developed a number of receptors that allow for discrimination between friend or foe DNA and RNA. Appearance of exogenous RNA in cytoplasm provides a signal of danger and triggers cellular responses that facilitate eradication of a pathogen. Recognition of exogenous RNA is additionally complicated by fact that large amount of endogenous RNA is present in cytoplasm Thus, number of different receptors, found in eukaryotic cells, is able to recognize that nucleic acid. First group of those receptors consist endosomal Toll like receptors, namely TLR3, TLR7, TLR8 and TLR13. Those receptors recognize RNA released from pathogens that enter the cell by endocytosis. The second group includes cytoplasmic sensors like PKR and the family of RLRs comprised of RIG-I, MDA5 and LGP2. Cytoplasmic receptors recognize RNA from pathogens invading the cell by non-endocytic pathway. In both cases binding of RNA by its receptors results in activation of the signalling cascades that lead to the production of interferon and other cytokines.

Analysis of Structural Flexibility of Damaged DNA Using Thiol-Tethered Oligonucleotide Duplexes.

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Masashi Fujita

Full Text Available Bent structures are formed in DNA by the binding of small molecules or proteins. We developed a chemical method to detect bent DNA structures. Oligonucleotide duplexes in which two mercaptoalkyl groups were attached to the positions facing each other across the major groove were prepared. When the duplex contained the cisplatin adduct, which was proved to induce static helix bending, interstrand disulfide bond formation under an oxygen atmosphere was detected by HPLC analyses, but not in the non-adducted duplex, when the two thiol-tethered nucleosides were separated by six base pairs. When the insert was five and seven base pairs, the disulfide bond was formed and was not formed, respectively, regardless of the cisplatin adduct formation. The same reaction was observed in the duplexes containing an abasic site analog and the (6–4 photoproduct. Compared with the cisplatin case, the disulfide bond formation was slower in these duplexes, but the reaction rate was nearly independent of the linker length. These results indicate that dynamic structural changes of the abasic site- and (6–4 photoproduct-containing duplexes could be detected by our method. It is strongly suggested that the UV-damaged DNA-binding protein, which specifically binds these duplexes and functions at the first step of global-genome nucleotide excision repair, recognizes the easily bendable nature of damaged DNA.

Airborne imaging for heritage documentation using the Fotokite tethered flying camera

Science.gov (United States)

Verhoeven, Geert; Lupashin, Sergei; Briese, Christian; Doneus, Michael

2014-05-01

safe operation of these devices is still an issue, certainly when flying on locations which can be crowded (such as students on excavations or tourists walking around historic places). As the future of UAS regulation remains unclear, this talk presents an alternative approach to aerial imaging: the Fotokite. Developed at the ETH Zürich, the Fotokite is a tethered flying camera that is essentially a multi-copter connected to the ground with a taut tether to achieve controlled flight. Crucially, it relies solely on onboard IMU (Inertial Measurement Unit) measurements to fly, launches in seconds, and is classified as not a UAS (Unmanned Aerial System), e.g. in the latest FAA (Federal Aviation Administration) UAS proposal. As a result it may be used for imaging cultural heritage in a variety of environments and settings with minimal training by non-experienced pilots. Furthermore, it is subject to less extensive certification, regulation and import/export restrictions, making it a viable solution for use at a greater range of sites than traditional methods. Unlike a balloon or a kite it is not subject to particular weather conditions and, thanks to active stabilization, is capable of a variety of intelligent flight modes. Finally, it is compact and lightweight, making it easy to transport and deploy, and its lack of reliance on GNSS (Global Navigation Satellite System) makes it possible to use in urban, overbuilt areas. After outlining its operating principles, the talk will present some archaeological case studies in which the Fotokite was used, hereby assessing its capabilities compared to the conventional UAS's on the market.

Somatostatin receptors

DEFF Research Database (Denmark)

Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

2003-01-01

functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M₁, M₂, and M₄ receptor knockout mice

DEFF Research Database (Denmark)

Joseph, Lauren; Thomsen, Morgane

2017-01-01

Muscarinic M1/M4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (SD) effects, but the receptor subtypes mediating those...

Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

Science.gov (United States)

Taupin, J L; Anderson, P

1994-12-01

The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

Exciplex ensemble modulated by excitation mode in intramolecular charge-transfer dyad: effects of temperature, solvent polarity, and wavelength on photochemistry and photophysics of tethered naphthalene-dicyanoethene system.

Science.gov (United States)

Aoki, Yoshiaki; Matsuki, Nobuo; Mori, Tadashi; Ikeda, Hiroshi; Inoue, Yoshihisa

2014-09-19

Solvent, temperature, and excitation wavelength significantly affected the photochemical outcomes of a naphthalene-dicyanoethene system tethered by different number (n) of methylene groups (1-3). The effect of irradiation wavelength was almost negligible for 2a but pronounced for 3a. The temperature dependence and theoretical calculations indicated the diversity of exciplex conformations, an ensemble of which can be effectively altered by changing excitation wavelength to eventually switch the regioselectivity of photoreactions.

Mediator-dependent Nuclear Receptor Functions

Science.gov (United States)

Chen, Wei; Roeder, Robert

2011-01-01

As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

International Nuclear Information System (INIS)

Schliebs, R.; Walch, C.

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

Energy Technology Data Exchange (ETDEWEB)

Schliebs, R; Walch, C [Leipzig Univ. (German Democratic Republic). Bereich Medizin; Stewart, M G [Open Univ., Milton Keynes (UK)

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author).

Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

Science.gov (United States)

Keller, H; Givel, F; Perroud, M; Wahli, W

1995-07-01

Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling

Energy Technology Data Exchange (ETDEWEB)

Kumar, Manjeet; Kaur, Supinder; Nazir, Aamir; Tripathi, Raj Kamal, E-mail: rajkamalcdri@gmail.com

2016-05-20

HIV-1 Nef modulates cellular function that enhances viral replication in vivo which culminate into AIDS pathogenesis. With no enzymatic activity, Nef regulates cellular function through host protein interaction. Interestingly, trans-cellular introduction of recombinant Nef protein in Caenorhabditis elegans results in AIDS like pathogenesis which might share common pathophysiology because the gene sequence of C. elegans and humans share considerable homology. Therefore employing C. elegans based initial screen complemented with sequence based homology search we identified GCC185 as novel host protein interacting with HIV-1 Nef. The detailed molecular characterization revealed N-terminal EEEE{sub 65} acidic domain of Nef as key region for interaction. GCC185 is a tethering protein that binds with Rab9 transport vesicles. Our results show that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase. In agreement with this, our studies identified novel host GCC185 protein that interacts with Nef EEEE65 acidic domain interfering GCC185-Rab9 vesicle membrane fusion responsible for retrograde vesicular transport of CI-MPR from late endosomes to TGN. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. -- Highlights: •Nef, an accessory protein of HIV-1 interacts with host factor and culminates into AIDS pathogenesis. •Using Caenorhabditis elegans based screen system, novel Nef interacting cellular protein GCC185 was identified. •Molecular characterization of Nef and human protein GCC185 revealed Nef EEEE{sub 65} key region interacted with full length GCC185. •Nef impeded the GCC185-Rab 9 interaction and

AT2 Receptor and Tissue Injury

DEFF Research Database (Denmark)

Namsolleck, Pawel; Recarti, Chiara; Foulquier, Sébastien

2014-01-01

The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT1 receptor (AT1R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well...... established. In the past twenty years, protective actions of the RAS, not only in the cardiovascular, but also in the nervous system, have been demonstrated. The so-called protective arm of the RAS includes AT2-receptors and Mas receptors (AT2R and MasR) and is characterized by effects different from...... and often opposing those of the AT1R. These include anti-inflammation, anti-fibrosis, anti-apoptosis and neuroregeneration that can counterbalance pathological processes and enable recovery from disease. The recent development of novel, small-molecule AT2R agonists offers a therapeutic potential in humans...

Muscarinic Receptor Signaling in Colon Cancer

Energy Technology Data Exchange (ETDEWEB)

Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

2011-03-02

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

Muscarinic Receptor Signaling in Colon Cancer

International Nuclear Information System (INIS)

Rosenvinge, Erik C. von; Raufman, Jean-Pierre

2011-01-01

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

Muscarinic Receptor Signaling in Colon Cancer

Directory of Open Access Journals (Sweden)

Jean-Pierre Raufman

2011-03-01

Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

β1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo

Science.gov (United States)

Jiang, Youde; Zhang, Qiuhua; Ye, Eun-Ah

2014-01-01

Purpose Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of β2-adrenergic receptor signaling. Methods Using retinas from 3-month-old β2-adrenergic receptor-deficient mice, we treated mice with our novel β1-/β2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on β1-adrenergic receptors due to the absence of β2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for β1- and β2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-α, SOCS3, IRS-1Ser307, and IRTyr960. Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. Results A 2-month treatment of β2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel β1- and β2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-α and SOCS3) observed in untreated β2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating β1-adrenergic receptors on retinal endothelial cells or Müller cells can compensate for the loss of β2-adrenergic receptor signaling on Müller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. Conclusions Since our previous studies with β1-adrenergic receptor knockout mice confirmed that the reverse also occurs (β2-adrenergic receptor stimulation can compensate for the loss of β1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance–based retinal cell apoptosis. PMID:24966659

G protein-coupled receptors in Anopheles gambiae.

Science.gov (United States)

Hill, Catherine A; Fox, A Nicole; Pitts, R Jason; Kent, Lauren B; Tan, Perciliz L; Chrystal, Mathew A; Cravchik, Anibal; Collins, Frank H; Robertson, Hugh M; Zwiebel, Laurence J

2002-10-04

We used bioinformatic approaches to identify a total of 276 G protein-coupled receptors (GPCRs) from the Anopheles gambiae genome. These include GPCRs that are likely to play roles in pathways affecting almost every aspect of the mosquito's life cycle. Seventy-nine candidate odorant receptors were characterized for tissue expression and, along with 76 putative gustatory receptors, for their molecular evolution relative to Drosophila melanogaster. Examples of lineage-specific gene expansions were observed as well as a single instance of unusually high sequence conservation.

Role of sigma-1 receptors in neurodegenerative diseases

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Linda Nguyen

2015-01-01

Full Text Available Neurodegenerative diseases with distinct genetic etiologies and pathological phenotypes appear to share common mechanisms of neuronal cellular dysfunction, including excitotoxicity, calcium dysregulation, oxidative damage, ER stress and mitochondrial dysfunction. Glial cells, including microglia and astrocytes, play an increasingly recognized role in both the promotion and prevention of neurodegeneration. Sigma receptors, particularly the sigma-1 receptor subtype, which are expressed in both neurons and glia of multiple regions within the central nervous system, are a unique class of intracellular proteins that can modulate many biological mechanisms associated with neurodegeneration. These receptors therefore represent compelling putative targets for pharmacologically treating neurodegenerative disorders. In this review, we provide an overview of the biological mechanisms frequently associated with neurodegeneration, and discuss how sigma-1 receptors may alter these mechanisms to preserve or restore neuronal function. In addition, we speculate on their therapeutic potential in the treatment of various neurodegenerative disorders.

Cationic Protic Imidazolylidene NHC Complexes of Cp*IrCl+ and Cp*RhCl+ with a Pyridyl Tether Formed at Ambient Temperature

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Douglas B. Grotjahn

2018-02-01

Full Text Available Protic NHC (PNHC complexes with N1H, N2-alkyl/aryl imidazolylidene ligands are relatively rare, and routes for their synthesis differ from what is used to make non-protic analogs. Prior work from our group and others showed that in the presence of a tethering ligand (phosphine or in one case, pyridine, CpM and Cp*M (M = Ir, Ru PNHC complexes could be made by heating. Here, we find that the use of ionizing agents to activate [Cp*MIIICl(μ-Cl]2 (M = Ir, Rh allows for what we believe is unprecedented ambient temperature formation of PNHC complexes from neutral imidazoles; the product complexes are able to perform transfer hydrogenation.

The Role of Adenosine Receptors in Psychostimulant Addiction

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Inmaculada Ballesteros-Yáñez

2018-01-01

Full Text Available Adenosine receptors (AR are a family of G-protein coupled receptors, comprised of four members, named A1, A2A, A2B, and A3 receptors, found widely distributed in almost all human body tissues and organs. To date, they are known to participate in a large variety of physiopathological responses, which include vasodilation, pain, and inflammation. In particular, in the central nervous system (CNS, adenosine acts as a neuromodulator, exerting different functions depending on the type of AR and consequent cellular signaling involved. In terms of molecular pathways and second messengers involved, A1 and A3 receptors inhibit adenylyl cyclase (AC, through Gi/o proteins, while A2A and A2B receptors stimulate it through Gs proteins. In the CNS, A1 receptors are widely distributed in the cortex, hippocampus, and cerebellum, A2A receptors are localized mainly in the striatum and olfactory bulb, while A2B and A3 receptors are found at low levels of expression. In addition, AR are able to form heteromers, both among themselves (e.g., A1/A2A, as well as with other subtypes (e.g., A2A/D2, opening a whole range of possibilities in the field of the pharmacology of AR. Nowadays, we know that adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission and therefore reward systems, being A1 receptors colocalized in heteromeric complexes with D1 receptors, and A2A receptors with D2 receptors. This review documents the present state of knowledge of the contribution of AR, particularly A1 and A2A, to psychostimulants-mediated effects, including locomotor activity, discrimination, seeking and reward, and discuss their therapeutic relevance to psychostimulant addiction. Studies presented in this review reinforce the potential of A1 agonists as an effective strategy to counteract psychostimulant-induced effects. Furthermore, different experimental data support the hypothesis that A2A/D2 heterodimers are

Tethered lives: A couple-based perspective on the consequences of parenthood for time use, occupation, and wages.

Science.gov (United States)

Killewald, Alexandra; García-Manglano, Javier

2016-11-01

Prior research on parenthood effects has typically used single-sex models and estimated average effects. By contrast, we estimate population-level variability in partners' changes in housework hours, paid work hours, occupation traits, and wages after becoming parents, and we explore whether one partner's adjustment offsets or supplements the other's. We find tradeoffs between spouses on paid work adjustments to parenthood, but complementarity in adjustments to housework hours, occupation traits, and wages. The effect of parenthood on wives' behaviors is larger and more variable than on husbands' behaviors in every domain. The modest variation between husbands in work responses to parenthood explains little of the variation in the motherhood penalty, while variation in wives' own behaviors plays a larger role. We refer to this pattern as tethered autonomy: variation across American couples in work responses to parenthood is shaped primarily by variation in wives' adjustments, while husbands' work acts largely as a fixed point. Copyright © 2016 Elsevier Inc. All rights reserved.

Gold nanoparticles tethered cinnamic acid: preparation, characterization, and cytotoxic effects on MCF-7 breast cancer cell lines

Science.gov (United States)

Subramanian, Karthika; Ponnuchamy, Kumar

2018-04-01

The main objective of the study is to tether citrate-stabilized gold nanoparticles (CS©GNPs) with cinnamic acid (CA) and evaluating them against MCF-7 breast cancer cells. To achieve CA CS©GNPs, CS©GNPs prepared were blended with CA under controlled experimental conditions followed by high-throughput characterization. The result from the study demonstrates that positively charged hydrogen moiety present in O-H group of CA provides an opportunity for binding of CS©GNPs via hydrogen bonding evidenced by color change (ruby to light purple) and spectroscopic analysis (UV-visible and FT-IR spectroscopy). The size and shape of CA CS©GNPs were not the same as CS©GNPs substantiated by transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. At the end, cytotoxic and morphological assessment against MCF-7 breast cancer cells shows effective suppression of tumor cells and thereby promoting them as promising nanoscale drug delivery system in near future.

Recruitment of activation receptors at inhibitory NK cell immune synapses.

Directory of Open Access Journals (Sweden)

Nicolas Schleinitz

2008-09-01

Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

TRAIL death receptors and cancer therapeutics

International Nuclear Information System (INIS)

Huang Ying; Sheikh, M. Saeed

2007-01-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) also known as Apo2L is an apoptotic molecule that belongs to the tumor necrosis factor superfamily of cytokines. It mediates its apoptotic effects via its cognate death receptors including DR4 and DR5. Agonistic monoclonal antibodies have also been developed that selectively activate TRAIL death receptors to mediate apoptosis. Multiple clinically relevant agents also upregulate the expression of TRAIL death receptors, and cooperate with TRAIL as well as DR4 and DR5-specific agonistic antibodies to exhibit tumor cell killing. TRAIL is currently in phase I clinical trials, whereas DR4 and DR5-specific agonistic antibodies have been tested in phase I and II studies. Thus, TRAIL has clearly distinguished itself from the other family members including TNF-alpha and FasL both of which could not make it to the clinic due to their toxic nature. It is therefore, evident that the future of TRAIL-based therapeutic approaches looks brighter

Functional properties of Virus-Encoded and Virus-Regulated 7TM Receptors

DEFF Research Database (Denmark)

Spiess, Katja; Rosenkilde, Mette Marie

2014-01-01

During co-evolution with their hosts, viruses have developed several survival strategies that involve exploitation of 7TM receptors. These include virus-encoded 7TM receptors and ligands and viral regulation of endogenous receptors. Many functional properties have been ascribed to virus-exploited...