WorldWideScience

Sample records for relay cells targeting

  1. Cell-Edge Multi-User Relaying with Overhearing

    DEFF Research Database (Denmark)

    Sun, Fan; Kim, Tae Min; Paulraj, Arogyaswami

    2013-01-01

    Carefully designed protocols can turn overheard interference into useful side information to allow simultaneous transmission of multiple communication flows and increase the spectral efficiency in interference-limited regime. In this letter, we propose a novel scheme in a typical cell-edge scenar....... By exploiting the overhearing link through proper relay precoding and adaptive receiver processing, rate performance can be significantly improved compared to the conventional transmission which does not utilize overhearing....

  2. Relay-aided multi-cell broadcasting with random network coding

    DEFF Research Database (Denmark)

    Lu, Lu; Sun, Fan; Xiao, Ming

    2010-01-01

    We investigate a relay-aided multi-cell broadcasting system using random network codes, where the focus is on devising efficient scheduling algorithms between relay and base stations. Two scheduling algorithms are proposed based on different feedback strategies; namely, a one-step scheduling...

  3. Protective relay

    International Nuclear Information System (INIS)

    Lim, Mu Ji; Jung, Hae Sang

    1974-10-01

    This book is divided into two chapters, which deals with protective relay. The first chapter deals with the basic knowledge of relay on development of relay, classification of protective relay, rating of protective relay general structure of protective relay, detecting of ground protection, about point of contact, operating relay and trip relaying. The second chapter is about structure and explanation of relay on classification by structure such as motor type and moving-coil type, explanation of other relays over current relay, over voltage relay, short voltage relay, relay for power, relay for direction, test of over voltage relay, test of short voltage relay and test of directional circuit relay.

  4. Panchromatic Response in Solid-State Dye-Sensitized Solar Cells Containing Phosphorescent Energy Relay Dyes

    KAUST Repository

    Yum, Jun-Ho; Hardin, Brianâ E.; Moon, Soo-Jin; Baranoff, Etienne; Nà ¼ esch, Frank; McGehee, Michaelâ D.; Grà ¤ tzel, Michael; Nazeeruddin, Mohammadâ K.

    2009-01-01

    Running relay: Incorporating an energyrelay dye (ERD) into the hole transporter of a dye-sensitized solar cell increased power-conversion efficiency by 29% by extending light harvesting into the blue region. In the operating mechanism (see picture

  5. Incorporating Multiple Energy Relay Dyes in Liquid Dye-Sensitized Solar Cells

    KAUST Repository

    Yum, Jun-Ho; Hardin, Brian E.; Hoke, Eric T.; Baranoff, Etienne; Zakeeruddin, Shaik M.; Nazeeruddin, Mohammad K.; Torres, Tomas; McGehee, Michael D.; Grä tzel, Michael

    2011-01-01

    Panchromatic response is essential to increase the light-harvesting efficiency in solar conversion systems. Herein we show increased light harvesting from using multiple energy relay dyes inside dye-sensitized solar cells. Additional photoresponse

  6. Incorporating Multiple Energy Relay Dyes in Liquid Dye-Sensitized Solar Cells

    KAUST Repository

    Yum, Jun-Ho

    2011-01-05

    Panchromatic response is essential to increase the light-harvesting efficiency in solar conversion systems. Herein we show increased light harvesting from using multiple energy relay dyes inside dye-sensitized solar cells. Additional photoresponse from 400-590 nm matching the optical window of the zinc phthalocyanine sensitizer was observed due to Förster resonance energy transfer (FRET) from the two energy relay dyes to the sensitizing dye. The complementary absorption spectra of the energy relay dyes and high excitation transfer efficiencies result in a 35% increase in photovoltaic performance. © 2011 Wiley-VCH Verlag GmbH& Co. KGaA.

  7. Spike and burst coding in thalamocortical relay cells.

    Directory of Open Access Journals (Sweden)

    Fleur Zeldenrust

    2018-02-01

    Full Text Available Mammalian thalamocortical relay (TCR neurons switch their firing activity between a tonic spiking and a bursting regime. In a combined experimental and computational study, we investigated the features in the input signal that single spikes and bursts in the output spike train represent and how this code is influenced by the membrane voltage state of the neuron. Identical frozen Gaussian noise current traces were injected into TCR neurons in rat brain slices as well as in a validated three-compartment TCR model cell. The resulting membrane voltage traces and spike trains were analyzed by calculating the coherence and impedance. Reverse correlation techniques gave the Event-Triggered Average (ETA and the Event-Triggered Covariance (ETC. This demonstrated that the feature selectivity started relatively long before the events (up to 300 ms and showed a clear distinction between spikes (selective for fluctuations and bursts (selective for integration. The model cell was fine-tuned to mimic the frozen noise initiated spike and burst responses to within experimental accuracy, especially for the mixed mode regimes. The information content carried by the various types of events in the signal as well as by the whole signal was calculated. Bursts phase-lock to and transfer information at lower frequencies than single spikes. On depolarization the neuron transits smoothly from the predominantly bursting regime to a spiking regime, in which it is more sensitive to high-frequency fluctuations. The model was then used to elucidate properties that could not be assessed experimentally, in particular the role of two important subthreshold voltage-dependent currents: the low threshold activated calcium current (IT and the cyclic nucleotide modulated h current (Ih. The ETAs of those currents and their underlying activation/inactivation states not only explained the state dependence of the firing regime but also the long-lasting concerted dynamic action of the two

  8. High Excitation Transfer Efficiency from Energy Relay Dyes in Dye-Sensitized Solar Cells

    KAUST Repository

    Hardin, Brian E.

    2010-08-11

    The energy relay dye, 4-(Dicyanomethylene)-2-methyl-6-(4- dimethylaminostyryl)-4H-pyran (DCM), was used with a near-infrared sensitizing dye, TT1, to increase the overall power conversion efficiency of a dye-sensitized solar cell (DSC) from 3.5% to 4.5%. The unattached DCM dyes exhibit an average excitation transfer efficiency (EÌ?TE) of 96% inside TT1-covered, mesostructured TiO2 films. Further performance increases were limited by the solubility of DCM in an acetonitrile based electrolyte. This demonstration shows that energy relay dyes can be efficiently implemented in optimized dye-sensitized solar cells, but also highlights the need to design highly soluble energy relay dyes with high molar extinction coefficients. © 2010 American Chemical Society.

  9. High Excitation Transfer Efficiency from Energy Relay Dyes in Dye-Sensitized Solar Cells

    KAUST Repository

    Hardin, Brian E.; Yum, Jun-Ho; Hoke, Eric T.; Jun, Young Chul; Péchy, Peter; Torres, Tomás; Brongersma, Mark L.; Nazeeruddin, Md. Khaja; Grätzel, Michael; McGehee, Michael D.

    2010-01-01

    The energy relay dye, 4-(Dicyanomethylene)-2-methyl-6-(4- dimethylaminostyryl)-4H-pyran (DCM), was used with a near-infrared sensitizing dye, TT1, to increase the overall power conversion efficiency of a dye-sensitized solar cell (DSC) from 3

  10. Evaluation of Potential Relay Locations in a Urban Macro-Cell Scenario with Applicability to LTE-A

    DEFF Research Database (Denmark)

    Rodriguez, Ignacio; Coletti, Claudio; Sørensen, Troels Bundgaard

    2012-01-01

    . This paper presents a measurement-based study focusing on the performance evaluation of the relay backhaul link for different potential relay locations and antenna configurations in a real urban macro-cell scenario. Based on the assumption that a similar network deployment would apply for LTE-A, a fully......Relay base stations are expected to play an important role in extending coverage for beyond 3G networks, such as LTE-A. However, the signal quality experienced on the backhaul link between the macro-cell and the relay node has a major impact on the performance of the multi-hop transmission...... operational 3G network has been used for measuring both received signal strength and Signal-to-Interference-Ratio (SIR). Furthermore, the results have been used to estimate the performance of the multi-hop transmission under simplifying assumptions. The experimental results show that by increasing the relay...

  11. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila.

    Science.gov (United States)

    Sousa-Nunes, Rita; Yee, Lih Ling; Gould, Alex P

    2011-03-24

    Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated. The signals triggering entry into and exit from this reversible dormant state are not well understood. In the developing Drosophila central nervous system, multipotent self-renewing progenitors called neuroblasts undergo quiescence in a stereotypical spatiotemporal pattern. Entry into quiescence is regulated by Hox proteins and an internal neuroblast timer. Exit from quiescence (reactivation) is subject to a nutritional checkpoint requiring dietary amino acids. Organ co-cultures also implicate an unidentified signal from an adipose/hepatic-like tissue called the fat body. Here we provide in vivo evidence that Slimfast amino-acid sensing and Target of rapamycin (TOR) signalling activate a fat-body-derived signal (FDS) required for neuroblast reactivation. Downstream of this signal, Insulin-like receptor signalling and the Phosphatidylinositol 3-kinase (PI3K)/TOR network are required in neuroblasts for exit from quiescence. We demonstrate that nutritionally regulated glial cells provide the source of Insulin-like peptides (ILPs) relevant for timely neuroblast reactivation but not for overall larval growth. Conversely, ILPs secreted into the haemolymph by median neurosecretory cells systemically control organismal size but do not reactivate neuroblasts. Drosophila thus contains two segregated ILP pools, one regulating proliferation within the central nervous system and the other controlling tissue growth systemically. Our findings support a model in which amino acids trigger the cell cycle re-entry of neural progenitors via a fat-body-glia-neuroblasts relay. This mechanism indicates that dietary nutrients and remote organs, as well as local niches, are key regulators of transitions in stem-cell behaviour.

  12. Modeling the efficiency of Förster resonant energy transfer from energy relay dyes in dye-sensitized solar cells

    KAUST Repository

    Hoke, Eric T.; Hardin, Brian E.; McGehee, Michael D.

    2010-01-01

    Förster resonant energy transfer can improve the spectral breadth, absorption and energy conversion efficiency of dye sensitized solar cells. In this design, unattached relay dyes absorb the high energy photons and transfer the excitation

  13. Compatibility Study of Protective Relaying in a Grid-Connected Fuel Cell

    Energy Technology Data Exchange (ETDEWEB)

    Staunton, R.H.

    2004-04-15

    A 200-kW fuel cell produced by International Fuel Cells (IFC), a United Technologies Company, began operation at the National Transportation Research Center (NTRC) in early June 2003. The NTRC is a joint Oak Ridge National laboratory (ORNL) and University of Tennessee research facility located in Knoxville, Tennessee. This research activity investigated the protective relaying functions of this fully commercialized fuel cell power plant, which uses ''synthesized'' protective relays. The project's goal is to characterize the compatibility between the fuel cell's interconnection protection system and the local distribution system or electric power system (EPS). ORNL, with assistance from the Electric Power Research Institute-Power Electronics Applications Center (EPRI-PEAC) in Knoxville, Tennessee, monitored and characterized the system compatibility over a period of 6 months. Distribution utility engineers are distrustful of or simply uncomfortable with the protective relaying and hardware provided as part of distributed generation (DG) plants. Part of this mistrust is due to the fact that utilities generally rely on hardware from certain manufacturers whose reliability is well established based on performance over many years or even decades. Another source of concern is the fact that fuel cells and other types of DG do not use conventional relays but, instead, the protective functions of conventional relays are simulated by digital circuits in the distributed generator's grid interface control unit. Furthermore, the testing and validation of internal protection circuits of DG are difficult to accomplish and can be changed by the vendor at any time. This study investigated and documented the safety and protective relaying present in the IFC fuel cell, collected data on the operation of the fuel cell, recorded event data during EPS disturbances, and assessed the compatibility of the synthesized protective circuits and the local

  14. Two-way cooperative AF relaying in spectrum-sharing systems: Enhancing cell-edge performance

    KAUST Repository

    Xia, Minghua

    2012-09-01

    In this contribution, two-way cooperative amplify-and-forward (AF) relaying technique is integrated into spectrumsharing wireless systems to improve spectral efficiency of secondary users (SUs). In order to share the available spectrum resources originally dedicated to primary users (PUs), the transmit power of a SU is optimized with respect to the average tolerable interference power at primary receivers. By analyzing outage probability and achievable data rate at the base station and at a cell-edge SU, our results reveal that the uplink performance is dominated by the average tolerable interference power at primary receivers, while the downlink always behaves like conventional one-way AF relaying and its performance is dominated by the average signal-to-noise ratio (SNR). These important findings provide fresh perspectives for system designers to improve spectral efficiency of secondary users in next-generation broadband spectrum-sharing wireless systems. © 2012 IEEE.

  15. Modeling the efficiency of Förster resonant energy transfer from energy relay dyes in dye-sensitized solar cells

    KAUST Repository

    Hoke, Eric T.

    2010-02-11

    Förster resonant energy transfer can improve the spectral breadth, absorption and energy conversion efficiency of dye sensitized solar cells. In this design, unattached relay dyes absorb the high energy photons and transfer the excitation to sensitizing dye molecules by Förster resonant energy transfer. We use an analytic theory to calculate the excitation transfer efficiency from the relay dye to the sensitizing dye accounting for dynamic quenching and relay dye diffusion. We present calculations for pores of cylindrical and spherical geometry and examine the effects of the Förster radius, the pore size, sensitizing dye surface concentration, collisional quenching rate, and relay dye lifetime. We find that the excitation transfer efficiency can easily exceed 90% for appropriately chosen dyes and propose two different strategies for selecting dyes to achieve record power conversion efficiencies. © 2010 Optical Society of America.

  16. Panchromatic Response in Solid-State Dye-Sensitized Solar Cells Containing Phosphorescent Energy Relay Dyes

    KAUST Repository

    Yum, Jun-Ho

    2009-11-23

    Running relay: Incorporating an energyrelay dye (ERD) into the hole transporter of a dye-sensitized solar cell increased power-conversion efficiency by 29% by extending light harvesting into the blue region. In the operating mechanism (see picture), absorption of red photons by the sensitizer transfers an electron into TiO2 and a hole into the electrolyte. Blue photons absorbed by the ERD are transferred by FRET to the sensitizer. Chemical Equitation Presentation © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

  17. Relay race

    CERN Multimedia

    Staff Association

    2011-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 19th May starting at 12:15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details on the course, and how to register your team for the relay race, can be found at: https://espace.cern.ch/Running-Club/CERN-Relay Some advice for all runners from the medical service can also be found here: https://espace.cern.ch/Running-Club/CERN-Relay/RelayPagePictures/MedicalServiceAnnoncement.pdf

  18. Relay race

    CERN Document Server

    Staff Association

    2011-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 19th May starting at 12·15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details on the course, and how to register your team for the relay race, can be found at: https://espace.cern.ch/Running-Club/CERN-Relay Some advice for all runners from the medical service can also be found here: https://espace.cern.ch/Running-Club/CERN-Relay/RelayPagePictures/MedicalServiceAnnoncement.pdf

  19. Increased light harvesting in dye-sensitized solar cells with energy relay dyes

    KAUST Repository

    Hardin, Brian E.

    2009-06-21

    Conventional dye-sensitized solar cells have excellent charge collection efficiencies, high open-circuit voltages and good fill factors. However, dye-sensitized solar cells do not completely absorb all of the photons from the visible and near-infrared domain and consequently have lower short-circuit photocurrent densities than inorganic photovoltaic devices. Here, we present a new design where high-energy photons are absorbed by highly photoluminescent chromophores unattached to the titania and undergo Förster resonant energy transfer to the sensitizing dye. This novel architecture allows for broader spectral absorption, an increase in dye loading, and relaxes the design requirements for the sensitizing dye. We demonstrate a 26% increase in power conversion efficiency when using an energy relay dye (PTCDI) with an organic sensitizing dye (TT1). We estimate the average excitation transfer efficiency in this system to be at least 47%. This system offers a viable pathway to develop more efficient dye-sensitized solar cells.

  20. Target-specific NMR detection of protein–ligand interactions with antibody-relayed {sup 15}N-group selective STD

    Energy Technology Data Exchange (ETDEWEB)

    Hetényi, Anasztázia [University of Szeged, Department of Medical Chemistry (Hungary); Hegedűs, Zsófia [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary); Fajka-Boja, Roberta; Monostori, Éva [Biological Research Center of the Hungarian Academy of Sciences, Lymphocyte Signal Transduction Laboratory, Institute of Genetics (Hungary); Kövér, Katalin E. [University of Debrecen, Department of Inorganic and Analytical Chemistry (Hungary); Martinek, Tamás A., E-mail: martinek@pharm.u-szeged.hu [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary)

    2016-12-15

    Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein–ligand interactions is a key element. {sup 1}H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed {sup 15}N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A {sup 15}N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

  1. Relay power supplies for the system of proton beam slow guidance onto internal targets of the Serpukhov synchrotron

    International Nuclear Information System (INIS)

    Belov, S.A.; Kardash, A.A.; Medvedev, V.A.; Perebejnos, V.K.; Shirokov, V.G.

    1979-01-01

    A static supply system for slow beam guiding on targets used in the IHEP synchrotron is discussed. As a regulating element use is made of a module-type gate bridge circuit. The power unit rated at an operating current of up to 200 A at a supply voltage of up to 200 V consists of 12 paralleled modules. Every module contains four transistors, four diodes and a part of a storage capacitor (200 μF). One module is rated at a current of 16 A. The regulator has been investigated in the pulse-width modulation mode and in the mode of relay control with normal and leading hysteresis loops. The minimum modulation of the secondary-particle beam density has been obtained when using leading hysteresis loops for regulation. In addition to the main task of guiding on targets the system provides shaping trapezoidal current pulses in the current range from 10 to 200 A at a current plateau stability of 0.5% and better

  2. Embryonic Cell Grafts in a Culture Model of Spinal Cord Lesion: Neuronal Relay Formation is Essential for Functional Regeneration

    Directory of Open Access Journals (Sweden)

    Anne Tscherter

    2016-09-01

    Full Text Available Presently there exists no cure for spinal cord injury. However, transplantation of embryonic tissue into spinal cord lesions resulted in axon outgrowth across the lesion site and some functional recovery, fostering hope for future stem cell therapies. Although in vivo evidence for functional recovery is given, the exact cellular mechanism of the graft support remains elusive: either the grafted cells provide a permissive environment for the host tissue to regenerate itself or the grafts actually integrate functionally into the host neuronal network reconnecting the separated spinal cord circuits. We tested the two hypotheses in an in vitro spinal cord lesion model that is based on propagation of activity between two rat organotypic spinal cord slices in culture. Transplantation of dissociated cells from E14 rat spinal cord or forebrain re-established the relay of activity over the lesion site and, thus, provoked functional regeneration. Combining patch-clamp recordings from transplanted cells with network activity measurements from the host tissue on multi-electrode arrays we here show that neurons differentiate from the grafted cells and integrate into the host circuits. Optogenetic silencing of neurons developed from transplanted embryonic mouse forebrain cells provides clear evidence that they replace the lost neuronal connections to relay and synchronize activity between the separated spinal cord circuits. In contrast, transplantation of neurospheres induced neither the differentiation of mature neurons from the grafts nor an improvement of functional regeneration. Together these findings suggest, that the formation of neuronal relays from grafted embryonic cells is essential to re-connect segregated spinal cord circuits.

  3. Target cells in internal dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Goessner, W

    2003-07-01

    Data related to radium induced bone sarcomas in humans are used as a model for defining target cells on bone surfaces and in the bone marrow. The differential distribution of radiation induced bone sarcoma types with a high ratio of non-bone producing, mainly fibroblastic tumours, challenges the ICRP concept that the bone lining cells are target cells. Multipotential mesenchymal stem cells are located within the range of alpha particles, and are the most likely target cells for the fibroblastic type of bone sarcoma. The histogenesis of bone sarcomas after irradiation with alpha emitters shows that their final histopathology is not dependent on a single target cell. Each target cell has a microenvironment, which has to be regarded as a synergistic morpho-functional tissue unit. For this the concept of 'histion', a term used in general pathology, is proposed. Interactions between target cells that have been hit by alpha-particles, leading to lethal, mutational or transformation events with all components of a 'histion', will prove critical to understanding the pathogenesis of both deterministic and stochastic late effects. (author)

  4. Target cells in internal dosimetry

    International Nuclear Information System (INIS)

    Goessner, W.

    2003-01-01

    Data related to radium induced bone sarcomas in humans are used as a model for defining target cells on bone surfaces and in the bone marrow. The differential distribution of radiation induced bone sarcoma types with a high ratio of non-bone producing, mainly fibroblastic tumours, challenges the ICRP concept that the bone lining cells are target cells. Multipotential mesenchymal stem cells are located within the range of alpha particles, and are the most likely target cells for the fibroblastic type of bone sarcoma. The histogenesis of bone sarcomas after irradiation with alpha emitters shows that their final histopathology is not dependent on a single target cell. Each target cell has a microenvironment, which has to be regarded as a synergistic morpho-functional tissue unit. For this the concept of 'histion', a term used in general pathology, is proposed. Interactions between target cells that have been hit by alpha-particles, leading to lethal, mutational or transformation events with all components of a 'histion', will prove critical to understanding the pathogenesis of both deterministic and stochastic late effects. (author)

  5. Telecommunications Relay Services

    Science.gov (United States)

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Telecommunications Relay Services On this page: What are telecommunication ... additional information about telecommunication relay services? What are telecommunication relay services? Title IV of the Americans with ...

  6. Strong, reliable and precise synaptic connections between thalamic relay cells and neurones of the nucleus reticularis in juvenile rats

    Science.gov (United States)

    Gentet, Luc J; Ulrich, Daniel

    2003-01-01

    The thalamic reticular nucleus (nRT) is composed entirely of GABAergic inhibitory neurones that receive input from pyramidal cortical neurones and excitatory relay cells of the ventrobasal complex of the thalamus (VB). It plays a major role in the synchrony of thalamic networks, yet the synaptic connections it receives from VB cells have never been fully physiologically characterised. Here, whole-cell current-clamp recordings were obtained from 22 synaptically connected VB-nRT cell pairs in slices of juvenile (P14–20) rats. At 34–36 °C, single presynaptic APs evoked unitary EPSPs in nRT cells with a peak amplitude of 7.4 ± 1.5 mV (mean ± s.e.m.) and a decay time constant of 15.1 ± 0.9 ms. Only four out of 22 pairs showed transmission failures at a mean rate of 6.8 ± 1.1 %. An NMDA receptor (NMDAR)-mediated component was significant at rest and subsequent EPSPs in a train were depressed. Only one out of 14 pairs tested was reciprocally connected; the observed IPSPs in the VB cell had a peak amplitude of 0.8 mV and were completely abolished in the presence of 10 μm bicuculline. Thus, synaptic connections from VB cells to nRT neurones are mainly ‘drivers’, while a small subset of cells form closed disynaptic loops. PMID:12563005

  7. Relay race

    CERN Multimedia

    Staff Association

    2012-01-01

    The CERN Relay Race will take place around the Meyrin site on Thursday 24th May at 12:00. This annual event is for teams of six runners covering distances of 1000 m, 800 m, 800 m, 500 m, 500 m and 300 m respectively. Teams may be entered in the Seniors, Veterans, Ladies, Mixed or Open categories. There will also this year be a Nordic Walking event, as part of the Medical Service’s initiative “Move more, eat better!” The registration fee is 10 CHF per runner, and each runner will receive a souvenir prize. There will be a programme of entertainment from 12:00 on the arrival area (the lawn in front of Restaurant 1): 12:00 - 12:45  Music from the Old Bottom Street band 12:15 Start of the race 12:45 - 13h Demonstrations by the Fitness club and Dancing club 13:00 Results and prize giving (including a raffle to win an iPad2 3G offered by the Micro club) 13:20 à 14:00 Music from “What’s next” And many information st...

  8. Energy efficient circuit design using nanoelectromechanical relays

    Science.gov (United States)

    Venkatasubramanian, Ramakrishnan

    Nano-electromechanical (NEM) relays are a promising class of emerging devices that offer zero off-state leakage and behave like an ideal switch. Recent advances in planar fabrication technology have demonstrated that microelectromechanical (MEMS) scale miniature relays could be manufactured reliably and could be used to build fully functional, complex integrated circuits. The zero leakage operation of relays has renewed the interest in relay based low power logic design. This dissertation explores circuit architectures using NEM relays and NEMS-CMOS heterogeneous integration. Novel circuit topologies for sequential logic, memory, and power management circuits have been proposed taking into consideration the NEM relay device properties and optimizing for energy efficiency and area. In nanoscale electromechanical devices, dispersion forces like Van der Waals' force (vdW) affect the pull-in stability of the relay devices significantly. Verilog-A electromechanical model of the suspended gate relay operating at 1V with a nominal air gap of 5 - 10nm has been developed taking into account all the electrical, mechanical and dispersion effects. This dissertation explores different relay based latch and flip-flop topologies. It has been shown that as few as 4 relay cells could be used to build flip-flops. An integrated voltage doubler based flip flop that improves the performance by 2X by overdriving Vgb has been proposed. Three NEM relay based parallel readout memory bitcell architectures have been proposed that have faster access time, and remove the reliability issues associated with previously reported serial readout architectures. A paradigm shift in design of power switches using NEM relays is proposed. An interesting property of the relay device is that the ON state resistance (Ron) of the NEM relay switch is constant and is insensitive to the gate slew rate. This coupled with infinite OFF state resistance (Roff ) offers significant area and power advantages over CMOS

  9. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....... to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...

  10. Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

    Science.gov (United States)

    Pineda, M.; Eftimie, R.

    2017-12-01

    The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

  11. Increased light harvesting in dye-sensitized solar cells with energy relay dyes

    KAUST Repository

    Hardin, Brian E.; Hoke, Eric T.; Armstrong, Paul B.; Yum, Jun-Ho; Comte, Pascal; Torres, Tomá s; Fré chet, Jean M. J.; Nazeeruddin, Md Khaja; Grä tzel, Michael; McGehee, Michael D.

    2009-01-01

    Conventional dye-sensitized solar cells have excellent charge collection efficiencies, high open-circuit voltages and good fill factors. However, dye-sensitized solar cells do not completely absorb all of the photons from the visible and near

  12. Efficient incremental relaying

    KAUST Repository

    Fareed, Muhammad Mehboob; Alouini, Mohamed-Slim

    2013-01-01

    We propose a novel relaying scheme which improves the spectral efficiency of cooperative diversity systems by utilizing limited feedback from destination. Our scheme capitalizes on the fact that relaying is only required when direct transmission

  13. Efficient incremental relaying

    KAUST Repository

    Fareed, Muhammad Mehboob

    2013-07-01

    We propose a novel relaying scheme which improves the spectral efficiency of cooperative diversity systems by utilizing limited feedback from destination. Our scheme capitalizes on the fact that relaying is only required when direct transmission suffers deep fading. We calculate the packet error rate for the proposed efficient incremental relaying scheme with both amplify and forward and decode and forward relaying. Numerical results are also presented to verify their analytical counterparts. © 2013 IEEE.

  14. 80537 based distance relay

    DEFF Research Database (Denmark)

    Pedersen, Knud Ole Helgesen

    1999-01-01

    A method for implementing a digital distance relay in the power system is described.Instructions are given on how to program this relay on a 80537 based microcomputer system.The problem is used as a practical case study in the course 53113: Micocomputer applications in the power system.The relay...

  15. Cell Phone Usage among Adolescents in Uganda: Acceptability for Relaying Health Information

    Science.gov (United States)

    Mitchell, Kimberly J.; Bull, Sheana; Kiwanuka, Julius; Ybarra, Michele L.

    2011-01-01

    The increase in cell phone use has manifested a growing interest in using this technology for health promotion. The portability and "always on" features of the cell phone, along with increasing capability for the devices to carry and transfer data suggest that they will reach more people than computers and the Internet in coming years.…

  16. Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells.

    Directory of Open Access Journals (Sweden)

    Pablo Martínez-Cañada

    2018-01-01

    Full Text Available Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs and interneurons (INs not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY. We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed ('push-pull' and phase-matched ('push-push', as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli

  17. Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on spatial response properties of relay cells

    Science.gov (United States)

    Martínez-Cañada, Pablo; Halnes, Geir; Fyhn, Marianne

    2018-01-01

    Despite half-a-century of research since the seminal work of Hubel and Wiesel, the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual signals is not properly understood. Placed on route from retina to primary visual cortex in the early visual pathway, a striking feature of the dLGN circuit is that both the relay cells (RCs) and interneurons (INs) not only receive feedforward input from retinal ganglion cells, but also a prominent feedback from cells in layer 6 of visual cortex. This feedback has been proposed to affect synchronicity and other temporal properties of the RC firing. It has also been seen to affect spatial properties such as the center-surround antagonism of thalamic receptive fields, i.e., the suppression of the response to very large stimuli compared to smaller, more optimal stimuli. Here we explore the spatial effects of cortical feedback on the RC response by means of a a comprehensive network model with biophysically detailed, single-compartment and multicompartment neuron models of RCs, INs and a population of orientation-selective layer 6 simple cells, consisting of pyramidal cells (PY). We have considered two different arrangements of synaptic feedback from the ON and OFF zones in the visual cortex to the dLGN: phase-reversed (‘push-pull’) and phase-matched (‘push-push’), as well as different spatial extents of the corticothalamic projection pattern. Our simulation results support that a phase-reversed arrangement provides a more effective way for cortical feedback to provide the increased center-surround antagonism seen in experiments both for flashing spots and, even more prominently, for patch gratings. This implies that ON-center RCs receive direct excitation from OFF-dominated cortical cells and indirect inhibitory feedback from ON-dominated cortical cells. The increased center-surround antagonism in the model is accompanied by spatial focusing, i.e., the maximum RC response occurs for smaller stimuli when

  18. Performance limitations of relay neurons.

    Directory of Open Access Journals (Sweden)

    Rahul Agarwal

    Full Text Available Relay cells are prevalent throughout sensory systems and receive two types of inputs: driving and modulating. The driving input contains receptive field properties that must be transmitted while the modulating input alters the specifics of transmission. For example, the visual thalamus contains relay neurons that receive driving inputs from the retina that encode a visual image, and modulating inputs from reticular activating system and layer 6 of visual cortex that control what aspects of the image will be relayed back to visual cortex for perception. What gets relayed depends on several factors such as attentional demands and a subject's goals. In this paper, we analyze a biophysical based model of a relay cell and use systems theoretic tools to construct analytic bounds on how well the cell transmits a driving input as a function of the neuron's electrophysiological properties, the modulating input, and the driving signal parameters. We assume that the modulating input belongs to a class of sinusoidal signals and that the driving input is an irregular train of pulses with inter-pulse intervals obeying an exponential distribution. Our analysis applies to any [Formula: see text] order model as long as the neuron does not spike without a driving input pulse and exhibits a refractory period. Our bounds on relay reliability contain performance obtained through simulation of a second and third order model, and suggest, for instance, that if the frequency of the modulating input increases or the DC offset decreases, then relay increases. Our analysis also shows, for the first time, how the biophysical properties of the neuron (e.g. ion channel dynamics define the oscillatory patterns needed in the modulating input for appropriately timed relay of sensory information. In our discussion, we describe how our bounds predict experimentally observed neural activity in the basal ganglia in (i health, (ii in Parkinson's disease (PD, and (iii in PD during

  19. High-performance ternary blend polymer solar cells involving both energy transfer and hole relay processes.

    Science.gov (United States)

    Lu, Luyao; Chen, Wei; Xu, Tao; Yu, Luping

    2015-06-04

    The integration of multiple materials with complementary absorptions into a single junction device is regarded as an efficient way to enhance the power conversion efficiency (PCE) of organic solar cells (OSCs). However, because of increased complexity with one more component, only limited high-performance ternary systems have been demonstrated previously. Here we report an efficient ternary blend OSC with a PCE of 9.2%. We show that the third component can reduce surface trap densities in the ternary blend. Detailed studies unravel that the improved performance results from synergistic effects of enlarged open circuit voltage, suppressed trap-assisted recombination, enhanced light absorption, increased hole extraction, efficient energy transfer and better morphology. The working mechanism and high device performance demonstrate new insights and design guidelines for high-performance ternary blend solar cells and suggest that ternary structure is a promising platform to boost the efficiency of OSCs.

  20. High-performance ternary blend polymer solar cells involving both energy transfer and hole relay processes

    OpenAIRE

    Lu, Luyao; Chen, Wei; Xu, Tao; Yu, Luping

    2015-01-01

    The integration of multiple materials with complementary absorptions into a single junction device is regarded as an efficient way to enhance the power conversion efficiency (PCE) of organic solar cells (OSCs). However, because of increased complexity with one more component, only limited high-performance ternary systems have been demonstrated previously. Here we report an efficient ternary blend OSC with a PCE of 9.2%. We show that the third component can reduce surface trap densities in the...

  1. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  2. CERN Relay Race

    CERN Document Server

    CERN Running Club

    2010-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 20 May, starting at 12.15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details on the route, and how to register your team for the relay race, can be found at: https://espace.cern.ch/Running-Club/CERN-Relay

  3. Radioisotope relay instrument

    International Nuclear Information System (INIS)

    Pozdnyakov, V.N.; Sazonov, O.L.; Taksar, I.M.; Tesnavs, Eh.R.; Yanushkovskij, V.A.

    1974-01-01

    The paper describes a radioisotope relay device containing a radiation source, a detector, an electronic relay block with a comparative threshold mechanism. The device differs from previously known ones in that, for the purpose of increasing stability and speed of action, the electronic relay block is a separate unit and contains two threshold pulse generators which are joined up, across series-connected ''and'' and ''or'' elements, with one of the inputs of the comparative threshold mechanism, whose second input is connected with a detector and whose outputs are connected with a relay element connected by feedback with the above-mentioned ''and'' elements. (author)

  4. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  5. Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Cancer stem cells (CSCs), a cell population with acquired perpetuating self-renewal properties which

  6. Power system relaying

    CERN Document Server

    Horowitz, Stanley H; Niemira, James K

    2013-01-01

    The previous three editions of Power System Relaying offer comprehensive and accessible coverage of the theory and fundamentals of relaying and have been widely adopted on university and industry courses worldwide. With the third edition, the authors have added new and detailed descriptions of power system phenomena such as stability, system-wide protection concepts and discussion of historic outages. Power System Relaying, 4th Edition continues its role as an outstanding textbook on power system protection for senior and graduate students in the field of electric power engineering and a refer

  7. CERN Relay Race

    CERN Document Server

    2008-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 5 June starting at 12:15 p.m. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details on how to register your team for the relay race are given on the Staff Association Bulletin web site. You can access the online registration form at: http://cern.ch/club-running-relay/form.html

  8. CERN Relay Race

    CERN Document Server

    2007-01-01

    The CERN relay race will take place around the Meyrin site on Wednesday 23 May starting at 12:15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details on how to register your team for the relay race are given on the Staff Association Bulletin web site. You can access the online registration form at: http://cern.ch/club-running-relay/form.html

  9. Ready, steady… relay!

    CERN Multimedia

    2008-01-01

    Thursday 5 June. With another year comes another success for CERN’s Relay Race. With 76 teams taking part it was the second highest turnout in the race’s history. ‘The Shabbys’ won the relay race in 10 minutes 51 seconds.As popular as ever, this year the relay race took on the atmosphere of a mini carnival. Gathering on the lawn outside Restaurant 1, various stalls and attractions added to the party feeling of the event, with beer courtesy of ‘AGLUP’, the Belgian beer club, and a wandering jazz group entertaining spectators and competitors alike. Reflecting the greater involvement of other associations in the relay race, the president of the Staff Association Clubs Committee, James Purvis, was the guest of honour, launching the start of the race and presenting the prizes. As regular followers of the race could have probably predicted, The Shabbys were once again victorious and claimed first place. The team members th...

  10. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

  11. CERN Relay Race 2009

    CERN Document Server

    2009-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 14th May starting at 12:15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. More details on how to register your team for the relay race

  12. CERN Relay Race

    CERN Document Server

    2006-01-01

    The CERN relay race will take place around the Meyrin site on Wednesday 17 May starting at 12:15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Details on how to register your team for the relay race are given on the Staff Association Bulletin web site.

  13. Modular relay control

    OpenAIRE

    Ivarsson, Mikael

    2010-01-01

    Enics Sweden AB, Västerås, is an electronics manufacturing services company with its main business in manufacturing electronics. Most, if not all, electronic devices that are manufactured are being widely tested before delivery to ensure proper functionality. Often during tests a large number of signals are measured by one to a few digital multimeters and are therefore controlled through relays. Relays are also used when applying stimuli with high currents or voltages to the unit under test. ...

  14. Scalable DeNoise-and-Forward in Bidirectional Relay Networks

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Krigslund, Rasmus; Popovski, Petar

    2010-01-01

    In this paper a scalable relaying scheme is proposed based on an existing concept called DeNoise-and-Forward, DNF. We call it Scalable DNF, S-DNF, and it targets the scenario with multiple communication flows through a single common relay. The idea of the scheme is to combine packets at the relay...... in order to save transmissions. To ensure decodability at the end-nodes, a priori information about the content of the combined packets must be available. This is gathered during the initial transmissions to the relay. The trade-off between decodability and number of necessary transmissions is analysed...

  15. Opportunistic relaying in multipath and slow fading channel: Relay selection and optimal relay selection period

    KAUST Repository

    Sungjoon Park,

    2011-11-01

    In this paper we present opportunistic relay communication strategies of decode and forward relaying. The channel that we are considering includes pathloss, shadowing, and fast fading effects. We find a simple outage probability formula for opportunistic relaying in the channel, and validate the results by comparing it with the exact outage probability. Also, we suggest a new relay selection algorithm that incorporates shadowing. We consider a protocol of broadcasting the channel gain of the previously selected relay. This saves resources in slow fading channel by reducing collisions in relay selection. We further investigate the optimal relay selection period to maximize the throughput while avoiding selection overhead. © 2011 IEEE.

  16. Targeting Stromal Recruitment by Prostate Cancer Cells

    Science.gov (United States)

    2006-03-01

    Ensinger, C., Tumer , Z., Tommerup, N. et al.: Hedgehog signaling in small-cell lung cancer : frequent in vivo but a rare event in vitro. Lung Cancer , 52...W81XWH-04-1-0157 TITLE: Targeting Stromal Recruitment by Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Jingxian Zhang, Ph.D...DATES COVERED (From - To) 15 Feb 2004 – 14 Feb 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Stromal Recruitment by Prostate Cancer

  17. Protective relaying theory and applications

    CERN Document Server

    Elmore, Walter A

    2003-01-01

    Targeting the latest microprocessor technologies for more sophisticated applications in the field of power system short circuit detection, this revised and updated source imparts fundamental concepts and breakthrough science for the isolation of faulty equipment and minimization of damage in power system apparatus. The Second Edition clearly describes key procedures, devices, and elements crucial to the protection and control of power system function and stability. It includes chapters and expertise from the most knowledgeable experts in the field of protective relaying, and describes micropro

  18. Firing-rate based network modeling of the dLGN circuit: Effects of cortical feedback on spatiotemporal response properties of relay cells.

    Science.gov (United States)

    Mobarhan, Milad Hobbi; Halnes, Geir; Martínez-Cañada, Pablo; Hafting, Torkel; Fyhn, Marianne; Einevoll, Gaute T

    2018-05-01

    Visually evoked signals in the retina pass through the dorsal geniculate nucleus (dLGN) on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-Gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. For this model the responses are found by direct evaluation of two- or three-dimensional integrals allowing for fast and comprehensive studies of putative effects of different candidate organizations of the cortical feedback. Our analysis identifies a special mixed configuration of excitatory and inhibitory cortical feedback which seems to best account for available experimental data. This configuration consists of (i) a slow (long-delay) and spatially widespread inhibitory feedback, combined with (ii) a fast (short-delayed) and spatially narrow excitatory feedback, where (iii) the excitatory/inhibitory ON-ON connections are accompanied respectively by inhibitory/excitatory OFF-ON connections, i.e. following a phase-reversed arrangement. The recent development of optogenetic and pharmacogenetic methods has provided new tools for more precise manipulation and investigation of the thalamocortical circuit, in particular for mice. Such data will expectedly allow the eDOG model to be better constrained by data from specific animal model systems than has been possible until now for cat. We have therefore made the Python tool pyLGN which allows for easy adaptation of the eDOG model to new situations.

  19. Targeting senescence cells in pancreatic cancer | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Targeting senescence cells in pancreatic cancer. Cellular senescence is a programmed response to oncogenic (tumour-causing) stress that aims to halt the expansion of cells with malignant potential. It does this by stopping the proliferation of pre-cancerous lesions and recruitment of the immune system for their elimination.

  20. Channel allocation and rate adaptation for relayed transmission over correlated fading channels

    KAUST Repository

    Hwang, Kyusung; Hossain, Md Jahangir; Ko, Youngchai; Alouini, Mohamed-Slim

    2009-01-01

    at both the source and relay nodes, we develop an optimal channel allocation and rate adaptation policy for a dual-hop relayed transmission. As such the overall transmit power for the relayed system is minimized while a target packet dropping rate (PDR

  1. Alternate MIMO relaying with three AF relays using interference alignment

    KAUST Repository

    Park, Kihong

    2012-06-01

    In this paper, we study a two-hop half-duplex relaying network with one source, one destination, and three amplify-and-forward (AF) relays equipped with M antennas each. We consider alternate transmission to compensate for the inherent loss of capacity pre-log factor 1/2 in half duplex mode, where source transmit message to two relays and the other relay alternately. The inter-relay interference caused by alternate transmission is aligned to make additional degrees of freedom (DOFs). It is shown that the proposed scheme enables us to exploit 3M/4 DOFs compared with the M/2 DOFs of conventional AF relaying. More specifically, suboptimal linear filter designs for a source and three relays are proposed to maximize the achievable sum-rate. We verify using some selected numerical results that the proposed filter designs give significant improvement of the sum-rate over a naive filter and conventional relaying schemes. © 2012 IEEE.

  2. Relay test program

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.K.; Kunkel, C.; Shteyngart, S.

    1994-02-01

    This report presents the results of a relay test program conducted by Brookhaven National Laboratory (BNL) under the sponsorship of the US Nuclear Regulatory Commission (NRC). The program is a continuation of an earlier test program the results of which were published in NUREG/CR-4867. The current program was carried out in two phases: electrical testing and vibration testing. The objective was primarily to focus on the electrical discontinuity or continuity of relays and circuit breaker tripping mechanisms subjected to electrical pulses and vibration loads. The electrical testing was conducted by KEMA-Powertest Company and the vibration testing was performed at Wyle Laboratories, Huntsville, Alabama. This report discusses the test procedures, presents the test data, includes an analysis of the data and provides recommendations regarding reliable relay testing

  3. Cell-specific targeting by heterobivalent ligands.

    Science.gov (United States)

    Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

    2011-07-20

    Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

  4. CERN Relay Race

    CERN Multimedia

    2011-01-01

    The CERN relay race will take place around the Meyrin site on Thursday 19 May starting at 12-15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. Thank you for your cooperation. Details of the course and of how to register your team for the relay race can be found here. Some advice for all runners from the Medical Service can also be found here.   

  5. Relay Selection with Limited and Noisy Feedback

    KAUST Repository

    Eltayeb, Mohammed E.; Elkhalil, Khalil; Mas'ud, Abdullahi Abubakar; Al-Naffouri, Tareq Y.

    2016-01-01

    Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Nonetheless, relay selection algorithms generally require error-free channel state information (CSI) from all cooperating relays. Practically, CSI

  6. Opportunistic Relay Selection With Limited Feedback

    KAUST Repository

    Eltayeb, Mohammed E.; Elkhalil, Khalil; Bahrami, Hamid Reza; Al-Naffouri, Tareq Y.

    2015-01-01

    Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Generally, relay selection algorithms require channel state information (CSI) feedback from all cooperating relays to make a selection decision

  7. CERN Relay Race

    CERN Multimedia

    2004-01-01

    The CERN Relay Race will take place around the Meyrin site on Wednesday 19 May between 12.15 and 12.35. If possible, please avoid driving on the site during this 20 minute period. If you do meet runners in your car, please STOP until they all have passed. Thank you for your understanding

  8. CERN Relay Race

    CERN Multimedia

    2003-01-01

    The CERN Relay Race will take place around the Meyrin site on Wednesday May 21st between 12h15 and 12h35. If possible, please avoid driving on the site during this 20 minute period. If you do meet runners in your car, please STOP until they all have passed. Thank you for your understanding

  9. CERN Relay Race

    CERN Multimedia

    2001-01-01

    The CERN Relay Race will take place around the Meyrin site on Wednesday 23 May between 12:20 and 12:35. If possible, please avoid driving on the site during this 15 minute period. If you do meet runners in your car, please stop until they all have passed. Thank you for your understanding.

  10. CERN Relay Race

    CERN Document Server

    2002-01-01

    The CERN Relay Race will take place around the Meyrin site on Wednesday 22 May between 12h20 and 12h35. If possible, please avoid driving on the site during this 15 minute period. If you do meet runners in your car, please STOP until they all have passed. Thank you for your understanding.

  11. CERN Relay Race

    CERN Multimedia

    2009-01-01

    The CERN relay race, now in its 39th year, is already a well-known tradition, but this year the organizers say the event will have even more of a festival feeling. Just off the starting line of the CERN relay race.For the past few years, spectators and runners at the CERN relay race have been able to enjoy a beer while listening to music from the CERN music and jazz clubs. But this year the organizers are aiming for "even more of a festival atmosphere". As David Nisbet, President of the CERN running club and organizer of the relay race, says: "Work is not just about getting your head down and doing the theory, it’s also about enjoying the company of your colleagues." This year, on top of music from the Santa Luis Band and the Canettes Blues Band, there will be demonstrations from the Aikido and softball clubs, a stretching session by the Fitness club, as well as various stalls and of course, the well-earned beer from AGLUP, the B...

  12. 2005 CERN Relay Race

    CERN Multimedia

    Patrice Loiez

    2005-01-01

    The CERN Relay Race takes place each year in May and sees participants from all areas of the CERN staff. The winners in 2005 were The Shabbys with Los Latinos Volantes in second and Charmilles Technologies a close third. To add a touch of colour and levity, the CERN Jazz Club provided music at the finishing line.

  13. Opportunistic relaying in multipath and slow fading channel: Relay selection and optimal relay selection period

    KAUST Repository

    Sungjoon Park,; Stark, Wayne E.

    2011-01-01

    In this paper we present opportunistic relay communication strategies of decode and forward relaying. The channel that we are considering includes pathloss, shadowing, and fast fading effects. We find a simple outage probability formula

  14. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  15. Targeting nanoparticles to dendritic cells for immunotherapy.

    NARCIS (Netherlands)

    Cruz, L.J.; Tacken, P.J.; Rueda, F.; Domingo, J.C.; Albericio, F.; Figdor, C.G.

    2012-01-01

    Dendritic cells (DCs) are key players in the initiation of adaptive immune responses and are currently exploited in immunotherapy for treatment of cancer and infectious diseases. Development of targeted nanodelivery systems carrying vaccine components, including antigens and adjuvants, to DCs in

  16. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  17. Iterative Relay Scheduling with Hybrid ARQ under Multiple User Equipment (Type II) Relay Environments

    KAUST Repository

    Nam, Sung Sik

    2018-01-09

    In this work, we propose an iterative relay scheduling with hybrid ARQ (IRS-HARQ) scheme which realizes fast jump-in/successive relaying and subframe-based decoding under the multiple user equipment (UE) relay environments applicable to the next-generation cellular systems (e.g., LTE-Advanced and beyond). The proposed IRS-HARQ aims to increase the achievable data rate by iteratively scheduling a relatively better UE relay closer to the end user in a probabilistic sense, provided that the relay-to-end user link should be operated in an open-loop and transparent mode. The latter is due to the fact that not only there are no dedicated control channels between the UE relay and the end user but also a new cell is not created. Under this open-loop and transparent mode, our proposed protocol is implemented by partially exploiting the channel state information based on the overhearing mechanism of ACK/NACK for HARQ. Further, the iterative scheduling enables UE-to-UE direct communication with proximity that offers spatial frequency reuse and energy saving.

  18. Therapeutic Approaches to Target Cancer Stem Cells

    International Nuclear Information System (INIS)

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  19. Oncolytic viral therapy: targeting cancer stem cells

    Directory of Open Access Journals (Sweden)

    Smith TT

    2014-02-01

    Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

  20. ABA signaling in guard cells entails a dynamic protein-protein interaction relay from the PYL-RCAR family receptors to ion channels.

    Science.gov (United States)

    Lee, Sung Chul; Lim, Chae Woo; Lan, Wenzhi; He, Kai; Luan, Sheng

    2013-03-01

    Plant hormone abscisic acid (ABA) serves as an integrator of environmental stresses such as drought to trigger stomatal closure by regulating specific ion channels in guard cells. We previously reported that SLAC1, an outward anion channel required for stomatal closure, was regulated via reversible protein phosphorylation events involving ABA signaling components, including protein phosphatase 2C members and a SnRK2-type kinase (OST1). In this study, we reconstituted the ABA signaling pathway as a protein-protein interaction relay from the PYL/RCAR-type receptors, to the PP2C-SnRK2 phosphatase-kinase pairs, to the ion channel SLAC1. The ABA receptors interacted with and inhibited PP2C phosphatase activity against the SnRK2-type kinase, releasing active SnRK2 kinase to phosphorylate, and activate the SLAC1 channel, leading to reduced guard cell turgor and stomatal closure. Both yeast two-hybrid and bimolecular fluorescence complementation assays were used to verify the interactions among the components in the pathway. These biochemical assays demonstrated activity modifications of phosphatases and kinases by their interaction partners. The SLAC1 channel activity was used as an endpoint readout for the strength of the signaling pathway, depending on the presence of different combinations of signaling components. Further study using transgenic plants overexpressing one of the ABA receptors demonstrated that changing the relative level of interacting partners would change ABA sensitivity.

  1. Frame Allocation and Scheduling for Relay Networks in the LTE Advanced Standard

    OpenAIRE

    Roth, Stefan

    2010-01-01

    The use of relays is seen as a promising way to extend cell coverage and increase rates in LTE Advanced networks. Instead of increasing the number of base stations (BS), relays with lower cost could provide similar gains. A relay will have a wireless link to the closest BS as only connection to the core network and will cover areas close to the cell edge or other areas with limited rates. Performing transmissions in several hops (BS-relay & relay-user) requires more radio resources than u...

  2. Metastasis Targeted Therapies in Renal Cell Cancer

    OpenAIRE

    K. Fehmi Narter; Bora Özveren

    2018-01-01

    Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

  3. Relay Selection for Cooperative Relaying in Wireless Energy Harvesting Networks

    Science.gov (United States)

    Zhu, Kaiyan; Wang, Fei; Li, Songsong; Jiang, Fengjiao; Cao, Lijie

    2018-01-01

    Energy harvesting from the surroundings is a promising solution to provide energy supply and extend the life of wireless sensor networks. Recently, energy harvesting has been shown as an attractive solution to prolong the operation of cooperative networks. In this paper, we propose a relay selection scheme to optimize the amplify-and-forward (AF) cooperative transmission in wireless energy harvesting cooperative networks. The harvesting energy and channel conditions are considered to select the optimal relay as cooperative relay to minimize the outage probability of the system. Simulation results show that our proposed relay selection scheme achieves better outage performance than other strategies.

  4. Opportunistic Relay Selection in Multicast Relay Networks using Compressive Sensing

    KAUST Repository

    Elkhalil, Khalil

    2014-12-01

    Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. However, for relay selection algorithms to make a selection decision, channel state information (CSI) from all cooperating relays is usually required at a central node. This requirement poses two important challenges. Firstly, CSI acquisition generates a great deal of feedback overhead (air-time) that could result in significant transmission delays. Secondly, the fed back channel information is usually corrupted by additive noise. This could lead to transmission outages if the central node selects the set of cooperating relays based on inaccurate feedback information. In this paper, we introduce a limited feedback relay selection algorithm for a multicast relay network. The proposed algorithm exploits the theory of compressive sensing to first obtain the identity of the “strong” relays with limited feedback. Following that, the CSI of the selected relays is estimated using linear minimum mean square error estimation. To minimize the effect of noise on the fed back CSI, we introduce a back-off strategy that optimally backs-off on the noisy estimated CSI. For a fixed group size, we provide closed form expressions for the scaling law of the maximum equivalent SNR for both Decode and Forward (DF) and Amplify and Forward (AF) cases. Numerical results show that the proposed algorithm drastically reduces the feedback air-time and achieves a rate close to that obtained by selection algorithms with dedicated error-free feedback channels.

  5. Optimized Policies for Improving Fairness of Location-based Relay Selection

    DEFF Research Database (Denmark)

    Nielsen, Jimmy Jessen; Olsen, Rasmus Løvenstein; Madsen, Tatiana Kozlova

    2013-01-01

    For WLAN systems in which relaying is used to improve throughput performance for nodes located at the cell edge, node mobility and information collection delays can have a significant impact on the performance of a relay selection scheme. In this paper we extend our existing Markov Chain modeling...... framework for relay selection to allow for efficient calculation of relay policies given either mean throughput or kth throughput percentile as optimization criterium. In a scenario with static access point, static relay, and a mobile destination node, the kth throughput percentile optimization...

  6. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  7. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  8. Alternate MIMO relaying with three AF relays using interference alignment

    KAUST Repository

    Park, Kihong; Alouini, Mohamed-Slim

    2012-01-01

    In this paper, we study a two-hop half-duplex relaying network with one source, one destination, and three amplify-and-forward (AF) relays equipped with M antennas each. We consider alternate transmission to compensate for the inherent loss

  9. Joint source and relay optimization for interference MIMO relay networks

    Science.gov (United States)

    Khandaker, Muhammad R. A.; Wong, Kai-Kit

    2017-12-01

    This paper considers multiple-input multiple-output (MIMO) relay communication in multi-cellular (interference) systems in which MIMO source-destination pairs communicate simultaneously. It is assumed that due to severe attenuation and/or shadowing effects, communication links can be established only with the aid of a relay node. The aim is to minimize the maximal mean-square-error (MSE) among all the receiving nodes under constrained source and relay transmit powers. Both one- and two-way amplify-and-forward (AF) relaying mechanisms are considered. Since the exactly optimal solution for this practically appealing problem is intractable, we first propose optimizing the source, relay, and receiver matrices in an alternating fashion. Then we contrive a simplified semidefinite programming (SDP) solution based on the error covariance matrix decomposition technique, avoiding the high complexity of the iterative process. Numerical results reveal the effectiveness of the proposed schemes.

  10. CERN Relay Race 2018

    CERN Document Server

    CERN Running club

    2018-01-01

    The CERN running club, in collaboration with the Staff Association, is happy to announce the 2018 relay race edition. It will take place on Thursday, May 24th and will consist as every year in a round trip of the CERN Meyrin site in teams of 6 members. It is a fun event, and you do not have to run fast to enjoy it. Registrations will be open from May 1st to May 22nd on the running club web site. All information concerning the race and the registration are available there too: http://runningclub.web.cern.ch/content/cern-relay-race. A video of the previous edition is also available here : http://cern.ch/go/Nk7C. As every year, there will be animations starting at noon on the lawn in front of restaurant 1, and information stands for many CERN associations and clubs will be available. The running club partners will also be participate in the event, namely Berthie Sport, Interfon and Uniqa.

  11. 47th Relay Race!

    CERN Document Server

    Staff Association

    2017-01-01

    On Thursday June 1st at 12.15, Fabiola Gianotti, our Director-General, will fire the starting shot for the 47th Relay Race. This Race is above all a festive CERN event, open for runners and walkers, as well as the people cheering them on throughout the race, and those who wish to participate in the various activities organised between 11.30 and 14.30 out on the lawn in front of Restaurant 1. In order to make this sports event accessible for everyone, our Director-General will allow for flexible lunch hours on the day, applicable for all the members of personnel. An alert for the closure of roads will be send out on the day of the event. The Staff Association and the CERN Running Club thank you in advance for your participation and your continued support throughout the years. This year the CERN Running Club has announced the participation of locally and internationally renowned runners, no less! A bit over a week from the Relay Race of 1st June, the number of teams is going up nicely (already almost 40). Am...

  12. CERN Relay Race

    CERN Multimedia

    Running Club

    2010-01-01

    This year’s CERN Relay Race will take place around the Meyrin site on Thursday 20th May at 12h00. This annual event is for teams of 6 runners covering distances of 1000m, 800m, 800m, 500m, 500m and 300m respectively. Teams may be entered in the Seniors, Veterans, Ladies, Mixed or Open categories. The registration fee is 10 CHF per runner, and each runner receives a souvenir prize. As usual, there will be a programme of entertainments from 12h in the arrival area, in front of the Restaurant no. 1. Drinks, food, CERN club information and music will be available for the pleasure of both runners and spectators. The race starts at 12h15, with results and prize giving at 13:15.   For details of the race, and of how to sign up a team, please visit: https://espace.cern.ch/Running-Club/CERN-Relay The event is organised by the CERN Running Club with the support of the CERN Staff Association.  

  13. Spatially Controlled Relay Beamforming

    Science.gov (United States)

    Kalogerias, Dionysios

    This thesis is about fusion of optimal stochastic motion control and physical layer communications. Distributed, networked communication systems, such as relay beamforming networks (e.g., Amplify & Forward (AF)), are typically designed without explicitly considering how the positions of the respective nodes might affect the quality of the communication. Optimum placement of network nodes, which could potentially improve the quality of the communication, is not typically considered. However, in most practical settings in physical layer communications, such as relay beamforming, the Channel State Information (CSI) observed by each node, per channel use, although it might be (modeled as) random, it is both spatially and temporally correlated. It is, therefore, reasonable to ask if and how the performance of the system could be improved by (predictively) controlling the positions of the network nodes (e.g., the relays), based on causal side (CSI) information, and exploitting the spatiotemporal dependencies of the wireless medium. In this work, we address this problem in the context of AF relay beamforming networks. This novel, cyber-physical system approach to relay beamforming is termed as "Spatially Controlled Relay Beamforming". First, we discuss wireless channel modeling, however, in a rigorous, Bayesian framework. Experimentally accurate and, at the same time, technically precise channel modeling is absolutely essential for designing and analyzing spatially controlled communication systems. In this work, we are interested in two distinct spatiotemporal statistical models, for describing the behavior of the log-scale magnitude of the wireless channel: 1. Stationary Gaussian Fields: In this case, the channel is assumed to evolve as a stationary, Gaussian stochastic field in continuous space and discrete time (say, for instance, time slots). Under such assumptions, spatial and temporal statistical interactions are determined by a set of time and space invariant

  14. Relays undergo seismic tests

    International Nuclear Information System (INIS)

    Burton, J.C.

    1977-01-01

    Utilities are required by the Nuclear Regulatory Commission to document that seismic vibration will not adversely affect critical electrical equipment. Seismic testing should be designed to determine the malfunction level (fragility testing). Input possibilities include a continuous sine, a decaying sine, a sine beat, random vibrations, and combinations of random vibrations and sine beat. The sine beat most accurately simulates a seismic event. Test frequencies have a broad range in order to accommodate a variety of relay types and cabinet mounting. Simulation of motion along three axes offers several options, but is best achieved by three in-phase single-axis vibration machines that are less likely to induce testing fatigue failure. Consensus on what constitutes relay failure favors a maximum two microsecond discontinuity. Performance tests should be conducted for at least two of the following: (1) nonoperating modes, (2) operating modes, or (3) the transition above the two modes, with the monitoring mode documented for all three. Results should specify a capability curve of maximum safe seismic acceleration and a graph plotting acceleration with sine-beat frequency

  15. MIMO Four-Way Relaying

    DEFF Research Database (Denmark)

    Liu, Huaping; Sun, Fan; De Carvalho, Elisabeth

    2013-01-01

    Two-way relaying in wireless systems has initiated a large research effort during the past few years. Nevertheless, it represents only a specific traffic pattern and it is of interest to investigate other traffic patterns where such a simultaneous processing of information flows can bring...... performance advantage. In this paper we consider a \\emph{four-way relaying} multiple-input multiple-output (MIMO) scenario, where each of the two Mobile Stations (MSs) has a two-way connection to the same Base Station (BS), while each connection is through a dedicated Relay Station (RS). The RSs are placed...... the sum-rate of the new scheme for Decode-and-Forward (DF) operational model for the RS. We compare the performance with state-of-the-art reference schemes, based on two-way relaying with DF. The results indicate that the sum-rate of the two-phase four-way relaying scheme largely outperforms the four...

  16. CERN Relay Race

    CERN Document Server

    2005-01-01

    The CERN Relay Race will take place around the Meyrin site on Wednesday 18 May between 12.15 and 12.35. This year, weather permitting, there will be some new attractions in the start/finish area on the field behind the Main Building. You will be able to: listen to music played by the CERN Jazz Club; buy drinks at the bar organised by the CERN Running Club; buy lunch served directly on the terrace by the restaurant Novae. ATTENTION: concerning traffic, the recommendations are the same as always: If possible, please avoid driving on the site during this 20 minute period. If you do meet runners in your car, please STOP until they all have passed. Thank you for your understanding.

  17. Voz sobre frame relay

    OpenAIRE

    D´Elia, Gabriel Anibal

    2000-01-01

    Esta tesis trata el tema de VOFR, desde la digitalización de la voz hasta su transmisión a través de dicha red, así también como la comparación con otros medios de transporte como VOIP. Dada las características del protocolo frame relay y su disponibilidad se eligió como el medio más apropiado para la transmisión de voz y datos en forma integrada sobre una misma red. El trabajo comienza con una breve explicación de la voz, su digitalización y forma actual de transmisión a través de una red di...

  18. Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.

    Science.gov (United States)

    Alvarez-Vallina, L; Yañez, R; Blanco, B; Gil, M; Russell, S J

    2000-04-01

    Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.

  19. Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

    Directory of Open Access Journals (Sweden)

    Thomas Heiberg

    2016-05-01

    Full Text Available Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs and interneurons (INs form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition and regulation of spatial

  20. Biophysical Network Modelling of the dLGN Circuit: Different Effects of Triadic and Axonal Inhibition on Visual Responses of Relay Cells.

    Science.gov (United States)

    Heiberg, Thomas; Hagen, Espen; Halnes, Geir; Einevoll, Gaute T

    2016-05-01

    Despite its prominent placement between the retina and primary visual cortex in the early visual pathway, the role of the dorsal lateral geniculate nucleus (dLGN) in molding and regulating the visual signals entering the brain is still poorly understood. A striking feature of the dLGN circuit is that relay cells (RCs) and interneurons (INs) form so-called triadic synapses, where an IN dendritic terminal can be simultaneously postsynaptic to a retinal ganglion cell (GC) input and presynaptic to an RC dendrite, allowing for so-called triadic inhibition. Taking advantage of a recently developed biophysically detailed multicompartmental model for an IN, we here investigate putative effects of these different inhibitory actions of INs, i.e., triadic inhibition and standard axonal inhibition, on the response properties of RCs. We compute and investigate so-called area-response curves, that is, trial-averaged visual spike responses vs. spot size, for circular flashing spots in a network of RCs and INs. The model parameters are grossly tuned to give results in qualitative accordance with previous in vivo data of responses to such stimuli for cat GCs and RCs. We particularly investigate how the model ingredients affect salient response properties such as the receptive-field center size of RCs and INs, maximal responses and center-surround antagonisms. For example, while triadic inhibition not involving firing of IN action potentials was found to provide only a non-linear gain control of the conversion of input spikes to output spikes by RCs, axonal inhibition was in contrast found to substantially affect the receptive-field center size: the larger the inhibition, the more the RC center size shrinks compared to the GC providing the feedforward excitation. Thus, a possible role of the different inhibitory actions from INs to RCs in the dLGN circuit is to provide separate mechanisms for overall gain control (direct triadic inhibition) and regulation of spatial resolution

  1. Control circuit for transformer relay

    International Nuclear Information System (INIS)

    Wyatt, G.A.

    1984-01-01

    A control circuit for a transformer relay which will automatically momentarily control the transformer relay to a selected state upon energization of the control circuit. The control circuit has an energy storage element and a current director coupled in series and adapted to be coupled with the secondary winding of the transformer relay. A device for discharge is coupled across the energy storage element. The energy storage element and current director will momentarily allow a unidirectional flow of current in the secondary winding of the transformer relay upon application of energy to the control circuit. When energy is not applied to the control circuit the device for discharge will allow the energy storage element to discharge and be available for another operation of the control circuit

  2. Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies

    National Research Council Canada - National Science Library

    Huang, Shuang

    2004-01-01

    .... Our proposal is designed to develop an endothelial cell-targeted adenoviral vector and to use the targeted vector to express high levels of anticancer therapeutic genes in the sites of angiogenenic...

  3. Targeting of porous hybrid silica nanoparticles to cancer cells

    NARCIS (Netherlands)

    Rosenholm, J.M.; Meinander, A.; Peuhu, E.; Niemi, R.; Eriksson, J.E.; Sahlgren, C.; Lindén, M.

    2009-01-01

    Mesoporous silica nanoparticles functionalized by surface hyperbranching polymerization of polyethylene imine), PEI, were further modified by introducing both fluorescent and targeting moieties, with the aim of specifically targeting cancer cells. Owing to the high abundance of folate receptors in

  4. The 2009 Relay Race

    CERN Multimedia

    2009-01-01

    The 2009 CERN Relay Race was as popular as ever, with a record number of 88 teams competing. var flash_video_player=get_video_player_path(); insert_player_for_external('Video/Public/Movies/2009/CERN-MOVIE-2009-048/CERN-MOVIE-2009-048-0753-kbps-480x360-25-fps-audio-64-kbps-44-kHz-stereo', 'mms://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2009/CERN-MOVIE-2009-048/CERN-MOVIE-2009-048-Multirate-200-to-753-kbps-480x360.wmv', 'false', 288, 216, 'https://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2009/CERN-MOVIE-2009-048/CERN-MOVIE-2009-048-posterframe-480x360-at-10-percent.jpg', '1178303', true, 'Video/Public/Movies/2009/CERN-MOVIE-2009-048/CERN-MOVIE-2009-048-0600-kbps-maxH-360-25-fps-audio-128-kbps-48-kHz-stereo.mp4'); Even the rain didn’t dampen the spirits, and it still managed to capture the ‘festival feeling’ with live music, beer and stalls from various CERN clubs set up outside Restaurant 1. The Powercuts on the podium after win...

  5. A time relay

    Energy Technology Data Exchange (ETDEWEB)

    Yosimura, K.; Sudzuki, Y.

    1981-06-18

    The synchronous micromotor of the time relay by means of a two staged cylindrical gear drive drives the gear wheel and the shaft of an actuating mechanism. The shaped drum of a cam mechanism, equipped with a vertical groove, which interacts in its upper part with a lever for driving the first commutating subassembly and in the lower, with a bent sector of a spring and plate movable contact of the second commutating subassembly, is attached to the lower end of the mechanism's shaft (V). The L-shaped lever of the second commutating subassembly's drive rests on a vertical rocking axle, located parallel to the shaft. Both pairs of spring and plate contacts are bracketed in two dielectric brackets which provide for a plane parallel disposition of the cited contacts. The operational time setting for the unit is a function of the initial angular position of the shaft, which is provided for by the attachment of a handle on its upper end.

  6. Outage performance of two-way DF relaying systems with a new relay selection metric

    KAUST Repository

    Hyadi, Amal; Benjillali, Mustapha; Alouini, Mohamed-Slim

    2012-01-01

    This paper investigates a new constrained relay selection scheme for two-way relaying systems where two end terminals communicate simultaneously via a relay. The introduced technique is based on the maximization of the weighted sum rate of both

  7. A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

    KAUST Repository

    Alsharoa, Ahmad M.; Ghazzai, Hakim; Alouini, Mohamed-Slim

    2013-01-01

    In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward

  8. Decode and Zero-Forcing Forward Relaying with Relay Selection in Cognitive Radio Systems

    KAUST Repository

    Park, Kihong; Alouini, Mohamed-Slim

    2014-01-01

    In this paper, we investigate a cognitive radio (CR) relay network with multiple relay nodes that help forwarding the signal of CR users. Best relay selection is considered to take advantage of its low complexity of implementation. When the primary

  9. Reactive relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz; Alouini, Mohamed-Slim; Qaraqe, Khalid A.; Hasna, Mazen Omar

    2012-01-01

    Best relay selection is a bandwidth efficient technique for multiple relay environments without compromising the system performance. The problem of relay selection is more challenging in underlay cognitive networks due to strict interference

  10. Relay Selection and Resource Allocation in One-Way and Two-Way Cognitive Relay Networks

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-01-01

    In this work, the problem of relay selection and resource power allocation in one- way and two-way cognitive relay networks using half duplex channels with different relaying protocols is investigated. Optimization problems for both single

  11. Relayed Regioselective Alkynylation/Olefination of Unsymmetrical Cyclic Diaryliodonium Species Catalyzed by Cu and Pd: Affording Fluorescent Cytotoxic Benzoxazoles.

    Science.gov (United States)

    Zhu, Daqian; Liu, Panpan; Lu, Wenhua; Wang, Haiwen; Luo, Bingling; Hu, Yumin; Huang, Peng; Wen, Shijun

    2015-12-21

    Although cyclic diaryliodonium species have the potential to act as valuable synthons for cascade transformations, they still remain largely unexplored. The regioselectivity associated with unsymmetrical cyclic diaryliodonium species has previously been known to pose a challenge. A regioselective relayed alkynylation and olefination of unsymmetrical cyclic diaryliodonium species has been achieved by installation of a directing amido group. These relayed transformations were delayed until an oxazole ring had formed, delivering a series of unique fluorescent benzoxazoles. Moreover, some of these synthetic benzoxazoles showed apparent inhibitory activity against malignant cancer cells. Further confocal visualization revealed that benzoxazoles targeted cell nuclei. These findings might provide a novel structural scaffold to develop desirable anticancer agents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  13. Risky business: target choice in adoptive cell therapy.

    Science.gov (United States)

    Morgan, Richard A

    2013-11-14

    In this issue of Blood, Casucci et al present an elegant study that describes a potential new target for adoptive cell transfer (ACT), in this case CD44 splice variant 6 (CD44v6), and detail why it may be a good target for ACT and how to manage expected off-tumor/on-target toxicities.

  14. Performance of hybrid-ARQ with incremental redundancy over relay channels

    KAUST Repository

    Chelli, Ali

    2012-12-01

    In this paper, we consider a relay network consisting of a source, a relay, and a destination. The source transmits a message to the destination using hybrid automatic repeat request (HARQ) with incremental redundancy (IR). The relay overhears the transmitted messages over the different HARQ rounds and tries to decode the data packet. In case of successful decoding at the relay, both the relay and the source cooperate to transmit the message to the destination. A maximum number M of HARQ rounds is considered. The channel realizations are independent for different HARQ rounds. We assume Rayleigh fading channels for the links source-relay, source-destination, and relay-destination. We investigate the performance of HARQ-IR over relay channel from an information theoretic perspective. Analytical expressions are derived for the information outage probability, the average number of transmissions, and the average transmission rate. We illustrate through our investigation the benefit of relaying. We also show the impact of the target outage probability and the maximum number M of HARQ rounds on the outage probability, the average number of transmissions, and the average transmission rate. © 2012 IEEE.

  15. Extending roGFP Emission via Förster-Type Resonance Energy Transfer Relay Enables Simultaneous Dual Compartment Ratiometric Redox Imaging in Live Cells.

    Science.gov (United States)

    Norcross, Stevie; Trull, Keelan J; Snaider, Jordan; Doan, Sara; Tat, Kiet; Huang, Libai; Tantama, Mathew

    2017-11-22

    Reactive oxygen species (ROS) mediate both intercellular and intraorganellar signaling, and ROS propagate oxidative stress between cellular compartments such as mitochondria and the cytosol. Each cellular compartment contains its own sources of ROS as well as antioxidant mechanisms, which contribute to dynamic fluctuations in ROS levels that occur during signaling, metabolism, and stress. However, the coupling of redox dynamics between cellular compartments has not been well studied because of the lack of available sensors to simultaneously measure more than one subcellular compartment in the same cell. Currently, the redox-sensitive green fluorescent protein, roGFP, has been used extensively to study compartment-specific redox dynamics because it provides a quantitative ratiometric readout and it is amenable to subcellular targeting as a genetically encoded sensor. Here, we report a new family of genetically encoded fluorescent protein sensors that extend the fluorescence emission of roGFP via Förster-type resonance energy transfer to an acceptor red fluorescent protein for dual-color live-cell microscopy. We characterize the redox and optical properties of the sensor proteins, and we demonstrate that they can be used to simultaneously measure cytosolic and mitochondrial ROS in living cells. Furthermore, we use these sensors to reveal cell-to-cell heterogeneity in redox coupling between the cytosol and mitochondria when neuroblastoma cells are exposed to reductive and metabolic stresses.

  16. Human immune cell targeting of protein nanoparticles - caveospheres

    Science.gov (United States)

    Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

    2016-04-01

    Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

  17. Speech-to-Speech Relay Service

    Science.gov (United States)

    Consumer Guide Speech to Speech Relay Service Speech-to-Speech (STS) is one form of Telecommunications Relay Service (TRS). TRS is a service that allows persons with hearing and speech disabilities ...

  18. Relay selection from an effective capacity perspective

    KAUST Repository

    Yang, Yuli; Ma, Hao; Aï ssa, Sonia

    2013-01-01

    proposed scheme in certain scenarios. Moreover, the analysis presented herein offers a convenient tool to the relaying transmission design, specifically on which relay selection scheme should be used as well as how to choose the receiving strategy between

  19. Relay self interference minimisation using tapped filter

    KAUST Repository

    Jazzar, Saleh; Al-Naffouri, Tareq Y.

    2013-01-01

    In this paper we introduce a self interference (SI) estimation and minimisation technique for amplify and forward relays. Relays are used to help forward signals between a transmitter and a receiver. This helps increase the signal coverage

  20. Handover Framework for Relay Enhanced LTE Networks

    DEFF Research Database (Denmark)

    Teyeb, Oumer Mohammed; Van Phan, Vinh; Raaf, Bernhard

    2009-01-01

    Relaying is one of the proposed technologies for future releases of UTRAN Long Term Evolution (LTE) networks. Introducing relaying is expected to increase the coverage and capacity of LTE networks. In order to enable relaying, the architecture, protocol and radio resource management procedures...... of LTE, such as handover, have to be modified. A user can be handed over not only between two base stations, but also between relays and base stations, and between two relays. With the introduction of relaying, there is a need for a new procedure to hand over a relay and all its associated users...... to another base station, allowing a flexible and dynamic relay deployment. In this paper, we extend the LTE release 8 handover mechanisms so that it can accommodate these new handover functionalities in a flexible manner....

  1. 76 FR 24442 - Structure and Practices of the Video Relay Service Program; Telecommunications Relay Services and...

    Science.gov (United States)

    2011-05-02

    ... same meaning as the terms ``small business,'' ``small organization,'' and ``small governmental...] Structure and Practices of the Video Relay Service Program; Telecommunications Relay Services and Speech-to... Commission's Structure and Practices of the Video Relay Service Program; Telecommunications Relay Services...

  2. Buoyancy-activated cell sorting using targeted biotinylated albumin microbubbles.

    Directory of Open Access Journals (Sweden)

    Yu-Ren Liou

    Full Text Available Cell analysis often requires the isolation of certain cell types. Various isolation methods have been applied to cell sorting, including fluorescence-activated cell sorting and magnetic-activated cell sorting. However, these conventional approaches involve exerting mechanical forces on the cells, thus risking cell damage. In this study we applied a novel isolation method called buoyancy-activated cell sorting, which involves using biotinylated albumin microbubbles (biotin-MBs conjugated with antibodies (i.e., targeted biotin-MBs. Albumin MBs are widely used as contrast agents in ultrasound imaging due to their good biocompatibility and stability. For conjugating antibodies, biotin is conjugated onto the albumin MB shell via covalent bonds and the biotinylated antibodies are conjugated using an avidin-biotin system. The albumin microbubbles had a mean diameter of 2 μm with a polydispersity index of 0.16. For cell separation, the MDA-MB-231 cells are incubated with the targeted biotin-MBs conjugated with anti-CD44 for 10 min, centrifuged at 10 g for 1 min, and then allowed 1 hour at 4 °C for separation. The results indicate that targeted biotin-MBs conjugated with anti-CD44 antibodies can be used to separate MDA-MB-231 breast cancer cells; more than 90% of the cells were collected in the MB layer when the ratio of the MBs to cells was higher than 70:1. Furthermore, we found that the separating efficiency was higher for targeted biotin-MBs than for targeted avidin-incorporated albumin MBs (avidin-MBs, which is the most common way to make targeted albumin MBs. We also demonstrated that the recovery rate of targeted biotin-MBs was up to 88% and the sorting purity was higher than 84% for a a heterogenous cell population containing MDA-MB-231 cells (CD44(+ and MDA-MB-453 cells (CD44-, which are classified as basal-like breast cancer cells and luminal breast cancer cells, respectively. Knowing that the CD44(+ is a commonly used cancer-stem-cell

  3. Targeting therapy-resistant cancer stem cells by hyperthermia

    DEFF Research Database (Denmark)

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  4. Targeting Killing of Breast Tumor Stem Cells

    National Research Council Canada - National Science Library

    Chen, Si-Yi

    2005-01-01

    .... Toward the goal, we have prepared HA molecules from human umbilical cord hyaluronic acid by hydrolysed by Bee venom. However, we have encountered the technical difficulty to produce CD44-targeted liposomes that are incorporated with HA molecules. Due to the technical problems, this proposed study has been extended for additional one year.

  5. Cells, targets, and molecules in radiation biology

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1979-01-01

    Cellular damage and repair are discussed with regard to inactivation models, dose-effect curves and cancer research, repair relative to damage accumulation, potentially lethal damage, repair of potentially lethal vs. sublethal damage, cell killing and DNA damage due to nonionizing radiation, and anisotonicity vs. lethality due to nonionizing radiation. Other topics discussed are DNA damage and repair in cells exposed to ionizing radiation, kinetics of repair of single-strand DNA breaks, effects of actinomycin D on x-ray survival curve of hamster cells, misrepair and lethality, and perspective and prospects

  6. Quantum cryptography with an ideal local relay

    DEFF Research Database (Denmark)

    Spedalieri, Gaetana; Ottaviani, Carlo; Braunstein, Samuel L.

    2015-01-01

    We consider two remote parties connected to a relay by two quantum channels. To generate a secret key, they transmit coherent states to the relay, where the states are subject to a continuous-variable (CV) Bell detection. We study the ideal case where Alice's channel is lossless, i.e., the relay ...

  7. Robust distributed cognitive relay beamforming

    KAUST Repository

    Pandarakkottilil, Ubaidulla

    2012-05-01

    In this paper, we present a distributed relay beamformer design for a cognitive radio network in which a cognitive (or secondary) transmit node communicates with a secondary receive node assisted by a set of cognitive non-regenerative relays. The secondary nodes share the spectrum with a licensed primary user (PU) node, and each node is assumed to be equipped with a single transmit/receive antenna. The interference to the PU resulting from the transmission from the cognitive nodes is kept below a specified limit. The proposed robust cognitive relay beamformer design seeks to minimize the total relay transmit power while ensuring that the transceiver signal-to-interference- plus-noise ratio and PU interference constraints are satisfied. The proposed design takes into account a parameter of the error in the channel state information (CSI) to render the performance of the beamformer robust in the presence of imperfect CSI. Though the original problem is non-convex, we show that the proposed design can be reformulated as a tractable convex optimization problem that can be solved efficiently. Numerical results are provided and illustrate the performance of the proposed designs for different network operating conditions and parameters. © 2012 IEEE.

  8. Selective tumor cell targeting by the disaccharide moiety of bleomycin.

    Science.gov (United States)

    Yu, Zhiqiang; Schmaltz, Ryan M; Bozeman, Trevor C; Paul, Rakesh; Rishel, Michael J; Tsosie, Krystal S; Hecht, Sidney M

    2013-02-27

    In a recent study, the well-documented tumor targeting properties of the antitumor agent bleomycin (BLM) were studied in cell culture using microbubbles that had been derivatized with multiple copies of BLM. It was shown that BLM selectively targeted MCF-7 human breast carcinoma cells but not the "normal" breast cell line MCF-10A. Furthermore, it was found that the BLM analogue deglycobleomycin, which lacks the disaccharide moiety of BLM, did not target either cell line, indicating that the BLM disaccharide moiety is necessary for tumor selectivity. Not resolved in the earlier study were the issues of whether the BLM disaccharide moiety alone is sufficient for tumor cell targeting and the possible cellular uptake of the disaccharide. In the present study, we conjugated BLM, deglycoBLM, and BLM disaccharide to the cyanine dye Cy5**. It was found that the BLM and BLM disaccharide conjugates, but not the deglycoBLM conjugate, bound selectively to MCF-7 cells and were internalized. The same was also true for the prostate cancer cell line DU-145 (but not for normal PZ-HPV-7 prostate cells) and for the pancreatic cancer cell line BxPC-3 (but not for normal SVR A221a pancreas cells). The targeting efficiency of the disaccharide was only slightly less than that of BLM in MCF-7 and DU-145 cells and comparable to that of BLM in BxPC-3 cells. These results establish that the BLM disaccharide is both necessary and sufficient for tumor cell targeting, a finding with obvious implications for the design of novel tumor imaging and therapeutic agents.

  9. Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.

    Science.gov (United States)

    Zhang, Jingzhu; Link, Daniel C

    2016-11-01

    The targeting specificity of tissue-specific Cre-recombinase transgenes is a key to interpreting phenotypes associated with their use. The Ocn-Cre and Dmp1-Cre transgenes are widely used to target osteoblasts and osteocytes, respectively. Here, we used high-resolution microscopy of bone sections and flow cytometry to carefully define the targeting specificity of these transgenes. These transgenes were crossed with Cxcl12 gfp mice to identify Cxcl12-abundant reticular (CAR) cells, which are a perivascular mesenchymal stromal population implicated in hematopoietic stem/progenitor cell maintenance. We show that in addition to osteoblasts, Ocn-Cre targets a majority of CAR cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset of CAR cells, in which expression of osteoblast-lineage genes is enriched. Finally, we introduce a new tissue-specific Cre-recombinase, Tagln-Cre, which efficiently targets osteoblasts, a majority of CAR cells, and both venous sinusoidal and arteriolar pericytes. These data show that Ocn-Cre and Dmp1-Cre target broader stromal cell populations than previously appreciated and may aid in the design of future studies. Moreover, these data highlight the heterogeneity of mesenchymal stromal cells in the bone marrow and provide tools to interrogate this heterogeneity. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  10. An economically viable space power relay system

    Science.gov (United States)

    Bekey, Ivan; Boudreault, Richard

    1999-09-01

    This paper describes and analyzes the economics of a power relay system that takes advantage of recent technological advances to implement a system that is economically viable. A series of power relay systems are described and analyzed which transport power ranging from 1,250 megawatts to 5,000 megawatts, and distribute it to receiving sites at transcontinental distances. Two classes of systems are discussed—those with a single reflector and delivering all the power to a single rectenna, and a second type which has multiple reflectors and distributes it to 10 rectenna sites, sharing power among them. It is shown that when offering electricity at prices competitive to those prevalent in developed cities in the US that a low IRR is inevitable, and economic feasibility of a business is unlikely. However, when the target market is Japan where the prevalent electricity prices are much greater, that an IRR exceeding 65% is readily attainable. This is extremely attractive to potential investors, making capitalization of a venture likely. The paper shows that the capital investment required for the system can be less than 1 per installed watt, contributing less than 0.02 /KW-hr to the cost of energy provision. Since selling prices in feasible regions range from 0.18 to over 030 $/kW-hr, these costs are but a small fraction of the operating expenses. Thus a very large IRR is possible for such a business.

  11. Spoiled Onions: Exposing Malicious Tor Exit Relays

    OpenAIRE

    Winter, Philipp; Lindskog, Stefan

    2014-01-01

    Several hundred Tor exit relays together push more than 1 GiB/s of network traffic. However, it is easy for exit relays to snoop and tamper with anonymised network traffic and as all relays are run by independent volunteers, not all of them are innocuous. In this paper, we seek to expose malicious exit relays and document their actions. First, we monitored the Tor network after developing a fast and modular exit relay scanner. We implemented several scanning modules for detecting common attac...

  12. Targeted radiosensitization of cells expressing truncated DNA polymerase {beta}.

    NARCIS (Netherlands)

    Neijenhuis, S.; Verwijs-Janssen, M.; Broek, Bart van den; Begg, A.C.; Vens, C.

    2010-01-01

    Ionizing radiation (IR) is an effective anticancer treatment, although failures still occur. To improve radiotherapy, tumor-targeted strategies are needed to increase radiosensitivity of tumor cells, without influencing normal tissue radiosensitivity. Base excision repair (BER) and single-strand

  13. Target-specific delivery of doxorubicin to human glioblastoma cell ...

    Indian Academy of Sciences (India)

    Abdullah Tahir Bayraç

    2018-01-29

    Jan 29, 2018 ... was previously selected for specific recognition of glioblastoma and represented many advantageous ... antigens, receptors or any 3-D structure on the target cells ..... both PSMA (?) and PSMA (-) prostate cancers.

  14. Surface-modified gold nanorods for specific cell targeting

    Science.gov (United States)

    Wang, Chan-Ung; Arai, Yoshie; Kim, Insun; Jang, Wonhee; Lee, Seonghyun; Hafner, Jason H.; Jeoung, Eunhee; Jung, Deokho; Kwon, Youngeun

    2012-05-01

    Gold nanoparticles (GNPs) have unique properties that make them highly attractive materials for developing functional reagents for various biomedical applications including photothermal therapy, targeted drug delivery, and molecular imaging. For in vivo applications, GNPs need to be prepared with very little or negligible cytotoxicitiy. Most GNPs are, however, prepared using growth-directing surfactants such as cetyl trimethylammonium bromide (CTAB), which are known to have considerable cytotoxicity. In this paper, we describe an approach to remove CTAB to a non-toxic concentration. We optimized the conditions for surface modification with methoxypolyethylene glycol thiol (mPEG), which replaced CTAB and formed a protective layer on the surface of gold nanorods (GNRs). The cytotoxicities of pristine and surface-modified GNRs were measured in primary human umbilical vein endothelial cells and human cell lines derived from hepatic carcinoma cells, embryonic kidney cells, and thyroid papillary carcinoma cells. Cytotoxicity assays revealed that treating cells with GNRs did not significantly affect cell viability except for thyroid papillary carcinoma cells. Thyroid cancer cells were more susceptible to residual CTAB, so CTAB had to be further removed by dialysis in order to use GNRs for thyroid cell targeting. PEGylated GNRs are further modified to present monoclonal antibodies that recognize a specific surface marker, Na-I symporter, for thyroid cells. Antibody-conjugated GNRs specifically targeted human thyroid cells in vitro.

  15. Relay Selection with Limited and Noisy Feedback

    KAUST Repository

    Eltayeb, Mohammed E.

    2016-01-28

    Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Nonetheless, relay selection algorithms generally require error-free channel state information (CSI) from all cooperating relays. Practically, CSI acquisition generates a great deal of feedback overhead that could result in significant transmission delays. In addition to this, the fed back channel information is usually corrupted by additive noise. This could lead to transmission outages if the central node selects the set of cooperating relays based on inaccurate feedback information. In this paper, we propose a relay selection algorithm that tackles the above challenges. Instead of allocating each relay a dedicated channel for feedback, all relays share a pool of feedback channels. Following that, each relay feeds back its identity only if its effective channel (source-relay-destination) exceeds a threshold. After deriving closed-form expressions for the feedback load and the achievable rate, we show that the proposed algorithm drastically reduces the feedback overhead and achieves a rate close to that obtained by selection algorithms with dedicated error-free feedback from all relays. © 2015 IEEE.

  16. Targeting the bone marrow: applications in stem cell transplantation

    International Nuclear Information System (INIS)

    Orchard, K.; Cooper, M.

    2004-01-01

    Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT

  17. Cell Nucleus-Targeting Zwitterionic Carbon Dots.

    Science.gov (United States)

    Jung, Yun Kyung; Shin, Eeseul; Kim, Byeong-Su

    2015-12-22

    An innovative nucleus-targeting zwitterionic carbon dot (CD) vehicle has been developed for anticancer drug delivery and optical monitoring. The zwitterionic functional groups of the CDs introduced by a simple one-step synthesis using β-alanine as a passivating and zwitterionic ligand allow cytoplasmic uptake and subsequent nuclear translocation of the CDs. Moreover, multicolor fluorescence improves the accuracy of the CDs as an optical code. The CD-based drug delivery system constructed by non-covalent grafting of doxorubicin, exhibits superior antitumor efficacy owing to enhanced nuclear delivery in vitro and tumor accumulation in vivo, resulting in highly effective tumor growth inhibition. Since the zwitterionic CDs are highly biocompatible and effectively translocated into the nucleus, it provides a compelling solution to a multifunctional nanoparticle for substantially enhanced nuclear uptake of drugs and optical monitoring of translocation.

  18. B cells as a target of immune modulation

    Directory of Open Access Journals (Sweden)

    Hawker Kathleen

    2009-01-01

    Full Text Available B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts. MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell-targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.

  19. Cell targeting peptides as smart ligands for targeting of therapeutic or diagnostic agents: a systematic review.

    Science.gov (United States)

    Mousavizadeh, Ali; Jabbari, Ali; Akrami, Mohammad; Bardania, Hassan

    2017-10-01

    Cell targeting peptides (CTP) are small peptides which have high affinity and specificity to a cell or tissue targets. They are typically identified by using phage display and chemical synthetic peptide library methods. CTPs have attracted considerable attention as a new class of ligands to delivery specifically therapeutic and diagnostic agents, because of the fact they have several advantages including easy synthesis, smaller physical sizes, lower immunogenicity and cytotoxicity and their simple and better conjugation to nano-carriers and therapeutic or diagnostic agents compared to conventional antibodies. In this systematic review, we will focus on the basic concepts concerning the use of cell-targeting peptides (CTPs), following the approaches of selecting them from peptide libraries. We discuss several developed strategies for cell-specific delivery of different cargos by CTPs, which are designed for drug delivery and diagnostic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Threshold-Based Relay Selection for Detect-and-Forward Relaying in Cooperative Wireless Networks

    Directory of Open Access Journals (Sweden)

    Fan Yijia

    2010-01-01

    Full Text Available This paper studies two-hop cooperative demodulate-and-forward relaying using multiple relays in wireless networks. A threshold based relay selection scheme is considered, in which the reliable relays are determined by comparing source-relay SNR to a threshold, and one of the reliable relays is selected by the destination based on relay-destination SNR. The exact bit error rate of this scheme is derived, and a simple threshold function is proposed. It is shown that the network achieves full diversity order ( under the proposed threshold, where is the number of relays in the network. Unlike some other full diversity achieving protocols in the literature, the requirement that the instantaneous/average SNRs of the source-relay links be known at the destination is eliminated using the appropriate SNR threshold.

  1. Alternate transmission with half-duplex relaying in MIMO interference relay networks

    KAUST Repository

    Park, Seongho

    2013-12-01

    In this paper, we consider an alternate transmission scheme for a multiple-input multiple-output interference relay channel where multiple sources transmit their own signals to their corresponding destinations via one of two relaying groups alternately every time phase. Each of the relaying groups has arbitrary number of relays, and each relay operates in half-duplex amplify-and-forward mode. In our scheme, the received signals at the relay nodes consist of desired signals and two different interference signals such as the inter-source interferences and the inter-group interferences which are caused by the phase incoherence of relaying. As such, we propose an iterative interference alignment algorithm to mitigate the interferences. We show that our proposed scheme achieves additional degrees of freedom compared to the conventional half-duplex relaying system in the interference relay channels. © 2013 IEEE.

  2. Radioprotection of targeted and bystander cells by methylproamine

    International Nuclear Information System (INIS)

    Burdak-Rothkamm, Susanne; Smith, Andrea; Lobachevsky, Pavel; Martin, Roger; Prise, Kevin M.

    2015-01-01

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to 137 Cs γ-ray/X-ray irradiation and He 2+ microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for 137 Cs γ-rays and X-rays but not for He 2+ charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He 2+ ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He 2+ ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [de

  3. Magnetic stem cell targeting to the inner ear

    Science.gov (United States)

    Le, T. N.; Straatman, L.; Yanai, A.; Rahmanian, R.; Garnis, C.; Häfeli, U. O.; Poblete, T.; Westerberg, B. D.; Gregory-Evans, K.

    2017-12-01

    Severe sensorineural deafness is often accompanied by a loss of auditory neurons in addition to injury of the cochlear epithelium and hair cell loss. Cochlear implant function however depends on a healthy complement of neurons and their preservation is vital in achieving optimal results. We have developed a technique to target mesenchymal stem cells (MSCs) to a deafened rat cochlea. We then assessed the neuroprotective effect of systematically delivered MSCs on the survival and function of spiral ganglion neurons (SGNs). MSCs were labeled with superparamagnetic nanoparticles, injected via the systemic circulation, and targeted using a magnetized cochlea implant and external magnet. Neurotrophic factor concentrations, survival of SGNs, and auditory function were assessed at 1 week and 4 weeks after treatments and compared against multiple control groups. Significant numbers of magnetically targeted MSCs (>30 MSCs/section) were present in the cochlea with accompanied elevation of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor levels (p < 0.001). In addition we saw improved survival of SGNs (approximately 80% survival at 4 weeks). Hearing threshold levels in magnetically targeted rats were found to be significantly better than those of control rats (p < 0.05). These results indicate that magnetic targeting of MSCs to the cochlea can be accomplished with a magnetized cochlear permalloy implant and an external magnet. The targeted stem cells release neurotrophic factors which results in improved SGN survival and hearing recovery. Combining magnetic cell-based therapy and cochlear implantation may improve cochlear implant function in treating deafness.

  4. The mechanism of gene targeting in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Yinan Kan

    2014-04-01

    Full Text Available Gene targeting in human somatic cells is of importance because it can be used to either delineate the loss-of-function phenotype of a gene or correct a mutated gene back to wild-type. Both of these outcomes require a form of DNA double-strand break (DSB repair known as homologous recombination (HR. The mechanism of HR leading to gene targeting, however, is not well understood in human cells. Here, we demonstrate that a two-end, ends-out HR intermediate is valid for human gene targeting. Furthermore, the resolution step of this intermediate occurs via the classic DSB repair model of HR while synthesis-dependent strand annealing and Holliday Junction dissolution are, at best, minor pathways. Moreover, and in contrast to other systems, the positions of Holliday Junction resolution are evenly distributed along the homology arms of the targeting vector. Most unexpectedly, we demonstrate that when a meganuclease is used to introduce a chromosomal DSB to augment gene targeting, the mechanism of gene targeting is inverted to an ends-in process. Finally, we demonstrate that the anti-recombination activity of mismatch repair is a significant impediment to gene targeting. These observations significantly advance our understanding of HR and gene targeting in human cells.

  5. Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

    Science.gov (United States)

    Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

    2017-08-15

    MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

  6. Cooperative joint precoding in a downlink cellular system with shared relay: Design and performance evaluation

    KAUST Repository

    Kwon, JaeWoo; Park, Kihong; Ko, Youngchai; Yang, Hongchuan

    2012-01-01

    In this paper, we investigate a relay enhanced cellular system, where a relay station is located in the overlap area served by two base stations. We propose cooperative joint precoding schemes for the downlink transmission of such relay enhanced cellular system to maximize the system capacity while minimizing the interference at both the relay station and the mobile stations. We formulate the optimization problems to maximize the system capacity and design the multiuser precoding vectors at each base station and the relay station. We quantify the ergodic rate performance of the proposed multiuser precoding schemes through statistical analysis. The extensively derived ergodic expressions will facilitate the accurate performance evaluation of the proposed transmission schemes. Numerical results show that the proposed schemes can effectively cancel the interference and improve the sum rate and the outage performance for cell edge users. © 2002-2012 IEEE.

  7. Cooperative joint precoding in a downlink cellular system with shared relay: Design and performance evaluation

    KAUST Repository

    Kwon, JaeWoo

    2012-10-01

    In this paper, we investigate a relay enhanced cellular system, where a relay station is located in the overlap area served by two base stations. We propose cooperative joint precoding schemes for the downlink transmission of such relay enhanced cellular system to maximize the system capacity while minimizing the interference at both the relay station and the mobile stations. We formulate the optimization problems to maximize the system capacity and design the multiuser precoding vectors at each base station and the relay station. We quantify the ergodic rate performance of the proposed multiuser precoding schemes through statistical analysis. The extensively derived ergodic expressions will facilitate the accurate performance evaluation of the proposed transmission schemes. Numerical results show that the proposed schemes can effectively cancel the interference and improve the sum rate and the outage performance for cell edge users. © 2002-2012 IEEE.

  8. Targeting population heterogeneity for optimal cell factories

    DEFF Research Database (Denmark)

    Heins, Anna-Lena; Carlqvist, Magnus; Helmark, S.

    the heterogeneity level of the population. To further investigate these phenomena and gain a deeper understanding of population heterogeneity, Saccharomyces cerevisiae growth reporter strains based on the expression of green fluorescent protein (GFP) were constructed which enabled us to perform single cell level...... analysis, and thereby created the possibility to map population heterogeneity. A factorial design with pH, glucose concentration and oxygen level was performed in batch cultivations using the growth reporter strains to evaluate the effect of those environmental factors on heterogeneity level and amount......To achieve an efficient production process, it is essential to optimize both the strain and the cultivation conditions. Traditionally, a microbial population has been considered homogeneous in optimization studies of fermentation processes. However, research has shown that a typical microbial...

  9. Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles

    Directory of Open Access Journals (Sweden)

    James O. Park

    2011-01-01

    Full Text Available Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC], one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP specifically targeting glypican-3 (GPC3, a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high and HLF (negligible. These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3 and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP, and magnetic resonance imaging (MRI experiments showed similar findings (threefold R2 relaxivity. Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.

  10. Myeloid derived suppressor cells as therapeutic target in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Kim eDe Veirman

    2014-12-01

    Full Text Available Myeloid derived suppressor cells (MDSC are a heterogeneous population of immature myeloid cells that accumulate during pathological conditions such as cancer and are associated with a poor clinical outcome. MDSC expansion hampers the host anti-tumor immune response by inhibition of T cell proliferation, cytokine secretion and recruitment of regulatory T cells. In addition, MDSC exert non-immunological functions including the promotion of angiogenesis, tumor invasion and metastasis. Recent years, MDSC are considered as a potential target in solid tumors and hematological malignancies to enhance the effects of currently used immune modulating agents. This review focuses on the characteristics, distribution, functions, cell-cell interactions and targeting of MDSC in hematological malignancies including multiple myeloma, lymphoma and leukemia.

  11. Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

    Science.gov (United States)

    Stevens, A M

    2006-01-01

    During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

  12. Targeting dendritic cells in vivo for cancer therapy

    Directory of Open Access Journals (Sweden)

    Irina eCaminschi

    2012-02-01

    Full Text Available Monoclonal antibodies that recognise cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC for induction of immune responses. The encouraging anti-tumour immunity elicited using this immunisation strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialisation of DC-subsets, the immunological outcomes of targeting different DC-subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumour immunity. Finally, we review preclinical experiments and the progress towards targeting human DC in vivo.

  13. The quest for targets executing MYC-dependent cell transformation

    Directory of Open Access Journals (Sweden)

    Markus eHartl

    2016-06-01

    Full Text Available MYC represents a transcription factor with oncogenic potential converting multiple cellular signals into a broad transcriptional response, thereby controlling the expression of numerous protein-coding and non-coding RNAs important for cell proliferation, metabolism, differentiation, and apoptosis. Constitutive activation of MYC leads to neoplastic cell transformation, and deregulated MYC alleles are frequently observed in many human cancer cell types. Multiple approaches have been performed to isolate genes differentially expressed in cells containing aberrantly activated MYC proteins leading to the identification of thousands of putative targets. Functional analyses of genes differentially expressed in MYC-transformed cells had revealed that so far more than forty upregulated or downregulated MYC targets are actively involved in cell transformation or tumorigenesis. However, for determination which of the known, or yet unidentified targets are responsible for processing the oncogenic MYC program, further systematic and selective approaches are required. The search for critical targets in MYC-dependent tumor cells is exacerbated by the fact that during tumor development, cancer cells progressively evolve in a multistep process thereby acquiring their characteristic features in an additive manner. Functional expression cloning, combinatorial gene expression and appropriate in vivo tests could represent adequate tools for dissecting the complex scenario of MYC-specified cell transformation. In this context, the central goal is to identify a minimal set of targets that suffices to phenocopy oncogenic MYC. Recently developed genomic editing tools could be employed to confirm the requirement of crucial transformation-associated targets.Knowledge about essential MYC regulated genes is beneficial to expedite the development of specific inhibitors to interfere with growth and viability of human tumor cells in which MYC is aberrantly activated

  14. Radiation responses of stem cells: targeted and non-targeted effects

    International Nuclear Information System (INIS)

    Kavanagh, J.N.; Waring, E.J.; Prise, K.M.

    2015-01-01

    Stem cells are fundamental to the development of any tissue or organism via their ability to self-renew, which is aided by their unlimited proliferative capacity and their ability to produce fully differentiated offspring, often from multiple lineages. Stems cells are long lived and have the potential to accumulate mutations, including in response to radiation exposure. It is thought that stem cells have the potential to be induced into a cancer stem cell phenotype and that these may play an important role in resistance to radiotherapy. For radiation-induced carcinogenesis, the role of targeted and non-targeted effects is unclear with tissue or origin being important. Studies of genomic instability and bystander responses have shown consistent effects in haematopoietic models. Several models of radiation have predicted that stem cells play an important role in tumour initiation and that bystander responses could play a role in proliferation and self-renewal. (authors)

  15. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  16. Opportunistic Relay Selection With Limited Feedback

    KAUST Repository

    Eltayeb, Mohammed E.

    2015-08-01

    Relay selection is a simple technique that achieves spatial diversity in cooperative relay networks. Generally, relay selection algorithms require channel state information (CSI) feedback from all cooperating relays to make a selection decision. This requirement poses two important challenges, which are often neglected in the literature. Firstly, the fed back channel information is usually corrupted by additive noise. Secondly, CSI feedback generates a great deal of feedback overhead (air-time) that could result in significant performance hits. In this paper, we propose a compressive sensing (CS) based relay selection algorithm that reduces the feedback overhead of relay networks under the assumption of noisy feedback channels. The proposed algorithm exploits CS to first obtain the identity of a set of relays with favorable channel conditions. Following that, the CSI of the identified relays is estimated using least squares estimation without any additional feedback. Both single and multiple relay selection cases are considered. After deriving closed-form expressions for the asymptotic end-to-end SNR at the destination and the feedback load for different relaying protocols, we show that CS-based selection drastically reduces the feedback load and achieves a rate close to that obtained by selection algorithms with dedicated error-free feedback. © 1972-2012 IEEE.

  17. The cancer cell adhesion resistome: mechanisms, targeting and translational approaches.

    Science.gov (United States)

    Dickreuter, Ellen; Cordes, Nils

    2017-06-27

    Cell adhesion-mediated resistance limits the success of cancer therapies and is a great obstacle to overcome in the clinic. Since the 1990s, where it became clear that adhesion of tumor cells to the extracellular matrix is an important mediator of therapy resistance, a lot of work has been conducted to understand the fundamental underlying mechanisms and two paradigms were deduced: cell adhesion-mediated radioresistance (CAM-RR) and cell adhesion-mediated drug resistance (CAM-DR). Preclinical work has evidently demonstrated that targeting of integrins, adapter proteins and associated kinases comprising the cell adhesion resistome is a promising strategy to sensitize cancer cells to both radiotherapy and chemotherapy. Moreover, the cell adhesion resistome fundamentally contributes to adaptation mechanisms induced by radiochemotherapy as well as molecular drugs to secure a balanced homeostasis of cancer cells for survival and growth. Intriguingly, this phenomenon provides a basis for synthetic lethal targeted therapies simultaneously administered to standard radiochemotherapy. In this review, we summarize current knowledge about the cell adhesion resistome and highlight targeting strategies to override CAM-RR and CAM-DR.

  18. Nipah virus infection and glycoprotein targeting in endothelial cells

    Directory of Open Access Journals (Sweden)

    Maisner Andrea

    2010-11-01

    Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

  19. Immunologic targeting of FOXP3 in inflammatory breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Smita Nair

    Full Text Available The forkhead transcription factor FOXP3 is necessary for induction of regulatory T lymphocytes (Tregs and their immunosuppressive function. We have previously demonstrated that targeting Tregs by vaccination of mice with murine FOXP3 mRNA-transfected dendritic cells (DCs elicits FOXP3-specific T cell responses and enhances tumor immunity. It is clear that FOXP3 expression is not restricted to T-cell lineage and herein, using RT-PCR, flow cytometry, and western immunoblot we demonstrate for the first time that FOXP3 is expressed in inflammatory breast cancer (IBC cells, SUM149 (triple negative, ErbB1-activated and SUM190 (ErbB2-overexpressing. Importantly, FOXP3-specific T cells generated in vitro using human FOXP3 RNA-transfected DCs as stimulators efficiently lyse SUM149 cells. Interestingly, an isogenic model (rSUM149 derived from SUM149 with an enhanced anti-apoptotic phenotype was resistant to FOXP3-specific T cell mediated lysis. The MHC class I cellular processing mechanism was intact in both cell lines at the protein and transcription levels suggesting that the resistance to cytolysis by rSUM149 cells was not related to MHC class I expression or to the MHC class I antigen processing machinery in these cells. Our data suggest that FOXP3 may be an effective tumor target in IBC cells however increased anti-apoptotic signaling can lead to immune evasion.

  20. Targeted cancer cell death induced by biofunctionalized magnetic nanowires

    KAUST Repository

    Contreras, Maria F.

    2014-02-01

    Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

  1. Targeted cancer cell death induced by biofunctionalized magnetic nanowires

    KAUST Repository

    Contreras, Maria F.; Ravasi, Timothy; Kosel, Jü rgen

    2014-01-01

    Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

  2. Performance analysis of opportunistic nonregenerative relaying

    KAUST Repository

    Tourki, Kamel; Alouini, Mohamed-Slim; Qaraqe, Khalid A.; Yang, Hongchuan

    2013-01-01

    Opportunistic relaying in cooperative communication depends on careful relay selection. However, the traditional centralized method used for opportunistic amplify-and-forward protocols requires precise measurements of channel state information at the destination. In this paper, we adopt the max-min criterion as a relay selection framework for opportunistic amplify-and-forward cooperative communications, which was exhaustively used for the decode-and-forward protocol, and offer an accurate performance analysis based on exact statistics of the local signal-to-noise ratios of the best relay. Furthermore, we evaluate the asymptotical performance and deduce the diversity order of our proposed scheme. Finally, we validate our analysis by showing that performance simulation results coincide with our analytical results over Rayleigh fading channels, and we compare the max-min relay selection with their centralized channel state information-based and partial relay selection counterparts.

  3. Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

    Science.gov (United States)

    Wang, Denong; Wu, Lisa; Liu, Xiaohe

    2017-01-01

    We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

  4. Relay Precoder Optimization in MIMO-Relay Networks With Imperfect CSI

    KAUST Repository

    Pandarakkottilil, Ubaidulla; Chockalingam, A.

    2011-01-01

    In this paper, we consider robust joint designs of relay precoder and destination receive filters in a nonregenerative multiple-input multiple-output (MIMO) relay network. The network consists of multiple source-destination node pairs assisted by a

  5. Alternate transmission with half-duplex relaying in MIMO interference relay networks

    KAUST Repository

    Park, Seongho; Ko, Youngchai; Park, Kihong; Alouini, Mohamed-Slim

    2013-01-01

    In this paper, we consider an alternate transmission scheme for a multiple-input multiple-output interference relay channel where multiple sources transmit their own signals to their corresponding destinations via one of two relaying groups

  6. Alternate transmission relaying based on interference alignment in 3-relay half-duplex MIMO systems

    KAUST Repository

    Park, Seongho; Park, Kihong; Ko, Youngchai; Alouini, Mohamed-Slim

    2012-01-01

    In a half-duplex relaying, the capacity pre-log factor 1/2 is a major drawback in spectral efficiency. This paper proposes a linear precoding/decoding scheme and an alternate relaying protocol in a dual-hop half-duplex system where three relays help the communication between the source and the destination. In our proposed scheme, we consider a phase incoherent method in relays in which the source alternately transmits message signals to the different relays. In addition, we propose a linear interference alignment scheme which can suppress the inter-relay interference resulting from the phase incoherence of relaying. Based on our analysis of degrees of freedom and our simulation results, we show that our proposed scheme achieves additional degrees of freedom compared to the conventional half-duplex relaying. © 2012 IEEE.

  7. SWIPT in Multiuser MIMO Decode-and-Forward Relay Broadcasting Channel with Energy Harvesting Relays

    KAUST Repository

    Benkhelifa, Fatma; Salem, Ahmed Sultan; Alouini, Mohamed-Slim

    2017-01-01

    In this paper, we consider a multiuser multiple- input multiple-output (MIMO) decode-and-forward (DF) relay broadcasting channel (BC) with single source, multiple energy harvesting relays and multiple destinations. Since the end-to-end sum rate

  8. Alternate transmission relaying based on interference alignment in 3-relay half-duplex MIMO systems

    KAUST Repository

    Park, Seongho

    2012-09-01

    In a half-duplex relaying, the capacity pre-log factor 1/2 is a major drawback in spectral efficiency. This paper proposes a linear precoding/decoding scheme and an alternate relaying protocol in a dual-hop half-duplex system where three relays help the communication between the source and the destination. In our proposed scheme, we consider a phase incoherent method in relays in which the source alternately transmits message signals to the different relays. In addition, we propose a linear interference alignment scheme which can suppress the inter-relay interference resulting from the phase incoherence of relaying. Based on our analysis of degrees of freedom and our simulation results, we show that our proposed scheme achieves additional degrees of freedom compared to the conventional half-duplex relaying. © 2012 IEEE.

  9. Electric equipment technical regulation on a relay

    International Nuclear Information System (INIS)

    1995-01-01

    It is about a relay for power protection. It describes the definitions of structure, a point of contact protection of contact, reclosing, relay scheme and input circuit. It explains normal use condition, special use condition, rated frequency, rated voltage and rated current, fluctuation range of permission of incoming relay. It deals with general structing outer case, correction device, operation indicator and outer terminal condition sort and method of the test. It adds the marks and pictures about currents

  10. Full-Duplex Relay Selection in Cognitive Underlay Networks

    KAUST Repository

    Khafagy, Mohammad Galal; Alouini, Mohamed-Slim; Aissa, Sonia

    2017-01-01

    In this work, we analyze the performance of full-duplex relay selection (FDRS) in spectrum-sharing networks. Contrary to half-duplex relaying, full-duplex relaying (FDR) enables simultaneous listening/forwarding at the secondary relay(s), thereby

  11. Targeting myeloid cells using nanoparticles to improve cancer immunotherapy.

    Science.gov (United States)

    Amoozgar, Zohreh; Goldberg, Michael S

    2015-08-30

    While nanoparticles have traditionally been used to deliver cytotoxic drugs directly to tumors to induce cancer cell death, emerging data suggest that nanoparticles are likely to generate a larger impact on oncology through the delivery of agents that can stimulate antitumor immunity. Tumor-targeted nanocarriers have generally been used to localize chemotherapeutics to tumors and thus decrease off-target toxicity while enhancing efficacy. Challengingly, tumor heterogeneity and evolution render tumor-intrinsic approaches likely to succumb to relapse. The immune system offers exquisite specificity, cytocidal potency, and long-term activity that leverage an adaptive memory response. For this reason, the ability to manipulate immune cell specificity and function would be desirable, and nanoparticles represent an exciting means by which to perform such manipulation. Dendritic cells and tumor-associated macrophages are cells of the myeloid lineage that function as natural phagocytes, so they naturally take up nanoparticles. Dendritic cells direct the specificity and potency of cellular immune responses that can be targeted for cancer vaccines. Herein, we discuss the specific criteria needed for efficient vaccine design, including but not limited to the route of administration, size, morphology, surface charge, targeting ligands, and nanoparticle composition. In contrast, tumor-associated macrophages are critical mediators of immunosuppression whose trans-migratory abilities can be exploited to localize therapeutics to the tumor core and which can be directly targeted for elimination or for repolarization to a tumor suppressive phenotype. It is likely that a combination of targeting dendritic cells to stimulate antitumor immunity and tumor-associated macrophages to reduce immune suppression will impart significant benefits and result in durable antitumor responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Adoptive T cell therapy targeting CD1 and MR1

    Directory of Open Access Journals (Sweden)

    Tingxi eGuo

    2015-05-01

    Full Text Available Adoptive T cell immunotherapy has demonstrated clinically relevant efficacy in treating malignant and infectious diseases. However, much of these therapies have been focused on enhancing, or generating de novo, effector functions of conventional T cells recognizing HLA molecules. Given the heterogeneity of HLA alleles, mismatched patients are ineligible for current HLA-restricted adoptive T cell therapies. CD1 and MR1 are class I-like monomorphic molecules and their restricted T cells possess unique T cell receptor specificity against entirely different classes of antigens. CD1 and MR1 molecules present lipid and vitamin B metabolite antigens, respectively, and offer a new front of targets for T cell therapies. This review will cover the recent progress in the basic research of CD1, MR1, and their restricted T cells that possess translational potential.

  13. Relay self interference minimisation using tapped filter

    KAUST Repository

    Jazzar, Saleh

    2013-05-01

    In this paper we introduce a self interference (SI) estimation and minimisation technique for amplify and forward relays. Relays are used to help forward signals between a transmitter and a receiver. This helps increase the signal coverage and reduce the required transmitted signal power. One problem that faces relays communications is the leaked signal from the relay\\'s output to its input. This will cause an SI problem where the new received signal at the relay\\'s input will be added with the unwanted leaked signal from the relay\\'s output. A Solution is proposed in this paper to estimate and minimise this SI which is based upon using a tapped filter at the destination. To get the optimum weights for this tapped filter, some channel parameters must be estimated first. This is performed blindly at the destination without the need of any training. This channel parameter estimation method is named the blind-self-interference-channel-estimation (BSICE) method. The next step in the proposed solution is to estimate the tapped filter\\'s weights. This is performed by minimising the mean squared error (MSE) at the destination. This proposed method is named the MSE-Optimum Weight (MSE-OW) method. Simulation results are provided in this paper to verify the performance of BSICE and MSE-OW methods. © 2013 IEEE.

  14. Analysis of errors of radiation relay, (1)

    International Nuclear Information System (INIS)

    Koyanagi, Takami; Nakajima, Sinichi

    1976-01-01

    The statistical error of liquid level controlled by radiation relay is analysed and a method of minimizing the error is proposed. This method comes to the problem of optimum setting of the time constant of radiation relay. The equations for obtaining the value of time constant are presented and the numerical results are shown in a table and plotted in a figure. The optimum time constant of the upper level control relay is entirely different from that of the lower level control relay. (auth.)

  15. Experimental evaluation of earthquake induced relay chattering

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.; Hofmayer, C.; Shteyngart, S.

    1990-01-01

    An experimental evaluation of relay performance under vibratory environments is discussed in this paper. Single frequency excitation was used for most tests. Limited tests were performed with random multifrequency inputs. The capacity of each relay was established based on a two-millisecond chatter criterion. The experimental techniques are described and the effects of parameters in controlling the relay capacity levels are illustrated with test data. A wide variation of the capacity levels was observed due to the influence of parameters related to the design of the relay and nature of the input motion. 3 refs., 15 figs

  16. Targeting cancer cells using 3-bromopyruvate for selective cancer treatment

    Directory of Open Access Journals (Sweden)

    Hussam H Baghdadi

    2017-01-01

    Full Text Available Cancer treatment deserves more research efforts despite intensive conventional treatment modalities for many types of malignancies. Metastasis and resistance to chemotherapy and radiotherapy receive a lot of global research efforts. The current advances in cancer biology may improve targeting the critical metabolic differences that distinguish cancer cells from normal cells. Cancer cells are highly glycolytic for energy production, exhibit the Warburg effect, establish aggressive acidic microenvironment, maintain cancer stem cells, exhibit resistance to chemotherapy, have low antioxidant systems but different ΔΨm (delta psi, mitochondrial transmembrane potential, express P-glycoprotein for multidrug resistance, upregulate glucose transporters and monocarboxylate transporters and are under high steady-state reactive oxygen species conditions. Normal cells differ in all these aspects. Lactate produced through the Warburg effect helps cancer metastasis. Targeting glycolysis reactions for energy production in cancer cells seems promising in decreasing the proliferation and metastasis of cancer cells. 3-bromopyruvate makes use of cancer biology in treating cancer cells, cancer stem cells and preventing metastasis in human cancer as discussed in this review. Updated advances are analyzed here, which include research analysis of background, experience, readings in the field of cancer biology, oncology and biochemistry.

  17. Nitric oxide mediated bystander responses induced by microbeam targeted cells

    International Nuclear Information System (INIS)

    Shao, C.; Prise, K.M.; Folkard, M.; Michael, B.D.

    2003-01-01

    Considerable evidence has recently been accumulated in support of the existence of a 'bystander effect', which cells having received no irradiation show biological consequences from their vicinal irradiated cells. The application of microbeams is providing new insights into the radiation-induced bystander effect. The present study found that when a fraction of radioresistant human glioblastoma cells were individually targeted with a precise number of helium ions generated from the Gray Cancer Institute Charged Particle Microbeam, micronucleus (MN) induction significantly exceeded the expected value that was calculated from the number of MN observed when all of the cells were targeted assuming no bystander effect occurring. Even when only a single cell within a population was hit by one helium ion, the MN induction in the population could be increased by 16%. These results provide direct evidence of radiation-induced bystander effect. Moreover, MN was effectively induced in the unirradiated primary human fibroblasts and glioblastoma cells either co-cultured with irradiated cells or treated with the medium harvested from irradiated cells, indicating a signal molecule was produced from the irradiated cells. However, when c-PTIO, a nitric oxide (NO)-specific scavenger, was present in the medium during and after irradiation until MN analysis, the production of MN in all of the above cases was reduced to low levels. Consequently, NO plays an important role in the radiation-induced bystander effect

  18. 78 FR 40407 - Structure and Practices of the Video Relay Service Program: Telecommunications Relay Services and...

    Science.gov (United States)

    2013-07-05

    ...] Structure and Practices of the Video Relay Service Program: Telecommunications Relay Services and Speech-to... telecommunications relay services (TRS) program continues to offer functional equivalence to all eligible users and..., identified by CG Docket Nos. 10-51 and 03-123, by any of the following methods: Electronic Filers: Comments...

  19. Immunotherapeutic strategies targeting Natural killer T cell responses in cancer

    Science.gov (United States)

    Shissler, Susannah C.; Bollino, Dominique R.; Tiper, Irina V.; Bates, Joshua; Derakhshandeh, Roshanak; Webb, Tonya J.

    2017-01-01

    Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T-cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where Type II cells generally suppress tumor immunity while Type I NKT cells can enhance antitumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell targeted therapies for the treatment of cancer. PMID:27393665

  20. Next-Generation NASA Earth-Orbiting Relay Satellites: Fusing Optical and Microwave Communications

    Science.gov (United States)

    Israel, David J.; Shaw, Harry

    2018-01-01

    NASA is currently considering architectures and concepts for the generation of relay satellites that will replace the Tracking and Data Relay Satellite (TDRS) constellation, which has been flying since 1983. TDRS-M, the last of the second TDRS generation, launched in August 2017, extending the life of the TDRS constellation beyond 2030. However, opportunities exist to re-engineer the concepts of geosynchronous Earth relay satellites. The needs of the relay satellite customers have changed dramatically over the last 34 years since the first TDRS launch. There is a demand for greater bandwidth as the availability of the traditional RF spectrum for space communications diminishes and the demand for ground station access grows. The next generation of NASA relay satellites will provide for operations that have factored in these new constraints. In this paper, we describe a heterogeneous constellation of geosynchronous relay satellites employing optical and RF communications. The new constellation will enable new optical communications services formed by user-to-space relay, space relay-to-space relay and space relay-to-ground links. It will build upon the experience from the Lunar Laser Communications Demonstration from 2013 and the Laser Communications Relay Demonstration to be launched in 2019.Simultaneous to establishment of the optical communications space segment, spacecraft in the TDRS constellation will be replaced with RF relay satellites with targeted subsets of the TDRS capabilities. This disaggregation of the TDRS service model will allow for flexibility in replenishing the needs of legacy users as well as addition of new capabilities for future users. It will also permit the U.S. government access to launch capabilities such as rideshare and to hosted payloads that were not previously available.In this paper, we also explore how the next generation of Earth relay satellites provides a significant boost in the opportunities for commercial providers to the

  1. Next-Generation NASA Earth-Orbiting Relay Satellites: Fusing Microwave and Optical Communications

    Science.gov (United States)

    Israel, David J.

    2018-01-01

    NASA is currently considering architectures and concepts for the generation of relay satellites that will replace the Tracking and Data Relay Satellite (TDRS) constellation, which has been flying since 1983. TDRS-M, the last of the second TDRS generation, launched in August 2017, extending the life of the TDRS constellation beyond 2030. However, opportunities exist to re-engineer the concepts of geosynchronous Earth relay satellites. The needs of the relay satellite customers have changed dramatically over the last 34 years since the first TDRS launch. There is a demand for greater bandwidth as the availability of the traditional RF spectrum for space communications diminishes and the demand for ground station access grows. The next generation of NASA relay satellites will provide for operations that have factored in these new constraints. In this paper, we describe a heterogeneous constellation of geosynchronous relay satellites employing optical and RF communications. The new constellation will enable new optical communications services formed by user-to-space relay, space relay-to-space relay and space relay-to-ground links. It will build upon the experience from the Lunar Laser Communications Demonstration from 2013 and the Laser Communications Relay Demonstration to be launched in 2019.Simultaneous to establishment of the optical communications space segment, spacecraft in the TDRS constellation will be replaced with RF relay satellites with targeted subsets of the TDRS capabilities. This disaggregation of the TDRS service model will allow for flexibility in replenishing the needs of legacy users as well as addition of new capabilities for future users. It will also permit the U.S. government access to launch capabilities such as rideshare and to hosted payloads that were not previously available. In this paper, we also explore how the next generation of Earth relay satellites provides a significant boost in the opportunities for commercial providers to the

  2. ATR-dependent bystander effects in non-targeted cells

    International Nuclear Information System (INIS)

    Burdak-Rothkamm, S.

    2007-01-01

    Complete text of publication follows. Radiation induced non-targeted bystander effects have been reported for a range of endpoints including the induction of γH2AX foci which serve as a marker for DNA double strand breaks. We have recently reported the induction of γH2AX foci in non-targeted bystander cells up to 48 hours after irradiation and the involvement of reactive oxygen species (ROS) and TGF-beta 1 in the induction of γH2AX foci (Oncogene (2007) 26:993-1002). Here, we wanted to determine the role of the PI3-like kinases ATM, ATR and DNA-PK in DNA damage signalling in bystander cells. Conditioned medium from T98G cells irradiated with 2 Gy of X-rays was transferred onto non-irradiated cells that were subsequently analysed for the induction of γH2AX, ATR and 53BP1 foci as well as clonogenic survival. Irradiated T98G glioma cells generated signals that induced γH2AX and 53BP1 foci in cells treated with the conditioned medium from irradiated cells. These foci co-localised with ATR foci. Inhibition of ATM and DNA-PK could not suppress the induction of bystander γH2AX foci whereas the mutation of ATR in Seckel cells abrogated bystander foci induction. A restriction of bystander foci to the S-phase of the cell cycle both in T98G cells and in ATR- proficient fibroblasts was observed. These results identify ATR as a central player within the bystander signalling cascade leading to γH2AX and 53BP1 foci formation, and suggest a mechanism of DNA damage induction in non-targeted cells. Further investigations have shown decreased clonogenic cell survival in bystander T98G and ATR wild-type fibroblasts. ATR mutated Seckel cells and also ATM-/- fibroblasts were resistant to this effect suggesting a role for both ATR and ATM in the bystander signalling cascade with regard to cell survival. Taken together, these observations support a hypothesis of DNA damage-induced accumulation of stalled replication forks in bystander cells which are subsequently processed by

  3. On the performance of spectrum sharing systems with two-way relaying and multiuser diversity

    KAUST Repository

    Yang, Liang

    2012-08-01

    In this letter, we consider a spectrum sharing network with two-way relaying and multi-user diversity. More specifically, one secondary transmitter with the best channel quality is selected and splits its partial power to relay its received signals to the primary users by using the amplify-and-forward relaying protocol. We derive a tight approximation for the resulting outage probability. Based on this formula, the performance of the spectral sharing region and the cell coverage are analyzed. Numerical results are given to verify our analysis and are discussed to illustrate the advantages of our newly proposed scheme. © 1997-2012 IEEE.

  4. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Directory of Open Access Journals (Sweden)

    Yacoby Iftach

    2008-04-01

    Full Text Available Abstract Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates.

  5. Killing cancer cells by targeted drug-carrying phage nanomedicines

    Science.gov (United States)

    Bar, Hagit; Yacoby, Iftach; Benhar, Itai

    2008-01-01

    Background Systemic administration of chemotherapeutic agents, in addition to its anti-tumor benefits, results in indiscriminate drug distribution and severe toxicity. This shortcoming may be overcome by targeted drug-carrying platforms that ferry the drug to the tumor site while limiting exposure to non-target tissues and organs. Results We present a new form of targeted anti-cancer therapy in the form of targeted drug-carrying phage nanoparticles. Our approach is based on genetically-modified and chemically manipulated filamentous bacteriophages. The genetic manipulation endows the phages with the ability to display a host-specificity-conferring ligand. The phages are loaded with a large payload of a cytotoxic drug by chemical conjugation. In the presented examples we used anti ErbB2 and anti ERGR antibodies as targeting moieties, the drug hygromycin conjugated to the phages by a covalent amide bond, or the drug doxorubicin conjugated to genetically-engineered cathepsin-B sites on the phage coat. We show that targeting of phage nanomedicines via specific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release, resulting in growth inhibition of the target cells in vitro with a potentiation factor of >1000 over the corresponding free drugs. Conclusion The results of the proof-of concept study presented here reveal important features regarding the potential of filamentous phages to serve as drug-delivery platform, on the affect of drug solubility or hydrophobicity on the target specificity of the platform and on the effect of drug release mechanism on the potency of the platform. These results define targeted drug-carrying filamentous phage nanoparticles as a unique type of antibody-drug conjugates. PMID:18387177

  6. Relay Selection and Resource Allocation in One-Way and Two-Way Cognitive Relay Networks

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-05-08

    In this work, the problem of relay selection and resource power allocation in one- way and two-way cognitive relay networks using half duplex channels with different relaying protocols is investigated. Optimization problems for both single and multiple relay selection that maximize the sum rate of the secondary network without degrading the quality of service of the primary network by respecting a tolerated interference threshold were formulated. Single relay selection and optimal power allocation for two-way relaying cognitive radio networks using decode-and-forward and amplify-and-forward protocols were studied. Dual decomposition and subgradient methods were used to find the optimal power allocation. The transmission process to exchange two different messages between two transceivers for two-way relaying technique takes place in two time slots. In the first slot, the transceivers transmit their signals simultaneously to the relay. Then, during the second slot the relay broadcasts its signal to the terminals. Moreover, improvement of both spectral and energy efficiency can be achieved compared with the one-way relaying technique. As an extension, a multiple relay selection for both one-way and two-way relaying under cognitive radio scenario using amplify-and-forward were discussed. A strong optimization tool based on genetic and iterative algorithms was employed to solve the 
formulated optimization problems for both single and multiple relay selection, where discrete relay power levels were considered. Simulation results show that the practical and low-complexity heuristic approaches achieve almost the same performance of the optimal relay selection schemes either with discrete or continuous power distributions while providing a considerable saving in terms of computational complexity.

  7. An RSS based location estimation technique for cognitive relay networks

    KAUST Repository

    Qaraqe, Khalid A.; Hussain, Syed Imtiaz; Ç elebi, Hasari Burak; Abdallah, Mohamed M.; Alouini, Mohamed-Slim

    2010-01-01

    In this paper, a received signal strength (RSS) based location estimation method is proposed for a cooperative wireless relay network where the relay is a cognitive radio. We propose a method for the considered cognitive relay network to determine

  8. Error-rate performance analysis of opportunistic regenerative relaying

    KAUST Repository

    Tourki, Kamel; Yang, Hongchuan; Alouini, Mohamed-Slim

    2011-01-01

    In this paper, we investigate an opportunistic relaying scheme where the selected relay assists the source-destination (direct) communication. In our study, we consider a regenerative opportunistic relaying scheme in which the direct path can

  9. New results on performance analysis of opportunistic regenerative relaying

    KAUST Repository

    Tourki, Kamel; Yang, Hongchuan; Alouini, Mohamed-Slim; Qaraqe, Khalid A.

    2013-01-01

    In this paper, we investigate an opportunistic relaying scheme where the selected relay assists the source-destination (direct) communication. In our study, we consider a regenerative opportunistic relaying scheme in which the direct path may

  10. Accurate performance analysis of opportunistic decode-and-forward relaying

    KAUST Repository

    Tourki, Kamel; Yang, Hongchuan; Alouini, Mohamed-Slim

    2011-01-01

    In this paper, we investigate an opportunistic relaying scheme where the selected relay assists the source-destination (direct) communication. In our study, we consider a regenerative opportunistic relaying scheme in which the direct path may

  11. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Mechanoresponsive stem cells to target cancer metastases through biophysical cues.

    Science.gov (United States)

    Liu, Linan; Zhang, Shirley X; Liao, Wenbin; Farhoodi, Henry P; Wong, Chi W; Chen, Claire C; Ségaliny, Aude I; Chacko, Jenu V; Nguyen, Lily P; Lu, Mengrou; Polovin, George; Pone, Egest J; Downing, Timothy L; Lawson, Devon A; Digman, Michelle A; Zhao, Weian

    2017-07-26

    Despite decades of effort, little progress has been made to improve the treatment of cancer metastases. To leverage the central role of the mechanoenvironment in cancer metastasis, we present a mechanoresponsive cell system (MRCS) to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home to and target cancer metastases in response to specific mechanical cues to deliver therapeutics to effectively kill cancer cells, as demonstrated in a metastatic breast cancer mouse model. Our data suggest a strong correlation between collagen cross-linking and increased tissue stiffness at the metastatic sites, where our MRCS is specifically activated by the specific cancer-associated mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs constitutively expressing therapeutics. MRCS indicates that biophysical cues, specifically matrix stiffness, are appealing targets for cancer treatment due to their long persistence in the body (measured in years), making them refractory to the development of resistance to treatment. Our MRCS can serve as a platform for future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and it should help to elucidate mechanobiology and reveal what cells "feel" in the microenvironment in vivo. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  13. Targeted genome editing in human repopulating haematopoietic stem cells

    NARCIS (Netherlands)

    P. Genovese (Pietro); G. Schiroli (Giulia); G. Escobar (Giulia); T. Di Tomaso (Tiziano); C. Firrito (Claudia); A. Calabria (Andrea); D. Moi (Davide); R. Mazzieri (Roberta); C. Bonini (Chiara); M.V. Holmes (Michael); P.D. Gregory (Philip); M. van der Burg (Mirjam); B. Gentner (Bernhard); E. Montini (Eugenio); A. Lombardo (Angelo); L. Naldini (Luigi)

    2014-01-01

    textabstractTargeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that

  14. Liposomes to target peripheral neurons and Schwann cells.

    Directory of Open Access Journals (Sweden)

    Sooyeon Lee

    Full Text Available While a wealth of literature for tissue-specific liposomes is emerging, optimal formulations to target the cells of the peripheral nervous system (PNS are lacking. In this study, we asked whether a novel formulation of phospholipid-based liposomes could be optimized for preferential uptake by microvascular endothelia, peripheral neurons and Schwann cells. Here, we report a unique formulation consisting of a phospholipid, a polymer surfactant and cholesterol that result in enhanced uptake by targeted cells. Using fluorescently labeled liposomes, we followed particle internalization and trafficking through a distinct route from dextran and escape from degradative compartments, such as lysosomes. In cultures of non-myelinating Schwann cells, liposomes associate with the lipid raft marker Cholera toxin, and their internalization is inhibited by disruption of lipid rafts or actin polymerization. In contrast, pharmacological inhibition of clathrin-mediated endocytosis does not significantly impact liposome entry. To evaluate the efficacy of liposome targeting in tissues, we utilized myelinating explant cultures of dorsal root ganglia and isolated diaphragm preparations, both of which contain peripheral neurons and myelinating Schwann cells. In these models, we detected preferential liposome uptake into neurons and glial cells in comparison to surrounding muscle tissue. Furthermore, in vivo liposome administration by intramuscular or intravenous injection confirmed that the particles were delivered to myelinated peripheral nerves. Within the CNS, we detected the liposomes in choroid epithelium, but not in myelinated white matter regions or in brain parenchyma. The described nanoparticles represent a novel neurophilic delivery vehicle for targeting small therapeutic compounds, biological molecules, or imaging reagents into peripheral neurons and Schwann cells, and provide a major advancement toward developing effective therapies for peripheral

  15. Targeting cancer stem cells: emerging role of Nanog transcription factor

    Directory of Open Access Journals (Sweden)

    Wang ML

    2013-09-01

    Full Text Available Mong-Lien Wang,1 Shih-Hwa Chiou,2,3 Cheng-Wen Wu1,4–61Institute of Biochemistry and Molecular Biology, 2Institute of Pharmacology, National Yang Ming University, Taipei, Taiwan; 3Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; 4Institute of Microbiology and Immunology, 5Institute of Clinical Medicine, National Yang Ming University, Taipei, Taiwan; 6Institute of Biomedical Science, Academia Sinica, Taipei, TaiwanAbstract: The involvement of stemness factors in cancer initiation and progression has drawn much attention recently, especially after the finding that introducing four stemness factors in somatic cells is able to reprogram the cells back to an embryonic stem cell-like state. Following accumulating data revealing abnormal elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2, in several types of cancer stem cells; the importance and therapeutic potential of targeting these stemness regulators in cancers has turned to research focus. Nanog determines cell fate in both embryonic and cancer stem cells; activating Nanog at an inappropriate time would result in cancer stem cells rather than normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog is correlated with poor survival outcome of patients with various types of cancer. The discoveries of downstream regulatory pathways directly or indirectly mediated by Nanog indicate that Nanog regulates several aspects of cancer development such as tumor cell proliferation, self-renewal, motility, epithelial-mesenchymal transition, immune evasion, and drug-resistance, which are all defined features for cancer stem cells. The current review paper illustrates the central role of Nanog in the regulatory networks of cancer malignant development and stemness acquirement, as well as in the communication between cancer cells and the surrounding stroma. Though a more defined model is needed to test the

  16. Breast cancer stem cells, EMT and therapeutic targets

    Energy Technology Data Exchange (ETDEWEB)

    Kotiyal, Srishti; Bhattacharya, Susinjan, E-mail: s.bhattacharya@jiit.ac.in

    2014-10-10

    Highlights: • Therapeutic targeting or inhibition of the key molecules of signaling pathways can control growth of breast cancer stem cells (BCSCs). • Development of BCSCs also involves miRNA interactions. • Therapeutic achievement can be done by targeting identified targets in the BCSC pathways. - Abstract: A small heterogeneous population of breast cancer cells acts as seeds to induce new tumor growth. These seeds or breast cancer stem cells (BCSCs) exhibit great phenotypical plasticity which allows them to undergo “epithelial to mesenchymal transition” (EMT) at the site of primary tumor and a future reverse transition. Apart from metastasis they are also responsible for maintaining the tumor and conferring it with drug and radiation resistance and a tendency for post-treatment relapse. Many of the signaling pathways involved in induction of EMT are involved in CSC generation and regulation. Here we are briefly reviewing the mechanism of TGF-β, Wnt, Notch, TNF-α, NF-κB, RTK signalling pathways which are involved in EMT as well as BCSCs maintenance. Therapeutic targeting or inhibition of the key/accessory players of these pathways could control growth of BCSCs and hence malignant cancer. Additionally several miRNAs are dysregulated in cancer stem cells indicating their roles as oncogenes or tumor suppressors. This review also lists the miRNA interactions identified in BCSCs and discusses on some newly identified targets in the BCSC regulatory pathways like SHIP2, nicastrin, Pin 1, IGF-1R, pro-inflammatory cytokines and syndecan which can be targeted for therapeutic achievements.

  17. Opportunistic Relay Selection with Cooperative Macro Diversity

    Directory of Open Access Journals (Sweden)

    Yu Chia-Hao

    2010-01-01

    Full Text Available We apply a fully opportunistic relay selection scheme to study cooperative diversity in a semianalytical manner. In our framework, idle Mobile Stations (MSs are capable of being used as Relay Stations (RSs and no relaying is required if the direct path is strong. Our relay selection scheme is fully selection based: either the direct path or one of the relaying paths is selected. Macro diversity, which is often ignored in analytical works, is taken into account together with micro diversity by using a complete channel model that includes both shadow fading and fast fading effects. The stochastic geometry of the network is taken into account by having a random number of randomly located MSs. The outage probability analysis of the selection differs from the case where only fast fading is considered. Under our framework, distribution of the received power is formulated using different Channel State Information (CSI assumptions to simulate both optimistic and practical environments. The results show that the relay selection gain can be significant given a suitable amount of candidate RSs. Also, while relay selection according to incomplete CSI is diversity suboptimal compared to relay selection based on full CSI, the loss in average throughput is not too significant. This is a consequence of the dominance of geometry over fast fading.

  18. Microcomputer relay regulator in the CAMAC standard

    International Nuclear Information System (INIS)

    Nikolaev, V.P.

    1984-01-01

    The digital relay regulator is developed on the base of the KM001 microcomputer and KK06 controller for automatic control ob ects with transfer functions describing a broad class of systems using actuating motors (stabilitation, follow-up systems). The CAMAC relay-unit realizes the regulation law and provides the possibility to control analogous values by 8 channels

  19. Membrane Targeting of P-type ATPases in Plant Cells

    International Nuclear Information System (INIS)

    Harper, Jeffrey F.

    2004-01-01

    How membrane proteins are targeted to specific subcellular locations is a very complex and poorly understood area of research. Our long-term goal is to use P-type ATPases (ion pumps), in a model plant system Arabidopsis, as a paradigm to understand how members of a family of closely related membrane proteins can be targeted to different subcellular locations. The research is divided into two specific aims. The first aim is focused on determining the targeting destination of all 10 ACA-type calcium pumps (Arabidopsis Calcium ATPase) in Arabidopsis. ACAs represent a plant specific-subfamily of plasma membrane-type calcium pumps. In contrast to animals, the plant homologs have been found in multiple membrane systems, including the ER (ACA2), tonoplast (ACA4) and plasma membrane (ACA8). Their high degree of similarity provides a unique opportunity to use a comparative approach to delineate the membrane specific targeting information for each pump. One hypothesis to be tested is that an endomembrane located ACA can be re-directed to the plasma membrane by including targeting information from a plasma membrane isoform, ACA8. Our approach is to engineer domain swaps between pumps and monitor the targeting of chimeric proteins in plant cells using a Green Fluorescence Protein (GFP) as a tag. The second aim is to test the hypothesis that heterologous transporters can be engineered into plants and targeted to the plasma membrane by fusing them to a plasma membrane proton pump. As a test case we are evaluating the targeting properties of fusions made between a yeast sodium/proton exchanger (Sod2) and a proton pump (AHA2). This fusion may potentially lead to a new strategy for engineering salt resistant plants. Together these aims are designed to provide fundamental insights into the biogenesis and function of plant cell membrane systems

  20. Decode and Zero-Forcing Forward Relaying with Relay Selection in Cognitive Radio Systems

    KAUST Repository

    Park, Kihong

    2014-05-01

    In this paper, we investigate a cognitive radio (CR) relay network with multiple relay nodes that help forwarding the signal of CR users. Best relay selection is considered to take advantage of its low complexity of implementation. When the primary user (PU) is located close to the relay nodes, the performance of the secondary network is severely degraded due to the interference power constraint during the transmission in the second hop. We propose a decode and zero-forcing forward scheme to suppress the interference power at the relay nodes and analyze the statistics of the end-to-end signal-to-noise ratio when the relay nodes are located arbitrarily and experience therefore non-identical Rayleigh fading channels. Numerical results validate our theoretical results and show that our proposed scheme improves the performance of the CR network when the PU is close to the relay nodes. © 2014 IEEE.

  1. On the achievable degrees of freedom of alternate MIMO relaying with multiple AF relays

    KAUST Repository

    Park, Kihong

    2012-03-01

    In this paper, we consider a two-hop relaying network where one source, one destination, and multiple amplify-and-forward (AF) relays equipped with M antennas operate in a half-duplex mode. In order to compensate for the inherent loss of capacity pre-log factor of 1/2 due to half-duplex relaying, we propose a new transmission protocol which combines alternate relaying and inter-relay interference alignment. We prove that the proposed scheme can (i) exploits M degrees of freedom (DOFs) and (ii) perfectly recover the pre-log factor loss if the number of relays is at least six. From our selected numerical results, we show that our proposed scheme gives significant improvement over conventional AF relaying which offers only M/2 DOFs. © 2012 IEEE.

  2. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    Science.gov (United States)

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  3. Bilayer expurgated LDPC codes with uncoded relaying

    Directory of Open Access Journals (Sweden)

    Md. Noor-A-Rahim

    2017-08-01

    Full Text Available Bilayer low-density parity-check (LDPC codes are an effective coding technique for decode-and-forward relaying, where the relay forwards extra parity bits to help the destination to decode the source bits correctly. In the existing bilayer coding scheme, these parity bits are protected by an error correcting code and assumed reliably available at the receiver. We propose an uncoded relaying scheme, where the extra parity bits are forwarded to the destination without any protection. Through density evolution analysis and simulation results, we show that our proposed scheme achieves better performance in terms of bit erasure probability than the existing relaying scheme. In addition, our proposed scheme results in lower complexity at the relay.

  4. On Alternate Relaying with Improper Gaussian Signaling

    KAUST Repository

    Gaafar, Mohamed

    2016-06-06

    In this letter, we investigate the potential benefits of adopting improper Gaussian signaling (IGS) in a two-hop alternate relaying (AR) system. Given the known benefits of using IGS in interference-limited networks, we propose to use IGS to relieve the inter-relay interference (IRI) impact on the AR system assuming no channel state information is available at the source. In this regard, we assume that the two relays use IGS and the source uses proper Gaussian signaling (PGS). Then, we optimize the degree of impropriety of the relays signal, measured by the circularity coefficient, to maximize the total achievable rate. Simulation results show that using IGS yields a significant performance improvement over PGS, especially when the first hop is a bottleneck due to weak source-relay channel gains and/or strong IRI.

  5. On Alternate Relaying with Improper Gaussian Signaling

    KAUST Repository

    Gaafar, Mohamed; Amin, Osama; Ikhlef, Aissa; Chaaban, Anas; Alouini, Mohamed-Slim

    2016-01-01

    In this letter, we investigate the potential benefits of adopting improper Gaussian signaling (IGS) in a two-hop alternate relaying (AR) system. Given the known benefits of using IGS in interference-limited networks, we propose to use IGS to relieve the inter-relay interference (IRI) impact on the AR system assuming no channel state information is available at the source. In this regard, we assume that the two relays use IGS and the source uses proper Gaussian signaling (PGS). Then, we optimize the degree of impropriety of the relays signal, measured by the circularity coefficient, to maximize the total achievable rate. Simulation results show that using IGS yields a significant performance improvement over PGS, especially when the first hop is a bottleneck due to weak source-relay channel gains and/or strong IRI.

  6. Targeting neuroblastoma stem cells with retinoic acid and proteasome inhibitor.

    Directory of Open Access Journals (Sweden)

    Barbara Hämmerle

    Full Text Available Neuroblastma cell lines contain a side-population of cells which express stemness markers. These stem-like cells may represent the potential underlying mechanism for resistance to conventional therapy and recurrence of neuroblastoma in patients.To develop novel strategies for targeting the side-population of neurobastomas, we analyzed the effects of 13-cis-retinoic acid (RA combined with the proteasome inhibitor MG132. The short-term action of the treatment was compared with effects after a 5-day recovery period during which both chemicals were withdrawn. RA induced growth arrest and differentiation of SH-SY5Y and SK-N-BE(2 neuroblastoma cell lines. Inhibition of the proteasome caused apoptosis in both cell lines, thus, revealing the critical role of this pathway in the regulated degradation of proteins involved in neuroblastoma proliferation and survival. The combination of RA with MG132 induced apoptosis in a dose-dependent manner, in addition to promoting G2/M arrest in treated cultures. Interestingly, expression of stem cell markers such as Nestin, Sox2, and Oct4 were reduced after the recovery period of combined treatment as compared with untreated cells or treated cells with either compound alone. Consistent with this, neurosphere formation was significantly impaired by the combined treatment of RA and MG132.Given that stem-like cells are associated with resistant to conventional therapy and are thought to be responsible for relapse, our results suggest that dual therapy of RA and proteasome inhibitor might be beneficial for targeting the side-population of cells associated residual disease in high-risk neuroblastoma.

  7. The polarized double cell target of the SMC

    International Nuclear Information System (INIS)

    Adams, D.; Adeva, B.; Arik, E.; Arvidson, A.; Badelek, B.; Ballintijn, M.K.; Bardin, G.; Baum, G.; Berglund, P.; Betev, L.; Bird, I.G.; Birsa, R.; Bjoerkholm, P.; Bonner, B.E.; Botton, N. de; Boutemeur, M.; Bradamante, F.; Bravar, A.; Bressan, A.; Bueltmann, S.; Burtin, E.; Cavata, C.; Crabb, D.; Cranshaw, J.; Cuhadar, T.; Torre, S. Dalla; Dantzig, R. van; Derro, B.; Deshpande, A.; Dhawan, S.; Dulya, C.; Dyring, A.; Eichblatt, S.; Faivre, J.C.; Fasching, D.; Feinstein, F.; Fernandez, C.; Forthmann, S.; Frois, B.; Gallas, A.; Garzon, J.A.; Gaussiran, T.; Gilly, H.; Giorgi, M.; Goeler, E. von; Goertz, S.; Gracia, G.; Groot, N. de; Perdekamp, M. Grosse; Guelmez, E.; Haft, K.; Harrach, D. von; Hasegawa, T.; Hautle, P.; Hayashi, N.; Heusch, C.A.; Horikawa, N.; Hughes, V.W.; Igo, G.; Ishimoto, S.; Iwata, T.; Kabuss, E.M.; Kageya, T.; Karev, A.; Kessler, H.J.; Ketel, T.J.; Kiryluk, J.; Kishi, A.; Kisselev, Yu.; Klostermann, L.; Kraemer, D.; Krivokhijine, V.; Kroeger, W.; Kurek, K.; Kyynaeraeinen, J.; Lamanna, M.; Landgraf, U.; Layda, T.; Le Goff, J.M.; Lehar, F.; Lesquen, A. de; Lichtenstadt, J.; Lindqvist, T.; Litmaath, M.; Lowe, M.; Magnon, A.; Mallot, G.K.; Marie, F.; Martin, A.; Martino, J.; Matsuda, T.; Mayes, B.; McCarthy, J.S.; Medved, K.; Meyer, W.; Middelkoop, G. van; Miller, D.; Miyachi, Y.; Mori, K.; Moromisato, J.; Nassalski, J.; Naumann, L.; Neganov, B.; Niinikoski, T.O.; Oberski, J.E.J.; Ogawa, A.; Ozben, C.; Parks, D.P.; Pereira, H.; Penzo, A.; Perrot-Kunne, F.; Peshekhonov, D.; Piegaia, R.; Pinsky, L.; Platchkov, S.; Plo, M.; Pose, D.; Postma, H.; Pretz, J.; Pussieux, T.; Pyrlik, J.; Raedel, G.; Reyhancan, I.; Reicherz, G.; Rieubland, J.M.; Rijllart, A.; Roberts, J.B.; Rock, S.; Rodriguez, M.; Rondio, E.; Rosado, A.; Roscherr, B.; Sabo, I.; Saborido, J.; Sandacz, A.; Savin, I.; Schiavon, P.; Schiller, A.; Schueler, K.P.; Segel, R.; Seitz, R.; Semertzidis, Y.; Sever, F.; Shanahan, P.; Sichtermann, E.P.; Simeoni, F.; Smirnov, G.I.; Staude, A.; Steinmetz, A.; Stiegler, U.; Stuhrmann, H.; Szleper, M.; Teichert, K.M.; Tessarotto, F.; Thers, D.; Tlaczala, W.; Trentalange, S.; Tripet, A.; Unel, G.; Velasco, M.; Vogt, J.; Voss, R.; Weinstein, R.; Whitten, C.; Windmolders, R.; Willumeit, R.; Wislicki, W.; Witzmann, A.; Zanetti, A.M.; Zaremba, K.; Zhao, J.

    1999-01-01

    The polarized target of the Spin Muon Collaboration at CERN was used for deep inelastic muon scattering experiments during 1993-1996 with a polarized muon beam to investigate the spin structure of the nucleon. Most of the experiments were carried out with longitudinal target polarization and 190 GeV muons, and some were done with transverse polarization and 100 GeV muons. Protons as well as deuterons were polarized by dynamic nuclear polarization (DNP) in three kinds of solid materials -- butanol, ammonia, and deuterated butanol -- with maximum degrees of polarization of 94%, 91% and 60%, respectively. Considerable attention was paid to the accuracies of the NMR polarization measurements and their analyses, the accuracies achieved were between 2.0% and 3.2%. The SMC target system with two cells of opposite polarizations, each cell 65 cm long and 5 cm in diameter, constitutes the largest polarized target system ever built and facilitates accurate spin asymmetry measurements. The design considerations, construction and performance of the target are reviewed

  8. On joint power allocation and multipath routing in femto-relay networks

    OpenAIRE

    Hoteit , Sahar; Duhamel , Pierre; Lasaulce , Samson

    2016-01-01

    International audience; —Transmit power allocation techniques are very important to manage interference in small-cell networks. While available power allocation algorithms in the literature rely on a predefined routing protocol, we propose in this paper a power-efficient two-step algorithm that allows power allocation and routing to be performed jointly in femto-relay networks. First, we propose an interference-based partitioning method to cluster the femto-relays, then we adopt an iterative ...

  9. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  10. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    Energy Technology Data Exchange (ETDEWEB)

    Pissuwan, Dakrong [University of Technology Sydney, Institute for Nanoscale Technology (Australia); Valenzuela, Stella M. [University of Technology Sydney, Department of Medical and Molecular Biosciences (Australia)], E-mail: stella.valenzuela@uts.edu.au; Killingsworth, Murray C. [Sydney South West Pathology Service (Australia)], E-mail: murray.killingsworth@swsahs.nsw.gov.au; Xu, Xiaoda; Cortie, Michael B. [University of Technology Sydney, Institute for Nanoscale Technology (Australia)], E-mail: michael.cortie@uts.edu.au

    2007-12-15

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation ({approx}1x10{sup 5} to 1x10{sup 10} W/m{sup 2}). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10{sup 2} W/m{sup 2} being sufficient, provided that a total fluence of {approx}30 J/cm{sup 2} is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm{sup 2} resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

  11. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    Science.gov (United States)

    Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

    2007-12-01

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (˜1×105 to 1×1010 W/m2). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5×102 W/m2 being sufficient, provided that a total fluence of ˜30 J/cm2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.

  12. Targeted destruction of murine macrophage cells with bioconjugated gold nanorods

    International Nuclear Information System (INIS)

    Pissuwan, Dakrong; Valenzuela, Stella M.; Killingsworth, Murray C.; Xu, Xiaoda; Cortie, Michael B.

    2007-01-01

    Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells, which can then be destroyed using relatively high power laser radiation (∼1x10 5 to 1x10 10 W/m 2 ). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show that high intensity laser radiation is not necessary, with even 5x10 2 W/m 2 being sufficient, provided that a total fluence of ∼30 J/cm 2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages, as our model system and a 5 mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods to a laser fluence of 30 J/cm 2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells

  13. Are ovarian cancer stem cells the target for innovative immunotherapy?

    Directory of Open Access Journals (Sweden)

    Wang L

    2018-05-01

    Full Text Available Liang Wang, Tianmin Xu, Manhua Cui Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China Abstract: Cancer stem cells (CSCs, a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment. Since CSCs are generally resistant to conventional therapies (chemotherapy and radiotherapy, immunotherapy is a more effective method that has been implemented in the clinic. Chimeric antigen receptor (CAR- T cell, an adoptive cellular immunotherapy, which results in apparent elimination of tumor in both hematologic and solid cancers, could be used for ovarian cancer. This review covers the basic conception of CSCs and OCSCs, the implication of epigenetic mechanism underlying cancer evolution considering CSC model, the immunotherapies reported for ovarian cancer targeting OCSCs currently, and the relationship between immune system and hierarchy cancer organized by CSCs. Particularly, the promising prospects and potential pitfalls of targeting OCSC surface markers to design CAR-T cellular immunotherapy are discussed here. Keywords: cancer stem cells, ovarian cancer, epigenetics, tumor cell surface marker, immunotherapy, CAR

  14. [Cancer stem cells as the therapeutic target of tomorrow].

    Science.gov (United States)

    Hatina, Jiří

    2017-02-01

    The concept of hierarchical organization of tumour cell population, with cancer stem cells positioned at the apex of the cell hierarchy, can explain at least some crucial aspects of biological and clinical behaviour of cancer, like its propensity to relapse as well as the development of therapeutic resistance. The underlying biological properties of cancer stem cells are crucially dependent on various signals, inhibition of which provides an attractive opportunity to attack pharmacologically cancer stem cells. Currently, a lot of such stemness-inhibitors undergo various phases of clinical testing. Interestingly, numerous old drugs that are in routine use in human and veterinary medicine for non-oncological indications appear to be able to specifically target cancer stem cells as well. As cancer stem cells, at least for most tumours, represent usually only a minor tumour cell fraction, it is quite probable that the main focus of the clinical use of the stemness inhibitors would consist in their rational combinations with traditional anticancer treatment modalities. A highly important goal for the future research is to identify reliable and clinically applicable predictive markers that would allow to apply these novel anticancer drugs on the individual basis within the context of personalized medicine.

  15. Diffusion tensor driven contour closing for cell microinjection targeting.

    Science.gov (United States)

    Becattini, Gabriele; Mattos, Leonardo S; Caldwell, Darwin G

    2010-01-01

    This article introduces a novel approach to robust automatic detection of unstained living cells in bright-field (BF) microscope images with the goal of producing a target list for an automated microinjection system. The overall image analysis process is described and includes: preprocessing, ridge enhancement, image segmentation, shape analysis and injection point definition. The developed algorithm implements a new version of anisotropic contour completion (ACC) based on the partial differential equation (PDE) for heat diffusion which improves the cell segmentation process by elongating the edges only along their tangent direction. The developed ACC algorithm is equivalent to a dilation of the binary edge image with a continuous elliptic structural element that takes into account local orientation of the contours preventing extension towards normal direction. Experiments carried out on real images of 10 to 50 microm CHO-K1 adherent cells show a remarkable reliability in the algorithm along with up to 85% success for cell detection and injection point definition.

  16. Engineered Proteins Program Mammalian Cells to Target Inflammatory Disease Sites.

    Science.gov (United States)

    Qudrat, Anam; Mosabbir, Abdullah Al; Truong, Kevin

    2017-06-22

    Disease sites in atherosclerosis and cancer feature cell masses (e.g., plaques/tumors), a low pH extracellular microenvironment, and various pro-inflammatory cytokines such as tumor necrosis factor α (TNFα). The ability to engineer a cell to seek TNFα sources allows for targeted therapeutic delivery. To accomplish this, here we introduced a system of proteins: an engineered TNFα chimeric receptor (named TNFR1chi), a previously engineered Ca 2+ -activated RhoA (named CaRQ), vesicular stomatitis virus glycoprotein G (VSVG), and thymidine kinase. Upon binding TNFα, TNFR1chi generates a Ca 2+ signal that in turn activates CaRQ-mediated non-apoptotic blebs that allow migration toward the TNFα source. Next, the addition of VSVG, upon low pH induction, causes membrane fusion of the engineered and TNFα source cells. Finally, after ganciclovir treatment cells undergo death via the thymidine kinase suicide mechanism. Hence, we assembled a system of proteins that forms the basis of engineering a cell to target inflammatory disease sites characterized by TNFα secretion and a low-pH microenvironment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. PET imaging of T cells: Target identification and feasibility assessment.

    Science.gov (United States)

    Auberson, Yves P; Briard, Emmanuelle; Rudolph, Bettina; Kaupmann, Klemen; Smith, Paul; Oberhauser, Berndt

    2018-06-01

    Imaging T cells using positron emission tomography (PET) would be highly useful for diagnosis and monitoring in immunology and oncology patients. There are however no obvious targets that can be used to develop imaging agents for this purpose. We evaluated several potential target proteins with selective expression in T cells, and for which lead molecules were available: PKC , Lck, ZAP70 and Itk. Ultimately, we focused on Itk (interleukin-2-inducible T cell kinase) and identified a tool molecule with properties suitable for in vivo imaging of T cells, (5aR)-5,5-difluoro-5a-methyl-N-(1-((S)-3-(methylsulfonyl)-phenyl)(tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)-1,4,4a,5,5a,6-hexahydro-cyclopropa[f]-indazole-3-carboxamide (23). While not having the optimal profile for clinical use, this molecule indicates that it might be possible to develop Itk-selective PET ligands for imaging the distribution of T cells in patients. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. PSMA-targeted bispecific Fab conjugates that engage T cells.

    Science.gov (United States)

    Patterson, James T; Isaacson, Jason; Kerwin, Lisa; Atassi, Ghazi; Duggal, Rohit; Bresson, Damien; Zhu, Tong; Zhou, Heyue; Fu, Yanwen; Kaufmann, Gunnar F

    2017-12-15

    Bioconjugate formats provide alternative strategies for antigen targeting with bispecific antibodies. Here, PSMA-targeted Fab conjugates were generated using different bispecific formats. Interchain disulfide bridging of an αCD3 Fab enabled installation of either the PSMA-targeting small molecule DUPA (SynFab) or the attachment of an αPSMA Fab (BisFab) by covalent linkage. Optimization of the reducing conditions was critical for selective interchain disulfide reduction and good bioconjugate yield. Activity of αPSMA/CD3 Fab conjugates was tested by in vitro cytotoxicity assays using prostate cancer cell lines. Both bispecific formats demonstrated excellent potency and antigen selectivity. Copyright © 2017. Published by Elsevier Ltd.

  19. Liver cell-targeted delivery of therapeutic molecules.

    Science.gov (United States)

    Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

    2016-01-01

    The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

  20. The polarized double cell target of the SMC

    CERN Document Server

    Adams, D; Adeva, B; Arik, E; Arvidson, A; Badelek, B; Ballintijn, M K; Bardin, G; Baum, G; Berglund, P; Betev, L; Bird, I G; Birsa, R; Björkholm, P; Bonner, B E; De Botton, N R; Boutemeur, M; Bradamante, Franco; Bravar, A; Bressan, A; Bültmann, S; Burtin, E; Cavata, C; Crabb, D; Cranshaw, J; Çuhadar-Dönszelmann, T; Dalla Torre, S; Van Dantzig, R; Derro, B R; Deshpande, A A; Dhawan, S K; Dulya, C M; Dyring, A; Eichblatt, S; Faivre, Jean-Claude; Fasching, D; Feinstein, F; Fernández, C; Forthmann, S; Frois, Bernard; Gallas, A; Garzón, J A; Gaussiran, T; Gilly, H; Giorgi, M A; von Goeler, E; Görtz, S; Gracia, G; De Groot, N; Grosse-Perdekamp, M; Gülmez, E; Haft, K; Von Harrach, D; Hasegawa, T; Hautle, P; Hayashi, N; Heusch, C A; Horikawa, N; Hughes, V W; Igo, G; Ishimoto, S; Iwata, T; Kabuss, E M; Kageya, T; Karev, A G; Kessler, H J; Ketel, T; Kiryluk, J; Kishi, A; Kiselev, Yu F; Klostermann, L; Krämer, Dietrich; Krivokhizhin, V G; Kröger, W; Kurek, K; Kyynäräinen, J; Lamanna, M; Landgraf, U; Layda, T; Le Goff, J M; Lehár, F; de Lesquen, A; Lichtenstadt, J; Lindqvist, T; Litmaath, M; Loewe, M; Magnon, A; Mallot, G K; Marie, F; Martin, A; Martino, J; Matsuda, T; Mayes, B W; McCarthy, J S; Medved, K S; Meyer, W T; Van Middelkoop, G; Miller, D; Miyachi, Y; Mori, K; Moromisato, J H; Nassalski, J P; Naumann, Lutz; Neganov, B S; Niinikoski, T O; Oberski, J; Ogawa, A; Ozben, C; Parks, D P; Pereira, H; Penzo, Aldo L; Perrot-Kunne, F; Peshekhonov, V D; Piegaia, R; Pinsky, L; Platchkov, S K; Pló, M; Pose, D; Postma, H; Pretz, J; Pussieux, T; Pyrlik, J; Rädel, G; Reyhancan, I; Reicherz, G; Rijllart, A; Roberts, J B; Rock, S E; Rodríguez, M; Rondio, Ewa; Rosado, A; Roscherr, B; Sabo, I; Saborido, J; Sandacz, A; Savin, I A; Schiavon, R P; Schiller, A; Schüler, K P; Segel, R E; Seitz, R; Semertzidis, Y K; Sever, F; Shanahan, P; Sichtermann, E P; Simeoni, F; Smirnov, G I; Staude, A; Steinmetz, A; Stiegler, U; Stuhrmann, H B; Szleper, M; Teichert, K M; Tessarotto, F; Thers, D; Tlaczala, W; Trentalange, S; Tripet, A; Ünel, G; Velasco, M; Vogt, J; Voss, Rüdiger; Weinstein, R; Whitten, C; Windmolders, R; Willumeit, R; Wislicki, W; Witzmann, A; Zanetti, A M; Zaremba, K; Zhao, J

    1999-01-01

    The polarized target of the Spin Muon Collaboration at CERN was used for deep inelastic muon scattering experiments during 1993 to 1996 with a polarized muon beam to investigate the spin structure of the nucleon. Most of the experiments were carried out with longitudinal target polarization and 190 GeV muons, and some were done with transverse polarization and 100 GeV muons. Protons as well as deuterons were polarized by dynamic nuclear polarization (DNP) in three kinds of solid materials $-$ butanol, ammonia, and deuterated butanol, with maximum degrees of polarization of 94, 91, and 60 \\%, respectively. Considerable attention was paid to the accuracies of the NMR polarization measurements and their analyses. The achieved accuracies were between 2.0 and 3.2 \\%. The SMC target system with two cells of opposite polarizations, each cell 65 cm long and 5 cm in diameter, constitutes the largest polarized target system ever built and facilitates accurate spin asymmetry measurements. The design considerations, the ...

  1. Setting value optimization method in integration for relay protection based on improved quantum particle swarm optimization algorithm

    Science.gov (United States)

    Yang, Guo Sheng; Wang, Xiao Yang; Li, Xue Dong

    2018-03-01

    With the establishment of the integrated model of relay protection and the scale of the power system expanding, the global setting and optimization of relay protection is an extremely difficult task. This paper presents a kind of application in relay protection of global optimization improved particle swarm optimization algorithm and the inverse time current protection as an example, selecting reliability of the relay protection, selectivity, quick action and flexibility as the four requires to establish the optimization targets, and optimizing protection setting values of the whole system. Finally, in the case of actual power system, the optimized setting value results of the proposed method in this paper are compared with the particle swarm algorithm. The results show that the improved quantum particle swarm optimization algorithm has strong search ability, good robustness, and it is suitable for optimizing setting value in the relay protection of the whole power system.

  2. Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms.

    Science.gov (United States)

    Kanwar, Jagat R; Samarasinghe, Rasika M; Kamalapuram, Sishir K; Kanwar, Rupinder K

    2017-01-01

    Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re-growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Targeting Gas6/TAM in cancer cells and tumor microenvironment.

    Science.gov (United States)

    Wu, Guiling; Ma, Zhiqiang; Cheng, Yicheng; Hu, Wei; Deng, Chao; Jiang, Shuai; Li, Tian; Chen, Fulin; Yang, Yang

    2018-01-31

    Growth arrest-specific 6, also known as Gas6, is a human gene encoding the Gas6 protein, which was originally found to be upregulated in growth-arrested fibroblasts. Gas6 is a member of the vitamin K-dependent family of proteins expressed in many human tissues and regulates several biological processes in cells, including proliferation, survival and migration, by binding to its receptors Tyro3, Axl and Mer (TAM). In recent years, the roles of Gas6/TAM signalling in cancer cells and the tumour microenvironment have been studied, and some progress has made in targeted therapy, providing new potential directions for future investigations of cancer treatment. In this review, we introduce the Gas6 and TAM receptors and describe their involvement in different cancers and discuss the roles of Gas6 in cancer cells, the tumour microenvironment and metastasis. Finally, we introduce recent studies on Gas6/TAM targeting in cancer therapy, which will assist in the experimental design of future analyses and increase the potential use of Gas6 as a therapeutic target for cancer.

  4. The cell's nucleolus: an emerging target for chemotherapeutic intervention.

    Science.gov (United States)

    Pickard, Amanda J; Bierbach, Ulrich

    2013-09-01

    The transient nucleolus plays a central role in the up-regulated synthesis of ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell growth. This function, in conjunction with its unique pathohistological features in malignant cells and its ability to mediate apoptosis, renders this sub-nuclear structure a potential target for chemotherapeutic agents. In this Minireview, structurally and functionally diverse small molecules are discussed that have been reported to either interact with the nucleolus directly or perturb its function indirectly by acting on its dynamic components. These molecules include all major classes of nucleic-acid-targeted agents, antimetabolites, kinase inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides, as well as nanoparticles. Together, these molecules are invaluable probes of structure and function of the nucleolus. They also provide a unique opportunity to develop novel strategies for more selective and therefore better-tolerated chemotherapeutic intervention. In this regard, inhibition of RNA polymerase-I-mediated rRNA synthesis appears to be a promising mechanism for killing cancer cells. The recent development of molecules targeted at G-quadruplex-forming rRNA gene sequences, which are currently undergoing clinical trials, seems to attest to the success of this approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

    Directory of Open Access Journals (Sweden)

    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  6. Romidepsin targets multiple survival signaling pathways in malignant T cells

    International Nuclear Information System (INIS)

    Valdez, B C; Brammer, J E; Li, Y; Murray, D; Liu, Y; Hosing, C; Nieto, Y; Champlin, R E; Andersson, B S

    2015-01-01

    Romidepsin is a cyclic molecule that inhibits histone deacetylases. It is Food and Drug Administration-approved for treatment of cutaneous and peripheral T-cell lymphoma, but its precise mechanism of action against malignant T cells is unknown. To better understand the biological effects of romidepsin in these cells, we exposed PEER and SUPT1 T-cell lines, and a primary sample from T-cell lymphoma patient (Patient J) to romidepsin. We then examined the consequences in some key oncogenic signaling pathways. Romidepsin displayed IC 50 values of 10.8, 7.9 and 7.0 nm in PEER, SUPT1 and Patient J cells, respectively. Strong inhibition of histone deacetylases and demethylases, increased production of reactive oxygen species and decreased mitochondrial membrane potential were observed, which may contribute to the observed DNA-damage response and apoptosis. The stress-activated protein kinase/c-Jun N-terminal kinase signaling pathway and unfolded protein response in the endoplasmic reticulum were activated, whereas the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) and β-catenin pro-survival pathways were inhibited. The decreased level of β-catenin correlated with the upregulation of its inhibitor SFRP1 through romidepsin-mediated hypomethylation of its gene promoter. Our results provide new insights into how romidepsin invokes malignant T-cell killing, show evidence of its associated DNA hypomethylating activity and offer a rationale for the development of romidepsin-containing combination therapies

  7. New small molecules targeting apoptosis and cell viability in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Doris Maugg

    Full Text Available Despite the option of multimodal therapy in the treatment strategies of osteosarcoma (OS, the most common primary malignant bone tumor, the standard therapy has not changed over the last decades and still involves multidrug chemotherapy and radical surgery. Although successfully applied in many patients a large number of patients eventually develop recurrent or metastatic disease in which current therapeutic regimens often lack efficacy. Thus, new therapeutic strategies are urgently needed. In this study, we performed a phenotypic high-throughput screening campaign using a 25,000 small-molecule diversity library to identify new small molecules selectively targeting osteosarcoma cells. We could identify two new small molecules that specifically reduced cell viability in OS cell lines U2OS and HOS, but affected neither hepatocellular carcinoma cell line (HepG2 nor primary human osteoblasts (hOB. In addition, the two compounds induced caspase 3 and 7 activity in the U2OS cell line. Compared to conventional drugs generally used in OS treatment such as doxorubicin, we indeed observed a greater sensitivity of OS cell viability to the newly identified compounds compared to doxorubicin and staurosporine. The p53-negative OS cell line Saos-2 almost completely lacked sensitivity to compound treatment that could indicate a role of p53 in the drug response. Taken together, our data show potential implications for designing more efficient therapies in OS.

  8. Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

    International Nuclear Information System (INIS)

    Chang, Lihong; Huang, Jiancong; Wang, Kai; Li, Jingjia; Yan, Ruicheng; Zhu, Ling; Ye, Jin; Wu, Xifu; Zhuang, Shimin; Li, Daqing; Zhang, Gehua

    2016-01-01

    The Mre11-Rad50-Nbs1 (MRN) complex is well known for its crucial role in initiating DNA double strand breaks (DSBs) repair pathways to resistant irradiation (IR) injury and thus facilitating radioresistance which severely reduces radiocurability of nasopharyngeal cancer (NPC). Targeting native cellular MRN function would sensitize NPC cells to IR. A recombinant adenovirus containing a mutant Rad50 gene (Ad-RAD50) expressing Rad50 zinc hook domain but lacking the ATPase domain and the Mre11 interaction domain was constructed to disrupt native cellular MRN functions. The effects of Ad-RAD50 on the MRN functions were assessed in NPC cells lines using western blot, co-immunoprecipitation and confocal microscopy analyses. The increased radiosensitivity of transient Ad-RAD50 to IR was examined in NPC cells, including MTT assay, colony formation. The molecular mechanisms of radiosensitization were confirmed by neutral comet assay and western bolts. Nude mice subcutaneous injection, tumor growth curve and TUNEL assay were used to evaluate tumor regression and apoptosis in vivo. Rad50 is remarkably upregulated in NPC cells after IR, implying the critical role of Rad50 in MRN functions. The transient expression of this mutant Rad50 decreased the levels of native cellular Rad50, Mre11 and Nbs1, weakened the interactions among these proteins, abrogated the G2/M arrest induced by DSBs and reduced the DNA repair ability in NPC cells. A combination of IR and mutant RAD50 therapy produced significant tumor cytotoxicity in vitro, with a corresponding increase in DNA damage, prevented proliferation and cell viability. Furthermore, Ad-RAD50 sensitized NPC cells to IR by causing dramatic tumor regression and inducing apoptosis in vivo. Our findings define a novel therapeutic approach to NPC radiosensitization via targeted native cellular Rad50 disruption. The online version of this article (doi:10.1186/s12885-016-2190-8) contains supplementary material, which is available to

  9. Radioprotection of targeted and bystander cells by methylproamine

    Energy Technology Data Exchange (ETDEWEB)

    Burdak-Rothkamm, Susanne [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); Oxford University Hospitals, Cellular Pathology, Oxford (United Kingdom); Smith, Andrea; Lobachevsky, Pavel; Martin, Roger [Peter MacCallum Cancer Centre, Molecular Radiation Biology Laboratory, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Prise, Kevin M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom)

    2014-09-23

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to {sup 137}Cs γ-ray/X-ray irradiation and He{sup 2+} microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for {sup 137}Cs γ-rays and X-rays but not for He{sup 2+} charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He{sup 2+} ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He{sup 2+} ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [German] Radioprotektive Agenzien sind sowohl in der Strahlentherapie von Krebserkrankungen als auch im Strahlenschutz im Zusammenhang mit akzidenteller Exposition von Bedeutung. Methylproamine ist die Leitsubstanz einer Klasse von

  10. Targeting Gallium to Cancer Cells through the Folate Receptor

    Directory of Open Access Journals (Sweden)

    Nerissa Viola-Villegas

    2008-01-01

    Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG 'spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N, N′, N′, N′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

  11. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Science.gov (United States)

    Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

    2009-07-01

    Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  12. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  13. Targeting Gallium to Cancer Cells through the Folate Receptor

    Directory of Open Access Journals (Sweden)

    Nerissa Viola-Villegas

    2008-01-01

    Full Text Available The development of gallium(III compounds as anti-cancer agents for both treatment and diagnosis is a rapidly developing field of research. Problems remain in exploring the full potential of gallium(III as a safe and successful therapeutic agent or as an imaging agent. One of the major issues is that gallium(III compounds have little tropism for cancer cells. We have combined the targeting properties of folic acid (FA with long chain liquid polymer poly(ethylene glycol (PEG ‘spacers’. This FA-PEG unit has been coupled to the gallium coordination complex of 1,4,7,10-tetraazacyclo-dodecane-N,N′,N′′,N′′′-tetraacetic acid (DOTA through amide linkages for delivery into target cells overexpressing the folate receptor (FR. In vitro cytotoxicity assays were conducted against a multi-drug resistant ovarian cell line (A2780/AD that overexpresses the FR and contrasted against a FR free Chinese hamster ovary (CHO cell line. Results are rationalized taking into account stability studies conducted in RPMI 1640 media and HEPES buffer at pH 7.4.

  14. 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.

  15. 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.

  16. Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells.

    Science.gov (United States)

    Herce, Henry D; Schumacher, Dominik; Schneider, Anselm F L; Ludwig, Anne K; Mann, Florian A; Fillies, Marion; Kasper, Marc-André; Reinke, Stefan; Krause, Eberhard; Leonhardt, Heinrich; Cardoso, M Cristina; Hackenberger, Christian P R

    2017-08-01

    Functional antibody delivery in living cells would enable the labelling and manipulation of intracellular antigens, which constitutes a long-thought goal in cell biology and medicine. Here we present a modular strategy to create functional cell-permeable nanobodies capable of targeted labelling and manipulation of intracellular antigens in living cells. The cell-permeable nanobodies are formed by the site-specific attachment of intracellularly stable (or cleavable) cyclic arginine-rich cell-penetrating peptides to camelid-derived single-chain VHH antibody fragments. We used this strategy for the non-endocytic delivery of two recombinant nanobodies into living cells, which enabled the relocalization of the polymerase clamp PCNA (proliferating cell nuclear antigen) and tumour suppressor p53 to the nucleolus, and thereby allowed the detection of protein-protein interactions that involve these two proteins in living cells. Furthermore, cell-permeable nanobodies permitted the co-transport of therapeutically relevant proteins, such as Mecp2, into the cells. This technology constitutes a major step in the labelling, delivery and targeted manipulation of intracellular antigens. Ultimately, this approach opens the door towards immunostaining in living cells and the expansion of immunotherapies to intracellular antigen targets.

  17. Cell-permeable nanobodies for targeted immunolabelling and antigen manipulation in living cells

    Science.gov (United States)

    Herce, Henry D.; Schumacher, Dominik; Schneider, Anselm F. L.; Ludwig, Anne K.; Mann, Florian A.; Fillies, Marion; Kasper, Marc-André; Reinke, Stefan; Krause, Eberhard; Leonhardt, Heinrich; Cardoso, M. Cristina; Hackenberger, Christian P. R.

    2017-08-01

    Functional antibody delivery in living cells would enable the labelling and manipulation of intracellular antigens, which constitutes a long-thought goal in cell biology and medicine. Here we present a modular strategy to create functional cell-permeable nanobodies capable of targeted labelling and manipulation of intracellular antigens in living cells. The cell-permeable nanobodies are formed by the site-specific attachment of intracellularly stable (or cleavable) cyclic arginine-rich cell-penetrating peptides to camelid-derived single-chain VHH antibody fragments. We used this strategy for the non-endocytic delivery of two recombinant nanobodies into living cells, which enabled the relocalization of the polymerase clamp PCNA (proliferating cell nuclear antigen) and tumour suppressor p53 to the nucleolus, and thereby allowed the detection of protein-protein interactions that involve these two proteins in living cells. Furthermore, cell-permeable nanobodies permitted the co-transport of therapeutically relevant proteins, such as Mecp2, into the cells. This technology constitutes a major step in the labelling, delivery and targeted manipulation of intracellular antigens. Ultimately, this approach opens the door towards immunostaining in living cells and the expansion of immunotherapies to intracellular antigen targets.

  18. A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.

    Science.gov (United States)

    Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min

    2012-12-01

    According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.

  19. RNA interference targeting raptor inhibits proliferation of gastric cancer cells

    International Nuclear Information System (INIS)

    Wu, William Ka Kei; Lee, Chung Wa; Cho, Chi Hin; Chan, Francis Ka Leung; Yu, Jun; Sung, Joseph Jao Yiu

    2011-01-01

    Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G 0 /G 1 -phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D 3 and p21 Waf1 , which stabilizes cyclin D/cdk4 complex for G 1 -S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

  20. Studies on ADCC (antibody-dependent cell-mediated cytotoxicity) using sheep red blood cells as target cells, 2

    International Nuclear Information System (INIS)

    Ichikawa, Yukinobu; Takaya, Masatoshi; Arimori, Shigeru

    1979-01-01

    A non-specific cytotoxic mediator from effector cells (human peripheral blood leukocytes) was investigated in the ADCC (antibody-dependent cell-mediated cytotoxicity) system using antibody-coated sheep red blood cells (SRBC) as target cells. 51 Cr-labelled homologous (sheep) or heterologous (human) red blood cells were used as adjacent cells. Either crude lymphocyte fraction, phagocyte depleted fraction or granulocyte rich fraction separated from human peripheral leukocytes showed moderate cytotoxic effect on homologous adjacent cells, however no cytotoxic activity on heterologous adjacent cells was demonstrated in any leukocyte fraction. This suggests that the cytotoxic effects on homologous adjacent cells were resulted from the translocation of antibody molecules to adjacent cells from antibody-coated target cells. We concluded that the cytotoxic mechanism in this ADCC system was not mediated by non-specific soluble factors released from either human peripheral lymphocytes, monocytes or granulocytes. (author)

  1. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    International Nuclear Information System (INIS)

    Peres, Elodie A.; Valable, Samuel; Guillamo, Jean-Sebastien; Marteau, Lena; Bernaudin, Jean-Francois; Roussel, Simon; Lechapt-Zalcman, Emmanuele; Bernaudin, Myriam; Petit, Edwige

    2011-01-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  2. Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

    Science.gov (United States)

    Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

    2015-01-01

    Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

  3. Application of a proposed overcurrent relay in radial distribution networks

    Energy Technology Data Exchange (ETDEWEB)

    Conde, A.; Vazquez, E. [Universidad Autonoma de Nuevo Leon, Facultad de Ingenieria Mecanica y Electrica, A.P. 36-F, CU, CP 66450, San Nicolas de los Garza, Nuevo Leon (Mexico)

    2011-02-15

    This paper contains the application criteria and coordination process for a proposed overcurrent relay in a radial power system with feed from one or multiple sources. This relay uses independent functions to detect faults and to calculate the operation time. Also this relay uses a time element function that allows it to reduce the time relay operation, enhancing the backup protection. Some of the proposed approaches improve the sensitivity of the relay. The selection of the best approach in the proposed relay is defined by the needs of the application. The proposed protection can be considered as an additional function protection to conventional overcurrent relays. (author)

  4. Time of arrival based location estimation for cooperative relay networks

    KAUST Repository

    Çelebi, Hasari Burak

    2010-09-01

    In this paper, we investigate the performance of a cooperative relay network performing location estimation through time of arrival (TOA). We derive Cramer-Rao lower bound (CRLB) for the location estimates using the relay network. The analysis is extended to obtain average CRLB considering the signal fluctuations in both relay and direct links. The effects of the channel fading of both relay and direct links and amplification factor and location of the relay node on average CRLB are investigated. Simulation results show that the channel fading of both relay and direct links and amplification factor and location of relay node affect the accuracy of TOA based location estimation. ©2010 IEEE.

  5. Time of arrival based location estimation for cooperative relay networks

    KAUST Repository

    Ç elebi, Hasari Burak; Abdallah, Mohamed M.; Hussain, Syed Imtiaz; Qaraqe, Khalid A.; Alouini, Mohamed-Slim

    2010-01-01

    In this paper, we investigate the performance of a cooperative relay network performing location estimation through time of arrival (TOA). We derive Cramer-Rao lower bound (CRLB) for the location estimates using the relay network. The analysis is extended to obtain average CRLB considering the signal fluctuations in both relay and direct links. The effects of the channel fading of both relay and direct links and amplification factor and location of the relay node on average CRLB are investigated. Simulation results show that the channel fading of both relay and direct links and amplification factor and location of relay node affect the accuracy of TOA based location estimation. ©2010 IEEE.

  6. Concise Review: Cell Surface N-Linked Glycoproteins as Potential Stem Cell Markers and Drug Targets.

    Science.gov (United States)

    Boheler, Kenneth R; Gundry, Rebekah L

    2017-01-01

    Stem cells and their derivatives hold great promise to advance regenerative medicine. Critical to the progression of this field is the identification and utilization of antibody-accessible cell-surface proteins for immunophenotyping and cell sorting-techniques essential for assessment and isolation of defined cell populations with known functional and therapeutic properties. Beyond their utility for cell identification and selection, cell-surface proteins are also major targets for pharmacological intervention. Although comprehensive cell-surface protein maps are highly valuable, they have been difficult to define until recently. In this review, we discuss the application of a contemporary targeted chemoproteomic-based technique for defining the cell-surface proteomes of stem and progenitor cells. In applying this approach to pluripotent stem cells (PSCs), these studies have improved the biological understanding of these cells, led to the enhanced use and development of antibodies suitable for immunophenotyping and sorting, and contributed to the repurposing of existing drugs without the need for high-throughput screening. The utility of this latter approach was first demonstrated with human PSCs (hPSCs) through the identification of small molecules that are selectively toxic to hPSCs and have the potential for eliminating confounding and tumorigenic cells in hPSC-derived progeny destined for research and transplantation. Overall, the cutting-edge technologies reviewed here will accelerate the development of novel cell-surface protein targets for immunophenotyping, new reagents to improve the isolation of therapeutically qualified cells, and pharmacological studies to advance the treatment of intractable diseases amenable to cell-replacement therapies. Stem Cells Translational Medicine 2017;6:131-138. © 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  7. Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells

    Directory of Open Access Journals (Sweden)

    Ahmad Hamad

    2013-01-01

    Full Text Available Chronic myeloid leukemia (CML is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML that have the potential to target CML stem cells and potentially provide cure for CML.

  8. Distributed Antenna Channels with Regenerative Relaying: Relay Selection and Asymptotic Capacity

    Directory of Open Access Journals (Sweden)

    Aitor del Coso

    2007-11-01

    Full Text Available Multiple-input-multiple-output (MIMO techniques have been widely proposed as a means to improve capacity and reliability of wireless channels, and have become the most promising technology for next generation networks. However, their practical deployment in current wireless devices is severely affected by antenna correlation, which reduces their impact on performance. One approach to solve this limitation is relaying diversity. In relay channels, a set of N wireless nodes aids a source-destination communication by relaying the source data, thus creating a distributed antenna array with uncorrelated path gains. In this paper, we study this multiple relay channel (MRC following a decode-and-forward (D&F strategy (i.e., regenerative forwarding, and derive its achievable rate under AWGN. A half-duplex constraint on relays is assumed, as well as distributed channel knowledge at both transmitter and receiver sides of the communication. For this channel, we obtain the optimum relay selection algorithm and the optimum power allocation within the network so that the transmission rate is maximized. Likewise, we bound the ergodic performance of the achievable rate and derive its asymptotic behavior in the number of relays. Results show that the achievable rate of regenerative MRC grows as the logarithm of the Lambert W function of the total number of relays, that is, 𝒞=log⁡2(W0(N. Therefore, D&F relaying, cannot achieve the capacity of actual MISO channels.

  9. Partial relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz; Alouini, Mohamed-Slim; Hasna, Mazen Omar; Qaraqe, Khalid A.

    2012-01-01

    In a communication system with multiple cooperative relays, selecting the best relay utilizes the available spectrum more efficiently. However, selective relaying poses a different problem in underlay cognitive networks compared to the traditional cooperative networks due to interference thresholds to the primary users. In most cases, a best relay is the one which provides the maximum end-to-end signal to noise ratio (SNR). This approach needs plenty of instantaneous channel state information (CSI). The CSI burden could be reduced by partial relay selection. In this paper, a partial relay selection scheme is presented and analyzed for an underlay cognitive network with fixed gain relays operating in the vicinity of a primary user. The system model is adopted in a way that each node needs minimal CSI to perform its task. The best relay is chosen on the basis of maximum source to relay link SNR which then forwards the message to the destination. We derive closed form expressions for the received SNR distributions, system outage, probability of bit error and average channel capacity of the system. The derived results are confirmed through simulations. © 2012 IEEE.

  10. Partial relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz

    2012-05-01

    In a communication system with multiple cooperative relays, selecting the best relay utilizes the available spectrum more efficiently. However, selective relaying poses a different problem in underlay cognitive networks compared to the traditional cooperative networks due to interference thresholds to the primary users. In most cases, a best relay is the one which provides the maximum end-to-end signal to noise ratio (SNR). This approach needs plenty of instantaneous channel state information (CSI). The CSI burden could be reduced by partial relay selection. In this paper, a partial relay selection scheme is presented and analyzed for an underlay cognitive network with fixed gain relays operating in the vicinity of a primary user. The system model is adopted in a way that each node needs minimal CSI to perform its task. The best relay is chosen on the basis of maximum source to relay link SNR which then forwards the message to the destination. We derive closed form expressions for the received SNR distributions, system outage, probability of bit error and average channel capacity of the system. The derived results are confirmed through simulations. © 2012 IEEE.

  11. Optimized Power Allocation and Relay Location Selection in Cooperative Relay Networks

    Directory of Open Access Journals (Sweden)

    Jianrong Bao

    2017-01-01

    Full Text Available An incremental selection hybrid decode-amplify forward (ISHDAF scheme for the two-hop single relay systems and a relay selection strategy based on the hybrid decode-amplify-and-forward (HDAF scheme for the multirelay systems are proposed along with an optimized power allocation for the Internet of Thing (IoT. Given total power as the constraint and outage probability as an objective function, the proposed scheme possesses good power efficiency better than the equal power allocation. By the ISHDAF scheme and HDAF relay selection strategy, an optimized power allocation for both the source and relay nodes is obtained, as well as an effective reduction of outage probability. In addition, the optimal relay location for maximizing the gain of the proposed algorithm is also investigated and designed. Simulation results show that, in both single relay and multirelay selection systems, some outage probability gains by the proposed scheme can be obtained. In the comparison of the optimized power allocation scheme with the equal power allocation one, nearly 0.1695 gains are obtained in the ISHDAF single relay network at a total power of 2 dB, and about 0.083 gains are obtained in the HDAF relay selection system with 2 relays at a total power of 2 dB.

  12. LTE-Advanced Relay Technology and Standardization

    CERN Document Server

    Yuan, Yifei

    2013-01-01

    LTE-Advanced Relay Technology and Standardization provides a timely reference work for relay technology with the finalizing of LTE Release 10 specifications. LTE-Advanced is quickly becoming the global standard for 4G cellular communications. The relay technology, as one of the key features in LTE-Advanced, helps not only to improve the system coverage and capacity, but also to save the costs of laying wireline backhaul. As a leading researcher in the field of LTE-Advanced standards, the author provides an in-depth description of LTE-A relay technology, and explains in detail the standard specification and design principles.     Readers from both academic and industrial fields can find sections of interest to them: Sections 2 & 4 could benefit researchers in academia and those who are engaged in exploratory work, while Sections 3 & 4 are more useful to engineers. Dr. Yifei Yuan is the Technical Director at the Standards Department of ZTE Inc.

  13. Reversal thyristor-relay direct current commutator

    International Nuclear Information System (INIS)

    Ivanenko, A.I.

    1982-01-01

    A thyristor-relay commutator used for alteration of the leading magnetic field direction in experiments with polarized neutrons is described. The commutator flowsheet is presented. Thyristors, connected so as to allow the relay trigger operation mode, are used as controllable electronic relay. Two connected in series coils with the total inductance of the order of 0.28 H serve as the electronic relay load. The arc-free current commutation is effected at the moment of the minimal current across the load terminals, which allows to easily reverse the current up to 10 A at a volatage, v <= 150 V. The experience gained within a year of operation has shown that the commutator meets the requirements of reliability and tuning

  14. Developing a Domain Model for Relay Circuits

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth

    2009-01-01

    In this paper we stepwise develop a domain model for relay circuits as used in railway control systems. First we provide an abstract, property-oriented model of networks consisting of components that can be glued together with connectors. This model is strongly inspired by a network model...... for railways madeby Bjørner et.al., however our model is more general: the components can be of any kind and can later be refined to e.g. railway components or circuit components. Then we show how the abstract network model can be refined into an explicit model for relay circuits. The circuit model describes...... the statics as well as the dynamics of relay circuits, i.e. how a relay circuit can be composed legally from electrical components as well as how the components may change state over time. Finally the circuit model is transformed into an executable model, and we show how a concrete circuit can be defined...

  15. Targeted gene therapy and cell reprogramming in Fanconi anemia

    Science.gov (United States)

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-01-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. PMID:24859981

  16. Targeted gene therapy and cell reprogramming in Fanconi anemia.

    Science.gov (United States)

    Rio, Paula; Baños, Rocio; Lombardo, Angelo; Quintana-Bustamante, Oscar; Alvarez, Lara; Garate, Zita; Genovese, Pietro; Almarza, Elena; Valeri, Antonio; Díez, Begoña; Navarro, Susana; Torres, Yaima; Trujillo, Juan P; Murillas, Rodolfo; Segovia, Jose C; Samper, Enrique; Surralles, Jordi; Gregory, Philip D; Holmes, Michael C; Naldini, Luigi; Bueren, Juan A

    2014-06-01

    Gene targeting is progressively becoming a realistic therapeutic alternative in clinics. It is unknown, however, whether this technology will be suitable for the treatment of DNA repair deficiency syndromes such as Fanconi anemia (FA), with defects in homology-directed DNA repair. In this study, we used zinc finger nucleases and integrase-defective lentiviral vectors to demonstrate for the first time that FANCA can be efficiently and specifically targeted into the AAVS1 safe harbor locus in fibroblasts from FA-A patients. Strikingly, up to 40% of FA fibroblasts showed gene targeting 42 days after gene editing. Given the low number of hematopoietic precursors in the bone marrow of FA patients, gene-edited FA fibroblasts were then reprogrammed and re-differentiated toward the hematopoietic lineage. Analyses of gene-edited FA-iPSCs confirmed the specific integration of FANCA in the AAVS1 locus in all tested clones. Moreover, the hematopoietic differentiation of these iPSCs efficiently generated disease-free hematopoietic progenitors. Taken together, our results demonstrate for the first time the feasibility of correcting the phenotype of a DNA repair deficiency syndrome using gene-targeting and cell reprogramming strategies. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

  17. Evaluation of Harmonics Impact on Digital Relays

    Directory of Open Access Journals (Sweden)

    Kinan Wannous

    2018-04-01

    Full Text Available This paper presents the concept of the impact of harmonic distortion on a digital protection relay. The aim is to verify and determine the reasons of a mal-trip or failure to trip the protection relays; the suggested solution of the harmonic distortion is explained by a mathematical model in the Matlab Simulink programming environment. The digital relays have been tested under harmonic distortions in order to verify the function of the relays algorithm under abnormal conditions. The comparison between the protection relay algorithm under abnormal conditions and a mathematical model in the Matlab Simulink programming environment based on injected harmonics of high values is provided. The test is separated into different levels; the first level is based on the harmonic effect of an individual harmonic and mixed harmonics. The test includes the effect of the harmonics in the location of the fault point into distance protection zones. This paper is a new proposal in the signal processing of power quality disturbances using Matlab Simulink and the power quality impact on the measurements of the power system quantities; the test simulates the function of protection in power systems in terms of calculating the current and voltage values of short circuits and their faults. The paper includes several tests: frequency variations and decomposition of voltage waveforms with Fourier transforms (model and commercial relay, the effect of the power factor on the location of fault points, the relation between the tripping time and the total harmonic distortion (THD levels in a commercial relay, and a comparison of the THD capture between the commercial relay and the model.

  18. Relay selection from an effective capacity perspective

    KAUST Repository

    Yang, Yuli

    2013-09-01

    In this work, we consider a cooperative network where multiple relay nodes having different modulation capabilities assist the end-to-end communication between a source and its destination. Firstly, we evaluate the effective capacity (EC) performance of the network under study. According to the analysis, an EC-based relay selection criterion is proposed. Based on the proposed selection rule and half-duplex decode-and-forward protocol, the activated relays cooperatively help with the packet transmission from the source. At the destination, packet combining is taken into account to improve the quality of service. Compared to the popular scheme, opportunistic relay selection, numerical results are provided to prove the validity and advantages of our proposed scheme in certain scenarios. Moreover, the analysis presented herein offers a convenient tool to the relaying transmission design, specifically on which relay selection scheme should be used as well as how to choose the receiving strategy between with and without packet combining at the destination. © 2013 IEEE.

  19. Relay testing parametric investigation of seismic fragility

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.; Hofmayer, C.; Kassir, M.; Pepper, S.

    1989-01-01

    The seismic capacity of most electrical equipment is governed by malfunction of relays. An evaluation of the existing relay test data base at Brookhaven National Laboratory (BNL) has indicated that the seismic fragility of a relay may depend on various parameters related to the design or the input motion. In particular, the electrical mode, contact state, adjustment, chatter duration acceptance limit, and the frequency and the direction of the vibration input have been considered to influence the relay fragility level. For a particular relay type, the dynamics of its moving parts depends on the exact model number and vintage and hence, these parameters may also influence the fragility level. In order to investigate the effect of most of these parameters on the seismic fragility level, BNL has conducted a relay test program. The testing has been performed at Wyle Laboratories. Establishing the correlation between the single frequency fragility test input and the corresponding multifrequency response spectrum (TRS) is also an objective of this test program. This paper discusses the methodology used for testing and presents a brief summary of important test results. 1 ref., 10 figs

  20. Airborne relay-based regional positioning system.

    Science.gov (United States)

    Lee, Kyuman; Noh, Hongjun; Lim, Jaesung

    2015-05-28

    Ground-based pseudolite systems have some limitations, such as low vertical accuracy, multipath effects and near-far problems. These problems are not significant in airborne-based pseudolite systems. However, the monitoring of pseudolite positions is required because of the mobility of the platforms on which the pseudolites are mounted, and this causes performance degradation. To address these pseudolite system limitations, we propose an airborne relay-based regional positioning system that consists of a master station, reference stations, airborne relays and a user. In the proposed system, navigation signals are generated from the reference stations located on the ground and are relayed via the airborne relays. Unlike in conventional airborne-based systems, the user in the proposed system sequentially estimates both the locations of airborne relays and his/her own position. Therefore, a delay due to monitoring does not occur, and the accuracy is not affected by the movement of airborne relays. We conducted several simulations to evaluate the performance of the proposed system. Based on the simulation results, we demonstrated that the proposed system guarantees a higher accuracy than airborne-based pseudolite systems, and it is feasible despite the existence of clock offsets among reference stations.

  1. Relay Runners Catch The Rays

    CERN Multimedia

    2004-01-01

    Athletes sizzled around CERN on Wednesday 19 May at the 34th annual relay race. On one of the warmest days of the year so far, sunkissed competitors ran for the finish line and then straight for the drinks table. The Shabbys were on fire again, hurtling across the line first in a time of 10 min. 42.6 sec. and making an even stronger claim to being hailed as the traditional winners of the race with their fourth triumph in a row. Also on form were the Lynx Runners who won the Veteran's trophy, continuing their winning ways since 2002 and placing 29th overall. Ildefons Magrans of the ALICE Quarks on the Loose team ran the fastest 1000m in a time of 2 min. 47 sec. Second-placed Charmilles Technologies won the Open category in a time of 11 min. 03 sec., taking the prize for teams whose members work in different departments or who come from outside CERN. The OPALadies won the women's trophy and placed 48th. With 9 trophies up for grabs, more than 300 people in 55 teams ran the fun run, covering distances of 1000m ...

  2. Physical Layer Security Using Two-Path Successive Relaying

    Directory of Open Access Journals (Sweden)

    Qian Yu Liau

    2016-06-01

    Full Text Available Relaying is one of the useful techniques to enhance wireless physical-layer security. Existing literature shows that employing full-duplex relay instead of conventional half-duplex relay improves secrecy capacity and secrecy outage probability, but this is at the price of sophisticated implementation. As an alternative, two-path successive relaying has been proposed to emulate operation of full-duplex relay by scheduling a pair of half-duplex relays to assist the source transmission alternately. However, the performance of two-path successive relaying in secrecy communication remains unexplored. This paper proposes a secrecy two-path successive relaying protocol for a scenario with one source, one destination and two half-duplex relays. The relays operate alternately in a time division mode to forward messages continuously from source to destination in the presence of an eavesdropper. Analytical results reveal that the use of two half-duplex relays in the proposed scheme contributes towards a quadratically lower probability of interception compared to full-duplex relaying. Numerical simulations show that the proposed protocol achieves the ergodic achievable secrecy rate of full-duplex relaying while delivering the lowest probability of interception and secrecy outage probability compared to the existing half duplex relaying, full duplex relaying and full duplex jamming schemes.

  3. Obtaining Target for Solar Cells with Unconventional Supports

    Directory of Open Access Journals (Sweden)

    Mariana Buga

    2011-09-01

    Full Text Available The main technological aim is to develop experimental models of magnetron targets of CuInS2 and CuInSe2, controlled Ga doped in concentrations ranging between 7% and 17%. Advantage of using CuInS2 in manufacturing of solar cells is the presence of nontoxic sulfur. The optimum concentration of Ga determine surely the best crystalline phase of CuInS2 and results are an improvement of the absorbtion band and therefore an increase of quantum efficiency of the quaternary mixture – CIGS in double thin layer.

  4. A Stochastic Geometry Approach to Full-Duplex MIMO Relay Network

    Directory of Open Access Journals (Sweden)

    Mhd Nour Hindia

    2018-01-01

    Full Text Available Cellular networks are extensively modeled by placing the base stations on a grid, with relays and destinations being placed deterministically. These networks are idealized for not considering the interferences when evaluating the coverage/outage and capacity. Realistic models that can overcome such limitation are desirable. Specifically, in a cellular downlink environment, the full-duplex (FD relaying and destination are prone to interferences from unintended sources and relays. However, this paper considered two-hop cellular network in which the mobile nodes aid the sources by relaying the signal to the dead zone. Further, we model the locations of the sources, relays, and destination nodes as a point process on the plane and analyze the performance of two different hops in the downlink. Then, we obtain the success probability and the ergodic capacity of the two-hop MIMO relay scheme, accounting for the interference from all other adjacent cells. We deploy stochastic geometry and point process theory to rigorously analyze the two-hop scheme with/without interference cancellation. These attained expressions are amenable to numerical evaluation and are corroborated by simulation results.

  5. Tumor initiating cells and chemoresistance: which is the best strategy to target colon cancer stem cells?

    Science.gov (United States)

    Paldino, Emanuela; Tesori, Valentina; Casalbore, Patrizia; Gasbarrini, Antonio; Puglisi, Maria Ausiliatrice

    2014-01-01

    There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called "cancer stem cells" (CSCs). In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  6. Calibration and Evaluation of Fixed and Mobile Relay-Based System Level Simulator

    Directory of Open Access Journals (Sweden)

    Shahid Mumtaz

    2010-01-01

    Full Text Available Future wireless communication systems are expected to provide more stable and higher data rate transmissions in the whole OFDMA networks, but the mobile stations (MSs in the cell boundary experience poor spectral efficiency due to the path loss from the transmitting antenna and interference from adjacent cells. Therefore, satisfying QoS (Quality of Service requirements of each MS at the cell boundary has been an important issue. To resolve this spectral efficiency problem at the cell boundary, deploying relay stations has been actively considered. As multihop/relay has complex interactions between the routing and medium access control decisions, the extent to which analytical expressions can be used to explore its benefits is limited. Consequently, simulations tend to be the preferred way of assessing the performance of relays. In this paper, we evaluate the performance of relay-assisted OFDMA networks by means of system level simulator (SLS. We consistently observed that the throughput is increased and the outage is decreased in the relay-assisted OFDMA network, which is converted to range extension without any capacity penalty, for the realistic range of values of the propagation and other system parameters investigated.

  7. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Dudás, József; Fullár, Alexandra; Romani, Angela; Pritz, Christian; Kovalszky, Ilona; Hans Schartinger, Volker; Mathias Sprinzl, Georg; Riechelmann, Herbert

    2013-01-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells

  8. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dudás, József, E-mail: jozsef.dudas@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullár, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Romani, Angela, E-mail: angela.romani@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Pritz, Christian, E-mail: christian.pritz@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest (Hungary); Hans Schartinger, Volker, E-mail: volker.schartinger@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Mathias Sprinzl, Georg, E-mail: georg.sprinzl@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: herbert.riechelmann@i-med.ac.at [Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

    2013-04-01

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.

  9. Mannosylated biodegradable polyethyleneimine for targeted DNA delivery to dendritic cells

    Directory of Open Access Journals (Sweden)

    Sun X

    2012-06-01

    Full Text Available Xun Sun, Simu Chen, Jianfeng Han, Zhirong ZhangKey Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of ChinaBackground: To establish a potential gene-delivery system with the ability to deliver plasmid DNA to dendritic cells (DCs more efficiently and specifically, we designed and synthesized a low-molecular-weight polyethyleneimine and triethyleneglycol polymer (PEI–TEG and a series of its mannosylated derivatives.Methods: PEI–TEG was synthesized from PEI2000 and PEI600 with TEG as the cross-linker. PEI–TEG was then linked to mannose via a phenylisothiocyanate bridge to obtain man-PEI–TEG conjugates. The DNA conveyance abilities of PEI–TEG, man-PEI–TEG, as well as control PEI25k were evaluated by measuring their zeta potential, particle size, and DNA-binding abilities. The in vitro cytotoxicity, cell uptake, and transfection efficiency of these PEI/DNA complexes were examined on the DC2.4 cell line. Finally, a maturation experiment evaluated the effect of costimulatory molecules CD40, CD80, and CD86 on murine bone marrow-derived DCs (BMDCs using flow cytometry.Results: PEI–TEG and man-PEI–TEG were successfully synthesized and were shown to retain the excellent properties of PEI25k for condensing DNA. Compared with PEI–TEG as well as PEI25k, the man-PEI–TEG had less cytotoxicity and performed better in both cellular uptake and transfection assays in vitro. The results of the maturation experiment showed that all the PEI/DNA complexes induced an adequate upregulation of surface markers for DC maturation.Conclusion: These results demonstrated that man-PEI–TEG can be employed as a DC-targeting gene-delivery system.Keywords: dendritic cells, DCs, mannose, polyethyleneimine, PEI, gene delivery

  10. Visualization and targeted disruption of protein interactions in living cells

    Science.gov (United States)

    Herce, Henry D.; Deng, Wen; Helma, Jonas; Leonhardt, Heinrich; Cardoso, M. Cristina

    2013-01-01

    Protein–protein interactions are the basis of all processes in living cells, but most studies of these interactions rely on biochemical in vitro assays. Here we present a simple and versatile fluorescent-three-hybrid (F3H) strategy to visualize and target protein–protein interactions. A high-affinity nanobody anchors a GFP-fusion protein of interest at a defined cellular structure and the enrichment of red-labelled interacting proteins is measured at these sites. With this approach, we visualize the p53–HDM2 interaction in living cells and directly monitor the disruption of this interaction by Nutlin 3, a drug developed to boost p53 activity in cancer therapy. We further use this approach to develop a cell-permeable vector that releases a highly specific peptide disrupting the p53 and HDM2 interaction. The availability of multiple anchor sites and the simple optical readout of this nanobody-based capture assay enable systematic and versatile analyses of protein–protein interactions in practically any cell type and species. PMID:24154492

  11. Prostate Stem Cell Antigen: A Prospective Therapeutic and Diagnostic Target

    Science.gov (United States)

    Raff, Adam B.; Gray, Andrew; Kast, W. Martin

    2009-01-01

    The development of novel clinical tools to combat cancer is an intense field of research and recent efforts have been directed at the identification of proteins that may provide diagnostic, prognostic and/or therapeutic applications due to their restricted expression. To date, a number of protein candidates have emerged as potential clinical tools in the treatment of prostate cancer. Discovered over ten year ago, prostate stem cell antigen (PSCA) is a cell surface antigen that belongs to the Ly-6/Thy-1 family of glycosylphosphatidylinositol-anchored proteins. PSCA is highly overexpressed in human prostate cancer, with limited expression in normal tissues, making it an ideal target for both diagnosis and therapy. Several studies have now clearly correlated the expression of PSCA with relevant clinical benchmarks, such as Gleason score and metastasis, while others have demonstrated the efficacy of PSCA targeting in treatment through various modalities. The purpose of this review is to present the current body of knowledge about PSCA and its potential role in the treatment of human prostate cancer. PMID:18838214

  12. Testicular cell junction: a novel target for male contraception.

    Science.gov (United States)

    Lee, Nikki P Y; Wong, Elissa W P; Mruk, Dolores D; Cheng, C Yan

    2009-01-01

    Even though various contraceptive methods are widely available, the number of unwanted pregnancies is still on the rise in developing countries, pressurizing the already resource limited nations. One of the major underlying reasons is the lack of effective, low cost, and safe contraceptives for couples. During the past decade, some studies were performed using animal models to decipher if the Sertoli-germ cell junction in the testis is a target for male fertility regulation. Some of these study models were based on the use of hormones and/or chemicals to disrupt the hypothalamic-pituitary-testicular axis (e.g., androgen-based implants or pills) and others utilized a panel of chemical entities or synthetic peptides to perturb spermatogenesis either reversibly or non-reversibly. Among them, adjudin, a potential male contraceptive, is one of the compounds exerting its action on the unique adherens junctions, known as ectoplasmic specializations, in the testis. Since the testis is equipped with inter-connected cell junctions, an initial targeting of one junction type may affect the others and these accumulative effects could lead to spermatogenic arrest. This review attempts to cover an innovative theme on how male infertility can be achieved by inducing junction instability and defects in the testis, opening a new window of research for male contraceptive development. While it will still take much time and effort of intensive investigation before a product can reach the consumable market, these findings have provided hope for better family planning involving men.

  13. Optimal relay selection and power allocation for cognitive two-way relaying networks

    KAUST Repository

    Pandarakkottilil, Ubaidulla; Aï ssa, Sonia

    2012-01-01

    In this paper, we present an optimal scheme for power allocation and relay selection in a cognitive radio network where a pair of cognitive (or secondary) transceiver nodes communicate with each other assisted by a set of cognitive two-way relays

  14. On the achievable degrees of freedom of alternate MIMO relaying with multiple AF relays

    KAUST Repository

    Park, Kihong; Alouini, Mohamed-Slim; Park, Seongho; Ko, Youngchai

    2012-01-01

    In this paper, we consider a two-hop relaying network where one source, one destination, and multiple amplify-and-forward (AF) relays equipped with M antennas operate in a half-duplex mode. In order to compensate for the inherent loss of capacity

  15. Reactive relay selection in underlay cognitive networks with fixed gain relays

    KAUST Repository

    Hussain, Syed Imtiaz

    2012-06-01

    Best relay selection is a bandwidth efficient technique for multiple relay environments without compromising the system performance. The problem of relay selection is more challenging in underlay cognitive networks due to strict interference constraints to the primary users. Generally, relay selection is done on the basis of maximum end-to-end signal to noise ratio (SNR). However, it requires large amounts of channel state information (CSI) at different network nodes. In this paper, we present and analyze a reactive relay selection scheme in underlay cognitive networks where the relays are operating with fixed gains near a primary user. The system model minimizes the amount of CSI required at different nodes and the destination selects the best relay on the basis of maximum relay to destination SNR. We derive close form expressions for the received SNR statistics, outage probability, bit error probability and average channel capacity of the system. Simulation results are also presented to confirm the validity of the derived expressions. © 2012 IEEE.

  16. Individual Channel Estimation in a Diamond Relay Network Using Relay-Assisted Training

    Directory of Open Access Journals (Sweden)

    Xianwen He

    2017-01-01

    Full Text Available We consider the training design and channel estimation in the amplify-and-forward (AF diamond relay network. Our strategy is to transmit the source training in time-multiplexing (TM mode while each relay node superimposes its own relay training over the amplified received data signal without bandwidth expansion. The principal challenge is to obtain accurate channel state information (CSI of second-hop link due to the multiaccess interference (MAI and cooperative data interference (CDI. To maintain the orthogonality between data and training, a modified relay-assisted training scheme is proposed to migrate the CDI, where some of the cooperative data at the relay are discarded to accommodate relay training. Meanwhile, a couple of optimal zero-correlation zone (ZCZ relay-assisted sequences are designed to avoid MAI. At the destination node, the received signals from the two relay nodes are combined to achieve spatial diversity and enhanced data reliability. The simulation results are presented to validate the performance of the proposed schemes.

  17. Iterative Relay Scheduling with Hybrid ARQ under Multiple User Equipment (Type II) Relay Environments

    KAUST Repository

    Nam, Sung Sik; Alouini, Mohamed-Slim; Choi, Seyeong

    2018-01-01

    -generation cellular systems (e.g., LTE-Advanced and beyond). The proposed IRS-HARQ aims to increase the achievable data rate by iteratively scheduling a relatively better UE relay closer to the end user in a probabilistic sense, provided that the relay-to-end user

  18. Stem Cell-Based Cell Carrier for Targeted Oncolytic Virotherapy: Translational Opportunity and Open Questions

    Directory of Open Access Journals (Sweden)

    Janice Kim

    2015-11-01

    Full Text Available Oncolytic virotherapy for cancer is an innovative therapeutic option where the ability of a virus to promote cell lysis is harnessed and reprogrammed to selectively destroy cancer cells. Such treatment modalities exhibited antitumor activity in preclinical and clinical settings and appear to be well tolerated when tested in clinical trials. However, the clinical success of oncolytic virotherapy has been significantly hampered due to the inability to target systematic metastasis. This is partly due to the inability of the therapeutic virus to survive in the patient circulation, in order to target tumors at distant sites. An early study from various laboratories demonstrated that cells infected with oncolytic virus can protect the therapeutic payload form the host immune system as well as function as factories for virus production and enhance the therapeutic efficacy of oncolytic virus. While a variety of cell lineages possessed potential as cell carriers, copious investigation has established stem cells as a very attractive cell carrier system in oncolytic virotherapy. The ideal cell carrier desire to be susceptible to viral infection as well as support viral infection, maintain immunosuppressive properties to shield the loaded viruses from the host immune system, and most importantly possess an intrinsic tumor homing ability to deliver loaded viruses directly to the site of the metastasis—all qualities stem cells exhibit. In this review, we summarize the recent work in the development of stem cell-based carrier for oncolytic virotherapy, discuss the advantages and disadvantages of a variety of cell carriers, especially focusing on why stem cells have emerged as the leading candidate, and finally propose a future direction for stem cell-based targeted oncolytic virotherapy that involves its establishment as a viable treatment option for cancer patients in the clinical setting.

  19. Capacity Bounds and Mapping Design for Binary Symmetric Relay Channels

    Directory of Open Access Journals (Sweden)

    Majid Nasiri Khormuji

    2012-12-01

    Full Text Available Capacity bounds for a three-node binary symmetric relay channel with orthogonal components at the destination are studied. The cut-set upper bound and the rates achievable using decode-and-forward (DF, partial DF and compress-and-forward (CF relaying are first evaluated. Then relaying strategies with finite memory-length are considered. An efficient algorithm for optimizing the relay functions is presented. The Boolean Fourier transform is then employed to unveil the structure of the optimized mappings. Interestingly, the optimized relay functions exhibit a simple structure. Numerical results illustrate that the rates achieved using the optimized low-dimensional functions are either comparable to those achieved by CF or superior to those achieved by DF relaying. In particular, the optimized low-dimensional relaying scheme can improve on DF relaying when the quality of the source-relay link is worse than or comparable to that of other links.

  20. Buffer-Aided Relaying with Adaptive Link Selection

    DEFF Research Database (Denmark)

    Zlatanov, Nikola; Schober, Robert; Popovski, Petar

    2013-01-01

    In this paper, we consider a simple network consisting of a source, a half-duplex decode-and-forward relay, and a destination. We propose a new relaying protocol employing adaptive link selection, i.e., in any given time slot, based on the channel state information of the source-relay and the relay......-destination link a decision is made whether the source or the relay transmits. In order to avoid data loss at the relay, adaptive link selection requires the relay to be equipped with a buffer such that data can be queued until the relay-destination link is selected for transmission. We study both delay......-constrained and delay-unconstrained transmission. For the delay-unconstrained case, we characterize the optimal link selection policy, derive the corresponding throughput, and develop an optimal power allocation scheme. For the delay-constrained case, we propose to starve the buffer of the relay by choosing...

  1. Phenotypic high-throughput screening elucidates target pathway in breast cancer stem cell-like cells.

    Science.gov (United States)

    Carmody, Leigh C; Germain, Andrew R; VerPlank, Lynn; Nag, Partha P; Muñoz, Benito; Perez, Jose R; Palmer, Michelle A J

    2012-10-01

    Cancer stem cells (CSCs) are resistant to standard cancer treatments and are likely responsible for cancer recurrence, but few therapies target this subpopulation. Due to the difficulty in propagating CSCs outside of the tumor environment, previous work identified CSC-like cells by inducing human breast epithelial cells into an epithelial-to-mesenchymal transdifferentiated state (HMLE_sh_ECad). A phenotypic screen was conducted against HMLE_sh_ECad with 300 718 compounds from the Molecular Libraries Small Molecule Repository to identify selective inhibitors of CSC growth. The screen yielded 2244 hits that were evaluated for toxicity and selectivity toward an isogenic control cell line. An acyl hydrazone scaffold emerged as a potent and selective scaffold targeting HMLE_sh_ECad. Fifty-three analogues were acquired and tested; compounds ranged in potency from 790 nM to inactive against HMLE_sh_ECad. Of the analogues, ML239 was best-in-class with an IC(50)= 1.18 µM against HMLE_sh_ECad, demonstrated a >23-fold selectivity over the control line, and was toxic to another CSC-like line, HMLE_shTwist, and a breast carcinoma cell line, MDA-MB-231. Gene expression studies conducted with ML239-treated cells showed altered gene expression in the NF-κB pathway in the HMLE_sh_ECad line but not in the isogenic control line. Future studies will be directed toward the identification of ML239 target(s).

  2. Coordinated Direct and Relay Transmission with Linear Non-Regenerative Relay Beamforming

    DEFF Research Database (Denmark)

    Sun, Fan; De Carvalho, Elisabeth; Popovski, Petar

    2012-01-01

    Joint processing of multiple communication flows in wireless systems has given rise to a number of novel transmission techniques, notably the two-way relaying, but also more general traffic scenarios, such as coordinated direct and relay (CDR) transmissions. In a CDR scheme the relay has a central...... role in managing the interference and boosting the overall system performance. In this letter we consider the case in which an amplify-and-forward relay has multiple antennas and can use beamforming to support the coordinated transmissions. We focus on one representative traffic type with one uplink...... user and one downlink user. Two different criteria for relay beamforming are analyzed: maximal weighted sum-rate and maximization of the worst-case weighted SNR. We propose iterative optimal solutions, as well as low-complexity near-optimal solutions....

  3. A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-09-01

    In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward (AF) protocol are optimally selected to maximize the sum rate of the secondary users without degrading the Quality of Service (QoS) of the primary users by respecting a tolerated interference threshold. A strong optimization tool based on genetic algorithm is employed to solve our formulated optimization problem where discrete relay power levels are considered. Our simulation results show that the practical heuristic approach achieves almost the same performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions. Copyright © 2013 by the Institute of Electrical and Electronic Engineers, Inc.

  4. Neoadjuvant targeted therapy in patients with renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2015-01-01

    Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

  5. New targeted treatments for cutaneous T-cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Martine Bagot

    2017-01-01

    Full Text Available Cutaneous T-cell lymphomas (CTCLs represent a group of rare and heterogeneous diseases that are very difficult to treat at advanced stages. The development of monoclonal antibodies is a new hope for the treatment of these diseases. Alemtuzumab (Campath is a humanized IgG1 kappa monoclonal antibody specific for CD52, an antigen expressed by most T and B lymphocytes. Alemtuzumab may frequently induce long-term remissions in patients with Sezary syndrome but high-dose treatments lead to severe cytopenia, immune depletion, and opportunistic infections. This treatment is less efficient in mycosis fungoides (MF. Brentuximab vedotin is a chimeric anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E, a cytotoxic antitubulin agent. Brentuximab vedotin is a very interesting new treatment for advanced tumor MF, Sezary syndrome, and primary cutaneous CD30+ lymphoproliferative disorders. The main limiting adverse event is neurosensitive peripheral neuropathy. Mogamulizumab is a humanized anti-C-C chemokine receptor Type 4 monoclonal antibody with a defucosylated Fc region leading to increased antibody-dependent cellular cytotoxicity. Mogamulizumab is very efficient on aggressive peripheral T-cell lymphomas, particularly adult T-cell leukemia/lymphoma and CTCLs, especially on the blood component of tumor cells. The main limiting events are related to the concomitant depletion of regulatory T-cells. IPH4102 is a humanized monoclonal antibody that targets the immune receptor KIR3DL2/CD158k. Preclinical results with this antibody offer proofs of concept for the clinical development of IPH4102 to treat patients with advanced CTCL.

  6. Analyzing the impact of relay station characteristics on uplink performance in cellular network

    NARCIS (Netherlands)

    Dimitrova, D.C.; van den Berg, Hans Leo; Heijenk, Geert

    2009-01-01

    Uplink users in cellular networks, such as UMTS/ HSPA, located at the edge of the cell generally suffer from poor channel conditions. Deploying intermediate relay nodes is seen as a promising approach towards extending cell coverage. This paper focuses on the role of packet scheduling in cellular

  7. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    International Nuclear Information System (INIS)

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F.

    2016-01-01

    Terbium layered hydroxide nanoparticles (Tb_2(OH)_5NO_3) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb_2(OH)_5NO_3 resulted in the preparation of two optimized nanoparticles. In particular, Tb_2(OH)_5NO_3:Eu and Tb_2(OH)_5NO_3-FA were prepared when Tb_2(OH)_5NO_3 was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb_2(OH)_5NO_3, could render these nanoparticles appropriate for biomedical applications.

  8. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    Energy Technology Data Exchange (ETDEWEB)

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F., E-mail: ghanotakis@uoc.gr [University of Crete, Department of Chemistry (Greece)

    2016-07-15

    Terbium layered hydroxide nanoparticles (Tb{sub 2}(OH){sub 5}NO{sub 3}) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb{sub 2}(OH){sub 5}NO{sub 3} resulted in the preparation of two optimized nanoparticles. In particular, Tb{sub 2}(OH){sub 5}NO{sub 3}:Eu and Tb{sub 2}(OH){sub 5}NO{sub 3}-FA were prepared when Tb{sub 2}(OH){sub 5}NO{sub 3} was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb{sub 2}(OH){sub 5}NO{sub 3}, could render these nanoparticles appropriate for biomedical applications.

  9. HIV-derived vectors for gene therapy targeting dendritic cells.

    Science.gov (United States)

    Rossetti, Maura; Cavarelli, Mariangela; Gregori, Silvia; Scarlatti, Gabriella

    2013-01-01

    Human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vectors (LV) have the potential to mediate stable therapeutic gene transfer. However, similarly to other viral vectors, their benefit is compromised by the induction of an immune response toward transgene-expressing cells that closely mimics antiviral immunity. LV share with the parental HIV the ability to activate dendritic cells (DC), while lack the peculiar ability of subverting DC functions, which is responsible for HIV immune escape. Understanding the interaction between LV and DC, with plasmacytoid and myeloid DC playing fundamental and distinct roles, has paved the way to novel approaches aimed at regulating transgene-specific immune responses. Thanks to the ability to target either DC subsets LV might be a powerful tool to induce immunity (i.e., gene therapy of cancer), cell death (i.e., in HIV/AIDS infection), or tolerance (i.e., gene therapy strategies for monogenic diseases). In this chapter, similarities and differences between the LV-mediated and HIV-mediated induction of immune responses, with specific focus on their interactions with DC, are discussed.

  10. Discrete radioisotopic relays of a cyclic action

    International Nuclear Information System (INIS)

    Klempner, K.S.; Vasil'ev, A.G.

    1975-01-01

    A functional diagram of discrete radioisotopic relay equipment (RRP) with cyclic action was examined. An analysis of its rapid action and reliability under stationary conditions and transition regimes is presented. A structural diagram of radioisotopic relay equipment shows three radiation detectors, a pulse standardizer, an integrator and a power amplifier with a threshold cut-off device. It was established that the basic properties of the RRP - rapid action and reliability - are determined entirely by the counting rate of the average frequency of pulses from the radiation detector, n 0 and n 1 , in the 0 and 1 states (absence of current in the electromagnetic relay winding and activation of the winding of the output relay), capacities N 1 and N 2 of the dual counters, and the frequency of the transition threshold, f, of the generator. Formulas are presented which allow making engineering calculations for determining the optimum RRP parameters. High speed and reliability are shown, which are determined by the production purposes of the relay

  11. Cognitive Relay Networks: A Comprehensive Survey

    Directory of Open Access Journals (Sweden)

    Ayesha Naeem

    2015-07-01

    Full Text Available Cognitive radio is an emerging technology to deal with the scarcity and requirement of radio spectrum by dynamically assigning spectrum to unlicensed user . This revolutionary technology shifts the paradigm in the wireless system design by all owing unlicensed user the ability to sense, adapt and share the dynamic spectrum. Cognitive radio technology have been applied to different networks and applications ranging from wireless to public saf ety, smart grid, medical, rela y and cellular applications to increase the throughput and spectrum efficiency of the network. Among these applications, cognitive relay networks is one of the application where cognitive radio technology has been applied. Cognitiv e rela y network increases the network throughput by reducing the complete pa th loss and also by ensuring cooper ation among secondary users and cooperation among primary and secondary users. In this paper , our aim is to provide a survey on cognitive relay network. We also provide a detailed review on existing schemes in cognitive relay networks on the basis of relaying protocol, relay cooperation and channel model.

  12. RNA interference targets arbovirus replication in Culicoides cells.

    Science.gov (United States)

    Schnettler, Esther; Ratinier, Maxime; Watson, Mick; Shaw, Andrew E; McFarlane, Melanie; Varela, Mariana; Elliott, Richard M; Palmarini, Massimo; Kohl, Alain

    2013-03-01

    Arboviruses are transmitted to vertebrate hosts by biting arthropod vectors such as mosquitoes, ticks, and midges. These viruses replicate in both arthropods and vertebrates and are thus exposed to different antiviral responses in these organisms. RNA interference (RNAi) is a sequence-specific RNA degradation mechanism that has been shown to play a major role in the antiviral response against arboviruses in mosquitoes. Culicoides midges are important vectors of arboviruses, known to transmit pathogens of humans and livestock such as bluetongue virus (BTV) (Reoviridae), Oropouche virus (Bunyaviridae), and likely the recently discovered Schmallenberg virus (Bunyaviridae). In this study, we investigated whether Culicoides cells possess an antiviral RNAi response and whether this is effective against arboviruses, including those with double-stranded RNA (dsRNA) genomes, such as BTV. Using reporter gene-based assays, we established the presence of a functional RNAi response in Culicoides sonorensis-derived KC cells which is effective in inhibiting BTV infection. Sequencing of small RNAs from KC and Aedes aegypti-derived Aag2 cells infected with BTV or the unrelated Schmallenberg virus resulted in the production of virus-derived small interfering RNAs (viRNAs) of 21 nucleotides, similar to the viRNAs produced during arbovirus infections of mosquitoes. In addition, viRNA profiles strongly suggest that the BTV dsRNA genome is accessible to a Dicer-type nuclease. Thus, we show for the first time that midge cells target arbovirus replication by mounting an antiviral RNAi response mainly resembling that of other insect vectors of arboviruses.

  13. Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy.

    Science.gov (United States)

    Sharrow, Allison C; Perkins, Brandy; Collector, Michael I; Yu, Wayne; Simons, Brian W; Jones, Richard J

    2016-08-01

    The cancer stem cell (CSC) paradigm hypothesizes that successful clinical eradication of CSCs may lead to durable remission for patients with ovarian cancer. Despite mounting evidence in support of ovarian CSCs, their phenotype and clinical relevance remain unclear. We and others have found high aldehyde dehydrogenase 1 (ALDH(high)) expression in a variety of normal and malignant stem cells, and sought to better characterize ALDH(high) cells in ovarian cancer. We compared ALDH(high) to ALDH(low) cells in two ovarian cancer models representing distinct subtypes: FNAR-C1 cells, derived from a spontaneous rat endometrioid carcinoma, and the human SKOV3 cell line (described as both serous and clear cell subtypes). We assessed these populations for stem cell features then analyzed expression by microarray and qPCR. ALDH(high) cells displayed CSC properties, including: smaller size, quiescence, regenerating the phenotypic diversity of the cell lines in vitro, lack of contact inhibition, nonadherent growth, multi-drug resistance, and in vivo tumorigenicity. Microarray and qPCR analysis of the expression of markers reported by others to enrich for ovarian CSCs revealed that ALDH(high) cells of both models showed downregulation of CD24, but inconsistent expression of CD44, KIT and CD133. However, the following druggable targets were consistently expressed in the ALDH(high) cells from both models: mTOR signaling, her-2/neu, CD47 and FGF18/FGFR3. Based on functional characterization, ALDH(high) ovarian cancer cells represent an ovarian CSC population. Differential gene expression identified druggable targets that have the potential for therapeutic efficacy against ovarian CSCs from multiple subtypes. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Novel Hedgehog pathway targets against basal cell carcinoma

    International Nuclear Information System (INIS)

    Tang, Jean Y.; So, P.-L.; Epstein, Ervin H.

    2007-01-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence

  15. Active targeting of tumor cells using light emitting bacteria

    International Nuclear Information System (INIS)

    Moon, Sung Min; Min, Jung Joon; Hong, Yeong Jin; Kim, Hyun Ju; Le, Uuenchi N.; Rhee, Joon Haeng; Song, Ho Chun; Heo, Young Jun; Bom, Hee Seung; Choy, Hyon E

    2004-01-01

    The presence of bacteria and viruses in human tumors has been recognized for more than 50 years. Today, with the discovery of bacterial strains that specifically target tumors, and aided by genomic sequencing and genetic engineering, there is new interest in the use of bacteria as tumor vectors. Here, we show that bacteria injected intravenously into live animals entered and replicated in solid tumors and metastases using the novel imaging technology of biophotonics. Bioluminescence operon (LuxCDABE) or fluorescence protein, GFP) has been cloned into pUC19 plasmid to engineer pUC19lux or pUC19gfp. Engineered plasmid was transformed into different kinds of wild type (MG1655) or mutant E. coli (DH5, ppGpp, fnr, purE, crpA, flagella, etc.) strains to construct light emitting bacteria. Xenograft tumor model has been established using CT26 colon cancer cell line. Light emitting bacteria was injected via tail vein into tumor bearing mouse. In vivo bioluminescence imaging has been done after 20 min to 14 days of bacterial injection. We observed localization of tumors by light-emitting E. coli in tumor (CT-26) bearing mice. We confirmed the presence of light-emitting bacteria under the fluorescence microscope with E. coli expressing GFP. Althoug varying mutants strain with deficient invading function has been found in tumor tissues, mutant strains of movement (flagella) couldn't show any light signal from the tumor tissue under the cooled CCD camera, indicating bacteria may actively target the tumor cells. Based on their 'tumor-finding' nature, bacteria may be designed to carry multiple genes or drugs for detection and treatment of cancer, such as prodrug-converting enzymes, toxins, angiogenesis inhibitors and cytokines

  16. Osteosarcoma target therapy with stem cell transplant: A case review

    International Nuclear Information System (INIS)

    Fawzy, A.

    2005-01-01

    Full text: Radioisotopes with medium-energy beta emission and half life of a few days are attractive option for systemic delivery of targeted irradiation. Samarium-153 ethylene diamine tetra-ethylene phosphonale (153Sm-EDTMP), a bone-seeking radiopharmaceutical, provides therapeutic irradiation to osteoblastic osseous lesion. The usual dose of Sm-153 in metastatic disease is 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is thrombocytopenia. As local radiotherapy has only a limited therapeutic role in the treatment of osteosarcoma, and some types of the tumour portray an unpredictable response to chemotherapy. High dose Sm-153 (30mCi/Kg) was proposed for the target management of recurrent osteosarcoma, this was followed by stem cell transplant (peripheral-blood progenitor, PBPCs). A female child, 10 years old, with polyostotic osteosarcoma with local recurrence in the right hipbone was chosen for therapy. She had left knee prosthesis, right lower limb dis-articulation, and was given chemotherapy in multiple regions. She was subjected to MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, which showed negative uptake. She received 30mCi/Kg Sm-153 (660mCi in total dose), with no major events occurring in the post-injection period. After 10 days the patient went into pancytopenia, which necessitated haematological support. By day 14, there was minimal radiation in the whole body image and the child received her bone marrow transplant. There was marked improvement in the tumour size after 6 weeks of therapy, with improvement in the alkaline phosphatase level (from 1350Iu, before treatment to 350 post treatment). This was confirmed by serial MDP bone scan. High dose Sm-153 with stem cell transplant is considered view a promising method in the management of osteosarcoma. (author)

  17. Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

    Science.gov (United States)

    Gravis, Gwenaelle; Faure, Marjorie; Rybikowski, Stanislas; Dermeche, Slimane; Tyran, Marguerite; Calderon, Benoit; Thomassin, Jeanne; Walz, Jochen; Salem, Naji

    2015-11-01

    Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

  18. Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

    Directory of Open Access Journals (Sweden)

    Ander Abarrategi

    2016-01-01

    Full Text Available Osteosarcoma (OS is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.

  19. Counterfactual quantum cryptography network with untrusted relay

    Science.gov (United States)

    Chen, Yuanyuan; Gu, Xuemei; Jiang, Dong; Xie, Ling; Chen, Lijun

    2015-07-01

    Counterfactual quantum cryptography allows two remote parties to share a secret key even though a physical particle is not in fact transmitted through the quantum channel. In order to extend the scope of counterfactual quantum cryptography, we use an untrusted relay to construct a multi-user network. The implementation issues are discussed to show that the scheme can be realized with current technologies. We also prove the practical security advantages of the scheme by eliminating the probability that an eavesdropper can directly access the signal or an untrusted relay can perform false operations.

  20. CERN Relay Race: information for drivers

    CERN Multimedia

    2012-01-01

    The CERN relay race will take place around the Meyrin site on Thursday, 24 May starting at 12.15. If possible, please avoid driving on the site during this 20-minute period. If you do meet runners while driving your car, please STOP until they have all passed. In addition, there will be a Nordic Walking event which will finish around 12.50. This should not block the roads, but please drive carefully during this time. Thank you for your cooperation. Details on how to register your team for the relay race can be found here.

  1. Deep space optical communication via relay satellite

    Science.gov (United States)

    Dolinar, S.; Vilnrotter, V.; Gagliardi, R.

    1981-01-01

    The application of optical communications for a deep space link via an earth-orbiting relay satellite is discussed. The system uses optical frequencies for the free-space channel and RF links for atmospheric transmission. The relay satellite is in geostationary orbit and contains the optics necessary for data processing and formatting. It returns the data to earth through the RF terrestrial link and also transmits an optical beacon to the satellite for spacecraft return pointing and for the alignment of the transmitting optics. Future work will turn to modulation and coding, pointing and tracking, and optical-RF interfacing.

  2. Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

    International Nuclear Information System (INIS)

    Jhanwar-Uniyal, Meena; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj

    2015-01-01

    Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM

  3. Regulatory T Cells As Potential Targets for HIV Cure Research

    Science.gov (United States)

    Kleinman, Adam J.; Sivanandham, Ranjit; Pandrea, Ivona; Chougnet, Claire A.; Apetrei, Cristian

    2018-01-01

    T regulatory cells (Tregs) are a key component of the immune system, which maintain a delicate balance between overactive responses and immunosuppression. As such, Treg deficiencies are linked to autoimmune disorders and alter the immune control of pathogens. In HIV infection, Tregs play major roles, both beneficial and detrimental. They regulate the immune system such that inflammation and spread of virus through activated T cells is suppressed. However, suppression of immune activation also limits viral clearance and promotes reservoir formation. Tregs can be directly targeted by HIV, thereby harboring a fraction of the viral reservoir. The vital role of Tregs in the pathogenesis and control of HIV makes them a subject of interest for manipulation in the search of an HIV cure. Here, we discuss the origin and generation, homeostasis, and functions of Tregs, particularly their roles and effects in HIV infection. We also present various Treg manipulation strategies, including Treg depletion techniques and interventions that alter Treg function, which may be used in different cure strategies, to simultaneously boost HIV-specific immune responses and induce reactivation of the latent virus.

  4. Glioblastoma: Molecular Pathways, Stem Cells and Therapeutic Targets

    Energy Technology Data Exchange (ETDEWEB)

    Jhanwar-Uniyal, Meena, E-mail: meena_jhanwar@nymc.edu; Labagnara, Michael; Friedman, Marissa; Kwasnicki, Amanda; Murali, Raj [Department of Neurosurgery, New York Medical College, Valhalla, NY 10595 (United States)

    2015-03-25

    Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM.

  5. Targeting sarcoma tumor-initiating cells through differentiation therapy

    Directory of Open Access Journals (Sweden)

    Dan Han

    2017-05-01

    Full Text Available Human leukocyte antigen class I (HLA-I down-regulation has been reported in many human cancers to be associated with poor clinical outcome. However, its connection to tumor-initiating cells (TICs remains unknown. In this study, we report that HLA-I is down-regulated in a subpopulation of cells that have high tumor initiating capacity in different types of human sarcomas. Detailed characterization revealed their distinct molecular profiles regarding proliferation, apoptosis and stemness programs. Notably, these TICs can be induced to differentiate along distinct mesenchymal lineages, including the osteogenic pathway. The retinoic acid receptor signaling pathway is overexpressed in HLA-1 negative TICs. All-trans retinoic acid treatment successfully induced osteogenic differentiation of this subpopulation, in vitro and in vivo, resulting in significantly decreased tumor formation. Thus, our findings indicate down-regulated HLA-I is a shared feature of TICs in a variety of human sarcomas, and differentiation therapy strategies may specifically target undifferentiated TICs and inhibit tumor formation.

  6. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

    International Nuclear Information System (INIS)

    Cheng, Gang; Zielonka, Jacek; McAllister, Donna M; Mackinnon, A Craig Jr; Joseph, Joy; Dwinell, Michael B; Kalyanaraman, Balaraman

    2013-01-01

    Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect

  7. Improper Gaussian signaling in full-duplex relay channels with residual self-interference

    KAUST Repository

    Gaafar, Mohamed

    2016-07-26

    We study the potential employment of improper Gaussian signaling (IGS) in full-duplex cooperative settings with residual self-interference (RSI). IGS is recently shown to outperform traditional proper Gaussian signaling (PGS) in several interference-limited channel settings. In this work, IGS is employed in an attempt to alleviate the RSI adverse effect in full-duplex relaying (FDR). To this end, we derive a tight upper bound expression for the end-to-end outage probability in terms of the relay signal parameters represented in its power and circularity coefficient. We further show that the derived upper bound is either monotonic or unimodal in the relay\\'s circularity coefficient. This result allows for easily locating the global optimal point using known numerical methods. Based on the analysis, IGS allows FDR systems to operate even with high RSI. It is shown that, while the communication totally fails with PGS as the RSI increases, the IGS outage probability approaches a fixed value that depends on the channel statistics and target rate. The obtained results show that IGS can leverage higher relay power budgets than PGS to improve the performance, meanwhile it relieves its RSI impact via tuning the signal impropriety. © 2016 IEEE.

  8. Full-Duplex Relaying with Improper Gaussian Signaling over Nakagami-m Fading Channels

    KAUST Repository

    Gaafar, Mohamed

    2017-10-04

    We study the potential employment of improper Gaussian signaling (IGS) in full-duplex relaying (FDR) with non-negligible residual self-interference (RSI) under Nakagami- m fading. IGS is recently shown to outperform traditional proper Gaussian signaling (PGS) in several interference-limited settings. In this work, IGS is employed as an attempt to alleviate RSI. We use two performance metrics, namely, the outage probability and the ergodic rate. First, we provide upper and lower bounds for the system performance in terms of the relay transmit power and circularity coefficient, a measure of the signal impropriety. Then, we numerically optimize the relay signal parameters based only on the channel statistics to improve the system performance. Based on the analysis, IGS allows FDR to operate even with high RSI. The results show that IGS can leverage higher power budgets to enhance the performance, meanwhile it relieves RSI impact via tuning the signal impropriety. Interestingly, one-dimensional optimization of the circularity coefficient, with maximum relay power, offers a similar performance as the joint optimization, which reduces the optimization complexity. From a throughput standpoint, it is shown that IGS-FDR can outperform not only PGS-FDR, but also half-duplex relaying with/without maximum ratio combining over certain regions of the target source rate.

  9. Energy Efficiency Analysis of a Two Dimensional Cooperative Wireless Sensor Network with Relay Selection

    Directory of Open Access Journals (Sweden)

    M. Kakitani

    2013-06-01

    Full Text Available The energy efficiency of non-cooperative and cooperative transmissions are investigated in a two-dimensional wireless sensor network, considering a target outage probability and the same end-to-end throughput for all transmission schemes. The impact of the relay selection method in the cooperative schemes is also analyzed. We show that under non line-of-sight conditions the relay selection method has a greater impact in the energy efficiency than the availability of a return channel. By its turn, under line-of-sight conditions a return channel is more valuable to the energy efficiency of cooperative transmission than the specific relay selection method. Finally, we demonstrate that the energy efficiency advantage of the cooperative over the non-cooperative transmission increases with the distance among nodes and with the nodes density.

  10. Outage performance of two-way DF relaying systems with a new relay selection metric

    KAUST Repository

    Hyadi, Amal

    2012-04-01

    This paper investigates a new constrained relay selection scheme for two-way relaying systems where two end terminals communicate simultaneously via a relay. The introduced technique is based on the maximization of the weighted sum rate of both users. To evaluate the performance of the proposed system, the outage probability is derived in a general case (where an arbitrary channel is considered), and then over independently but not necessarily identically distributed (i.n.i.d.) Rayleigh fading channels. The analytical results are verified through simulations. © 2012 IEEE.

  11. Advanced Strategic and Tactical Relay Request Management for the Mars Relay Operations Service

    Science.gov (United States)

    Allard, Daniel A.; Wallick, Michael N.; Gladden, Roy E.; Wang, Paul; Hy, Franklin H.

    2013-01-01

    This software provides a new set of capabilities for the Mars Relay Operations Service (MaROS) in support of Strategic and Tactical relay, including a highly interactive relay request Web user interface, mission control over relay planning time periods, and mission management of allowed strategic vs. tactical request parameters. Together, these new capabilities expand the scope of the system to include all elements critical for Tactical relay operations. Planning of replay activities spans a time period that is split into two distinct phases. The first phase is called Strategic, which begins at the time that relay opportunities are identified, and concludes at the point that the orbiter generates the flight sequences for on board execution. Any relay request changes from this point on are called Tactical. Tactical requests, otherwise called Orbit - er Relay State Changes (ORSC), are highly restricted in terms of what types of changes can be made, and the types of parameters that can be changed may differ from one orbiter to the next. For example, one orbiter may be able to delay the start of a relay request, while another may not. The legacy approach to ORSC management involves exchanges of e-mail with "requests for change" and "acknowledgement of approval," with no other tracking of changes outside of e-mail folders. MaROS Phases 1 and 2 provided the infrastructure for strategic relay for all supported missions. This new version, 3.0, introduces several capabilities that fully expand the scope of the system to include tactical relay. One new feature allows orbiter users to manage and "lock" Planning Periods, which allows the orbiter team to formalize the changeover from Strategic to Tactical operations. Another major feature allows users to interactively submit tactical request changes via a Web user interface. A third new feature allows orbiter missions to specify allowed tactical updates, which are automatically incorporated into the tactical change process

  12. Relay communications strategies for Mars exploration through 2020

    Science.gov (United States)

    Edwards, Charles D., Jr.; Arnold, B.; DePaula, R.; Kazz, G.; Lee, C.; Noreen, G.

    2005-01-01

    In this paper we will examine NASA's strategy for relay communications support of missions planned for this decade, and discuss options for longer-term relay network evolution in support of second-decade missions.

  13. Switched diversity strategies for dual-hop relaying systems

    KAUST Repository

    Gaaloul, Fakhreddine; Alouini, Mohamed-Slim; Radaydeh, Redha M.

    2011-01-01

    This paper investigates the effect of different switched diversity configurations on the implementation complexity and achieved performance of dual-hop amplify-and-forward (AF) relaying networks. A low-complexity model of the relay station

  14. protective relay studies for the nigerian national electric 330 kv

    African Journals Online (AJOL)

    user

    1985-09-01

    Sep 1, 1985 ... protective relay schemes of the National Electric Power Authority. Some of the basic ... Nigerian special system characteristics, schemes to correct existing protection inadequacies .... relays buried in the transformer. A reach of ...

  15. Dynamic Relaying in 3GPP LTE-Advanced Networks

    Directory of Open Access Journals (Sweden)

    Van Phan Vinh

    2009-01-01

    Full Text Available Relaying is one of the proposed technologies for LTE-Advanced networks. In order to enable a flexible and reliable relaying support, the currently adopted architectural structure of LTE networks has to be modified. In this paper, we extend the LTE architecture to enable dynamic relaying, while maintaining backward compatibility with LTE Release 8 user equipments, and without limiting the flexibility and reliability expected from relaying. With dynamic relaying, relays can be associated with base stations on a need basis rather than in a fixed manner which is based only on initial radio planning. Proposals are also given on how to further improve a relay enhanced LTE network by enabling multiple interfaces between the relay nodes and their controlling base stations, which can possibly be based on technologies different from LTE, so that load balancing can be realized. This load balancing can be either between different base stations or even between different networks.

  16. Capacity gains of buffer-aided moving relays

    KAUST Repository

    Zafar, Ammar

    2017-03-14

    This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

  17. Dynamic Relaying in 3GPP LTE-Advanced Networks

    DEFF Research Database (Denmark)

    Teyeb, Oumer Mohammed; Van Phan, Vinh; Redana, Simone

    2009-01-01

    Relaying is one of the proposed technologies for LTE-Advanced networks. In order to enable a flexible and reliable relaying support, the currently adopted architectural structure of LTE networks has to be modified. In this paper, we extend the LTE architecture to enable dynamic relaying, while...... maintaining backward compatibility with LTE Release 8 user equipments, and without limiting the flexibility and reliability expected from relaying.With dynamic relaying, relays can be associated with base stations on a need basis rather than in a fixed manner which is based only on initial radio planning....... Proposals are also given on how to further improve a relay enhanced LTE network by enabling multiple interfaces between the relay nodes and their controlling base stations, which can possibly be based on technologies different from LTE, so that load balancing can be realized. This load balancing can...

  18. Improper Signaling for Virtual Full-Duplex Relay Systems

    KAUST Repository

    Gaafar, Mohamed

    2017-02-14

    Virtual full-duplex (VFD) is a powerful solution to compensate the rate loss of half-duplex relaying without the need to full-duplex capable nodes. Inter-relay interference (IRI) challenges the operation of VFD relaying systems. Recently, improper signaling is employed at both relays of the VFD to mitigate the IRI by imposing the same signal characteristics for both relays. To further boost the achievable rate performance, asymmetric time sharing VFD relaying system is adopted with different improper signals at the half-duplex relays. The joint tuning of the three design parameters improves the achievable rate performance at different ranges of IRI and different relays locations. Extensive simulation results are presented and analyzed to show the achievable rate gain of the proposed system and understand the system behavior.

  19. Improper Signaling for Virtual Full-Duplex Relay Systems

    KAUST Repository

    Gaafar, Mohamed; Amin, Osama; Schaefer, Rafael F.; Alouini, Mohamed-Slim

    2017-01-01

    Virtual full-duplex (VFD) is a powerful solution to compensate the rate loss of half-duplex relaying without the need to full-duplex capable nodes. Inter-relay interference (IRI) challenges the operation of VFD relaying systems. Recently, improper signaling is employed at both relays of the VFD to mitigate the IRI by imposing the same signal characteristics for both relays. To further boost the achievable rate performance, asymmetric time sharing VFD relaying system is adopted with different improper signals at the half-duplex relays. The joint tuning of the three design parameters improves the achievable rate performance at different ranges of IRI and different relays locations. Extensive simulation results are presented and analyzed to show the achievable rate gain of the proposed system and understand the system behavior.

  20. Capacity gains of buffer-aided moving relays

    KAUST Repository

    Zafar, Ammar; Shaqfeh, Mohammad; Alnuweiri, Hussein; Alouini, Mohamed-Slim

    2017-01-01

    This work investigates the gain due to reduction in path loss by deploying buffer-aided moving relaying. In particular, the increase in gain due to moving relays is studied for dual-hop broadcast channels and the bidirectional relay channel. It is shown that the exploited gains in these channels due to buffer-aided relaying can be enhanced by utilizing the fact that a moving relay can communicate with the terminal closest to it and store the data in the buffer and then forward the data to the intended destination when it comes in close proximity with the destination. Numerical results show that for both the considered channels the achievable rates are increased as compared to the case of stationary relays. Numerical results also show that more significant increase in performance is seen when the relay moves to-and-fro between the source and the relay.

  1. IFMIF target and test cell - design and integration

    International Nuclear Information System (INIS)

    Heinzel, V.

    2007-01-01

    The International Fusion Material Irradiation Facility (IFMIF) aims at the qualification of appropriate materials for a Demonstration Fusion Power Plant (DEMO) to a fluence of up to 150 dpa (displacement per atom) at a DEMO typical neutron spectrum. It comprises two accelerators each providing a deuteron beam with 125 mA and 40 MeV. The deuterons strike a lithium target and create via stripping reactions neutrons. The neutrons are mainly forward directed into the High-Flux-Test-Module (HFTM). The Medium Flux-Test-Modules (MFTM) and the Low-Flux-Test-Modules (LFTM) are arranged in beam direction behind. In the HFTM a damage rate in steel of more than 20 dpa/fpy (displacement per atome per full power year) will be provide in a volume of 0.5 litre. The neutron spectrum is prone to produce helium and tritium in steel like in the first wall of a DEMO reactor. The Medium- Flux-Test-Modules are designed for creep fatigues in situ and tritium release test. The test modules are cooled with helium. The target is a lithium jet with a free surface towards the deuteron beams. The jet follows a concave curved so called back wall. Centrifugal forces increase the static pressure, which prevents lithium boiling at the beam tube pressure and the power release of 10 MW due to the deuteron beams. The target and Test Cell (TTC) houses the target and the test modules as well as the lithium supply tubes and a quench tank into which the lithium splashes after the target. The lithium containing components have a temperature of 250 to 350 C. Nuclear reactions mainly in beam direction contribute to heat releases in TTC components. The TTC is filled with a noble gas with almost atmospheric pressure. Natural convection transfers heat to the walls but also mitigates temperature peaks. The Forschungszentrum Karlsruhe (FZK) has developed or validated tools for: - The extended Monte Carlo Code McDeLicious for calculations of the neutron source term, dpa rates in the material specimens, activation

  2. Relay protection features of frequency-adjustable electric drive

    Science.gov (United States)

    Kuprienko, V. V.

    2018-03-01

    The features of relay protection of high-voltage electric motors in composition of the frequency-adjustable electric drive are considered in the article. The influence of frequency converters on the stability of the operation of various types of relay protection used on electric motors is noted. Variants of circuits for connecting relay protection devices are suggested. The need to develop special relay protection devices for a frequency-adjustable electric drive is substantiated.

  3. Microprocessor protection relays: new prospects or new problems?

    OpenAIRE

    Gurevich, Vladimir

    2006-01-01

    The internal architecture and principles of operation of microprocessor-based devices including so-called "microprocessor protective relays" have little in common with devices called "electric relays". But microprocessor-based relay protection devices are gradually driving out the traditional electromechanical and even electronic relay protection of virtually from all fields of power and electrical engineering. Advantages of microprocessor-based protection means over traditional ones are far ...

  4. Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

    Science.gov (United States)

    2014-05-01

    in May 2013, the difference between nude mice (which lack T- cells , but still have a partially functional adaptive and innate immune system) and NSG...Mangada J, Greiner DL, Handgretinger R. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human...Targeting of Cerebral Breast Cancer Metastases Using a T- Cell Receptor Mimic Antibody PRINCIPAL INVESTIGATOR: Ulrich Bickel

  5. Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

    International Nuclear Information System (INIS)

    Luce, A.; Courtin, A.; Levalois, C.; Altmeyer-Morel, S.; Chevillard, S.; Lebeau, J.; Romeo, P.H.

    2009-01-01

    Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after γ-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-α permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-α, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. (authors)

  6. Myeloid Conditioning with c-kit-Targeted CAR-T Cells Enables Donor Stem Cell Engraftment.

    Science.gov (United States)

    Arai, Yasuyuki; Choi, Uimook; Corsino, Cristina I; Koontz, Sherry M; Tajima, Masaki; Sweeney, Colin L; Black, Mary A; Feldman, Steven A; Dinauer, Mary C; Malech, Harry L

    2018-05-02

    We report a novel approach to bone marrow (BM) conditioning using c-kit-targeted chimeric antigen receptor T (c-kit CAR-T) cells in mice. Previous reports using anti-c-kit or anti-CD45 antibody linked to a toxin such as saporin have been promising. We developed a distinctly different approach using c-kit CAR-T cells. Initial studies demonstrated in vitro killing of hematopoietic stem cells by c-kit CAR-T cells but poor expansion in vivo and poor migration of CAR-T cells into BM. Pre-treatment of recipient mice with low-dose cyclophosphamide (125 mg/kg) together with CXCR4 transduction in the CAR-T cells enhanced trafficking to and expansion in BM (c-kit + population (9.0%-0.1%). Because congenic Thy1.1 CAR-T cells were used in the Thy1.2-recipient mice, anti-Thy1.1 antibody could be used to deplete CAR-T cells in vivo before donor BM transplant. This achieved 20%-40% multilineage engraftment. We applied this conditioning to achieve an average of 28% correction of chronic granulomatous disease mice by wild-type BM transplant. Our findings provide a proof of concept that c-kit CAR-T cells can achieve effective BM conditioning without chemo-/radiotherapy. Our work also demonstrates that co-expression of a trafficking receptor can enhance targeting of CAR-T cells to a designated tissue. Published by Elsevier Inc.

  7. 49 CFR 236.52 - Relayed cut-section.

    Science.gov (United States)

    2010-10-01

    ..., MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Rules and Instructions: All Systems Track Circuits § 236.52 Relayed cut-section. Where relayed cut-section is used in... 49 Transportation 4 2010-10-01 2010-10-01 false Relayed cut-section. 236.52 Section 236.52...

  8. 76 FR 72124 - Internet-Based Telecommunications Relay Service Numbering

    Science.gov (United States)

    2011-11-22

    ... Docket No. 10-191; FCC 11-123] Internet-Based Telecommunications Relay Service Numbering AGENCY: Federal..., the information collection associated with the Commission's Internet- Based Telecommunications Relay... Telecommunications Relay Service Numbering, CG Docket No. 03-123; WC Docket No. 05-196; WC Docket No. 10-191; FCC 11...

  9. 76 FR 65965 - Contributions to the Telecommunications Relay Services Fund

    Science.gov (United States)

    2011-10-25

    ...] Contributions to the Telecommunications Relay Services Fund AGENCY: Federal Communications Commission. ACTION... Telecommunications Relay Services (TRS) Fund in a manner prescribed by regulation that is consistent with and... . SUPPLEMENTARY INFORMATION: This is a summary of the Commission's Contributions to the Telecommunications Relay...

  10. Asymmetric Modulation Gains in Network Coded Relay Networks

    DEFF Research Database (Denmark)

    Roetter, Daniel Enrique Lucani; Fitzek, Frank

    2015-01-01

    Wireless relays have usually been considered in two ways. On the one hand, a physical layer approach focused on per-packet reliability and involving the relay on each packet transmission. On the other, recent approaches have relied on the judicious activation of the relay at the network level to ...

  11. A SDP based design of relay precoding for the power minimization of MIMO AF-relay networks

    KAUST Repository

    Rao, Anlei; Park, Kihong; Alouini, Mohamed-Slim

    2015-01-01

    Relay precoding for multiple-input and multiple-output (MIMO) relay networks has been approached by either optimizing the efficiency performance with given power consumption constraints or minimizing the power consumption with quality-of-service (Qo

  12. A low complexity algorithm for multiple relay selection in two-way relaying Cognitive Radio networks

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-06-01

    In this paper, a multiple relay selection scheme for two-way relaying cognitive radio network is investigated. We consider a cooperative Cognitive Radio (CR) system with spectrum sharing scenario using Amplify-and-Forward (AF) protocol, where licensed users and unlicensed users operate on the same frequency band. The main objective is to maximize the sum rate of the unlicensed users allowed to share the spectrum with the licensed users by respecting a tolerated interference threshold. A practical low complexity heuristic approach is proposed to solve our formulated optimization problem. Selected numerical results show that the proposed algorithm reaches a performance close to the performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions while providing a considerable saving in terms of computational complexity. In addition, these results show that our proposed scheme significantly outperforms the single relay selection scheme. © 2013 IEEE.

  13. Optimal relay selection and power allocation for cognitive two-way relaying networks

    KAUST Repository

    Pandarakkottilil, Ubaidulla

    2012-06-01

    In this paper, we present an optimal scheme for power allocation and relay selection in a cognitive radio network where a pair of cognitive (or secondary) transceiver nodes communicate with each other assisted by a set of cognitive two-way relays. The secondary nodes share the spectrum with a licensed primary user (PU), and each node is assumed to be equipped with a single transmit/receive antenna. The interference to the PU resulting from the transmission from the cognitive nodes is kept below a specified limit. We propose joint relay selection and optimal power allocation among the secondary user (SU) nodes achieving maximum throughput under transmit power and PU interference constraints. A closed-form solution for optimal allocation of transmit power among the SU transceivers and the SU relay is presented. Furthermore, numerical simulations and comparisons are presented to illustrate the performance of the proposed scheme. © 2012 IEEE.

  14. SWIPT in Multiuser MIMO Decode-and-Forward Relay Broadcasting Channel with Energy Harvesting Relays

    KAUST Repository

    Benkhelifa, Fatma

    2017-02-09

    In this paper, we consider a multiuser multiple- input multiple-output (MIMO) decode-and-forward (DF) relay broadcasting channel (BC) with single source, multiple energy harvesting relays and multiple destinations. Since the end-to-end sum rate maximization problem is intractable, we tackle a simplified problem where we maximize the sum of the harvested energy at the relays, we employ the block diagonalization (BD) procedure at the source, and we mitigate the interference between the relay- destination channels. The interference mitigation at the destinations is managed in two ways: either to fix the interference covariance matrices at the destination and update them at each iteration until convergence, or to cancel the interference using an algorithm similar to the BD method. We provide numerical results to show the relevance of our proposed solution.

  15. Modelling and Verification of Relay Interlocking Systems

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth; Bliguet, Marie Le; Kjær, Andreas

    2010-01-01

    This paper describes how relay interlocking systems as used by the Danish railways can be formally modelled and verified. Such systems are documented by circuit diagrams describing their static layout. It is explained how to derive a state transition system model for the dynamic behaviour...

  16. Relay Feedback Analysis for Double Integral Plants

    Directory of Open Access Journals (Sweden)

    Zhen Ye

    2011-01-01

    Full Text Available Double integral plants under relay feedback are studied. Complete results on the uniqueness of solutions, existence, and stability of the limit cycles are established using the point transformation method. Analytical expressions are also given for determining the amplitude and period of a limit cycle from the plant parameters.

  17. First Things First: Internet Relay Chat Openings.

    Science.gov (United States)

    Rintel, E. Sean; Mulholland, Joan; Pittam, Jeffery

    2001-01-01

    Argues that Internet Relay Chat (IRC) research needs to systematically address links between interaction structures, technological mediation and the instantiation and development of interpersonal relationships. Finds that openings that occur directly following user's entries into public IRC channels are often ambiguous, can disrupt relationship…

  18. CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

    Science.gov (United States)

    Golubovskaya, Vita; Berahovich, Robert; Zhou, Hua; Xu, Shirley; Harto, Hizkia; Li, Le; Chao, Cheng-Chi; Mao, Mike Ming; Wu, Lijun

    2017-10-21

    CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines. CD47-CAR-T cells effectively killed ovarian, pancreatic and other cancer cells and produced high level of cytokines that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also specifically killed ovarian, pancreatic, and cervical cancer cell lines and produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can be used as a novel cellular therapeutic agent for treating different types of cancer.

  19. The cell wall-targeting antibiotic stimulon of Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    Jacqueline Abranches

    Full Text Available Enterococcus faecalis is an opportunistic nosocomial pathogen that is highly resistant to a variety of environmental insults, including an intrinsic tolerance to antimicrobials that target the cell wall (CW. With the goal of determining the CW-stress stimulon of E. faecalis, the global transcriptional profile of E. faecalis OG1RF exposed to ampicillin, bacitracin, cephalotin or vancomycin was obtained via microarrays. Exposure to the β-lactams ampicillin and cephalotin resulted in the fewest transcriptional changes with 50 and 192 genes differentially expressed 60 min after treatment, respectively. On the other hand, treatment with bacitracin or vancomycin for 60 min affected the expression of, respectively, 377 and 297 genes. Despite the differences in the total number of genes affected, all antibiotics induced a very similar gene expression pattern with an overrepresentation of genes encoding hypothetical proteins, followed by genes encoding proteins associated with cell envelope metabolism as well as transport and binding proteins. In particular, all drug treatments, most notably bacitracin and vancomycin, resulted in an apparent metabolic downshift based on the repression of genes involved in translation, energy metabolism, transport and binding. Only 19 genes were up-regulated by all conditions at both the 30 and 60 min time points. Among those 19 genes, 4 genes encoding hypothetical proteins (EF0026, EF0797, EF1533 and EF3245 were inactivated and the respective mutant strains characterized in relation to antibiotic tolerance and virulence in the Galleria mellonella model. The phenotypes obtained for two of these mutants, ΔEF1533 and ΔEF3245, support further characterization of these genes as potential candidates for the development of novel preventive or therapeutic approaches.

  20. Mammalian target of rapamycin activity is required for expansion of CD34(+) hematopoietic progenitor cells

    NARCIS (Netherlands)

    Geest, Christian R.; Zwartkruis, Fried J.; Vellenga, Edo; Coffer, Paul J.; Buitenhuis, Miranda

    Background The mammalian target of rapamycin is a conserved protein kinase known to regulate protein synthesis, cell size and proliferation. Aberrant regulation of mammalian target of rapamycin activity has been observed in hematopoietic malignancies, including acute leukemias and myelodysplastic

  1. Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

    International Nuclear Information System (INIS)

    Kaleeba, Johnan A.R.; Berger, Edward A.

    2006-01-01

    The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of α3β1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor

  2. Relay Precoder Optimization in MIMO-Relay Networks With Imperfect CSI

    KAUST Repository

    Pandarakkottilil, Ubaidulla

    2011-11-01

    In this paper, we consider robust joint designs of relay precoder and destination receive filters in a nonregenerative multiple-input multiple-output (MIMO) relay network. The network consists of multiple source-destination node pairs assisted by a MIMO-relay node. The channel state information (CSI) available at the relay node is assumed to be imperfect. We consider robust designs for two models of CSI error. The first model is a stochastic error (SE) model, where the probability distribution of the CSI error is Gaussian. This model is applicable when the imperfect CSI is mainly due to errors in channel estimation. For this model, we propose robust minimum sum mean square error (SMSE), MSE-balancing, and relay transmit power minimizing precoder designs. The next model for the CSI error is a norm-bounded error (NBE) model, where the CSI error can be specified by an uncertainty set. This model is applicable when the CSI error is dominated by quantization errors. In this case, we adopt a worst-case design approach. For this model, we propose a robust precoder design that minimizes total relay transmit power under constraints on MSEs at the destination nodes. We show that the proposed robust design problems can be reformulated as convex optimization problems that can be solved efficiently using interior-point methods. We demonstrate the robust performance of the proposed design through simulations. © 2011 IEEE.

  3. Targeted and non-targeted effects in cell wall polysaccharides from transgenetically modified potato tubers

    NARCIS (Netherlands)

    Huang, J.H.

    2016-01-01

    The plant cell wall is a chemically complex network composed mainly of polysaccharides. Cell wall polysaccharides surround and protect plant cells and are responsible for the stability and rigidity of plant tissue. Pectin is a major component of primary cell wall and the middle lamella of plants.

  4. Using a micromachined magnetostatic relay in commutating a DC motor

    Science.gov (United States)

    Tai, Yu-Chong (Inventor); Wright, John A. (Inventor); Lilienthal, Gerald (Inventor)

    2004-01-01

    A DC motor is commutated by rotating a magnetic rotor to induce a magnetic field in at least one magnetostatic relay in the motor. Each relay is activated in response to the magnetic field to deliver power to at least one corresponding winding connected to the relay. In some cases, each relay delivers power first through a corresponding primary winding and then through a corresponding secondary winding to a common node. Specific examples include a four-pole, three-phase motor in which each relay is activated four times during one rotation of the magnetic rotor.

  5. Relay Architectures for 3GPP LTE-Advanced

    Directory of Open Access Journals (Sweden)

    Peters StevenW

    2009-01-01

    Full Text Available The Third Generation Partnership Project's Long Term Evolution-Advanced is considering relaying for cost-effective throughput enhancement and coverage extension. While analog repeaters have been used to enhance coverage in commercial cellular networks, the use of more sophisticated fixed relays is relatively new. The main challenge faced by relay deployments in cellular systems is overcoming the extra interference added by the presence of relays. Most prior work on relaying does not consider interference, however. This paper analyzes the performance of several emerging half-duplex relay strategies in interference-limited cellular systems: one-way, two-way, and shared relays. The performance of each strategy as a function of location, sectoring, and frequency reuse are compared with localized base station coordination. One-way relaying is shown to provide modest gains over single-hop cellular networks in some regimes. Shared relaying is shown to approach the gains of local base station coordination at reduced complexity, while two-way relaying further reduces complexity but only works well when the relay is close to the handset. Frequency reuse of one, where each sector uses the same spectrum, is shown to have the highest network throughput. Simulations with realistic channel models provide performance comparisons that reveal the importance of interference mitigation in multihop cellular networks.

  6. Tumor Initiating Cells and Chemoresistance: Which Is the Best Strategy to Target Colon Cancer Stem Cells?

    Directory of Open Access Journals (Sweden)

    Emanuela Paldino

    2014-01-01

    Full Text Available There is an emerging body of evidence that chemoresistance and minimal residual disease result from selective resistance of a cell subpopulation from the original tumor that is molecularly and phenotypically distinct. These cells are called “cancer stem cells” (CSCs. In this review, we analyze the potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies for metastatic colon cancer. These include induction of terminal epithelial differentiation of CSCs or targeting some genes expressed only in CSCs and involved in self-renewal and chemoresistance. Ideal targets could be cell regulators that simultaneously control the stemness and the resistance of CSCs. Another important aspect of cancer biology, which can also be harnessed to create novel broad-spectrum anticancer agents, is the Warburg effect, also known as aerobic glycolysis. Actually, little is yet known with regard to the metabolism of CSCs population, leaving an exciting unstudied avenue in the dawn of the emerging field of metabolomics.

  7. Opportunistic Fixed Gain Bidirectional Relaying with Outdated CSI

    KAUST Repository

    Khan, Fahd Ahmed; Tourki, Kamel; Alouini, Mohamed-Slim; Qaraqe, Khalid A.

    2015-01-01

    In a network with multiple relays, relay selection has been shown as an effective scheme to achieve diversity as well as to improve the overall throughput. This paper studies the impact of using outdated channel state information for relay selection on the performance of a network where two sources communicate with each other via fixed-gain amplify-and-forward relays. For a Rayleigh faded channel, closed-form expressions for the outage probability, moment generating function and symbol error rate are derived. Simulations results are also presented to corroborate the derived analytical results. It is shown that adding relays does not improve the performance if the channel is substantially outdated. Furthermore, relay location is also taken into consideration and it is shown that the performance can be improved by placing the relay closer to the source whose channel is more outdated. © 2015 IEEE.

  8. Opportunistic Fixed Gain Bidirectional Relaying with Outdated CSI

    KAUST Repository

    Khan, Fahd Ahmed

    2015-05-01

    In a network with multiple relays, relay selection has been shown as an effective scheme to achieve diversity as well as to improve the overall throughput. This paper studies the impact of using outdated channel state information for relay selection on the performance of a network where two sources communicate with each other via fixed-gain amplify-and-forward relays. For a Rayleigh faded channel, closed-form expressions for the outage probability, moment generating function and symbol error rate are derived. Simulations results are also presented to corroborate the derived analytical results. It is shown that adding relays does not improve the performance if the channel is substantially outdated. Furthermore, relay location is also taken into consideration and it is shown that the performance can be improved by placing the relay closer to the source whose channel is more outdated. © 2015 IEEE.

  9. Channel allocation and rate adaptation for relayed transmission over correlated fading channels

    KAUST Repository

    Hwang, Kyusung

    2009-09-01

    We consider, in this paper, channel allocation and rate adaptation scheme for relayed transmission over correlated fading channels via cross-layer design. Specifically, jointly considering the data link layer buffer occupancy and channel quality at both the source and relay nodes, we develop an optimal channel allocation and rate adaptation policy for a dual-hop relayed transmission. As such the overall transmit power for the relayed system is minimized while a target packet dropping rate (PDR) due to buffer over flows is guaranteed. In order to find such an optimal policy, the channel allocation and rate adaptation transmission framework is formulated as a constraint Markov decision process (CMDP). The PDR performance of the optimal policy is compared with that of two conventional suboptimal schemes, namely the channel quality based and the buffer occupancy based channel allocation schemes. Numerical results show that for a given power budget, the optimal scheme requires significantly less power than the conventional schemes in order to maintain a target PDR. ©2009 IEEE.

  10. Detecting drug-target binding in cells using fluorescence-activated cell sorting coupled with mass spectrometry analysis

    Science.gov (United States)

    Wilson, Kris; Webster, Scott P.; Iredale, John P.; Zheng, Xiaozhong; Homer, Natalie Z.; Pham, Nhan T.; Auer, Manfred; Mole, Damian J.

    2018-01-01

    The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity-the toxicity-affinity-permeability-selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.

  11. Nanovectors for Targeting and Delivery of Therapeutics to HER-2 NEU Positive Breast Cancer Cells

    National Research Council Canada - National Science Library

    Serda, Rita E

    2008-01-01

    Nanofabricated devices designed to carry drug and contrast agents to breast cancer cells are surface modified with targeting moieties that recognize unique or abundantly expressed molecules on the surface of tumor cells...

  12. T Cells that Recognize HPV Protein Can Target Virus-Infected Cells | Center for Cancer Research

    Science.gov (United States)

    Adoptive T-cell transfer (ACT) is a promising form of cancer immunotherapy. Treating patients with T cells isolated from a tumor and subsequently expanded in the lab can cause the complete regression of some melanomas and cervical cancers, but the treatment is currently restricted to a few cancer types. An approach that may be applied to a wider array of cancers involves modifying peripheral blood T cells with chimeric antigen receptors or T-cell receptors (TCR) that target specific tumor antigens. Unfortunately, epithelial cancers, which are the vast majority of cancers diagnosed, have proven difficult to treat this way because most identified antigens are shared with healthy tissues and targeting them leads to toxic side effects. However, cancers caused by persistent human papillomavirus (HPV) infection, including cervical, head and neck, anal, vaginal, vulvar, and penile cancers, may be particularly amenable to the latter form of ACT since the E6 and E7 viral proteins are essential for cancer formation but are not produced in normal tissues. To test this idea, Christian Hinrichs, M.D., and his colleagues examined tumor infiltrating lymphocytes (TILs) from a patient who experienced a prolonged disease-free period after her second surgical removal of metastatic anal cancer in the hopes of identifying a TCR against one of the HPV oncoproteins.

  13. Rational design of nanoparticles towards targeting antigen-presenting cells and improved T cell priming.

    Science.gov (United States)

    Zupančič, Eva; Curato, Caterina; Paisana, Maria; Rodrigues, Catarina; Porat, Ziv; Viana, Ana S; Afonso, Carlos A M; Pinto, João; Gaspar, Rogério; Moreira, João N; Satchi-Fainaro, Ronit; Jung, Steffen; Florindo, Helena F

    2017-07-28

    Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules. Ovalbumin (OVA) was used as a model antigen in combination with the engraftment of CD4 + and CD8 + T cells, carrying a transgenic OVA-responding T cell receptor (TCR), to trace and characterize the activation of antigen-specific CD4 + and CD8 + lymph node T cells upon NP vaccination. Accordingly, the phenotype and frequency of immune cell stimulation induced by the NP loaded with OVA, isolated or in combination with synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) motifs, were characterized. DC-NP interactions increased with incubation time, presenting internalization values between 50 and 60% and 30-40%, in vitro and in vivo, respectively. Interestingly, animal immunization with antigen-adsorbed NP up-regulated major histocompatibility complex (MHC) class II (MHCII), while NP entrapping the antigen up-regulated MHCI, suggesting a more efficient cross-presentation. On the other hand, rather surprisingly, the surfactant used in the NP formulation had a major impact on the activation of antigen presenting cells (APC). In fact, DC collected from lymph nodes of animals immunized with NP prepared using poly(vinil alcohol) (PVA), as a surfactant, expressed significantly higher levels of CD86, MHCI and MHCII. In addition, those NP prepared with PVA and co-entrapping OVA and the toll

  14. Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

    Science.gov (United States)

    Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

    2017-06-01

    Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.

  15. Relay entanglement and clusters of correlated spins

    Science.gov (United States)

    Doronin, S. I.; Zenchuk, A. I.

    2018-06-01

    Considering a spin-1/2 chain, we suppose that the entanglement passes from a given pair of particles to another one, thus establishing the relay transfer of entanglement along the chain. Therefore, we introduce the relay entanglement as a sum of all pairwise entanglements in a spin chain. For more detailed studying the effects of remote pairwise entanglements, we use the partial sums collecting entanglements between the spins separated by up to a certain number of nodes. The problem of entangled cluster formation is considered, and the geometric mean entanglement is introduced as a characteristic of quantum correlations in a cluster. Generally, the lifetime of a cluster decreases with an increase in its size.

  16. Anginex-conjugated liposomes for targeting of angiogenic endothelial cells

    NARCIS (Netherlands)

    Brandwijk, Ricardo J. M. G. E.; Mulder, Willem J. M.; Nicolay, Klaas; Mayo, Kevin H.; Thijssen, Victor L. J. L.; Griffioen, Arjan W.

    2007-01-01

    Identification of a tumor angiogenesis specific ligand would allow targeting of tumor vasculature. Lipidic vehicles can be used to deliver therapeutic agents for treatment of disease or contrast agents for molecular imaging. A targeting ligand would allow specific delivery of such formulations to

  17. Towards The Generation of Functionalized Magnetic Nanowires to Target Leukemic Cells

    KAUST Repository

    Alsharif, Nouf

    2016-01-01

    . In addition the NWs can be coated and functionalized to target cells of interest and, upon exposure to an alternating magnetic field, have been shown to induce cell death on several types of adherent cells, including several cancer cell types. For suspension

  18. Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in situ targeting of dendritic cells

    Science.gov (United States)

    Morelli, Adrian E.; Thomson, Angus W.

    2014-01-01

    Purpose of review Extensive research in murine transplant models over the past two decades has convincingly demonstrated the ability of regulatory dendritic cells (DCreg) to promote long-term allograft survival. We review important considerations regarding the source of therapeutic DCreg (donor or recipient) and their mode of action, in situ targeting of DCreg, and optimal therapeutic regimens to promote DCreg function. Recent findings Recent studies have defined protocols and mechanisms whereby ex vivo-generated DCreg of donor or recipient origin subvert allogeneic T cell responses and promote long-term organ transplant survival. Particular interest has focused on how donor antigen (Ag) is acquired, processed and presented by autologous DCs, on the stability of DCreg, and on in situ targeting of DC to promote their tolerogenic function. New evidence of the therapeutic efficacy of DCreg in a clinically-relevant non-human primate organ transplant model and production of clinical grade DCreg support early evaluation of DCreg therapy in human graft recipients. Summary We discuss strategies currently used to promote DC tolerogenicity, including DCreg therapy and in situ targeting of DC, with a view to improved understanding of underlying mechanisms and identification of the most promising strategies for therapeutic application. PMID:24926700

  19. Relaying Strategies and Protocols for Efficient Wireless Networks

    KAUST Repository

    Zafar, Ammar

    2014-10-01

    Next generation wireless networks are expected to provide high data rate and satisfy the Quality-of-Service (QoS) constraints of the users. A significant component of achieving these goals is to increase the effi ciency of wireless networks by either optimizing current architectures or exploring new technologies which achieve that. The latter includes revisiting technologies which were previously proposed, but due to a multitude of reasons were ignored at that time. One such technology is relaying which was initially proposed in the latter half of the 1960s and then was revived in the early 2000s. In this dissertation, we study relaying in conjunction with resource allocation to increase the effi ciency of wireless networks. In this regard, we differentiate between conventional relaying and relaying with buffers. Conventional relaying is traditional relaying where the relay forwards the signal it received immediately. On the other hand, in relaying with buffers or buffer-aided relaying as it is called, the relay can store received data in its buffer and forward it later on. This gives the benefit of taking advantage of good channel conditions as the relay can only transmit when the channel conditions are good. The dissertation starts with conventional relaying and considers the problem of minimizing the total consumed power while maintaining system QoS. After upper bounding the system performance, more practical algorithms which require reduced feedback overhead are explored. Buffer-aided relaying is then considered and the joint user-and-hop scheduler is introduced which exploits multi-user diversity (MUD) and 5 multi-hop diversity (MHD) gains together in dual-hop broadcast channels. Next joint user-and-hop scheduling is extended to the shared relay channel where two source-destination pairs share a single relay. The benefits of buffer-aided relaying in the bidirectional relay channel utilizing network coding are then explored. Finally, a new transmission protocol

  20. Adjustable electronic load-alarm relay

    International Nuclear Information System (INIS)

    Mason, C.H.; Sitton, R.S.

    1976-01-01

    An improved electronic alarm relay for monitoring the current drawn by an ac motor or other electrical load is described. The circuit is designed to measure the load with high accuracy and to have excellent alarm repeatability. Chattering and arcing of the relay contacts are minimal. The operator can adjust the set point easily and can re-set both the high and the low alarm points by means of one simple adjustment. The relay includes means for generating a signal voltage proportional to the motor current. In a preferred form of the invention a first operational amplifier is provided to generate a first constant reference voltage which is higher than a preselected value of the signal voltage. A second operational amplifier is provided to generate a second constant reference voltage which is lower than the aforementioned preselected value of the signal voltage. A circuit comprising a first resistor serially connected to a second resistor is connected across the outputs of the first and second amplifiers, and the junction of the two resistors is connected to the inverting terminal of the second amplifier. Means are provided to compare the aforementioned signal voltage with both the first and second reference voltages and to actuate an alarm if the signal voltage is higher than the first reference voltage or lower than the second reference voltage

  1. Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line

    International Nuclear Information System (INIS)

    Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O.; Coughlin, Jason J.; Garofoli, Daniella; Ewen, Catherine; Davidson, Courtney E.; Ghaffari, Mazyar; Kane, Kevin P.; Lacy, Paige; Logan, Michael R.; Befus, A. Dean; Bleackley, R. Chris; Moqbel, Redwan

    2008-01-01

    Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Our data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 μg/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo

  2. mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?

    NARCIS (Netherlands)

    Boone, J.; ten Kate, F. J. W.; Offerhaus, G. J. A.; van Diest, P. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

    2008-01-01

    AIMS: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been

  3. Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

    International Nuclear Information System (INIS)

    Yang, Yingbin; Cai, Shaoxi; Yang, Li; Yu, Shuhui; Jiang, Jiahuan; Yan, Xiaoqing; Zhang, Haoxing; Liu, Lan; Liu, Qun; Du, Jun; Cai, Shaohui; Sung, K.L. Paul

    2010-01-01

    Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

  4. Targeting eradication of malignant cells derived from human bone marrow mesenchymal stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yingbin [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); School of Life Science, Southwest University, Chongqing 400715 (China); Cai, Shaoxi, E-mail: sxcai@cqu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Yang, Li [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); College of Pharmacy, Jinan University, Guangzhou 510632 (China); Yu, Shuhui [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Library of Southwest University, Chongqing 400715 (China); Jiang, Jiahuan; Yan, Xiaoqing [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Zhang, Haoxing [School of Life Science, Southwest University, Chongqing 400715 (China); Liu, Lan [Department of Laboratory of Medicine, Children' s Hospital of Chongqin Medical University, Chongqing 400014 (China); Liu, Qun [College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041 (China); Du, Jun [Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat-Sen University, Guangzhou 510080 (China); Cai, Shaohui [College of Pharmacy, Jinan University, Guangzhou 510632 (China); Sung, K.L. Paul [Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044 (China); Departments of Orthopaedic Surgery and Bioengineering, University of California, SD 0412 (United States)

    2010-12-10

    Human bone marrow mesenchymal stromal cells (hBMSC) have been shown to participate in malignant transformation. However, hampered by the low frequency of malignant transformation of hBMSC, we do not yet know how to prevent malignant transformation of implanted hBMSC. In this study, in order to establish a model for the eradication of hBMSC-derived malignant cells, a gene fusion consisting of a human telomerase (hTERT) promoter modified with both c-Myc and myeloid zinc finger protein2 (MZF-2) binding elements and followed by the E. coli cytosine deaminase (CD) and luciferase genes was stably transferred into hBMSC via lentiviral transduction; n-phosphonacelyl-L-aspartic acid (PALA) selection was used to generate malignant cell colonies derived from transduced hBMSC after treatment with the carcinogenic reagent BPDE. Cells that were amplified after PALA selection were used for transplantation and 5-FC pro-drug cytotoxicity tests. The results showed that PALA-resistant malignant cells could be generated from hBMSC co-induced with lentiviral transduction and treatment with Benzo(a)pyrene Diol Epoxide (BPDE); the modification of c-Myc and MZF-2 binding elements could remarkably enhance the transcriptional activities of the hTERT promoter in malignant cells, whereas transcriptional activity was depressed in normal hBMSC; malignant cells stably expressing CD under the control of the modified hTERT promoter could be eliminated by 5-FC administration. This study has provided a method for targeted eradication of malignant cells derived from hBMSC.

  5. Targeting the BCR signalosome in B cell malignancies

    NARCIS (Netherlands)

    de Rooij, M.F.M.

    2017-01-01

    Chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM) are B-cell malignancies which are still incurable. In these lymphomas, the cells proliferate in specialized niches in lymph nodes and bone marrow, in which they are provided by stromal-derived

  6. A drug target that stimulates development of healthy stem cells

    Science.gov (United States)

    Scientists have overcome a major impediment to the development of effective stem cell therapies by studying mice that lack CD47, a protein found on the surface of both healthy and cancer cells. They discovered that cells obtained from the lungs of CD47-de

  7. Apoptosis and cancer stem cells : Implications for apoptosis targeted therapy

    NARCIS (Netherlands)

    Kruyt, Frank A. E.; Schuringa, Jan Jacob

    2010-01-01

    Evidence is accumulating showing that cancer stem cells or tumor-initiating cells are key drivers of tumor formation and progression. Successful therapy must therefore eliminate these cells, which is hampered by their high resistance to commonly used treatment modalities. Thus far, only a limited

  8. Development of micro solar charger with blocking relay; Gyakuryu boshi relay wo oyoshita kogata solar judenki no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Nanno, I.; Matsushita, Y. Oka, S. [Omron Corp., Kyoto (Japan)

    1997-11-25

    Heavy-current tiny-scale solar charger is tentatively built, equipped with a function of preventing overcharge and countercurrent in case of charging storage batteries using solar cells. Incorporated into this solar charger are a countercurrent prevention relay system, a low loss current detection system, and a MOSFET parallel connection, which allow the solar charger to be designed small in size in the presence of an increase in heat due to circuit loss. In the countercurrent prevention relay system, the countercurrent prevention diode is bypassed by MOSFETs when too large a current is generated. In the low loss current detection system, currents are detected by use of the ON resistance of the MOSFETs for the prevention of overcharge. In the MOSFET parallel connection, MOSFETs are connected in parallel for a decrease in the ON resistance. The tentatively built charger is then subjected to a performance evaluation test outside the building, and the test is carried out by measuring the temperatures of the MOSFETs and the air. As the result, it is found that the temperature of MOSFET junction of the 12A tiny-size solar charger is approximately 42.5 degC at the highest, low enough to clear the requirements. 4 refs., 7 figs., 4 tabs.

  9. An assessment of fire vulnerability for aged electrical relays

    International Nuclear Information System (INIS)

    Vigil, R.A.; Nowlen, S.P.

    1995-03-01

    There has been some concern that, as nuclear power plants age, protective measures taken to control and minimize the impact of fire may become ineffective, or significantly less effective, and hence result in an increased fire risk. One objective of the Fire Vulnerability of Aged Electrical Components Program is to assess the effects of aging and service wear on the fire vulnerability of electrical equipment. An increased fire vulnerability of components may lead to an overall increase in fire risk to the plant. Because of their widespread use in various electrical safety systems, electromechanical relays were chosen to be the initial components for evaluation. This test program assessed the impact of operational and thermal aging on the vulnerability of these relays to fire-induced damage. Only thermal effects of a fire were examined in this test program. The impact of smoke, corrosive materials, or fire suppression effects on relay performance were not addressed in this test program. The purpose of this test program was to assess whether the fire vulnerability of electrical relays increased with aging. The sequence followed for the test program was to: identify specific relay types, develop three fire scenarios, artificially age several relays, test the unaged and aged relays in the fire exposure scenarios, and compare the results. The relays tested were Agastat GPI, General Electric (GE) HMA, HGA, and HFA. At least two relays of each type were artificially aged and at least two relays of each type were new. Relays were operationally aged by cycling the relay under rated load for 2,000 operations. These relays were then thermally aged for 60 days with their coil energized

  10. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2016-03-01

    Full Text Available The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

  11. Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Christensen, Rikke; Sørensen, Flemming Brandt

    2011-01-01

    The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because...... better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein...

  12. An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

    Science.gov (United States)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-09-21

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

  13. Gastric cancer stem cells: A novel therapeutic target

    Science.gov (United States)

    Singh, Shree Ram

    2013-01-01

    Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

  14. CD19-Targeted CAR T Cells as Novel Cancer Immunotherapy for Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Davila, Marco L.; Brentjens, Renier J.

    2016-01-01

    Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the ju...

  15. Increasing the coverage area through relay node deployment in long term evolution advanced cellular networks

    Science.gov (United States)

    Aldhaibani, Jaafar A.; Ahmad, R. B.; Yahya, A.; Azeez, Suzan A.

    2015-05-01

    Wireless multi-hop relay networks have become very important technologies in mobile communications. These networks ensure high throughput and coverage extension with a low cost. The poor capacity at cell edges is not enough to meet with growing demand of high capacity and throughput irrespective of user's placement in the cellular network. In this paper we propose optimal placement of relay node that provides maximum achievable rate at users and enhances the throughput and coverage at cell edge region. The proposed scheme is based on the outage probability at users and taken on account the interference between nodes. Numerical analyses along with simulation results indicated there are an improvement in capacity for users at the cell edge is 40% increment from all cell capacity.

  16. Regulatory T Cells: Potential Target in Anticancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Chi-Mou Juang

    2007-09-01

    Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

  17. Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

    Directory of Open Access Journals (Sweden)

    Mathieu Dalvai

    Full Text Available Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly. We show that in ERalpha-positive breast cancer cells (MCF-7 the estrogen receptor gene and downstream target genes are cell cycle regulated with expression levels varying as much as three-fold between phases of the cell cycle. Steroid free culture conditions commonly used to assess the effect of hormones or antiestrogens on gene expression also block MCF-7 cells in G1-phase when several ERalpha target genes are overexpressed. Thus, cell cycle effects have to be taken into account when analyzing the impact of hormonal treatments on gene transcription. We found that antiestrogens repress transcription of several ERalpha target genes specifically in S phase. This observation corroborates the more rapid and strong impact of antiestrogen treatments on cell proliferation in thymidine, hydroxyurea or aphidicolin arrested cells and correlates with an increase of apoptosis compared to similar treatments in lovastatin or nocodazol treated cells. Hence, cell cycle effects synergize with the action of antiestrogens. An interesting therapeutic perspective could be to enhance the action of anti-estrogens by associating hormone-therapy with specific cell cycle drugs.

  18. Improper Gaussian signaling in full-duplex relay channels with residual self-interference

    KAUST Repository

    Gaafar, Mohamed; Khafagy, Mohammad Galal; Amin, Osama; Alouini, Mohamed-Slim

    2016-01-01

    We study the potential employment of improper Gaussian signaling (IGS) in full-duplex cooperative settings with residual self-interference (RSI). IGS is recently shown to outperform traditional proper Gaussian signaling (PGS) in several interference-limited channel settings. In this work, IGS is employed in an attempt to alleviate the RSI adverse effect in full-duplex relaying (FDR). To this end, we derive a tight upper bound expression for the end-to-end outage probability in terms of the relay signal parameters represented in its power and circularity coefficient. We further show that the derived upper bound is either monotonic or unimodal in the relay's circularity coefficient. This result allows for easily locating the global optimal point using known numerical methods. Based on the analysis, IGS allows FDR systems to operate even with high RSI. It is shown that, while the communication totally fails with PGS as the RSI increases, the IGS outage probability approaches a fixed value that depends on the channel statistics and target rate. The obtained results show that IGS can leverage higher relay power budgets than PGS to improve the performance, meanwhile it relieves its RSI impact via tuning the signal impropriety. © 2016 IEEE.

  19. Bandwidth and power allocation for two-way relaying in overlay cognitive radio systems

    KAUST Repository

    Alsharoa, Ahmad M.

    2014-12-01

    In this paper, the problem of both bandwidth and power allocation for two-way multiple relay systems in overlay cognitive radio (CR) setup is investigated. In the CR overlay mode, primary users (PUs) cooperate with cognitive users (CUs) for mutual benefits. In our framework, we propose that the CUs are allowed to allocate a part of the PUs spectrum to perform their cognitive transmission. In return, acting as an amplify-and-forward two-way relays, they are used to support PUs to achieve their target data rates over the remaining bandwidth. More specifically, CUs acts as relays for the PUs and gain some spectrum as long as they respect a specific power budget and primary quality-of-service constraints. In this context, we first derive closed-form expressions for optimal transmit power allocated to PUs and CUs in order to maximize the cognitive objective. Then, we employ a strong optimization tool based on particle swarm optimization algorithm to find the optimal relay amplification gains and optimal cognitive released bandwidths as well. Our numerical results illustrate the performance of our proposed algorithm for different utility metrics and analyze the impact of some system parameters on the achieved performance.

  20. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Villadsen, Klaus; Østrem, Ragnhild Garborg

    2017-01-01

    constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells...... and macrophages. There was unaltered secretion of cytokines following exposure of peptide-conjugated liposomes to endothelial cells, indicating that the materials were not inflammogenic. Liposomes with a peptide targeting the fibronectin receptor (integrin α5β1) were more effective in targeting of activated....... Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells....

  1. Targeting development of incretin-producing cells increases insulin secretion

    DEFF Research Database (Denmark)

    Petersen, Natalia; Reimann, Frank; van Es, Johan H

    2015-01-01

    the number of intestinal L cells, which produce GLP-1, is an alternative strategy to augment insulin responses and improve glucose tolerance. Blocking the NOTCH signaling pathway with the γ-secretase inhibitor dibenzazepine increased the number of L cells in intestinal organoid-based mouse and human culture...... of the development of incretin-producing cells in the intestine has potential as a therapeutic strategy to improve glycemic control....

  2. Cell cycle controls: potential targets for chemical carcinogens?

    OpenAIRE

    Afshari, C A; Barrett, J C

    1993-01-01

    The progression of the cell cycle is controlled by the action of both positive and negative growth regulators. The key players in this activity include a family of cyclins and cyclin-dependent kinases, which are themselves regulated by other kinases and phosphatases. Maintenance of balanced cell cycle controls may be directly linked to genomic stability. Loss of the check-points involved in cell cycle control may result in unrepaired DNA damage during DNA synthesis or mitosis leading to genet...

  3. Medulloblastoma stem cells: Promising targets in medulloblastoma therapy

    OpenAIRE

    Huang, Guo?Hao; Xu, Qing?Fu; Cui, You?Hong; Li, Ningning; Bian, Xiu?Wu; Lv, Sheng?Qing

    2016-01-01

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long?term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. Th...

  4. User Multiplexing in Relay Enhanced LTE-Advanced Networks

    DEFF Research Database (Denmark)

    Teyeb, Oumer Mohammed; Frederiksen, Frank; Redana, Simone

    2010-01-01

    is radio relaying. This uses relay nodes that act as surrogate base stations for mobile users whose radio links with the base stations are not experiencing good enough conditions. In the downlink, the data that is destined for the relayed users may first have to be multiplexed by the base station, sent...... over the wireless backhaul link towards the relay node, and de-multiplexed and forwarded to the individual users by the relay node. The reverse process also has to be undertaken in the uplink. In this paper, we present a novel multiplexing scheme which is able to adapt the addressing and bitmapping...... of user identification to the actual number of users being served by the relay nodes, and thus greatly reduce the multiplexing overhead....

  5. Generalized instantly decodable network coding for relay-assisted networks

    KAUST Repository

    Elmahdy, Adel M.

    2013-09-01

    In this paper, we investigate the problem of minimizing the frame completion delay for Instantly Decodable Network Coding (IDNC) in relay-assisted wireless multicast networks. We first propose a packet recovery algorithm in the single relay topology which employs generalized IDNC instead of strict IDNC previously proposed in the literature for the same relay-assisted topology. This use of generalized IDNC is supported by showing that it is a super-set of the strict IDNC scheme, and thus can generate coding combinations that are at least as efficient as strict IDNC in reducing the average completion delay. We then extend our study to the multiple relay topology and propose a joint generalized IDNC and relay selection algorithm. This proposed algorithm benefits from the reception diversity of the multiple relays to further reduce the average completion delay in the network. Simulation results show that our proposed solutions achieve much better performance compared to previous solutions in the literature. © 2013 IEEE.

  6. A performance analysis in AF full duplex relay selection network

    Science.gov (United States)

    Ngoc, Long Nguyen; Hong, Nhu Nguyen; Loan, Nguyen Thi Phuong; Kieu, Tam Nguyen; Voznak, Miroslav; Zdralek, Jaroslav

    2018-04-01

    This paper studies on the relaying selective matter in amplify-and-forward (AF) cooperation communication with full-duplex (FD) activity. Various relay choice models supposing the present of different instant information are investigated. We examine a maximal relaying choice that optimizes the instant FD channel capacity and asks for global channel state information (CSI) as well as partial CSI learning. To make comparison easy, accurate outage probability clauses and asymptote form of these strategies that give a diversity rank are extracted. From that, we can see clearly that the number of relays, noise factor, the transmittance coefficient as well as the information transfer power had impacted on their performance. Besides, the optimal relay selection (ORS) model can promote than that of the partial relay selection (PRS) model.

  7. Identification of human embryonic progenitor cell targeting peptides using phage display.

    Directory of Open Access Journals (Sweden)

    Paola A Bignone

    Full Text Available Human pluripotent stem (hPS cells are capable of differentiation into derivatives of all three primary embryonic germ layers and can self-renew indefinitely. They therefore offer a potentially scalable source of replacement cells to treat a variety of degenerative diseases. The ability to reprogram adult cells to induced pluripotent stem (iPS cells has now enabled the possibility of patient-specific hPS cells as a source of cells for disease modeling, drug discovery, and potentially, cell replacement therapies. While reprogramming technology has dramatically increased the availability of normal and diseased hPS cell lines for basic research, a major bottleneck is the critical unmet need for more efficient methods of deriving well-defined cell populations from hPS cells. Phage display is a powerful method for selecting affinity ligands that could be used for identifying and potentially purifying a variety of cell types derived from hPS cells. However, identification of specific progenitor cell-binding peptides using phage display may be hindered by the large cellular heterogeneity present in differentiating hPS cell populations. We therefore tested the hypothesis that peptides selected for their ability to bind a clonal cell line derived from hPS cells would bind early progenitor cell types emerging from differentiating hPS cells. The human embryonic stem (hES cell-derived embryonic progenitor cell line, W10, was used and cell-targeting peptides were identified. Competition studies demonstrated specificity of peptide binding to the target cell surface. Efficient peptide targeted cell labeling was accomplished using multivalent peptide-quantum dot complexes as detected by fluorescence microscopy and flow cytometry. The cell-binding peptides were selective for differentiated hPS cells, had little or no binding on pluripotent cells, but preferential binding to certain embryonic progenitor cell lines and early endodermal hPS cell derivatives. Taken

  8. Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0380 TITLE: Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias 5b. GRANT NUMBER...leukemias still have poor prognosis, particularly in the elderly, and require hematopoietic cell transplants to fully kill the tumor, which is both

  9. Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xiao, Xiubin [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China); Liu, Lianqing, E-mail: lqliu@sia.cn [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Xi, Ning, E-mail: xin@egr.msu.edu [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong (China); Wang, Yuechao; Dong, Zaili [State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, Weijing, E-mail: zhangwj3072@163.com [Department of Lymphoma, Affiliated Hospital of Military Medical Academy of Sciences, Beijing 100071 (China)

    2013-11-01

    CD20, a membrane protein highly expressed on most B-cell lymphomas, is an effective target demonstrated in clinical practice for treating B-cell non-Hodgkin's lymphoma (NHL). Rituximab is a monoclonal antibody against CD20. In this work, we applied atomic force microscopy (AFM) to map the nanoscale distribution of CD20 molecules on the surface of cancer cells from clinical B-cell NHL patients under the assistance of ROR1 fluorescence recognition (ROR1 is a specific cell surface marker exclusively expressed on cancer cells). First, the ROR1 fluorescence labeling experiments showed that ROR1 was expressed on cancer cells from B-cell lymphoma patients, but not on normal cells from healthy volunteers. Next, under the guidance of ROR1 fluorescence, the rituximab-conjugated AFM tips were moved to cancer cells to image the cellular morphologies and detect the CD20-rituximab interactions on the cell surfaces. The distribution maps of CD20 on cancer cells were constructed by obtaining arrays of (16×16) force curves in local areas (500×500 nm{sup 2}) on the cell surfaces. The experimental results provide a new approach to directly investigate the nanoscale distribution of target protein on single clinical cancer cells. - Highlights: • Cancer cells were recognized from healthy cells by ROR1 fluorescence labeling. • The nanoscale distribution of CD20 on cancer cells was characterized. • The distribution of CD20 was non-uniform on the surface of cancer cells.

  10. Targeting Wnt Signaling in Colon Cancer Stem Cells

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Vermeulen, Louis; Richel, Dick; Medema, Jan Paul

    2011-01-01

    The identification of cancer stem cell (CSC) populations in virtually all tumor types has widespread clinical consequences. CSCs are suggested to be the only cells within malignancies endowed with tumorigenic capacity and are, therefore, directly implicated in therapy resistance and minimal residual

  11. Survivin is a therapeutic target in Merkel cell carcinoma

    NARCIS (Netherlands)

    Arora, Reety; Shuda, Masahiro; Guastafierro, Anna; Feng, Huichen; Toptan, Tuna; Tolstov, Yanis; Normolle, Daniel; Vollmer, Laura L; Vogt, Andreas; Dömling, Alexander; Brodsky, Jeffrey L; Chang, Yuan; Moore, Patrick S

    2012-01-01

    Merkel cell polyomavirus (MCV) causes ~80% of primary and metastatic Merkel cell carcinomas (MCCs). By comparing digital transcriptome subtraction deep-sequencing profiles, we found that transcripts of the cellular survivin oncoprotein [BIRC5a (baculoviral inhibitor of apoptosis repeat-containing

  12. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere hour nickel cadmium spacecraft cells for the tracking data relay satellite system

    Science.gov (United States)

    Hall, S. W.

    1980-01-01

    Average end of charge voltages and pressures, and capacity output in ampere hours are presented. Test limits specify those values at which a cell is to be terminated from charge or discharge. Requirements are based on past cell performance data. The requirement does not constitute a limit for discontinuance from testing. The nickel cadmium batteries were screened for internal shorts, low capacity, electrolyte leakage, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test.

  13. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Directory of Open Access Journals (Sweden)

    John Koren

    Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  14. The kinematics of cytotoxic lymphocytes influence their ability to kill target cells.

    Directory of Open Access Journals (Sweden)

    Purnima Bhat

    Full Text Available Cytotoxic lymphocytes (CTL have been reported to show a range of motility patterns from rapid long-range tracking to complete arrest, but how and whether these kinematics affect their ability to kill target cells is not known. Many in vitro killing assays utilize cell lines and tumour-derived cells as targets, which may be of limited relevance to the kinetics of CTL-mediated killing of somatic cells. Here, live-cell microscopy is used to examine the interactions of CTL and primary murine skin cells presenting antigens. We developed a qualitative and quantitative killing assay using extended-duration fluorescence time-lapse microscopy coupled with large-volume objective software-based data analysis to obtain population data of cell-to-cell interactions, motility and apoptosis. In vivo and ex vivo activated antigen-specific cytotoxic lymphocytes were added to primary keratinocyte targets in culture with fluorometric detection of caspase-3 activation in targets as an objective determinant of apoptosis. We found that activated CTL achieved contact-dependent apoptosis of non-tumour targets after a period of prolonged attachment - on average 21 hours - which was determined by target cell type, amount of antigen, and activation status of CTL. Activation of CTL even without engagement of the T cell receptor was sufficient to mobilise cells significantly above baseline, while the addition of cognate antigen further enhanced their motility. Highly activated CTL showed markedly increased vector displacement, and velocity, and lead to increased antigen-specific target cell death. These data show that the inherent kinematics of CTL correlate directly with their ability to kill non-tumour cells presenting cognate antigen.

  15. New approaches to targeted drug delivery to tumour cells

    International Nuclear Information System (INIS)

    Severin, E S

    2015-01-01

    Basic approaches to the design of targeted drugs for the treatment of human malignant tumours have been considered. The stages of the development of these approaches have been described in detail and theoretically substantiated, and basic experimental results have been reported. Considerable attention is paid to the general characteristic of nanopharmacological drugs and to the description of mechanisms of cellular interactions with nanodrugs. The potentialities and limitations of application of nanodrugs for cancer therapy and treatment of other diseases have been considered. The use of nanodrugs conjugated with vector molecules seems to be the most promising trend of targeted therapy of malignant tumours. The bibliography includes 122 references

  16. Oct4 targets regulatory nodes to modulate stem cell function.

    Directory of Open Access Journals (Sweden)

    Pearl A Campbell

    2007-06-01

    Full Text Available Stem cells are characterized by two defining features, the ability to self-renew and to differentiate into highly specialized cell types. The POU homeodomain transcription factor Oct4 (Pou5f1 is an essential mediator of the embryonic stem cell state and has been implicated in lineage specific differentiation, adult stem cell identity, and cancer. Recent description of the regulatory networks which maintain 'ES' have highlighted a dual role for Oct4 in the transcriptional activation of genes required to maintain self-renewal and pluripotency while concomitantly repressing genes which facilitate lineage specific differentiation. However, the molecular mechanism by which Oct4 mediates differential activation or repression at these loci to either maintain stem cell identity or facilitate the emergence of alternate transcriptional programs required for the realization of lineage remains to be elucidated. To further investigate Oct4 function, we employed gene expression profiling together with a robust statistical analysis to identify genes highly correlated to Oct4. Gene Ontology analysis to categorize overrepresented genes has led to the identification of themes which may prove essential to stem cell identity, including chromatin structure, nuclear architecture, cell cycle control, DNA repair, and apoptosis. Our experiments have identified previously unappreciated roles for Oct4 for firstly, regulating chromatin structure in a state consistent with self-renewal and pluripotency, and secondly, facilitating the expression of genes that keeps the cell poised to respond to cues that lead to differentiation. Together, these data define the mechanism by which Oct4 orchestrates cellular regulatory pathways to enforce the stem cell state and provides important insight into stem cell function and cancer.

  17. A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.

    Science.gov (United States)

    Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong

    2018-06-11

    We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

  18. Cell Density Affects the Detection of Chk1 Target Engagement by the Selective Inhibitor V158411.

    Science.gov (United States)

    Geneste, Clara C; Massey, Andrew J

    2018-02-01

    Understanding drug target engagement and the relationship to downstream pharmacology is critical for drug discovery. Here we have evaluated target engagement of Chk1 by the small-molecule inhibitor V158411 using two different target engagement methods (autophosphorylation and cellular thermal shift assay [CETSA]). Target engagement measured by these methods was subsequently related to Chk1 inhibitor-dependent pharmacology. Inhibition of autophosphorylation was a robust method for measuring V158411 Chk1 target engagement. In comparison, while target engagement determined using CETSA appeared robust, the V158411 CETSA target engagement EC 50 values were 43- and 19-fold greater than the autophosphorylation IC 50 values. This difference was attributed to the higher cell density in the CETSA assay configuration. pChk1 (S296) IC 50 values determined using the CETSA assay conditions were 54- and 33-fold greater than those determined under standard conditions and were equivalent to the CETSA EC 50 values. Cellular conditions, especially cell density, influenced the target engagement of V158411 for Chk1. The effects of high cell density on apparent compound target engagement potency should be evaluated when using target engagement assays that necessitate high cell densities (such as the CETSA conditions used in this study). In such cases, the subsequent relation of these data to downstream pharmacological changes should therefore be interpreted with care.

  19. Full-Duplex Relay Selection in Cognitive Underlay Networks

    KAUST Repository

    Khafagy, Mohammad Galal

    2017-09-30

    In this work, we analyze the performance of full-duplex relay selection (FDRS) in spectrum-sharing networks. Contrary to half-duplex relaying, full-duplex relaying (FDR) enables simultaneous listening/forwarding at the secondary relay(s), thereby allowing for a higher spectral efficiency. However, since the source and relay simultaneously transmit in FDR, their superimposed signal at the primary receiver should now satisfy the existing interference constraint, which can considerably limit the secondary network throughput. In this regard, relay selection can offer an adequate solution to boost the secondary throughput while satisfying the imposed interference limit. We first analyze the performance of opportunistic FDRS with residual self-interference (RSI) by deriving the exact cumulative distribution function of its end-to-end signal-to-interference-plus-noise ratio under Nakagami-m fading. We also evaluate the offered diversity gain of relay selection for different full-duplex cooperation schemes in the presence/absence of a direct source-destination link. When the adopted RSI link gain model is sublinear in the relay power, which agrees with recent research findings, we show that remarkable diversity gain can be recovered even in the presence of an interfering direct link. Second, we evaluate the end-to-end performance of FDRS with interference constraints due to the presence of a primary receiver. Finally, the presented exact theoretical findings are verified by numerical simulations.

  20. Relay Telecommunications for the Coming Decade of Mars Exploration

    Science.gov (United States)

    Edwards, C.; DePaula, R.

    2010-01-01

    Over the past decade, an evolving network of relay-equipped orbiters has advanced our capabilities for Mars exploration. NASA's Mars Global Surveyor, 2001 Mars Odyssey, and Mars Reconnaissance Orbiter (MRO), as well as ESA's Mars Express Orbiter, have provided telecommunications relay services to the 2003 Mars Exploration Rovers, Spirit and Opportunity, and to the 2007 Phoenix Lander. Based on these successes, a roadmap for continued Mars relay services is in place for the coming decade. MRO and Odyssey will provide key relay support to the 2011 Mars Science Laboratory (MSL) mission, including capture of critical event telemetry during entry, descent, and landing, as well as support for command and telemetry during surface operations, utilizing new capabilities of the Electra relay payload on MRO and the Electra-Lite payload on MSL to allow significant increase in data return relative to earlier missions. Over the remainder of the decade a number of additional orbiter and lander missions are planned, representing new orbital relay service providers and new landed relay users. In this paper we will outline this Mars relay roadmap, quantifying relay performance over time, illustrating planned support scenarios, and identifying key challenges and technology infusion opportunities.

  1. Cooperative relay-based multicasting for energy and delay minimization

    KAUST Repository

    Atat, Rachad

    2012-08-01

    Relay-based multicasting for the purpose of cooperative content distribution is studied. Optimized relay selection is performed with the objective of minimizing the energy consumption or the content distribution delay within a cluster of cooperating mobiles. Two schemes are investigated. The first consists of the BS sending the data only to the relay, and the second scheme considers the scenario of threshold-based multicasting by the BS, where a relay is selected to transmit the data to the mobiles that were not able to receive the multicast data. Both schemes show significant superiority compared to the non-cooperative scenarios, in terms of energy consumption and delay reduction. © 2012 IEEE.

  2. Amplify-and-forward relaying in wireless communications

    CERN Document Server

    Rodriguez, Leonardo Jimenez; Le-Ngoc, Tho

    2015-01-01

    This SpringerBrief explores the advantage of relaying techniques in addressing the increasing demand for high data rates and reliable services over the air. It demonstrates how to design cost-effective relay systems that provide high spectral efficiency and fully exploit the diversity of the relay channel. The brief covers advances in achievable rates, power allocation schemes, and error performance for half-duplex (HD) and full-duplex (FD) amplify-and-forward (AF) single-relay systems. The authors discuss the capacity and respective optimal power allocation for a wide range of HD protocols ov

  3. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere-hour nickel-cadmium spacecraft cells for the tracking data relay satellite system

    Science.gov (United States)

    Harkness, J. D.

    1978-01-01

    Five cells provided by NASA's Goddard Space Flight Center were evaluated at room temperature and pressure (25 C plus or minus 2 C) with discharges at the 2 hour rate. Measurements of the cell containers following test, indicated an average increase of .006 inches at the plate thickness. Average end of charge voltages and pressures, and capacity output in ampere hours were determined. Three cells exceeded the voltage requirements of 1.52 volts during both c/10 charges at 20 C. All cells exceeded the voltage requirement of 1.52 volts during the 0 C overcharge test, although their end charges were below 1.50 volts. The pressure requirement of 65 psia was exceeded by both pressure transducer cells during c/10 charges at 25 C and 20 C and also during the 0 C overcharge test. The cells with pressure transducers reached a pressure of 20 psia before reaching the voltage limit of 1.550 volts during the pressure versus capacity test, and exhibited a pressure decay of 2 psia during the last 30 minutes of the 1 hour open circuit stand. Average capacity was 51.3 ampere hours.

  4. Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells

    Directory of Open Access Journals (Sweden)

    Parviz Mohammadi Ghalaei

    2014-01-01

    Full Text Available The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P<0.05. After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma.

  5. Modified Dynamic Decode-and-Forward Relaying Protocol for Type II Relay in LTE-Advanced and Beyond.

    Science.gov (United States)

    Nam, Sung Sik; Alouini, Mohamed-Slim; Choi, Seyeong

    2016-01-01

    In this paper, we propose a modified dynamic decode-and-forward (MoDDF) relaying protocol to meet the critical requirements for user equipment (UE) relays in next-generation cellular systems (e.g., LTE-Advanced and beyond). The proposed MoDDF realizes the fast jump-in relaying and the sequential decoding with an application of random codeset to encoding and re-encoding process at the source and the multiple UE relays, respectively. A subframe-by-subframe decoding based on the accumulated (or buffered) messages is employed to achieve energy, information, or mixed combining. Finally, possible early termination of decoding at the end user can lead to the higher spectral efficiency and more energy saving by reducing the frequency of redundant subframe transmission and decoding. These attractive features eliminate the need of directly exchanging control messages between multiple UE relays and the end user, which is an important prerequisite for the practical UE relay deployment.

  6. Performance analysis of two-way amplify and forward relaying with adaptive modulation over multiple relay network

    KAUST Repository

    Hwang, Kyusung

    2011-02-01

    In this letter, we propose two-way amplify-and-forward relaying in conjunction with adaptive modulation in order to improve spectral efficiency of relayed communication systems while monitoring the required error performance. We also consider a multiple relay network where only the best relay node is utilized so that the diversity order increases while maintaining a low complexity of implementation as the number of relays increases. Based on the best relay selection criterion, we offer an upper bound on the signal-to-noise ratio to keep the performance analysis tractable. Our numerical examples show that the proposed system offers a considerable gain in spectral efficiency while satisfying the error rate requirements. © 2011 IEEE.

  7. Performance analysis of two-way amplify and forward relaying with adaptive modulation over multiple relay network

    KAUST Repository

    Hwang, Kyusung; Ko, Youngchai; Alouini, Mohamed-Slim

    2011-01-01

    In this letter, we propose two-way amplify-and-forward relaying in conjunction with adaptive modulation in order to improve spectral efficiency of relayed communication systems while monitoring the required error performance. We also consider a multiple relay network where only the best relay node is utilized so that the diversity order increases while maintaining a low complexity of implementation as the number of relays increases. Based on the best relay selection criterion, we offer an upper bound on the signal-to-noise ratio to keep the performance analysis tractable. Our numerical examples show that the proposed system offers a considerable gain in spectral efficiency while satisfying the error rate requirements. © 2011 IEEE.

  8. Innovative T Cell-Targeted Therapy for Ovarian Cancer

    Science.gov (United States)

    2014-10-01

    cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 2010; 10(7): 467-78. 22. Gomes AQ, Martins DS...costimulator (ICOS) is critical for the development of human T(H)17 cells . Sci Transl Med 2010; 2(55): 55ra78. 36. Cua DJ, Tato CM. Innate IL-17...intestinal epithelial lympho- cytes (17, 18). In contrast, circulating γδ T cells can be found in the blood and lymphoid organs, and are dominated by γδ

  9. PDGF-receptor beta-targeted adenovirus redirects gene transfer from hepatocytes to activated stellate cells

    NARCIS (Netherlands)

    Schoemaker, Marieke H.; Rots, Marianne G.; Beljaars, Leonie; Ypma, Arjen Y.; Jansen, Peter L. M.; Poelstra, Klaas; Moshage, Albert; Haisma, Hidde J.

    2008-01-01

    Chronic liver damage may lead to liver fibrosis. In this process, hepatic activated stellate cells are the key players. Thus, activated stellate cells are attractive targets for antifibrotic gene therapy. Recombinant, adenovirus is a promising vehicle for delivering therapeutic genes to liver cells.

  10. Targeting of beta 1 integrins impairs DNA repair for radiosensitization of head and neck cancer cells

    NARCIS (Netherlands)

    Dickreuter, E.; Eke, I.; Krause, M.; Borgmann, K.; van Vugt, M. A.; Cordes, N.

    2016-01-01

    beta 1 Integrin-mediated cell-extracellular matrix interactions allow cancer cell survival and confer therapy resistance. It was shown that inhibition of beta 1 integrins sensitizes cells to radiotherapy. Here, we examined the impact of beta 1 integrin targeting on the repair of radiation-induced

  11. Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

    Science.gov (United States)

    Guo, Ling; Luo, Shi; Du, Zhengwu; Zhou, Meiling; Li, Peiwen; Fu, Yao; Sun, Xun; Huang, Yuan; Zhang, Zhirong

    2017-10-12

    Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.

  12. RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells.

    Science.gov (United States)

    Hesbacher, Sonja; Pfitzer, Lisa; Wiedorfer, Katharina; Angermeyer, Sabrina; Borst, Andreas; Haferkamp, Sebastian; Scholz, Claus-Jürgen; Wobser, Marion; Schrama, David; Houben, Roland

    2016-05-31

    The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.

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

    Science.gov (United States)

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

    2015-03-31

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

  14. Cell-penetrating antimicrobial peptides - prospectives for targeting intracellular infections

    DEFF Research Database (Denmark)

    Bahnsen, Jesper S; Franzyk, Henrik; Sayers, Edward J

    2015-01-01

    PURPOSE: To investigate the suitability of three antimicrobial peptides (AMPs) as cell-penetrating antimicrobial peptides. METHODS: Cellular uptake of three AMPs (PK-12-KKP, SA-3 and TPk) and a cell-penetrating peptide (penetratin), all 5(6)-carboxytetramethylrhodamine-labeled, were tested in He......La WT cells and analyzed by flow cytometry and confocal microscopy. Furthermore, the effects of the peptides on eukaryotic cell viability as well as their antimicrobial effect were tested. In addition, the disrupting ability of the peptides in the presence of bilayer membranes of different composition...... the cellular viability to an unacceptable degree. TPk showed acceptable uptake efficiency, high antimicrobial activity and relatively low toxicity, and it is the best potential lead peptide for further development....

  15. Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

    Science.gov (United States)

    Peponi, Evangelia; Drakos, Elias; Reyes, Guadalupe; Leventaki, Vasiliki; Rassidakis, George Z; Medeiros, L Jeffrey

    2006-12-01

    Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

  16. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    International Nuclear Information System (INIS)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-01-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ∼100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s −1 , recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells. (paper)

  17. Designing and modeling a centrifugal microfluidic device to separate target blood cells

    Science.gov (United States)

    Shamloo, Amir; Selahi, AmirAli; Madadelahi, Masoud

    2016-03-01

    The objective of this study is to design a novel and efficient portable lab-on-a-CD (LOCD) microfluidic device for separation of specific cells (target cells) using magnetic beads. In this study the results are shown for neutrophils as target cells. However, other kinds of target cells can be separated in a similar approach. The designed microfluidics can be utilized as a point of care system for neutrophil detection. This microfluidic system employs centrifugal and magnetic forces for separation. After model validation by the experimental data in the literature (that may be used as a design tool for developing centrifugo-magnetophoretic devices), two models are presented for separation of target cells using magnetic beads. The first model consists of one container in the inlet section and two containers in the outlets. Initially, the inlet container is filled with diluted blood sample which is a mixture of red blood cells (RBCs) plus neutrophils which are attached to Magnetic beads. It is shown that by using centrifugal and magnetic forces, this model can separate all neutrophils with recovery factor of ~100%. In the second model, due to excess of magnetic beads in usual experimental analysis (to ensure that all target cells are attached to them) the geometry is improved by adding a third outlet for these free magnetic beads. It is shown that at angular velocity of 45 rad s-1, recovery factor of 100% is achievable for RBCs, free magnetic beads and neutrophils as target cells.

  18. Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector.

    Directory of Open Access Journals (Sweden)

    Briana Jill Williams

    Full Text Available Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs with prostate specific membrane antigen (PSMA have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells. To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ. Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy.

  19. Candidate Medical Countermeasures Targeting Ebola Virus Cell Entry

    Science.gov (United States)

    2017-04-03

    Functionally, GP1,2 alone mediates virion 38 adsorption to host-cell surfaces, receptor binding, fusion of the virion envelope with host-cell 39...survived [60]. However, whether convalescent plasma directly led to recovery could never 123 be determined [61] because the treated individuals also...GP1,2 epitopes: the GP1-GP2 interface, 170 the GP1 glycan cap, and the GP1 mucin-like domain [76]. Administered to crab- eating macaques 171 (Macaca

  20. Candidate Medical Countermeasures Targeting Ebola Virus Cell Entry

    Science.gov (United States)

    2017-03-31

    ML, Hessell AJ, Oswald WB, Burton DR, Saphire EO. Structure of the 405 Ebola virus glycoprotein bound to an antibody from a human survivor. Nature...virus cell-entry inhibitors 21 17. Gallaher WR. Similar structural models of the transmembrane proteins of Ebola and 408 avian sarcoma viruses. Cell...85(4), 477-478 (1996). 409 18. Weissenhorn W, Carfí A, Lee K-H, Skehel JJ, Wiley DC. Crystal structure of the Ebola 410 virus membrane fusion

  1. CAM and Cell Fate Targeting: Molecular and Energetic Insights into Cell Growth and Differentiation

    Directory of Open Access Journals (Sweden)

    Carlo Ventura

    2005-01-01

    Full Text Available Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence–based CAM.

  2. Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

    Science.gov (United States)

    Haass, Nikolas K; Gabrielli, Brian

    2017-07-01

    The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

    Directory of Open Access Journals (Sweden)

    Cleo Goyvaerts

    2015-01-01

    Full Text Available In therapeutic antitumor vaccination, dendritic cells play the leading role since they decide if, how, when, and where a potent antitumor immune response will take place. Since the disentanglement of the complexity and merit of different antigen-presenting cell subtypes, antitumor immunotherapeutic research started to investigate the potential benefit of targeting these subtypes in situ. This review will discuss which antigen-presenting cell subtypes are at play and how they have been targeted and finally question the true meaning of targeting antitumor-based vaccines.

  4. Uplink Capacity of 802.16j Mobile Multihop Relay Networks with Transparent Relays

    DEFF Research Database (Denmark)

    Wang, Hua; Andrews, Jeffrey G.; Iversen, Villy Bæk

    2009-01-01

    -to-end spectral efficiency. Furthermore, the position and the number of relay stations (RSs) have a great impact on the capacity gain. These results are further verified in the evaluation of the system Erlang capacity. The study demonstrates that with proper deployment of RSs and use of MIMO transmission...

  5. The number and distribution of AMPA receptor channels containing fast kinetic GluA3 and GluA4 subunits at auditory nerve synapses depend on the target cells.

    Science.gov (United States)

    Rubio, María E; Matsui, Ko; Fukazawa, Yugo; Kamasawa, Naomi; Harada, Harumi; Itakura, Makoto; Molnár, Elek; Abe, Manabu; Sakimura, Kenji; Shigemoto, Ryuichi

    2017-11-01

    The neurotransmitter receptor subtype, number, density, and distribution relative to the location of transmitter release sites are key determinants of signal transmission. AMPA-type ionotropic glutamate receptors (AMPARs) containing GluA3 and GluA4 subunits are prominently expressed in subsets of neurons capable of firing action potentials at high frequencies, such as auditory relay neurons. The auditory nerve (AN) forms glutamatergic synapses on two types of relay neurons, bushy cells (BCs) and fusiform cells (FCs) of the cochlear nucleus. AN-BC and AN-FC synapses have distinct kinetics; thus, we investigated whether the number, density, and localization of GluA3 and GluA4 subunits in these synapses are differentially organized using quantitative freeze-fracture replica immunogold labeling. We identify a positive correlation between the number of AMPARs and the size of AN-BC and AN-FC synapses. Both types of AN synapses have similar numbers of AMPARs; however, the AN-BC have a higher density of AMPARs than AN-FC synapses, because the AN-BC synapses are smaller. A higher number and density of GluA3 subunits are observed at AN-BC synapses, whereas a higher number and density of GluA4 subunits are observed at AN-FC synapses. The intrasynaptic distribution of immunogold labeling revealed that AMPAR subunits, particularly GluA3, are concentrated at the center of the AN-BC synapses. The central distribution of AMPARs is absent in GluA3-knockout mice, and gold particles are evenly distributed along the postsynaptic density. GluA4 gold labeling was homogenously distributed along both synapse types. Thus, GluA3 and GluA4 subunits are distributed at AN synapses in a target-cell-dependent manner.

  6. Relay testing at Brookhaven National Laboratory

    International Nuclear Information System (INIS)

    Bandyopadhyay, K.; Hofmayer, C.

    1989-01-01

    Brookhaven National Laboratory (BNL) is conducting a seismic test program on relays. The purpose of the test program is to investigate the influence of various designs, electrical and vibration parameters on the seismic capacity levels. The first series of testing has been completed and performed at Wyle Laboratories. The major part of the test program consisted of single axis, single frequency sine dwell tests. Random multiaxis, multifrequency tests were also performed. Highlights of the test results as well as a description of the testing methods are presented in this paper. 10 figs

  7. Profiling the Targets of Protective CD8+ T Cell Responses to Infection

    Directory of Open Access Journals (Sweden)

    Joseph T. Bruder

    2017-12-01

    Full Text Available T cells are critical effectors of host immunity that target intracellular pathogens, such as the causative agents of HIV, tuberculosis, and malaria. The development of vaccines that induce effective cell-mediated immunity against such pathogens has proved challenging; for tuberculosis and malaria, many of the antigens targeted by protective T cells are not known. Here, we report a novel approach for screening large numbers of antigens as potential targets of T cells. Malaria provides an excellent model to test this antigen discovery platform because T cells are critical mediators of protection following immunization with live sporozoite vaccines and the specific antigen targets are unknown. We generated an adenovirus array by cloning 312 highly expressed pre-erythrocytic Plasmodium yoelii antigens into adenovirus vectors using high-throughput methodologies. The array was screened to identify antigen-specific CD8+ T cells induced by a live sporozoite vaccine regimen known to provide high levels of sterile protection mediated by CD8+ T cells. We identified 69 antigens that were targeted by CD8+ T cells induced by this vaccine regimen. The antigen that recalled the highest frequency of CD8+ T cells, PY02605, induced protective responses in mice, demonstrating proof of principle for this approach in identifying antigens for vaccine development.

  8. Tapping Stem Cells to Target AMD: Challenges and Prospects

    Directory of Open Access Journals (Sweden)

    Caroline Brandl

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD, the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs, in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

  9. Splenocytes cultured in low concentrations of IL-2 generate NK cell specificities toward syngenic and allogenic targets

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Jeppesen, M; Claesson, M H

    2000-01-01

    Splenocytes cultured in the presence of 30-60 units/ml IL-2 for 5 days develop natural killer activity toward syngeneic and allogeneic tumor cell targets. The IL-2 activated splenocytes, themselves, are partially resistant, whereas concanavalin A-activated T blast cells are completely resistant...... to killing. Surprisingly, major histocompatibility complex (MHC)-I-negative target cells are also resistant to natural killer (NK)-cell-mediated killing. Cells resistant to killing were unable to block NK-cell-mediated killing of sensitive targets as judged from cold target cell inhibition experiments......, and one type of target cells sensitive to killing did generally not cross-block killing of other killing-sensitive target cell types. Alloantigen exposure of splenocytes, i.e., one-way mixed lymphocyte cultures, partially prevents the development of NK-cell activity. Our data suggest that target...

  10. Mesenchymal Stem Cells after Polytrauma: Actor and Target

    Directory of Open Access Journals (Sweden)

    Markus Huber-Lang

    2016-01-01

    Full Text Available Mesenchymal stem cells (MSCs are multipotent cells that are considered indispensable in regeneration processes after tissue trauma. MSCs are recruited to damaged areas via several chemoattractant pathways where they function as “actors” in the healing process by the secretion of manifold pro- and anti-inflammatory, antimicrobial, pro- and anticoagulatory, and trophic/angiogenic factors, but also by proliferation and differentiation into the required cells. On the other hand, MSCs represent “targets” during the pathophysiological conditions after severe trauma, when excessively generated inflammatory mediators, complement activation factors, and damage- and pathogen-associated molecular patterns challenge MSCs and alter their functionality. This in turn leads to complement opsonization, lysis, clearance by macrophages, and reduced migratory and regenerative abilities which culminate in impaired tissue repair. We summarize relevant cellular and signaling mechanisms and provide an up-to-date overview about promising future therapeutic MSC strategies in the context of severe tissue trauma.

  11. Targeted Lymphoma Cell Death by Novel Signal Transduction Modifications

    Science.gov (United States)

    2011-07-01

    60 80 100 120 Jurkat R am os R aji M C 116 D O H H 2 W S U -W M W S U -C LL K arpas 519 C ell Lines A s C o n tr o l ( % ) Figure 6...Lym phom a cell Lines 0 20 40 60 80 100 120 Jurkat R am os R aji M C 116 D O H H 2 W S U -W M W S U -C LL K arpas 519 C ell Lines A s C o n tr o l...plemented with 10% FCS and incubated with AET- activated sheep red blood cells (SRBC) for 1 h. B-cells were collected at the interface after centrifugation

  12. Molecular targets on mast cells and basophils for novel therapies

    Czech Academy of Sciences Publication Activity Database

    Harvima, I.T.; Levi-Schaffer, F.; Dráber, Petr; Friedman, S.; Polakovičová, Iva; Gibbs, B.F.; Blank, U.; Nilsson, G.; Maurer, M.

    2014-01-01

    Roč. 134, č. 3 (2014), s. 530-544 ISSN 0091-6749 R&D Projects: GA MŠk LD12073; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GA14-09807S; GA ČR(CZ) GA14-00703S Institutional support: RVO:68378050 Keywords : cell activation * mast cells and basophils * treatment of allergic diseases Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.476, year: 2014

  13. CD25 targeted therapy of chemotherapy resistant leukemic stem cells using DR5 specific TRAIL peptide

    Directory of Open Access Journals (Sweden)

    Jayaprakasam Madhumathi

    2017-03-01

    Full Text Available Chemotherapy resistant leukemic stem cells (LSCs are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81.25% in AML and 100% in CML, ALL and CLL. IL2-TRAIL peptide showed cytotoxicity in relapsed patient samples and was more effective than TRAIL or IL2-TRAIL proteins. Additionally, DR5 specific IL2-TRAIL peptide was effective in targeting and killing LSCs purified from cell lines [IC50: 952 nM in HL60, 714 nM in MOLT4] and relapsed patient blood samples with higher efficacy (85% than IL2-TRAIL protein (46%. Hence, CD25 and DR5 specific targeting by IL2-TRAIL peptide may be an effective strategy for targeting drug resistant leukemic cells and LSCs.

  14. Glycoengineering of Human Cell Lines Using Zinc Finger Nuclease Gene Targeting

    DEFF Research Database (Denmark)

    Steentoft, Catharina; Bennett, Eric Paul; Clausen, Henrik

    2013-01-01

    Lectin affinity chromatography is a powerful technique for isolation of glycoproteins carrying a specific glycan structure of interest. However, the enormous diversity of glycans present on the cell surface, as well as on individual proteins, makes it difficult to isolate an entire glycoproteome...... with one or even a series of lectins. Here we present a technique to generate cell lines with homogenous truncated O-glycans using zinc finger nuclease gene targeting. Because of their simplified O-glycoproteome, the cells have been named SimpleCells. Glycoproteins from SimpleCells can be isolated...... in a single purification step by lectin chromatography performed on a long lectin column. This protocol describes Zinc finger nuclease gene targeting of human cells to simplify the glycoproteome, as well as lectin chromatography and isolation of glycopeptides from total cell lysates of SimpleCells....

  15. Performance of hybrid-ARQ with incremental redundancy over relay channels

    KAUST Repository

    Chelli, Ali; Alouini, Mohamed-Slim

    2012-01-01

    In this paper, we consider a relay network consisting of a source, a relay, and a destination. The source transmits a message to the destination using hybrid automatic repeat request (HARQ) with incremental redundancy (IR). The relay overhears

  16. A study of optimization problem for amplify-and-forward relaying over weibull fading channels

    KAUST Repository

    Ikki, Salama Said; Aissa, Sonia

    2010-01-01

    This paper addresses the power allocation and relay positioning problems in amplify-and-forward cooperative networks operating in Weibull fading environments. We study adaptive power allocation (PA) with fixed relay location, optimal relay location

  17. Prodrug strategy for cancer cell-specific targeting: A recent overview.

    Science.gov (United States)

    Zhang, Xian; Li, Xiang; You, Qidong; Zhang, Xiaojin

    2017-10-20

    The increasing development of targeted cancer therapy provides extensive possibilities in clinical trials, and numerous strategies have been explored. The prodrug is one of the most promising strategies in targeted cancer therapy to improve the selectivity and efficacy of cytotoxic compounds. Compared with normal tissues, cancer cells are characterized by unique aberrant markers, thus inactive prodrugs targeting these markers are excellent therapeutics to release active drugs, killing cancer cells without damaging normal tissues. In this review, we explore an integrated view of potential prodrugs applied in targeted cancer therapy based on aberrant cancer specific markers and some examples are provided for inspiring new ideas of prodrug strategy for cancer cell-specific targeting. Copyright © 2017. Published by Elsevier Masson SAS.

  18. Identification and Regulation of c-Myb Target Genes in MCF-7 Cells

    International Nuclear Information System (INIS)

    Quintana, Anita M; Liu, Fan; O'Rourke, John P; Ness, Scott A

    2011-01-01

    The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer cells

  19. Pulmonary tumors induced in the rat by the internal α irradiation; target cells and sensitive cells

    International Nuclear Information System (INIS)

    Fritsch, P.; Masse, R.; Nolibe, D.; Metivier, H.; Morin, M.; Lafuma, J.

    1977-01-01

    Over, 500 rat pulmonary tumors induced by inhalation of various radionuclides have been examined by means of the usual histological methods and ultrastructurally for part of them. Tumor grafts were obtained and several lines have been preserved for several years. The malignity of some varieties: circumscribed epidermoid carcinoma, fibrosarcoma derived from stromareaction, bronchiolo alveolar carcinoma was thus established. It was not possible to establish any relation between the turnover per day and the incidence of pulmonary tumors whatever the correction factor applied taking account of the distribution of the delivered dose. The possibility of showing unapparent lesions of the target cells by grafts of immunodepressed animals suggested that local regulating mechanisms are of particular significance [fr

  20. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

  1. Specifically targeted gene therapy for small-cell lung cancer

    DEFF Research Database (Denmark)

    Christensen, C.L.; Zandi, R.; Gjetting, T.

    2009-01-01

    Small-cell lung cancer (SCLC) is a highly malignant disease with poor prognosis. Hence, there is great demand for new therapies that can replace or supplement the current available treatment regimes. Gene therapy constitutes a promising strategy and relies on the principle of introducing exogenous...

  2. Monte Carlo Simulations of Necrotic Cell Targeted Alpha Therapy

    International Nuclear Information System (INIS)

    Penfold, S.N.; Brown, M.P.; Bezak, E.

    2011-01-01

    Full text: Hypoxic tumour cells are radioresistant and are significant contributors to the locoregional recurrences and distant metastases that mark treatment failure. Due to restricted circulatory supply, hypoxic tumor cells frequently become necrotic and thus necrotic areas often lie near hypoxic tumour areas. In this study we investigate the feasibility of binding an alpha-emitting conjugate to necrotic cells located in the proximity of hypoxic, viable tumour cells. Monte Carlo radiation transport simulations were performed to investigate the dose distribution resulting from the thorium 227 (Th227) decay chain in a representative tumour geometry. The Geant4 software toolkit was used to simulate the decay and interactions of the Th227 decay chain. The distribution of Th227 was based on a study by Thomlinson and Gray of human lung cancer histological samples (Thomlinson RH, Gray LH. Br J Cancer 1955; 9:539). The normalized dose distribution obtained with Geant4 from a cylindrical Th227 source in water is illustrated in Fig. I. The relative contribution of the different decay channels is displayed, together with a profile through the centre of the accumulated dose map. The results support the hypothesis that significant α-particle doses will be deposited in the hypoxic tumor tissue immediately surrounding the necrotic core (where the majority of Th227 will be located). As an internal a-particle generator, the Th227-radioimmunoconjugate shows potential as an efficient hypoxic tumour sterilizer.

  3. Mitochondria: An intriguing target for killing tumour-initiating cells

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Dong, L.; Neužil, Jiří

    2016-01-01

    Roč. 26, JAN 2016 (2016), s. 86-93 ISSN 1567-7249 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * ALPHA-TOCOPHERYL SUCCINATE * Therapeutic resistance * Mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.704, year: 2016

  4. Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

    Czech Academy of Sciences Publication Activity Database

    Azizi, A.; Kumar, A.; Diaz-Mitoma, F.; Městecký, Jiří

    2010-01-01

    Roč. 6, č. 11 (2010) ISSN 1553-7366 Institutional research plan: CEZ:AV0Z50200510 Keywords : PATCH M-CELLS * UROPATHOGENIC ESCHERICHIA-COLI * MUCOSAL IMMUNE-SYSTEM Subject RIV: EE - Microbiology, Virology Impact factor: 9.079, year: 2010

  5. The Need to Study, Mimic, and Target Stem Cell Niches

    NARCIS (Netherlands)

    Vishwakarma, Ajaykumar; Rouwkema, Jeroen; Jones, Peter Anthony; Karp, Jeffrey M.; Vishwakarma, Ajaykumar; Karp, Jeffrey M.

    2017-01-01

    Despite important advances in tissue repair and regeneration over the past few decades, complete functional repair of damaged or diseased human tissues has remained elusive. Recent discoveries in stem cell niche molecular biology and biomaterials engineering may hold the key to true regeneration.

  6. Homologous recombination in hybridoma cells: heavy chain chimeric antibody produced by gene targeting.

    OpenAIRE

    Fell, H P; Yarnold, S; Hellström, I; Hellström, K E; Folger, K R

    1989-01-01

    We demonstrate that murine myeloma cells can efficiently mediate homologous recombination. The murine myeloma cell line J558L was shown to appropriately recombine two transfected DNA molecules in approximately 30% of cells that received and integrated intact copies of both molecules. This activity was then exploited to direct major reconstructions of an endogenous locus within a hybridoma cell line. Production of antigen-specific chimeric heavy chain was achieved by targeting the human IgG1 h...

  7. CERN Relay Race: sporty and colourful

    CERN Multimedia

    Andy Butterworth, CERN Running Club

    2013-01-01

    On Thursday 23 May, the 43rd CERN Relay Race took place, with 108 teams on the starting line, the largest participation ever!       The DG was present at the start and said a few words to encourage the runners. At 12:15, the Solar Club and handbike racers, led by Jean-Yves Le Meur, were the first to set off. And as last year, the relay runners were accompanied by an enthusiastic group of Nordic walkers. The first team across the finish line was "Velo City", in a very fast time of 10'31". New this year was a prize category for the best fancy dress, which was won by Les Schtroumpfs from the BE Department. The challenge for the best represented department was won for the third year in a row by FP, but second and third were HR and IT, up from 6th and 9th places last year. To see all the pictures of the event, click here.

  8. Satellite-Relayed Intercontinental Quantum Network

    Science.gov (United States)

    Liao, Sheng-Kai; Cai, Wen-Qi; Handsteiner, Johannes; Liu, Bo; Yin, Juan; Zhang, Liang; Rauch, Dominik; Fink, Matthias; Ren, Ji-Gang; Liu, Wei-Yue; Li, Yang; Shen, Qi; Cao, Yuan; Li, Feng-Zhi; Wang, Jian-Feng; Huang, Yong-Mei; Deng, Lei; Xi, Tao; Ma, Lu; Hu, Tai; Li, Li; Liu, Nai-Le; Koidl, Franz; Wang, Peiyuan; Chen, Yu-Ao; Wang, Xiang-Bin; Steindorfer, Michael; Kirchner, Georg; Lu, Chao-Yang; Shu, Rong; Ursin, Rupert; Scheidl, Thomas; Peng, Cheng-Zhi; Wang, Jian-Yu; Zeilinger, Anton; Pan, Jian-Wei

    2018-01-01

    We perform decoy-state quantum key distribution between a low-Earth-orbit satellite and multiple ground stations located in Xinglong, Nanshan, and Graz, which establish satellite-to-ground secure keys with ˜kHz rate per passage of the satellite Micius over a ground station. The satellite thus establishes a secure key between itself and, say, Xinglong, and another key between itself and, say, Graz. Then, upon request from the ground command, Micius acts as a trusted relay. It performs bitwise exclusive or operations between the two keys and relays the result to one of the ground stations. That way, a secret key is created between China and Europe at locations separated by 7600 km on Earth. These keys are then used for intercontinental quantum-secured communication. This was, on the one hand, the transmission of images in a one-time pad configuration from China to Austria as well as from Austria to China. Also, a video conference was performed between the Austrian Academy of Sciences and the Chinese Academy of Sciences, which also included a 280 km optical ground connection between Xinglong and Beijing. Our work clearly confirms the Micius satellite as a robust platform for quantum key distribution with different ground stations on Earth, and points towards an efficient solution for an ultralong-distance global quantum network.

  9. Satellite-Relayed Intercontinental Quantum Network.

    Science.gov (United States)

    Liao, Sheng-Kai; Cai, Wen-Qi; Handsteiner, Johannes; Liu, Bo; Yin, Juan; Zhang, Liang; Rauch, Dominik; Fink, Matthias; Ren, Ji-Gang; Liu, Wei-Yue; Li, Yang; Shen, Qi; Cao, Yuan; Li, Feng-Zhi; Wang, Jian-Feng; Huang, Yong-Mei; Deng, Lei; Xi, Tao; Ma, Lu; Hu, Tai; Li, Li; Liu, Nai-Le; Koidl, Franz; Wang, Peiyuan; Chen, Yu-Ao; Wang, Xiang-Bin; Steindorfer, Michael; Kirchner, Georg; Lu, Chao-Yang; Shu, Rong; Ursin, Rupert; Scheidl, Thomas; Peng, Cheng-Zhi; Wang, Jian-Yu; Zeilinger, Anton; Pan, Jian-Wei

    2018-01-19

    We perform decoy-state quantum key distribution between a low-Earth-orbit satellite and multiple ground stations located in Xinglong, Nanshan, and Graz, which establish satellite-to-ground secure keys with ∼kHz rate per passage of the satellite Micius over a ground station. The satellite thus establishes a secure key between itself and, say, Xinglong, and another key between itself and, say, Graz. Then, upon request from the ground command, Micius acts as a trusted relay. It performs bitwise exclusive or operations between the two keys and relays the result to one of the ground stations. That way, a secret key is created between China and Europe at locations separated by 7600 km on Earth. These keys are then used for intercontinental quantum-secured communication. This was, on the one hand, the transmission of images in a one-time pad configuration from China to Austria as well as from Austria to China. Also, a video conference was performed between the Austrian Academy of Sciences and the Chinese Academy of Sciences, which also included a 280 km optical ground connection between Xinglong and Beijing. Our work clearly confirms the Micius satellite as a robust platform for quantum key distribution with different ground stations on Earth, and points towards an efficient solution for an ultralong-distance global quantum network.

  10. The CERN Relay Race: A Runaway Success!

    CERN Multimedia

    Staff Association

    2018-01-01

    24th May saw the traditional Relay Race take place at CERN, organised jointly by the Running Club and the CERN Staff Association. In 2018, the Relay Race lived up to expectations with a record number of participants, with no fewer than 848 entries across different categories! In total 135 teams of 6 runners and 38 walkers completed the course on the Meyrin site in beautiful sunshine. Congratulations to all those who took part! Ghislain Roy, President of the Staff Association, fired the starting pistol for the first batch of runners, which included a team from the Directorate, with the Director General also taking part. Demonstrating interest in this event at the highest level of the Organization. Thank you for this much-appreciated commitment! Also a number of very high-level runners brought added excitement to the 2018 edition. The 1000-meter men’s race was won by Marcin Patecki from the CERN Running Club in 2’40, just in front of Baptiste Fieux from the Berthie Sport team who came in at...

  11. Record Participation in the Relay Race!

    CERN Multimedia

    2002-01-01

    CERN has a more sporting spirit than ever before. This is not the result of any survey, but the impression you got as soon as you saw the 62 teams of six runners each speeding around the laboratory in the 32nd annual relay race. This year 11 more teams competed than in 2001.   First changeover: Hervé Cornet takes over from Camille Ruiz Llamas for The Shabbys, and Sebastian Dorthe from Daniel Matteazzi for Charmilles Technologies. Jérôme Bendotti (EP/TA1) just holding off the team from the WHO at the finish. A total of 372 people ran together last Wednesday in this year's relay race, making for a record participation. It also seems that women are becoming more and more attracted by this competition, since this year there were eight ladies teams, also a new record. The first team were The Shabbys in a time of 10 minutes 45 seconds, finishing almost before the second team had started its last 300 metre leg. The 6 runners in each team cover distances of 1000, 800, 800,...

  12. Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

    2018-06-30

    Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions

  13. Cancer Cell Signaling Pathways Targeted by Spice-Derived Nutraceuticals

    Science.gov (United States)

    Sung, Bokyung; Prasad, Sahdeo; Yadav, Vivek R.; Aggarwal, Bharat B.

    2012-01-01

    Extensive research within the last half a century has revealed that cancer is caused by dysregulation of as many as 500 different gene products. Most natural products target multiple gene products and thus are ideally suited for prevention and treatment of various chronic diseases, including cancer. Dietary agents such as spices have been used extensively in the Eastern world for a variety of ailments for millennia, and five centuries ago they took a golden journey to the Western world. Various spice-derived nutraceuticals, including 1′-acetoxychavicol acetate, anethole, capsaicin, car-damonin, curcumin, dibenzoylmethane, diosgenin, eugenol, gambogic acid, gingerol, thymoquinone, ursolic acid, xanthohumol, and zerumbone derived from galangal, anise, red chili, black cardamom, turmeric, licorice, fenugreek, clove, kokum, ginger, black cumin, rosemary, hop, and pinecone ginger, respectively, are the focus of this review. The modulation of various transcription factors, growth factors, protein kinases, and inflammatory mediators by these spice-derived nutraceuticals are described. The anticancer potential through the modulation of various targets is also the subject of this review. Although they have always been used to improve taste and color and as a preservative, they are now also used for prevention and treatment of a wide variety of chronic inflammatory diseases, including cancer. PMID:22149093

  14. 76 FR 58424 - Transmission Relay Loadability Reliability Standard

    Science.gov (United States)

    2011-09-21

    ... distribution providers to set load-responsive phase protection relays according to specific criteria to ensure...-part R.1.10 allows transmission owners, generation owners and distribution providers to set transformer.... Thus, requiring that transformer fault protection relays are set to not expose the transformer to a...

  15. Improper signaling in two-path relay channels

    KAUST Repository

    Gaafar, Mohamed

    2017-07-03

    Inter-relay interference (IRI) challenges the operation of two-path relaying systems. Furthermore, the unavailability of the channel state information (CSI) at the source and the limited detection capabilities at the relays prevent neither eliminating the interference nor adopting joint detection at the relays nodes. Improper signaling is a powerful signaling scheme that has the capability to reduce the interference impact at the receiver side and improves the achievable rate performance. Therefore, improper signaling is adopted at both relays, which have access to the global CSI. Then, improper signal characteristics are designed to maximize the total end-to-end achievable rate at the relays. To this end, both the power and the circularity coefficient, a measure of the impropriety degree of the signal, are optimized at the relays. Although the optimization problem is not convex, optimal power allocation for both relays for a fixed circularity coefficient is obtained. Moreover, the circularity coefficient is tuned to maximize the rate for a given power allocation. Finally, a joint solution of the optimization problem is proposed using a coordinate descent method based on alternate optimization. The simulation results show that employing improper signaling improves the achievable rate at medium and high IRI.

  16. 77 FR 16435 - Transmission Relay Loadability Reliability Standard

    Science.gov (United States)

    2012-03-21

    ... conditions on all applicable transmission lines and transformers. I. Background A. Relay Protection Systems 2... and a power swing. If a power swing is detected, the protection system, ``blocks,'' or prevents the... to the reliability of the Bulk-Power System by requiring load-responsive phase protection relay...

  17. Protective relaying of power systems using mathematical morphology

    CERN Document Server

    Wu, QH; Ji, TY

    2009-01-01

    Discusses the development of novel protective relaying algorithms, using Mathematical Morphology (MM). This book introduces the fundamental principles of MM, and brings together the applications of MM to develop different protective relaying algorithms for the protection of a variety of power system components.

  18. Resource allocation for relay assisted cognitive radio networks

    KAUST Repository

    Zafar, Ammar; Alouini, Mohamed-Slim; Chen, Yunfei; Radaydeh, Redha M.

    2012-01-01

    transmission power and the relay transmission power. Numerical results show that the optimal sensing time is dependent on the primary user's signal-to-noise-ratio (SNR). They also show that SCR increases with increase in the number of relays. © 2012 IEEE.

  19. 47 CFR 11.20 - State Relay Network.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false State Relay Network. 11.20 Section 11.20... Network. This network is composed of State Relay (SR) sources, leased common carrier communications facilities or any other available communication facilities. The network distributes State EAS messages...

  20. MaROS Strategic Relay Planning and Coordination Interfaces

    Science.gov (United States)

    Allard, Daniel A.

    2010-01-01

    The Mars Relay Operations Service (MaROS) is designed to provide planning and analysis tools in support of ongoing Mars Network relay operations. Strategic relay planning requires coordination between lander and orbiter mission ground data system (GDS) teams to schedule and execute relay communications passes. MaROS centralizes this process, correlating all data relevant to relay coordination to provide a cohesive picture of the relay state. Service users interact with the system through thin-layer command line and web user interface client applications. Users provide and utilize data such as lander view periods of orbiters, Deep Space Network (DSN) antenna tracks, and reports of relay pass performance. Users upload and download relevant relay data via formally defined and documented file structures including some described in Extensible Markup Language (XML). Clients interface with the system via an http-based Representational State Transfer (ReST) pattern using Javascript Object Notation (JSON) formats. This paper will provide a general overview of the service architecture and detail the software interfaces and considerations for interface design.

  1. Effects of Unified Power Flow Controller (UPFC) on Distance Relay ...

    African Journals Online (AJOL)

    This paper investigates the effects of UPFC on Distance Relay tripping characteristics in Nigerian 330kV (North-Central) Network. Its operation is based on impedance measurement at the relaying point. However, the system performance is often impeded by certain operational or structural factors such as load angle, the ...

  2. Cognitive Spectrum Efficient Multiple Access Technique using Relay Systems

    DEFF Research Database (Denmark)

    Frederiksen, Flemming Bjerge; Prasad, Ramjee

    2007-01-01

    Methods to enhance the use of the frequency spectrum by automatical spectrum sensing plus spectrum sharing in a cognitive radio technology context will be presented and discussed in this paper. Ideas to increase the coverage of cellular systems by relay channels, relay stations and collaborate...

  3. Efficient Resource Scheduling by Exploiting Relay Cache for Cellular Networks

    Directory of Open Access Journals (Sweden)

    Chun He

    2015-01-01

    Full Text Available In relay-enhanced cellular systems, throughput of User Equipment (UE is constrained by the bottleneck of the two-hop link, backhaul link (or the first hop link, and access link (the second hop link. To maximize the throughput, resource allocation should be coordinated between these two hops. A common resource scheduling algorithm, Adaptive Distributed Proportional Fair, only ensures that the throughput of the first hop is greater than or equal to that of the second hop. But it cannot guarantee a good balance of the throughput and fairness between the two hops. In this paper, we propose a Two-Hop Balanced Distributed Scheduling (TBS algorithm by exploiting relay cache for non-real-time data traffic. The evolved Node Basestation (eNB adaptively adjusts the number of Resource Blocks (RBs allocated to the backhaul link and direct links based on the cache information of relays. Each relay allocates RBs for relay UEs based on the size of the relay UE’s Transport Block. We also design a relay UE’s ACK feedback mechanism to update the data at relay cache. Simulation results show that the proposed TBS can effectively improve resource utilization and achieve a good trade-off between system throughput and fairness by balancing the throughput of backhaul and access link.

  4. An automated thermoelectric power apparatus using electro-optic relays

    International Nuclear Information System (INIS)

    Chakravarti, A.; Ranganathan, R.

    1992-01-01

    We report the design and construction of a thermoelectric power apparatus using home-made electro-optic relays with Z-80A microprocessor for automatic data acquisition and control. The advantages of such relays made out of LED-LDR combinations for the measurement of ΔE and ΔT are discussed in details. (author). 7 refs., 5 figs

  5. Duplex Schemes in Multiple Antenna Two-Hop Relaying

    Directory of Open Access Journals (Sweden)

    Anja Klein

    2008-04-01

    Full Text Available A novel scheme for two-hop relaying defined as space division duplex (SDD relaying is proposed. In SDD relaying, multiple antenna beamforming techniques are applied at the intermediate relay station (RS in order to separate downlink and uplink signals of a bi-directional two-hop communication between two nodes, namely, S1 and S2. For conventional amplify-and-forward two-hop relaying, there appears a loss in spectral efficiency due to the fact that the RS cannot receive and transmit simultaneously on the same channel resource. In SDD relaying, this loss in spectral efficiency is circumvented by giving up the strict separation of downlink and uplink signals by either time division duplex or frequency division duplex. Two novel concepts for the derivation of the linear beamforming filters at the RS are proposed; they can be designed either by a three-step or a one-step concept. In SDD relaying, receive signals at S1 are interfered by transmit signals of S1, and receive signals at S2 are interfered by transmit signals of S2. An efficient method in order to combat this kind of interference is proposed in this paper. Furthermore, it is shown how the overall spectral efficiency of SDD relaying can be improved if the channels from S1 and S2 to the RS have different qualities.

  6. Implementation of a Relay Coordination System for the Mars Network

    Science.gov (United States)

    Allard, Daniel A.

    2010-01-01

    Mars network relay operations involve the coordination of lander and orbiter teams through long-term and short-term planning, tactical changes and post-pass analysis. Much of this coordination is managed through email traffic and point-to-point file data exchanges. It is often difficult to construct a complete and accurate picture of the relay situation at any given moment, as there is no centralized store of correlated relay data. The Mars Relay Operations Service (MaROS) is being implemented to address the problem of relay coordination for current and next-generation relay missions. The service is provided for the purpose of coordinating communications sessions between landed spacecraft assets and orbiting spacecraft assets at Mars. The service centralizes a set of functions previously distributed across multiple spacecraft operations teams, and as such greatly improves visibility into the end-to-end strategic coordination process. Most of the process revolves around the scheduling of communications sessions between the spacecraft during periods of time when a landed asset on Mars is geometrically visible by an orbiting spacecraft. These "relay" sessions are used to transfer data both to and from the landed asset via the orbiting asset on behalf of Earth-based spacecraft operators. This paper will discuss the relay coordination problem space, overview the architecture and design selected to meet system requirements, and describe the first phase of system implementation

  7. 77 FR 1039 - Internet-Based Telecommunications Relay Service Numbering

    Science.gov (United States)

    2012-01-09

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 64 [WC Docket No. 10-191; Report No. 2939] Internet... toll-free numbers by users of Internet- based Telecommunications Relay Services (iTRS). DATES... any rules of particular applicability. Subject: Internet-Based Telecommunications Relay Service...

  8. Using the 5 P Relay in Task Groups

    Science.gov (United States)

    Stanley, Paula Helen

    2006-01-01

    This article describes the 5 P Relay, a group exercise that can increase the effectiveness of task groups. The 5 P Relay is based on the principles and concepts of the Invitational Model, which emphasizes the importance of assessing the effectiveness or health of five aspects of an organization's environment: people, places, programs, processes,…

  9. Analysis of Relay Selection Game in a Cooperative Communication Scenario

    DEFF Research Database (Denmark)

    Craciunescu, Razvan; Mihovska, Albena; Halunga, Simona

    This paper analysis the performances of a proposed set of functions that model the relay selection process in a cooperative communication scenario. The behavior and influence proposed functions create a mechanism for selecting the best relays to be used to send certain types of data. The mechanism...... of comparison between the bit error rate of the proposed mechanism and the direct communication....

  10. Improper signaling in two-path relay channels

    KAUST Repository

    Gaafar, Mohamed; Amin, Osama; Schaefer, Rafael F.; Alouini, Mohamed-Slim

    2017-01-01

    Inter-relay interference (IRI) challenges the operation of two-path relaying systems. Furthermore, the unavailability of the channel state information (CSI) at the source and the limited detection capabilities at the relays prevent neither eliminating the interference nor adopting joint detection at the relays nodes. Improper signaling is a powerful signaling scheme that has the capability to reduce the interference impact at the receiver side and improves the achievable rate performance. Therefore, improper signaling is adopted at both relays, which have access to the global CSI. Then, improper signal characteristics are designed to maximize the total end-to-end achievable rate at the relays. To this end, both the power and the circularity coefficient, a measure of the impropriety degree of the signal, are optimized at the relays. Although the optimization problem is not convex, optimal power allocation for both relays for a fixed circularity coefficient is obtained. Moreover, the circularity coefficient is tuned to maximize the rate for a given power allocation. Finally, a joint solution of the optimization problem is proposed using a coordinate descent method based on alternate optimization. The simulation results show that employing improper signaling improves the achievable rate at medium and high IRI.

  11. Protective Relay Studies for the Nigerian National Electric 330 KV ...

    African Journals Online (AJOL)

    The fundamental reasons for requiring these specific protective relaying features are also reviewed. Other protective relaying schemes that can accomplish the same basic protection objectives are presented. Based on the Nigerian special system characteristics, schemes to correct existing protection inadequacies are ...

  12. Relay Coordination in the Protection of Radially-Connected Power ...

    African Journals Online (AJOL)

    Protective relays detect intolerable or unwanted conditions within an assigned area, and then trip or open one or more circuit breakers to isolate the problem area before it can damage or otherwise interfere with the eective operation of the rest of the power system. It often happens that a substation feeder relay and ...

  13. Quasi-period oscillations of relay feedback systems

    International Nuclear Information System (INIS)

    Wen Guilin; Wang Qingguo; Lee, T.H.

    2007-01-01

    This paper presents an analytical method for investigation of the existence and stability of quasi-period oscillations (torus solutions) for a class of relay feedback systems. The idea is to analyze Poincare map from one switching surface to the next based on the Hopf bifurcation theory of maps. It is shown that there exist quasi-period oscillations in certain relay feedback systems

  14. Cooperative relay-based multicasting for energy and delay minimization

    KAUST Repository

    Atat, Rachad; Yaacoub, Elias E.; Alouini, Mohamed-Slim; Abu-Dayya, Adnan A.

    2012-01-01

    mobiles. Two schemes are investigated. The first consists of the BS sending the data only to the relay, and the second scheme considers the scenario of threshold-based multicasting by the BS, where a relay is selected to transmit the data to the mobiles

  15. Biallelic targeting of expressed genes in mouse embryonic stem cells using the Cas9 system

    NARCIS (Netherlands)

    Zhang, Yu; Vanoli, Fabio; LaRocque, Jeannine R.; Krawczyk, Przemek M.; Jasin, Maria

    2014-01-01

    Gene targeting - homologous recombination between transfected DNA and a chromosomal locus - is greatly stimulated by a DNA break in the target locus. Recently, the RNA-guided Cas9 endonuclease, involved in bacterial adaptive immunity, has been modified to function in mammalian cells. Unlike other

  16. Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations

    NARCIS (Netherlands)

    Bex, A.; Fournier, L.; Lassau, N.; Mulders, P.F.A.; Nathan, P.; Oyen, W.J.G.; Powles, T.

    2014-01-01

    CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to

  17. Purification-Free, Target-Selective Immobilization of a Protein from Cell Lysates.

    Science.gov (United States)

    Cha, Jaehyun; Kwon, Inchan

    2018-02-27

    Protein immobilization has been widely used for laboratory experiments and industrial processes. Preparation of a recombinant protein for immobilization usually requires laborious and expensive purification steps. Here, a novel purification-free, target-selective immobilization technique of a protein from cell lysates is reported. Purification steps are skipped by immobilizing a target protein containing a clickable non-natural amino acid (p-azidophenylalanine) in cell lysates onto alkyne-functionalized solid supports via bioorthogonal azide-alkyne cycloaddition. In order to achieve a target protein-selective immobilization, p-azidophenylalanine was introduced into an exogenous target protein, but not into endogenous non-target proteins using host cells with amber codon-free genomic DNAs. Immobilization of superfolder fluorescent protein (sfGFP) from cell lysates is as efficient as that of the purified sfGFP. Using two fluorescent proteins (sfGFP and mCherry), the authors also demonstrated that the target proteins are immobilized with a minimal immobilization of non-target proteins (target-selective immobilization). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Targeted therapies for renal cell carcinoma: review of adverse event management strategies.

    NARCIS (Netherlands)

    Eisen, T.; Sternberg, C.N.; Robert, C.; Mulders, P.F.; Pyle, L.; Zbinden, S.; Izzedine, H.; Escudier, B.

    2012-01-01

    With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted

  19. Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

    Science.gov (United States)

    Zhang, Wei; Liu, Yuan; Li, Yu Feng; Yue, Yun; Yang, Xinghua; Peng, Lin

    2016-01-01

    Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-x03BA;B. YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-x03BA;B and downregulation of NF-x03BA;B downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed

  20. Targeted deletion of RANKL in M cell inducer cells by the Col6a1-Cre driver.

    Science.gov (United States)

    Nagashima, Kazuki; Sawa, Shinichiro; Nitta, Takeshi; Prados, Alejandro; Koliaraki, Vasiliki; Kollias, George; Nakashima, Tomoki; Takayanagi, Hiroshi

    2017-11-04

    The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells. In order to investigate MCi cells more extensively, it will be necessary to develop experimental tools in addition to the Twist2-Cre driver mice and characterize such drivers in specificity and efficiency. Here we show that M cell differentiation and IgA production are impaired in the targeted deletion of RANKL by the Col6a1-Cre driver. We compared Col6a1-Cre with Twist2-Cre in terms of the specificity for mesenchymal cells in GALTs. Col6a1-Cre CAG-CAT-EGFP mice exhibited EGFP expression in podoplanin + CD31 - cells including MCi cells, while Twist2-Cre mice were shown to target endothelial cells and podoplanin + CD31 - cells. Tnfsf11 fl/Δ Col6a1-Cre mice exhibited the absence of M cells and severe IgA reduction together with an alteration in gut microbial composition. Moreover, we analyzed germ free mice to test whether changes in the microbiota are the cause of M cell deficiency. M cell differentiation was normal in the CPs/ILFs of germ free mice, indicating that MCi cells induce M cells independently of microbial colonization. This study demonstrates that Col6a1-Cre driver mice are as useful as Twist2-Cre driver mice for functional analyses of GALT-resident mesenchymal cells, including MCi cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Targeting CD8+ T-cell tolerance for cancer immunotherapy.

    Science.gov (United States)

    Jackson, Stephanie R; Yuan, Jinyun; Teague, Ryan M

    2014-01-01

    In the final issue of Science in 2013, the American Association of Science recognized progress in the field of cancer immunotherapy as the 'Breakthrough of the Year.' The achievements were actually twofold, owing to the early success of genetically engineered chimeric antigen receptors (CAR) and to the mounting clinical triumphs achieved with checkpoint blockade antibodies. While fundamentally very different, the common thread of these independent strategies is the ability to prevent or overcome mechanisms of CD8(+) T-cell tolerance for improved tumor immunity. Here we discuss how circumventing T-cell tolerance has provided experimental insights that have guided the field of clinical cancer immunotherapy to a place where real breakthroughs can finally be claimed.

  2. ALK signaling and target therapy in anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Fabrizio eTabbo

    2012-05-01

    Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  3. ALK Signaling and Target Therapy in Anaplastic Large Cell Lymphoma

    International Nuclear Information System (INIS)

    Tabbó, Fabrizio; Barreca, Antonella; Piva, Roberto; Inghirami, Giorgio

    2012-01-01

    The discovery by Morris et al. (1994) of the genes contributing to the t(2;5)(p23;q35) translocation has laid the foundation for a molecular based recognition of anaplastic large cell lymphoma and highlighted the need for a further stratification of T-cell neoplasia. Likewise the detection of anaplastic lymphoma kinase (ALK) genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

  4. AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

    Science.gov (United States)

    Luo, Yuxia; Frederick, Amy; Martin, John M; Scaria, Abraham; Cheng, Seng H; Armentano, Donna; Wadsworth, Samuel C; Vincent, Karen A

    2017-06-01

    Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.

  5. Nuclear targeting peptide scaffolds for lipofection of nondividing mammalian cells.

    Science.gov (United States)

    Subramanian, A; Ranganathan, P; Diamond, S L

    1999-09-01

    Lipofection of nondividing cells is inefficient because much of the transfected DNA is retained in endosomes, and that which escapes to the cytoplasm enters the nucleus at low rates. To improve the final rate-limiting step of nuclear import, we conjugated a nonclassical nuclear localization signal (NLS) containing the M9 sequence of heterogeneous nuclear ribonucleoprotein (hnRNP) A1, to a cationic peptide scaffold derived from a scrambled sequence of the SV40 T-antigen consensus NLS (ScT). The ScT was added to improve DNA binding of the M9 sequence. Lipofection of confluent endothelium with plasmid complexed with the M9-ScT conjugate resulted in 83% transfection and a 63-fold increase in marker gene expression. The M9-ScT conjugate localized fluorescent plasmid into the nucleus of permeabilized cells, and addition of the nuclear pore blocker wheat germ agglutinin prevented nuclear import. This method of gene transfer may lead to viral- and lipid-free transfection of nondividing cells.

  6. Analysis of the role of homology arms in gene-targeting vectors in human cells.

    Directory of Open Access Journals (Sweden)

    Ayako Ishii

    Full Text Available Random integration of targeting vectors into the genome is the primary obstacle in human somatic cell gene targeting. Non-homologous end-joining (NHEJ, a major pathway for repairing DNA double-strand breaks, is thought to be responsible for most random integration events; however, absence of DNA ligase IV (LIG4, the critical NHEJ ligase, does not significantly reduce random integration frequency of targeting vector in human cells, indicating robust integration events occurring via a LIG4-independent mechanism. To gain insights into the mechanism and robustness of LIG4-independent random integration, we employed various types of targeting vectors to examine their integration frequencies in LIG4-proficient and deficient human cell lines. We find that the integration frequency of targeting vector correlates well with the length of homology arms and with the amount of repetitive DNA sequences, especially SINEs, present in the arms. This correlation was prominent in LIG4-deficient cells, but was also seen in LIG4-proficient cells, thus providing evidence that LIG4-independent random integration occurs frequently even when NHEJ is functionally normal. Our results collectively suggest that random integration frequency of conventional targeting vectors is substantially influenced by homology arms, which typically harbor repetitive DNA sequences that serve to facilitate LIG4-independent random integration in human cells, regardless of the presence or absence of functional NHEJ.

  7. The effect of nonuniform magnetic targeting of intracoronary-delivering mesenchymal stem cells on coronary embolisation.

    Science.gov (United States)

    Huang, Zheyong; Shen, Yunli; Pei, Ning; Sun, Aijun; Xu, Jianfeng; Song, Yanan; Huang, Gangyong; Sun, Xiaoning; Zhang, Shuning; Qin, Qing; Zhu, Hongming; Yang, Shan; Yang, Xiangdong; Zou, Yunzeng; Qian, Juying; Ge, Junbo

    2013-12-01

    Magnetic targeting has been recently introduced to enhance cell retention in animals with acute myocardial infarction. However, it is unclear whether the magnetic accumulation of intravascular cells increases the risk of coronary embolism. Upon finite element analysis, we found that the permanent magnetic field was nonuniform, manifestated as attenuation along the vertical axis and polarisation along the horizontal axis. In the in vitro experiments, iron-labelled mesenchymal stem cells (MSCs) were accumulated in layers predominantly at the edge of the magnet. In an ischaemic rat model subjected to intracavitary MSCs injection, magnetic targeting induced unfavourable vascular embolisation and an inhomogeneous distribution of the donor cells, which prevented the enhanced cell retention from translating into additional functional benefit. These potential complications of magnetic targeting should be thoroughly investigated and overcome before clinical application. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A drug development perspective on targeting tumor-associated myeloid cells.

    Science.gov (United States)

    Majety, Meher; Runza, Valeria; Lehmann, Christian; Hoves, Sabine; Ries, Carola H

    2018-02-01

    Despite decades of research, cancer remains a devastating disease and new treatment options are needed. Today cancer is acknowledged as a multifactorial disease not only comprising of aberrant tumor cells but also the associated stroma including tumor vasculature, fibrotic plaques, and immune cells that interact in a complex heterotypic interplay. Myeloid cells represent one of the most abundant immune cell population within the tumor stroma and are equipped with a broad functional repertoire that promotes tumor growth by suppressing cytotoxic T cell activity, stimulating neoangiogenesis and tissue remodeling. Therefore, myeloid cells have become an attractive target for pharmacological intervention. In this review, we summarize the pharmacological approaches to therapeutically target tumor-associated myeloid cells with a focus on advanced programs that are clinically evaluated. In addition, for each therapeutic strategy, the preclinical rationale as well as advantages and challenges from a drug development perspective are discussed. © 2017 Federation of European Biochemical Societies.

  9. Whether and Where to Code in the Wireless Relay Channel

    DEFF Research Database (Denmark)

    Shi, Xiaomeng; Médard, Muriel; Roetter, Daniel Enrique Lucani

    2013-01-01

    The throughput benefits of random linear network codes have been studied extensively for wirelined and wireless erasure networks. It is often assumed that all nodes within a network perform coding operations. In energy-constrained systems, however, coding subgraphs should be chosen to control...... the number of coding nodes while maintaining throughput. In this paper, we explore the strategic use of network coding in the wireless packet erasure relay channel according to both throughput and energy metrics. In the relay channel, a single source communicates to a single sink through the aid of a half......-duplex relay. The fluid flow model is used to describe the case where both the source and the relay are coding, and Markov chain models are proposed to describe packet evolution if only the source or only the relay is coding. In addition to transmission energy, we take into account coding and reception...

  10. Multiple relay selection for delay-limited applications

    KAUST Repository

    Alsharoa, Ahmad M.

    2013-12-01

    A multiple relay selection system model that implements the decode-and-forward mode is investigated. All communication nodes are assumed to be equipped by multiple antennas. Furthermore, lattices space-time coded multiple-input multiple-output half duplex channel is applied. The main goal is to increase the throughput of the system by selecting multiple number of relays. The selection criteria depends on the maximum decoding delay at relays where the system implements a decoding time-out algorithm at each relay. This leads to a significant saving in the overall system power consumptions and attempts to solve the relays synchronization problem. All results are presented using numerical simulations. © 2012 IEEE.

  11. Sum-Rate Maximization of Coordinated Direct and Relay Systems

    DEFF Research Database (Denmark)

    Sun, Fan; Popovski, Petar; Thai, Chan

    2012-01-01

    Joint processing of multiple communication flows in wireless systems has given rise to a number of novel transmission techniques, notably the two-way relaying based on wireless network coding. Recently, a related set of techniques has emerged, termed coordinated direct and relay (CDR) transmissions......, where the constellation of traffic flows is more general than the two-way. Regardless of the actual traffic flows, in a CDR scheme the relay has a central role in managing the interference and boosting the overall system performance. In this paper we investigate the novel transmission modes, based...... on amplify-and-forward, that arise when the relay is equipped with multiple antennas and can use beamforming. We focus on one representative traffic type, with one uplink and one downlink users and consider the achievable sum-rate maximization relay beamforming. The beamforming criterion leads to a non...

  12. Beamforming Design for Coordinated Direct and Relay Systems

    DEFF Research Database (Denmark)

    Sun, Fan; De Carvalho, Elisabeth; Thai, Chan

    2012-01-01

    Joint processing of multiple communication flows in wireless systems has given rise to a number of novel transmission techniques, notably the two-way relaying based on wireless network coding. Recently, a related set of techniques has emerged, termed coordinated direct and relay (CDR) transmissions......, where the constellation of traffic flows is more general than the two-way. Regardless of the actual traffic flows, in a CDR scheme the relay has a central role in managing the interference. In this paper we investigate the novel transmission modes, based on amplify-and-forward, that arise when the relay...... an iterative solution, as well as derive an upper performance bound. The numerical results demonstrate a clear benefit from usage of multiple antennas at the relay node....

  13. Spectral efficiency enhancement with interference cancellation for wireless relay network

    DEFF Research Database (Denmark)

    Yomo, Hiroyuki; De Carvalho, Elisabeth

    The introduction of relaying into wireless communication system for coverage enhancement can cause severe decrease of spectral efficiency due to the requirement on extra radio resource. In this paper, we propose a method to increase spectral efficiency in such a wireless relay network by employing...... an interference cancellation technique. We focus on a typical scenario of relaying in a cellular system, where a mobile station (MS) requires the help of a relay station (RS) to communicate with the base station (BS). In such a case, interference cancellation can be used to achieve a small reuse distance...... of identical radio resource. We analyze a simple scenario with BS, single RS, and 2 MSs, and show that the proposed method has significant potential to enhance spectral efficiency in wireless relay networks....

  14. Effects of relay chatter in seismic probabilistic safety analysis

    International Nuclear Information System (INIS)

    Reed, J.W.; Shiu, K.K.

    1985-01-01

    In the Zion and Indian Point Probabilistic Safety Studies, relay chatter was dismissed as a credible event and hence was not formally included in the analyses. Although little discussion is given in the Zion and Indian Point PSA documentation concerning the basis for this decision, it has been expressed informally that it was assumed that the operators will be able to reset all relays in a timely manner. Currently, it is the opinion of many professionals that this may be an oversimplification. The three basic areas which must be considered in addressing relay chatter include the fragility of the relays per se, the reliability of the operators to reset the relays and finally the systems response aspects. Each of these areas is reviewed and the implications for seismic PSA are discussed. Finally, recommendations for future research are given

  15. An RSS based location estimation technique for cognitive relay networks

    KAUST Repository

    Qaraqe, Khalid A.

    2010-11-01

    In this paper, a received signal strength (RSS) based location estimation method is proposed for a cooperative wireless relay network where the relay is a cognitive radio. We propose a method for the considered cognitive relay network to determine the location of the source using the direct and the relayed signal at the destination. We derive the Cramer-Rao lower bound (CRLB) expressions separately for x and y coordinates of the location estimate. We analyze the effects of cognitive behaviour of the relay on the performance of the proposed method. We also discuss and quantify the reliability of the location estimate using the proposed technique if the source is not stationary. The overall performance of the proposed method is presented through simulations. ©2010 IEEE.

  16. Targeting Aberrant Glutathione Metabolism to Eradicate Human Acute Myelogenous Leukemia Cells*

    Science.gov (United States)

    Pei, Shanshan; Minhajuddin, Mohammad; Callahan, Kevin P.; Balys, Marlene; Ashton, John M.; Neering, Sarah J.; Lagadinou, Eleni D.; Corbett, Cheryl; Ye, Haobin; Liesveld, Jane L.; O'Dwyer, Kristen M.; Li, Zheng; Shi, Lei; Greninger, Patricia; Settleman, Jeffrey; Benes, Cyril; Hagen, Fred K.; Munger, Joshua; Crooks, Peter A.; Becker, Michael W.; Jordan, Craig T.

    2013-01-01

    The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34+) leukemic versus normal specimens. Our data indicate that CD34+ AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34+ AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34+ cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34+ AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34+ cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells. PMID:24089526

  17. GEM-loaded magnetic albumin nanospheres modified with cetuximab for simultaneous targeting, magnetic resonance imaging, and double-targeted thermochemotherapy of pancreatic cancer cells.

    Science.gov (United States)

    Wang, Ling; An, Yanli; Yuan, Chenyan; Zhang, Hao; Liang, Chen; Ding, Fengan; Gao, Qi; Zhang, Dongsheng

    2015-01-01

    Targeted delivery is a promising strategy to improve the diagnostic imaging and therapeutic effect of cancers. In this paper, novel cetuximab (C225)-conjugated, gemcitabine (GEM)-containing magnetic albumin nanospheres (C225-GEM/MANs) were fabricated and applied as a theranostic nanocarrier to conduct simultaneous targeting, magnetic resonance imaging (MRI), and double-targeted thermochemotherapy against pancreatic cancer cells. Fe3O4 nanoparticles (NPs) and GEM co-loaded albumin nanospheres (GEM/MANs) were prepared, and then C225 was further conjugated to synthesize C225-GEM/MANs. Their morphology, mean particle size, GEM encapsulation ratio, specific cell-binding ability, and thermal dynamic profiles were characterized. The effects of discriminating different EGFR-expressing pancreatic cancer cells (AsPC-1 and MIA PaCa-2) and monitoring cellular targeting effects were assessed by targeted MRI. Lastly, the antitumor efficiency of double/C225/magnetic-targeted and nontargeted thermochemotherapy was compared with chemotherapy alone using 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and flow cytometry (FCM) assay. When treated with targeted nanospheres, AsPC-1 cells showed a significantly less intense MRI T2 signal than MIA PaCa-2 cells, while both cells had similar signal strength when incubated with nontargeted nanospheres. T2 signal intensity was significantly lower when magnetic and C225 targeting were combined, rather than used alone. The inhibitory and apoptotic rates of each thermochemotherapy group were significantly higher than those of the chemotherapy-alone groups. Additionally, both MTT and FCM analysis verified that double-targeted thermochemotherapy had the highest targeted killing efficiency among all groups. The C225-GEM/MANs can distinguish various EGFR-expressing live pancreatic cancer cells, monitor diverse cellular targeting effects using targeted MRI imaging, and efficiently mediate double-targeted thermochemotherapy

  18. Targeting poly (ADP-ribose polymerase partially contributes to bufalin-induced cell death in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    He Huang

    Full Text Available Despite recent pharmaceutical advancements in therapeutic drugs, multiple myeloma (MM remains an incurable disease. Recently, ploy(ADP-ribose polymerase 1 (PARP1 has been shown as a potentially promising target for MM therapy. A previous report suggested bufalin, a component of traditional Chinese medicine ("Chan Su", might target PARP1. However, this hypothesis has not been verified. We here showed that bufalin could inhibit PARP1 activity in vitro and reduce DNA-damage-induced poly(ADP-ribosylation in MM cells. Molecular docking analysis revealed that the active site of bufalin interaction is within the catalytic domain of PAPR1. Thus, PARP1 is a putative target of bufalin. Furthermore, we showed, for the first time that the proliferation of MM cell lines (NCI-H929, U266, RPMI8226 and MM.1S and primary CD138(+ MM cells could be inhibited by bufalin, mainly via apoptosis and G2-M phase cell cycle arrest. MM cell apoptosis was confirmed by apoptotic cell morphology, Annexin-V positive cells, and the caspase3 activation. We further evaluated the role of PARP1 in bufalin-induced apoptosis, discovering that PARP1 overexpression partially suppressed bufalin-induced cell death. Moreover, bufalin can act as chemosensitizer to enhance the cell growth-inhibitory effects of topotecan, camptothecin, etoposide and vorinostat in MM cells. Collectively, our data suggest that bufalin is a novel PARP1 inhibitor and a potentially promising therapeutic agent against MM alone or in combination with other drugs.

  19. Chemosensitization of cancer cells by siRNA using targeted nanogel delivery

    International Nuclear Information System (INIS)

    Dickerson, Erin B; Blackburn, William H; Smith, Michael H; Kapa, Laura B; Lyon, L Andrew; McDonald, John F

    2010-01-01

    Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05). This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs

  20. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

    International Nuclear Information System (INIS)

    Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

    2012-01-01

    Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id + tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id + single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id + fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id + tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id + scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.