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Sample records for monocrystalline si targets

  1. Surface Damage Mechanism of Monocrystalline Si Under Mechanical Loading

    NASA Astrophysics Data System (ADS)

    Zhao, Qingliang; Zhang, Quanli; To, Suet; Guo, Bing

    2017-03-01

    Single-point diamond scratching and nanoindentation on monocrystalline silicon wafer were performed to investigate the surface damage mechanism of Si under the contact loading. The results showed that three typical stages of material removal appeared during dynamic scratching, and a chemical reaction of Si with the diamond indenter and oxygen occurred under the high temperature. In addition, the Raman spectra of the various points in the scratching groove indicated that the Si-I to β-Sn structure (Si-II) and the following β-Sn structure (Si-II) to amorphous Si transformation appeared under the rapid loading/unloading condition of the diamond grit, and the volume change induced by the phase transformation resulted in a critical depth (ductile-brittle transition) of cut (˜60 nm ± 15 nm) much lower than the theoretical calculated results (˜387 nm). Moreover, it also led to abnormal load-displacement curves in the nanoindentation tests, resulting in the appearance of elbow and pop-out effects (˜270 nm at 20 s, 50 mN), which were highly dependent on the loading/unloading conditions. In summary, phase transformation of Si promoted surface deformation and fracture under both static and dynamic mechanical loading.

  2. Physical assembly of Ag nanocrystals on enclosed surfaces in monocrystalline Si

    PubMed Central

    Martin, Michael S.; Theodore, N. David; Wei, Chao-Chen; Shao, Lin

    2014-01-01

    Growth of thin crystals on external substrate surfaces by many different methods is a well-known technique, but its extension to inner, enclosed surfaces of large defects in monocrystalline materials has not yet been reported. The literature on thin film growth and defects in materials can be leveraged to fabricate new structures for a variety of applications. Here we show a physical process of nucleation and evolution of nanocrystalline silver inside voids in monocrystalline silicon. We found that the Ag growth is hetero-epitaxial using a coincident site lattice. Alignment of Ag and Si atomic planes is uniformly observed by high resolution transmission electron microscopy and macroscopically by channeling Rutherford backscattering spectrometry. PMID:25376502

  3. Nanofabrication on monocrystalline silicon through friction-induced selective etching of Si3N4 mask.

    PubMed

    Guo, Jian; Yu, Bingjun; Wang, Xiaodong; Qian, Linmao

    2014-01-01

    A new fabrication method is proposed to produce nanostructures on monocrystalline silicon based on the friction-induced selective etching of its Si3N4 mask. With low-pressure chemical vapor deposition (LPCVD) Si3N4 film as etching mask on Si(100) surface, the fabrication can be realized by nanoscratching on the Si3N4 mask and post-etching in hydrofluoric acid (HF) and potassium hydroxide (KOH) solution in sequence. Scanning Auger nanoprobe analysis indicated that the HF solution could selectively etch the scratched Si3N4 mask and then provide the gap for post-etching of silicon substrate in KOH solution. Experimental results suggested that the fabrication depth increased with the increase of the scratching load or KOH etching period. Because of the excellent masking ability of the Si3N4 film, the maximum fabrication depth of nanostructure on silicon can reach several microns. Compared to the traditional friction-induced selective etching technique, the present method can fabricate structures with lesser damage and deeper depths. Since the proposed method has been demonstrated to be a less destructive and flexible way to fabricate a large-area texture structure, it will provide new opportunities for Si-based nanofabrication.

  4. Convoy electron production in polycrystalline and monocrystalline targets

    SciTech Connect

    Huldt, S.

    1980-01-01

    The velocity distribution of electrons ejected close to the forward direction by 0.8-2 MeV/A ions traversing various solid targets, including a Au monocrystal, is measured in coincidence with emerging charge-selected ions. The velocity spectrum is observed to be independent of outgoing projectile velocity and charge state for polycrystalline targets. Measurements on the Au crystal under channeling conditions show dependences on final charge state, and are tentatively explained by assuming that the main contribution to the production yield comes from the non-channeled fraction of the ions. A simple model for the creation of the forward-ejected electrons is proposed, which accounts for most of the experimental findings.

  5. Theoretically predicted and experimentally determined effects of the Si/(Si + C) gas phase ratio on the growth and character of monocrystalline beta silicon carbide films

    NASA Astrophysics Data System (ADS)

    Kim, H. J.; Davis, R. F.

    1986-10-01

    The effects of the Si/(Si + C) ratio in the reaction gas stream on the growth and properties of monocrystalline beta-SiC films grown on Si(100) substrates via chemical vapor deposition have been theoretically and experimentally studied. The amounts of condensed phases of beta-SiC and Si, and the partial pressures of the remaining Si and C-containing gases as a function of the Si/(Si + C) ratio in the source gases have been initially obtained from thermodynamic calculations using the 'SOLGASMIX-PV' computer program. Complementary and comparative experimental growth studies have shown that inclusion-free films having maximum values in growth rate and carrier concentration and a minimum value of resistivity were obtained near Si/(Si + C) = 0.5.

  6. Highly c-axis-oriented monocrystalline Pb(Zr, Ti)O₃ thin films on si wafer prepared by fast cooling immediately after sputter deposition.

    PubMed

    Yoshida, Shinya; Hanzawa, Hiroaki; Wasa, Kiyotaka; Esashi, Masayoshi; Tanaka, Shuji

    2014-09-01

    We successfully developed sputter deposition technology to obtain a highly c-axis-oriented monocrystalline Pb(Zr, Ti)O3 (PZT) thin film on a Si wafer by fast cooling (~-180°C/min) of the substrate after deposition. The c-axis orientation ratio of a fast-cooled film was about 90%, whereas that of a slow-cooled (~-40°C/min) film was only 10%. The c-axis-oriented monocrystalline Pb(Zr0.5, Ti0.5)O3 films showed reasonably large piezoelectric coefficients, e(31,f) = ~-11 C/m(2), with remarkably small dielectric constants, ϵ(r) = ~220. As a result, an excellent figure of merit (FOM) was obtained for piezoelectric microelectromechanical systems (MEMS) such as a piezoelectric gyroscope. This c-axis orientation technology on Si will extend industrial applications of PZT-based thin films and contribute further to the development of piezoelectric MEMS.

  7. In-plane thermal conductivity of sub-20 nm thick suspended mono-crystalline Si layers

    NASA Astrophysics Data System (ADS)

    Ferrando-Villalba, P.; Lopeandia, A. F.; Abad, Ll; Llobet, J.; Molina-Ruiz, M.; Garcia, G.; Gerbolès, M.; Alvarez, F. X.; Goñi, A. R.; Muñoz-Pascual, F. J.; Rodríguez-Viejo, J.

    2014-05-01

    We measure the thermal conductivity of a 17.5-nm-thick single crystalline Si layer by using a suspended structure developed from a silicon-on-insulator wafer, in which the Si layer bridges the suspended platforms. The obtained value of 19 Wm-1 K-1 at room temperature represents a tenfold reduction with respect to bulk Si. This design paves the way for subsequent lateral nanostructuration of the layer with lithographic techniques, to define different geometries such as Si nanowires, nanostrips or phononic grids. As a proof of concept, nanostrips of 0.5 × 10 μm have been defined by focused ion beam (FIB) in the ultrathin Si layer. After the FIB cutting process with Ga ions at 30 kV and 100 pA, the measured thermal conductivity dramatically decreased to 1.7 Wm-1 K-1, indicating that the structure became severely damaged (amorphous). Re-crystallization of the structure was promoted by laser annealing while monitoring the Raman spectra. The thermal conductivity of the layer increased again to a value of 9.5 Wm-1 K-1 at room temperature, below that of the single crystalline material due to phonon scattering at the grain boundaries.

  8. Experimental and computational investigation of microcrack behavior under combined environments in monocrystalline Si

    NASA Astrophysics Data System (ADS)

    Huang, W.-J.; Bringuier, S.; Paul, J.; Simmons-Potter, K.; Muralidharan, K.; Potter, B. G.

    2015-09-01

    An investigation of microindenter-induced crack evolution with independent variation of both temperature and relative humidity has been pursued in PV-grade Si wafers. Under static tensile strain conditions, an increase in subcritical crack elongation with increasing atmospheric water content was observed. To provide further insight into the potential physical and chemical conditions at the microcrack tip, micro-Raman measurements were performed. Preliminary results confirm a spatial variation in the frequency of the primary Si vibrational resonance within the cracktip region, associated with local stress state, whose magnitude is influenced by environmental conditions during the period of applied static strain. The experimental effort was paired with molecular dynamics (MD) investigations of microcrack evolution in single-crystal Si to furnish additional insight into mechanical contributions to crack elongation. The MD results demonstrate that crack-tip energetics and associated crack elongation velocity and morphology are intimately related to the crack and applied strain orientations with respect to the principal crystallographic axes. The resulting elastic strain energy release rate and the stress-strain response of the Si under these conditions form the basis for preliminary micro-scale peridynamics (PD) simulations of microcrack development under constant applied strain. These efforts will be integrated with the experimental results to further inform the mechanisms contributing to this important degradation mode in Si-based photovoltaics.

  9. In-plane thermal conductivity of sub-20 nm thick suspended mono-crystalline Si layers.

    PubMed

    Ferrando-Villalba, P; Lopeandia, A F; Abad, Ll; Llobet, J; Molina-Ruiz, M; Garcia, G; Gerbolès, M; Alvarez, F X; Goñi, A R; Muñoz-Pascual, F J; Rodríguez-Viejo, J

    2014-05-09

    We measure the thermal conductivity of a 17.5-nm-thick single crystalline Si layer by using a suspended structure developed from a silicon-on-insulator wafer, in which the Si layer bridges the suspended platforms. The obtained value of 19 Wm(-1) K(-1) at room temperature represents a tenfold reduction with respect to bulk Si. This design paves the way for subsequent lateral nanostructuration of the layer with lithographic techniques, to define different geometries such as Si nanowires, nanostrips or phononic grids. As a proof of concept, nanostrips of 0.5 × 10 μm have been defined by focused ion beam (FIB) in the ultrathin Si layer. After the FIB cutting process with Ga ions at 30 kV and 100 pA, the measured thermal conductivity dramatically decreased to 1.7 Wm(-1) K(-1), indicating that the structure became severely damaged (amorphous). Re-crystallization of the structure was promoted by laser annealing while monitoring the Raman spectra. The thermal conductivity of the layer increased again to a value of 9.5 Wm(-1) K(-1) at room temperature, below that of the single crystalline material due to phonon scattering at the grain boundaries.

  10. New monocrystalline Si{sub 1-x}Ge{sub x} solar cells

    SciTech Connect

    Losada, B.R.; Moehlecke, A.; Ruiz, J.M.; Luque, A.

    1995-08-01

    The development of solar cells on Si{sub 1-x}Ge{sub x} might be interesting because they might present more current photo-response than the silicon cells, based on the lower bandgap of the alloyed crystal. In particular the use of Si{sub 1-x}Ge{sub x} solar cells in dual bandgap concentration structures as GaAs/Si{sub 1-x}Ge{sub x} can lead to total efficiency increase of about 1% as compared to the GaAs/Si structure, according to our calculations. Our effort is devoted to solar cells with low content of Ge, lower than 20% at. This choice is based on two previous hypothesis (1) A low content of Ge suggests that the well known silicon cell process, slightly modified, can be applied to the Si{sub 1-x}Ge{sub x} cells. (2) Calculations suggest that for utilisation in tandem with GaAs cells, the gain of efficiency is low above 20at % Ge.

  11. Improvement of minority carrier life time in N-type monocrystalline Si by the Czochralski method

    NASA Astrophysics Data System (ADS)

    Baik, Sungsun; Pang, Ilsun; Kim, Jaemin; Kim, Kwanghun

    2016-07-01

    The installation amount of solar power plants increases every year. Multi-crystalline Si solar cells comprise a large share of the market of solar power plants. Multi-crystalline and single-crystalline Si solar cells are competing against one another in the market. Many single-crystalline companies are trying to develop and produce n-type solar cells with higher cell efficiency than that of p-type. In n-type wafers with high cell efficiency, wafer quality has become increasingly important. In order to make ingots with higher MCLT, the effects of both poly types related to metal impurities and pull speeds related to vacancy concentration on minority carrier life time were studied. In the final part of ingots, poly types related to the metal impurities are a dominant factor on MCLT. In the initial part of ingots, pull speeds related to vacancy concentration are a dominant factor on MCLT. [Figure not available: see fulltext.

  12. Design of monocrystalline Si/SiGe multi-quantum well microbolometer detector for infrared imaging systems

    NASA Astrophysics Data System (ADS)

    Shafique, Atia; Durmaz, Emre C.; Cetindogan, Barbaros; Yazici, Melik; Kaynak, Mehmet; Kaynak, Canan B.; Gurbuz, Yasar

    2016-05-01

    This paper presents the design, modelling and simulation results of silicon/silicon-germanium (Si/SiGe) multi-quantum well based bolometer detector for uncooled infrared imaging system. The microbolometer is designed to detect light in the long wave length infrared (LWIR) range from 8 to 14 μm with pixel size of 25 x 25 μm. The design optimization strategy leads to achieve the temperature coefficient of resistance (TCR) 4.5%/K with maximum germanium (Ge) concentration of 50%. The design of microbolometer entirely relies on standard CMOS and MEMS processes which makes it suitable candidate for commercial infrared imaging systems.

  13. Buried Porous Silicon-Germanium Layers in Monocrystalline Silicon Lattices

    NASA Technical Reports Server (NTRS)

    Fathauer, Robert W. (Inventor); George, Thomas (Inventor); Jones, Eric W. (Inventor)

    1998-01-01

    Monocrystalline semiconductor lattices with a buried porous semiconductor layer having different chemical composition is discussed and monocrystalline semiconductor superlattices with a buried porous semiconductor layers having different chemical composition than that of its monocrystalline semiconductor superlattice are discussed. Lattices of alternating layers of monocrystalline silicon and porous silicon-germanium have been produced. These single crystal lattices have been fabricated by epitaxial growth of Si and Si-Ge layers followed by patterning into mesa structures. The mesa structures are strain etched resulting in porosification of the Si-Ge layers with a minor amount of porosification of the monocrystalline Si layers. Thicker Si-Ge layers produced in a similar manner emitted visible light at room temperature.

  14. Characteristics of poly- and mono-crystalline BeO and SiO2 as thermal and cold neutron filters

    NASA Astrophysics Data System (ADS)

    Adib, M.; Habib, N.; Bashter, I. I.; Morcos, H. N.; El-Mesiry, M. S.; Mansy, M. S.

    2015-09-01

    A simple model along with a computer code "HEXA-FILTERS" is used to carry out the calculation of the total cross-sections of BeO and SiO2 having poly or mono-crystalline form as a function of neutron wavelength at room (R.T.) and liquid nitrogen (L.N.) temperatures. An overall agreement is indicated between the calculated neutron cross-sections and experimental data. Calculation shows that 25 cm thick of polycrystalline BeO cooled at liquid nitrogen temperature was found to be a good filter for neutron wavelengths longer than 0.46 nm. While, 50 cm of SiO2, with much less transmission, for neutrons with wavelengths longer than 0.85 nm. It was also found that 10 cm of BeO and 15 cm SiO2 thick mono-crystals cut along their (0 0 2) plane, with 0.5° FWHM on mosaic spread and cooled at L.N., are a good thermal neutron filter, with high effect-to-noise ratio.

  15. Photocarrier radiometry for predicting the degradation of electrical parameters of monocrystalline silicon (c-Si) solar cell irradiated by 100 KeV proton beams

    NASA Astrophysics Data System (ADS)

    Song, P.; Liu, J. Y.; Yuan, H. M.; Oliullah, Md.; Wang, F.; Wang, Y.

    2016-09-01

    In this study, the monocrystalline silicon (c-Si) solar cell irradiated by 100 KeV proton beams at various fluences is investigated. A one-dimensional two-layer carrier density wave model has been developed to estimate the minority carrier lifetime of n-region and p-region of the non-irradiated c-Si solar cell by best fitting with the experimental photocarrier radiometry (PCR) signal (the amplitude and the phase). Furthermore, the lifetime is used to determine the initial defect density of the quasi-neutral region (QNR) of the solar cell to predict its I-V characteristics. The theoretically predicted short-circuit current density (Jsc), and open-circuit voltage (Voc) of the non-irradiated samples are in good agreement with experiment. Then a three-region defect distribution model for the c-Si solar cell irradiated by proton beams is carried out to describe the defect density distribution according to Monte Carlo simulation results and the initial defect density of the non-irradiated sample. Finally, we find that the electrical measurements of Jsc and Voc of the solar cells irradiated at different fluences using 100 KeV proton beams are consistent with the PCR predicting results.

  16. Effect of cutting temperature on hardness of SiC and diamond in the nano-cutting process of monocrystalline silicon

    NASA Astrophysics Data System (ADS)

    Wang, Jiachun; Li, Yuntao; Liu, Xiaoxuan; Lv, Maoqiang

    2016-10-01

    In the process of cutting silicon by natural diamond tools, groove wear happens on the flank face of cutting tool frequently.Scholars believe that one of the wear reasons is mechanical scratching effect by hard particles like SiC. To reveal the mechanical scratching mechanism, it is essential to study changes in the mechanical properties of hard particles and diamond, especially the effect of cutting temperature on hardness of diamond and hard particles. Molecular dynamics (MD) model that contact-zone temperature between tool and workpiece was calculated by dividing zone while nano-cutting monocrystalline silicon was established, cutting temperature values in different regions were computed as the simulation was carried out.On this basis, the models of molecular dynamics simulation of SiC and diamond were established separately with setting the initial temperature to room temperature. The laws of length change of C-C bond and Si-C bond varing with increase of simulation temperature were studied. And drawing on predecessors' research on theoretical calculation of hardness of covalent crystals and the relationship between crystal valence electron density and bond length, the curves that the hardness of diamond and SiC varing with bond length were obtained. The effect of temperature on the hardness was calculated. Results show that, local cutting temperature can reach 1300K.The rise in cutting temperature leaded to a decrease in the diamond local atomic clusters hardness,SiC local atomic clusters hardness increased. As the cutting temperature was more than 1100K,diamond began to soften, the local clusters hardness was less than that of SiC.

  17. Photocarrier Radiometry for Noncontact Evaluation of Monocrystalline Silicon (c-Si) Solar Cell Irradiated by 1 MeV Electron Beams

    NASA Astrophysics Data System (ADS)

    Song, P.; Liu, J. Y.; Yuan, H. M.; Wang, F.; Wang, Y.

    2016-08-01

    In this paper, the monocrystalline silicon (c-Si) solar cell irradiated by 1 MeV electron beams was investigated using noncontact photocarrier radiometry (PCR). A theoretical 1D two-layer PCR model including the impedance effect of the p-n junction was used to characterize the transport properties (carrier lifetime, diffusion coefficient, and surface recombination velocities) of c-Si solar cells irradiated by 1 MeV electron beams with different fluences. The carrier transport parameters were derived by the best fit through PCR measurements. Furthermore, an Ev+0.56 eV trap was introduced into the band gap based on the minority carrier lifetime reduction. An I-V characteristic was obtained by both AFORS-HET simulation and experimental study, and the simulation results shows in good agreement with the experimental results. Moreover, the simulation and experiment results also indicate that the increase of fluences of electron beams results in the reduction of short-circuit current and open-circuit voltage.

  18. Growth, Characterization and Device Development in Monocrystalline Diamond Films

    DTIC Science & Technology

    1992-09-01

    AD-A256 283 Quarterly Letter Report Growth, Characterization and Device Development in Monocrystalline Diamond Films DT C * F LEC EGOT 2 1992L... Characterization and Device Development in s400003srrO8 Monocrystalline Diamond Films 1114SS 6. AUTHOR(S) N00179N66005 Robert F. Davis 4B855 7. PERFORMING...deposited on single crystal Si(100) substrates via in-situ carburization followed by bias-enhanced nucleation. Photoluminescence and Raman spectroscopy

  19. The Seebeck coefficient of monocrystalline α-SiC and polycrystalline β-SiC measured at 300-533 K

    NASA Astrophysics Data System (ADS)

    Abu-Ageel, N.; Aslam, M.; Ager, R.; Rimai, L.

    2000-01-01

    The temperature dependence of the Seebeck coefficient of polycrystalline icons/Journals/Common/beta" ALT="beta" ALIGN="TOP"/> -SiC films deposited on quartz substrates by laser ablation and of commercially available icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> -SiC wafers is reported in a temperature range of 300-533 K for the first time. The Seebeck emf of icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> -SiC substrates and icons/Journals/Common/beta" ALT="beta" ALIGN="TOP"/> -SiC samples ranges between -9 µV °C-1 and -108 µV °C-1 which is higher than that of commercial Pt thermocouples.

  20. Method of producing buried porous silicon-geramanium layers in monocrystalline silicon lattices

    NASA Technical Reports Server (NTRS)

    Fathauer, Robert W. (Inventor); George, Thomas (Inventor); Jones, Eric W. (Inventor)

    1997-01-01

    Lattices of alternating layers of monocrystalline silicon and porous silicon-germanium have been produced. These single crystal lattices have been fabricated by epitaxial growth of Si and Si--Ge layers followed by patterning into mesa structures. The mesa structures are stain etched resulting in porosification of the Si--Ge layers with a minor amount of porosification of the monocrystalline Si layers. Thicker Si--Ge layers produced in a similar manner emitted visible light at room temperature.

  1. Methods for manufacturing monocrystalline or near-monocrystalline cast materials

    DOEpatents

    Stoddard, Nathan G

    2014-04-29

    Methods are provided for casting one or more of a semiconductor, an oxide, and an intermetallic material. With such methods, a cast body of a monocrystalline form of the one or more of a semiconductor, an oxide, and an intermetallic material may be formed that is free of, or substantially free of, radially-distributed impurities and defects and having at least two dimensions that are each at least about 35 cm.

  2. Development of brazing foils to join monocrystalline tungsten alloys with ODS-EUROFER steel

    NASA Astrophysics Data System (ADS)

    Kalin, B. A.; Fedotov, V. T.; Sevrjukov, O. N.; Kalashnikov, A. N.; Suchkov, A. N.; Moeslang, A.; Rohde, M.

    2007-08-01

    Results on rapidly solidified filler metals for brazing W with W and monocrystalline W with EUROFER steel (FS) are presented. Rapidly quenched powder-type filler metals based on Ti bal-V-Cr-Be were developed to braze polycrystalline W with monocrystalline W. In addition, Fe bal-Ta-Ge-Si-B-Pd alloys were developed to braze monocrystalline W with FS for helium gas cooled divertors and plasma-facing components. The W to FS brazed joints were fabricated under vacuum at 1150 °C, using a Ta spacer of 0.1 mm in thickness to account for the different thermal expansions. The monocrystalline tungsten as well as the related brazed joints withstood 30 cycles between 750 °C/20 min and air cooling/3-5 min.

  3. The SiC Direct Target Prototype for SPES

    SciTech Connect

    Rizzi, V.; Andrighetto, A.; Barbui, M.; Carturan, S.; Cinausero, M.; Giacchini, M.; Gramegna, F.; Lollo, M.; Maggioni, G.; Prete, G.; Tonezzer, M.; Antonucci, C.; Cevolani, S.; Petrovich, C.; Biasetto, L.; Colombo, P.; Manzolaro, M.; Meneghetti, M.; Celona, L.; Chines, F.

    2007-10-26

    A R and D study for the realization of a Direct Target is in progress within the SPES project for RIBs production at the Laboratori Nazionali of Legnaro. A proton beam (40 MeV energy, 0.2 mA current) is supposed to impinge directly on a UCx multiple thin disks target, the power released by the proton beam is dissipated mainly through irradiation. A SiC target prototype with a 1:5 scale has been developed and tested. Thermal, mechanical and release calculations have been performed to fully characterize the prototype. An online test has been performed at the HRIBF facility of the Oak Ridge National Laboratory (ORNL), showing that our SiC target can sustain a proton beam current considerably higher than the maximum beam current used with the standard HRIBF target configuration.

  4. The SiC Direct Target Prototype for SPES

    SciTech Connect

    Rizzi, Valentina; Andrighetto, Alberto; Antonucci, C.; Barbui, Marina; Biasetto, Lisa; Carturan, S.; Celona, L.; Cevolani, S.; Chines, Francesco; Cinausero, Marco; Colombo, P.; Cuttone, G.; Di Bernardo, P.; Giacchini, Mauro; Gramegna, Fabiana; Lollo, M.; Maggioni, G.; Manzolaro, Mattia; Meneghetti, G.; Messina, G. Esteban; Petrovich, C.; Piga, L.; Prete, Gianfranco; Re, Maurizio; Rizzo, D.; Stracener, Daniel W; Tonezzer, Michele; Zanonato, P.

    2007-01-01

    A R&D study for the realization of a Direct Target is in progress within the SPES project for RIBs production at the Laboratori Nazionali of Legnaro. A proton beam (40 MeV energy, 0.2 niA current) is supposed to impinge directly on a UCx multiple thin disks target, the power released by the proton beam is dissipated mainly through irradiation. A SiC target prototype with a 1:5 scale has been developed and tested. Thermal, mechanical and release calculations have been performed to fully characterize the prototype. An online test has been performed at the HRIBF facility of the Oak Ridge National Laboratory (ORNL), showing that our Sic target can sustain a proton beam current considerably higher than the maximum beam current used with the standard HRIBF target configuration.

  5. Targeting siRNA Missiles to Her2+ Breast Cancer

    DTIC Science & Technology

    2009-06-01

    Nagai, H., Oniki, S., Oka, M., Horikawa, T., and Nishigori, C. (2006). Induction of cellular immunity against hair follicle melanocyte causes alopecia...Principal Investigator: Medina-Kauwe, Lali K. 4 INTRODUCTION: The purpose of this research is to test the hypothesis that recombinant Ad5 capsid...delivered the most potent cytotoxicity in order to incorporate it into the targeted complex and test it in vivo. We compared HER2- silencing siRNA

  6. Enhancing potency of siRNA targeting fusion genes by optimization outside of target sequence

    PubMed Central

    Gavrilov, Kseniya; Seo, Young-Eun; Tietjen, Gregory T.; Cui, Jiajia; Cheng, Christopher J.; Saltzman, W. Mark

    2015-01-01

    Canonical siRNA design algorithms have become remarkably effective at predicting favorable binding regions within a target mRNA, but in some cases (e.g., a fusion junction site) region choice is restricted. In these instances, alternative approaches are necessary to obtain a highly potent silencing molecule. Here we focus on strategies for rational optimization of two siRNAs that target the junction sites of fusion oncogenes BCR-ABL and TMPRSS2-ERG. We demonstrate that modifying the termini of these siRNAs with a terminal G-U wobble pair or a carefully selected pair of terminal asymmetry-enhancing mismatches can result in an increase in potency at low doses. Importantly, we observed that improvements in silencing at the mRNA level do not necessarily translate to reductions in protein level and/or cell death. Decline in protein level is also heavily influenced by targeted protein half-life, and delivery vehicle toxicity can confound measures of cell death due to silencing. Therefore, for BCR-ABL, which has a long protein half-life that is difficult to overcome using siRNA, we also developed a nontoxic transfection vector: poly(lactic-coglycolic acid) nanoparticles that release siRNA over many days. We show that this system can achieve effective killing of leukemic cells. These findings provide insights into the implications of siRNA sequence for potency and suggest strategies for the design of more effective therapeutic siRNA molecules. Furthermore, this work points to the importance of integrating studies of siRNA design and delivery, while heeding and addressing potential limitations such as restricted targetable mRNA regions, long protein half-lives, and nonspecific toxicities. PMID:26627251

  7. Methods and apparatuses for manufacturing monocrystalline cast silicon and monocrystalline cast silicon bodies for photovoltaics

    DOEpatents

    Stoddard, Nathan G [Gettysburg, PA

    2011-11-01

    Methods and apparatuses are provided for casting silicon for photovoltaic cells and other applications. With such methods and apparatuses, a cast body of monocrystalline silicon may be formed that is free of, or substantially free of, radially-distributed impurities and defects and having at least two dimensions that are each at least about 35 cm is provided.

  8. Methods and apparatus for manufacturing monocrystalline cast silicon and monocrystalline cast silicon bodies for photovoltaics

    DOEpatents

    Stoddard, Nathan G

    2014-01-14

    Methods and apparatuses are provided for casting silicon for photovoltaic cells and other applications. With such methods and apparatuses, a cast body of monocrystalline silicon may be formed that is free of, or substantially free of, radially-distributed impurities and defects and having at least two dimensions that are each at least about 35 cm is provided.

  9. Molecular dynamics investigations of mechanical behaviours in monocrystalline silicon due to nanoindentation at cryogenic temperatures and room temperature

    PubMed Central

    Du, Xiancheng; Zhao, Hongwei; Zhang, Lin; Yang, Yihan; Xu, Hailong; Fu, Haishuang; Li, Lijia

    2015-01-01

    Molecular dynamics simulations of nanoindentation tests on monocrystalline silicon (010) surface were conducted to investigate the mechanical properties and deformation mechanism from cryogenic temperature being 10 K to room temperature being 300 K. Furthermore, the load-displacement curves were obtained and the phase transformation was investigated at different temperatures. The results show that the phase transformation occurs both at cryogenic temperatures and at room temperature. By searching for the presence of the unique non-bonded fifth neighbour atom, the metastable phases (Si-III and Si-XII) with fourfold coordination could be distinguished from Si-I phase during the loading stage of nanoindentation process. The Si-II, Si-XIII, and amorphous phase were also found in the region beneath the indenter. Moreover, through the degree of alignment of the metastable phases along specific crystal orientation at different temperatures, it was found that the temperature had effect on the anisotropy of the monocrystalline silicon, and the simulation results indicate that the anisotropy of monocrystalline silicon is strengthened at low temperatures. PMID:26537978

  10. Molecular dynamics investigations of mechanical behaviours in monocrystalline silicon due to nanoindentation at cryogenic temperatures and room temperature.

    PubMed

    Du, Xiancheng; Zhao, Hongwei; Zhang, Lin; Yang, Yihan; Xu, Hailong; Fu, Haishuang; Li, Lijia

    2015-11-05

    Molecular dynamics simulations of nanoindentation tests on monocrystalline silicon (010) surface were conducted to investigate the mechanical properties and deformation mechanism from cryogenic temperature being 10 K to room temperature being 300 K. Furthermore, the load-displacement curves were obtained and the phase transformation was investigated at different temperatures. The results show that the phase transformation occurs both at cryogenic temperatures and at room temperature. By searching for the presence of the unique non-bonded fifth neighbour atom, the metastable phases (Si-III and Si-XII) with fourfold coordination could be distinguished from Si-I phase during the loading stage of nanoindentation process. The Si-II, Si-XIII, and amorphous phase were also found in the region beneath the indenter. Moreover, through the degree of alignment of the metastable phases along specific crystal orientation at different temperatures, it was found that the temperature had effect on the anisotropy of the monocrystalline silicon, and the simulation results indicate that the anisotropy of monocrystalline silicon is strengthened at low temperatures.

  11. siRNA-based topical microbicides targeting sexually transmitted diseases

    PubMed Central

    Katakowski, Joseph A

    2012-01-01

    Sexually transmitted infections (STIs) are a major cause of morbidity and mortality worldwide. Although a vaccine is available for HPV, no effective vaccines exist for the HIV-1 and HSV-2 viral pathogens, and there are no cures for these infections. Furthermore, recent setbacks in clinical trials, such as the failure of the STEP trial to prevent HIV-1 infection, have emphasized the need to develop alternative approaches to interrupt transmission of these pathogens. One alternative strategy is represented by the use of topically applied microbicides, and such agents are being developed against various viruses. RNAi-based microbicides have recently been demonstrated to prevent HSV-2 transmission, and may be useful for targeting multiple STIs. In this review, microbicides that are under development for the prevention of STIs are described, with a focus on topically applied microbicidal siRNAs. PMID:20373263

  12. Targeted tumor-penetrating siRNA nanocomplexes for credentialing the ovarian cancer target ID4

    PubMed Central

    Ren, Yin; Cheung, Hiu Wing; von Maltzhan, Geoffrey; Agrawal, Amit; Cowley, Glenn S.; Weir, Barbara A.; Boehm, Jesse S.; Tamayo, Pablo; Karst, Alison M.; Liu, Joyce F.; Hirsch, Michelle S.; Mesirov, Jill P.; Drapkin, Ronny; Root, David E.; Lo, Justin; Fogal, Valentina; Ruoslahti, Erkki; Hahn, William C.; Bhatia, Sangeeta N.

    2013-01-01

    The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance, because many of these targets are not amenable to manipulation by small molecules or antibodies. RNAi provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) comprised of siRNA complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We employed TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor-bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers, but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets. PMID:22896676

  13. Multi-target siRNA: Therapeutic Strategy for Hepatocellular Carcinoma

    PubMed Central

    Li, Tiejun; Xue, Yuwen; Wang, Guilan; Gu, Tingting; Li, Yunlong; Zhu, York Yuanyuan; Chen, Li

    2016-01-01

    Multiple targets RNAi strategy is a preferred way to treat multigenic diseases, especially cancers. In the study, multi-target siRNAs were designed to inhibit NET-1, EMS1 and VEGF genes in hepatocellular carcinoma (HCC) cells. And multi-target siRNAs showed better silencing effects on NET-1, EMS1 and VEGF, compared with single target siRNA. Moreover, multi-target siRNA showed greater suppression effects on proliferation, migration, invasion, angiogenesis and induced apoptosis in HCC cells. The results suggested that multi-target siRNA might be a preferred strategy for cancer therapy and NET-1, EMS1 and VEGF could be effective targets for HCC treatments. PMID:27390607

  14. Minimizing off-target effects by using diced siRNAs for RNA interference

    PubMed Central

    Myers, Jason W; Chi, Jen-Tsan; Gong, Delquin; Schaner, Marci E; Brown, Patrick O; Ferrell, James E

    2006-01-01

    Microarray studies have shown that individual synthetic small interfering RNAs (siRNAs) can have substantial off-target effects. Pools of siRNAs, produced by incubation of dsRNAs with recombinant Dicer or RNase III, can also be used to silence genes. Here we show that diced siRNA pools are highly complex, containing hundreds of different individual siRNAs. This high complexity could either compound the problem of off-target effects, since the number of potentially problematic siRNAs is high, or it could diminish the problem, since the concentration of any individual problematic siRNA is low. We therefore compared the off-target effects of diced siRNAs to chemically synthesized siRNAs. In agreement with previous reports, we found that two chemically synthesized siRNAs targeted against p38α MAPK (MAPK14) induced off-target changes in the abundance of hundreds of mRNAs. In contrast, three diced siRNA pools against p38α MAPK had almost no off-target effects. The off-target effects of a synthetic siRNA were reduced when the siRNA was diluted 3-fold in a diced pool and completely alleviated when it was diluted 30- or 300-fold, suggesting that when problematic siRNAs are present within a diced pool, their absolute concentration is too low to result in significant off-target effects. These data rationalize the observed high specificity of RNA interference in C. elegans and D. melanogaster, where gene suppression is mediated by endogenously-generated diced siRNA pools, and provide a strategy for improving the specificity of RNA interference experiments and screens in mammalian cells. PMID:19771225

  15. The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects

    PubMed Central

    Kamola, Piotr J.; Nakano, Yuko; Takahashi, Tomoko; Wilson, Paul A.; Ui-Tei, Kumiko

    2015-01-01

    RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA (miRNA) silencing. To better understand these off-target effects, we investigated the correlation between sequence features within various subsections of siRNA guide strands, and its corresponding target sequences, with off-target activities. Our results confirm previous reports that strength of base-pairing in the siRNA seed region is the primary factor determining the efficiency of off-target silencing. However, the degree of downregulation of off-target transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential. Here, we demonstrate that both the melting temperature (Tm) in a subsection of siRNA non-seed region, and the GC contents of its corresponding target sequences, are negatively correlated with the efficiency of off-target effect. Analysis of experimentally validated miRNA targets demonstrated a similar trend, indicating a putative conserved mechanistic feature of seed region-dependent targeting mechanism. These observations may prove useful as parameters for off-target prediction algorithms and improve siRNA ‘specificity’ design rules. PMID:26657993

  16. Femtosecond laser direct writing of monocrystalline hexagonal silver prisms

    SciTech Connect

    Vora, Kevin; Kang, SeungYeon; Moebius, Michael; Mazur, Eric

    2014-10-06

    Bottom-up growth methods and top-down patterning techniques are both used to fabricate metal nanostructures, each with a distinct advantage: One creates crystalline structures and the other offers precise positioning. Here, we present a technique that localizes the growth of metal crystals to the focal volume of a laser beam, combining advantages from both approaches. We report the fabrication of silver nanoprisms—hexagonal nanoscale silver crystals—through irradiation with focused femtosecond laser pulses. The growth of these nanoprisms is due to a nonlinear optical interaction between femtosecond laser pulses and a polyvinylpyrrolidone film doped with silver nitrate. The hexagonal nanoprisms have bases hundreds of nanometers in size and the crystal growth occurs over exposure times of less than 1 ms (8 orders of magnitude faster than traditional chemical techniques). Electron backscatter diffraction analysis shows that the hexagonal nanoprisms are monocrystalline. The fabrication method combines advantages from both wet chemistry and femtosecond laser direct-writing to grow silver crystals in targeted locations. The results presented in this letter offer an approach to directly positioning and growing silver crystals on a substrate, which can be used for plasmonic devices.

  17. Femtosecond laser direct writing of monocrystalline hexagonal silver prisms

    NASA Astrophysics Data System (ADS)

    Vora, Kevin; Kang, SeungYeon; Moebius, Michael; Mazur, Eric

    2014-10-01

    Bottom-up growth methods and top-down patterning techniques are both used to fabricate metal nanostructures, each with a distinct advantage: One creates crystalline structures and the other offers precise positioning. Here, we present a technique that localizes the growth of metal crystals to the focal volume of a laser beam, combining advantages from both approaches. We report the fabrication of silver nanoprisms—hexagonal nanoscale silver crystals—through irradiation with focused femtosecond laser pulses. The growth of these nanoprisms is due to a nonlinear optical interaction between femtosecond laser pulses and a polyvinylpyrrolidone film doped with silver nitrate. The hexagonal nanoprisms have bases hundreds of nanometers in size and the crystal growth occurs over exposure times of less than 1 ms (8 orders of magnitude faster than traditional chemical techniques). Electron backscatter diffraction analysis shows that the hexagonal nanoprisms are monocrystalline. The fabrication method combines advantages from both wet chemistry and femtosecond laser direct-writing to grow silver crystals in targeted locations. The results presented in this letter offer an approach to directly positioning and growing silver crystals on a substrate, which can be used for plasmonic devices.

  18. Self-assembly of microscopic chiplets at a liquid–liquid–solid interface forming a flexible segmented monocrystalline solar cell

    PubMed Central

    Knuesel, Robert J.; Jacobs, Heiko O.

    2010-01-01

    This paper introduces a method for self-assembling and electrically connecting small (20–60 micrometer) semiconductor chiplets at predetermined locations on flexible substrates with high speed (62500 chips/45 s), accuracy (0.9 micrometer, 0.14°), and yield (> 98%). The process takes place at the triple interface between silicone oil, water, and a penetrating solder-patterned substrate. The assembly is driven by a stepwise reduction of interfacial free energy where chips are first collected and preoriented at an oil-water interface before they assemble on a solder-patterned substrate that is pulled through the interface. Patterned transfer occurs in a progressing linear front as the liquid layers recede. The process eliminates the dependency on gravity and sedimentation of prior methods, thereby extending the minimal chip size to the sub-100 micrometer scale. It provides a new route for the field of printable electronics to enable the integration of microscopic high performance inorganic semiconductors on foreign substrates with the freedom to choose target location, pitch, and integration density. As an example we demonstrate a fault-tolerant segmented flexible monocrystalline silicon solar cell, reducing the amount of Si that is used when compared to conventional rigid cells. PMID:20080682

  19. Self-assembly of microscopic chiplets at a liquid-liquid-solid interface forming a flexible segmented monocrystalline solar cell.

    PubMed

    Knuesel, Robert J; Jacobs, Heiko O

    2010-01-19

    This paper introduces a method for self-assembling and electrically connecting small (20-60 micrometer) semiconductor chiplets at predetermined locations on flexible substrates with high speed (62500 chips/45 s), accuracy (0.9 micrometer, 0.14 degrees), and yield (> 98%). The process takes place at the triple interface between silicone oil, water, and a penetrating solder-patterned substrate. The assembly is driven by a stepwise reduction of interfacial free energy where chips are first collected and preoriented at an oil-water interface before they assemble on a solder-patterned substrate that is pulled through the interface. Patterned transfer occurs in a progressing linear front as the liquid layers recede. The process eliminates the dependency on gravity and sedimentation of prior methods, thereby extending the minimal chip size to the sub-100 micrometer scale. It provides a new route for the field of printable electronics to enable the integration of microscopic high performance inorganic semiconductors on foreign substrates with the freedom to choose target location, pitch, and integration density. As an example we demonstrate a fault-tolerant segmented flexible monocrystalline silicon solar cell, reducing the amount of Si that is used when compared to conventional rigid cells.

  20. Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy.

    PubMed

    Kim, Min Ju; Park, Jong-Sung; Lee, So Jin; Jang, Jiyeon; Park, Jin Su; Back, Seung Hyun; Bahn, Gahee; Park, Jae Hyung; Kang, Young Mo; Kim, Sun Hwa; Kwon, Ick Chan; Jo, Dong-Gyu; Kim, Kwangmeyung

    2015-10-28

    Notch pathway plays a pivotal role in synoviocytes involved in progression of rheumatoid arthritis (RA). Herein, we designed the Notch1 targeting siRNA delivery nanoparticles (siRNA-NPs) in order to confirm the anti-inflammatory effect in collagen-induced arthritis (CIA) model. The siRNA-NPs were successfully produced by encapsulating polymerized siRNA (poly-siRNA) into thiolated glycol chitosan (tGC) nanoparticles in aqueous condition. The in vitro Notch1 inhibition of siRNA-NPs in murine macrophage cell (RAW 264.7) was confirmed using confocal microscopy and real time PCR. Fluorescently labeled siRNA-NPs were successfully transfected in RAW 264.7 and modulated the expression of Notch1 in mRNA level. For in vivo study, siRNA-NPs exhibited the higher targeting efficiency in the arthritic joins of CIA mice, confirmed by the near-infrared fluorescence (NIRF) imaging. Furthermore, inhibition of Notch1 with siRNA-NPs resulted in retarded progression of inflammation, bone erosion, and cartilage damage in CIA mice. Novel Notch1 targeting siRNA delivery system of siRNA-NPs showed effective RA treatment by suppressing Notch1 signaling pathway without undesirable severe toxicity. Thus, Notch1 inhibiting siRNA-NPs demonstrated the great potential in RA therapeutics that was hard to be achieved using conventional drugs.

  1. Combined-environment influence on microcrack evolution in mono-crystalline silicon

    NASA Astrophysics Data System (ADS)

    Huang, W.-J.; Fortuno, Z. D.; Li, M.; Liu, J.; Liao, H.; Simmons-Potter, K.; Potter, B. G.

    2014-10-01

    The impact of combined environment conditions (mechanical state, temperature, and relative humidity) on microcrack propagation characteristics in p-type monocrystalline, photovoltaic-grade Si wafers was examined. A four-point bend apparatus was used to impose static strain conditions in 280 micron thick monocrystalline Si wafers containing microindentation-initiated crack centers. The specimen under test was simultaneously subjected to varied temperature and relative humidity conditions within a controlled environment chamber. Microcrack length was monitored after exposure to two sets of temperature and relative humidity conditions (i.e. 20° and 33%, 40° and 60% respectively) using scanning electron microscopy. Two primary stages of crack elongation behavior were observed under both of the combined environment conditions. Specifically, an early-time, more rapid growth period occurred, followed by more limited crack growth at later times. The deceleration of crack propagation is consistent with stress relaxation accompanying crack elongation under the constant strain conditions imposed. In general, an increase in the average microcrack propagation rate within both growth rate ranges and in the final overall change in average crack length was observed under elevated temperature and humidity conditions. These findings support the probable role of local crack-tip environment on microcrack evolution.

  2. Reducible hyaluronic acid-siRNA conjugate for target specific gene silencing.

    PubMed

    Park, Kitae; Yang, Jeong-A; Lee, Min-Young; Lee, Hwiwon; Hahn, Sei Kwang

    2013-07-17

    Despite wide applications of polymer-drug conjugates, there are only a few polymer-siRNA conjugates like poly(ethylene glycol) conjugated siRNA. In this work, reducible hyaluronic acid (HA)-siRNA conjugate was successfully developed for target specific systemic delivery of siRNA to the liver. The conjugation of siRNA to HA made it possible to form a compact nanocomplex of siRNA with relatively nontoxic linear polyethyleneimine (LPEI). After characterization of HA-siRNA conjugate by size exclusion chromatography (SEC) and gel electrophoresis, its complex formation with LPEI was investigated with a particle analyzer. The HA-siRNA/LPEI complex had a mean particle size of ca. 250 nm and a negative or neutral surface charge at physiological condition. The reducible HA-siRNA/LPEI complex showed a higher in vitro gene silencing efficiency than noncleavable HA-siRNA/LPEI complex. Furthermore, after systemic delivery, apolipoprotein B (ApoB) specific HA-siApoB/LPEI complex was target specifically delivered to the liver, which resulted in statistically significant reduction of ApoB mRNA expression in a dose dependent manner. The HA-siRNA conjugate can be effectively applied as a model system to the treatment of liver diseases using various siRNAs and relatively nontoxic polycations.

  3. Monocrystalline test structures, and use for calibrating instruments

    DOEpatents

    Cresswell, Michael W.; Ghoshtagore, R. N.; Linholm, Loren W.; Allen, Richard A.; Sniegowski, Jeffry J.

    1997-01-01

    An improved test structure for measurement of width of conductive lines formed on substrates as performed in semiconductor fabrication, and for calibrating instruments for such measurements, is formed from a monocrystalline starting material, having an insulative layer formed beneath its surface by ion implantation or the equivalent, leaving a monocrystalline layer on the surface. The monocrystalline surface layer is then processed by preferential etching to accurately define components of the test structure. The substrate can be removed from the rear side of the insulative layer to form a transparent window, such that the test structure can be inspected by transmissive-optical techniques. Measurements made using electrical and optical techniques can be correlated with other measurements, including measurements made using scanning probe microscopy.

  4. Topics in LIFE Target Survival: 11-SI-004 Final Report

    SciTech Connect

    Miles, Robin; Benett, Bill; Bond, Tiziana; Chang, Allan; Dawson, David; Fornasiero, Francesco; Hamilton, Julie; Havstad, Mark; Kucheyev, Sergei; LeBlanc, Mary; Rosso, Paul; Schebler, Greg; Van Cleve, Eli; Worsley, Marcus

    2014-10-20

    The LIFE target design incorporates many considerations to generate the desired fusion gain including the physics design, the cost of manufacturing of the target, the injectability of the target, the aerodynamic flight characteristics of the target, the ability to track and engage the target and to maintain the structural and thermal integrity of the target. This document describes the effort that was made in support of issues of survivability of the target during injection which included issues massmanufactural materials and processes which could be used in the target.

  5. Structure-Guided Control of siRNA Off-Target Effects.

    PubMed

    Suter, Scott R; Sheu-Gruttadauria, Jessica; Schirle, Nicole T; Valenzuela, Rachel; Ball-Jones, Alexi A; Onizuka, Kazumitsu; MacRae, Ian J; Beal, Peter A

    2016-07-20

    Short interfering RNAs (siRNAs) are promising therapeutics that make use of the RNA interference (RNAi) pathway, but liabilities arising from the native RNA structure necessitate chemical modification for drug development. Advances in the structural characterization of components of the human RNAi pathway have enabled structure-guided optimization of siRNA properties. Here we report the 2.3 Å resolution crystal structure of human Argonaute 2 (hAgo2), a key nuclease in the RNAi pathway, bound to an siRNA guide strand bearing an unnatural triazolyl nucleotide at position 1 (g1). Unlike natural nucleotides, this analogue inserts deeply into hAgo2's central RNA binding cleft and thus is able to modulate pairing between guide and target RNAs. The affinity of the hAgo2-siRNA complex for a seed-only matched target was significantly reduced by the triazolyl modification, while the affinity for a fully matched target was unchanged. In addition, siRNA potency for off-target repression was reduced (4-fold increase in IC50) by the modification, while on-target knockdown was improved (2-fold reduction in IC50). Controlling siRNA on-target versus microRNA (miRNA)-like off-target potency by projection of substituent groups into the hAgo2 central cleft from g1 is a new approach to enhance siRNA selectivity with a strong structural rationale.

  6. RGD-based active targeting of novel polycation liposomes bearing siRNA for cancer treatment.

    PubMed

    Yonenaga, Norihito; Kenjo, Eriya; Asai, Tomohiro; Tsuruta, Atsushi; Shimizu, Kosuke; Dewa, Takehisa; Nango, Mamoru; Oku, Naoto

    2012-06-10

    For the purpose of systemic delivery of siRNA, we previously developed polycation liposomes (PCLs) containing dicetylphosphate-tetraethylenepentamine (DCP-TEPA) as an effective siRNA carrier. In the present study, to endow these PCLs (TEPA-PCL) actively target cancer cells and angiogenic vessels, we decorated the PCLs with cyclic RGD, by using cyclic RGD-grafted distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG), and investigated the usefulness of this type of carrier (RGD-PEG-PCL) for active targeting. Firstly, the gene-silencing efficacy of siRNA for luciferase (siLuc2) formulated in RGD-PEG-PCL (RGD-PEG-PCL/siLuc2) was examined in vitro by using B16F10-luc2 murine melanoma cells stably expressing the luciferase 2 gene, where the siRNA was grafted with cholesterol at the 3'-end of the sense strand (siRNA-C) for the stable association of the siRNA with the PCL. RGD-PEG-PCL/siLuc2 showed high knockdown efficiency compared with siLuc2 formulated in PEGylated TEPA-PCL without cyclic RGD (PEG-PCL). Next, the gene-silencing efficacy of RGD-PEG-PCL/siLuc2 was examined in vivo by use of B16F10-luc2 lung metastatic model mice. The intravenous injection of RGD-PEG-PCL/siLuc2 showed high knockdown efficiency against metastatic B16F10-luc2 tumors in the lungs of the mice, as assessed with an in vivo imaging system. These data strongly suggest that systemic and active targeting siRNA delivery using RGD-PEG-PCL is useful for cancer RNAi therapy.

  7. Thick target yields of proton induced gamma-ray emission from Al, Si and P

    NASA Astrophysics Data System (ADS)

    Jokar, A.; Kakuee, O.; Lamehi-Rachti, M.; Fathollahi, V.

    2017-03-01

    Thick target excitation yield curves of gamma-rays from the reactions 27Al(p,p‧γ)27Al (Eγ = 844 and 1014 keV), 27Al(p,αγ)27Al (Eγ = 1369 keV), 28Si(p,p‧γ)28Si (Eγ = 1779 keV), 29Si(p,p‧γ)29Si (Eγ = 1273 keV) and 31P(p,p‧γ)31P (Eγ = 1266 keV) were measured by bombarding pure-element targets with protons at energies below 3 MeV. Gamma-rays were detected with a High Purity Ge detector placed at an angle of 90° with respect to the beam direction. The obtained thick target gamma-ray yields were compared with the previously published data. The overall systematic uncertainty of the thick target yield values was estimated to be better than ±9%.

  8. Polarization effects in femtosecond laser induced amorphization of monocrystalline silicon

    NASA Astrophysics Data System (ADS)

    Bai, Feng; Li, Hong-Jin; Huang, Yuan-Yuan; Fan, Wen-Zhong; Pan, Huai-Hai; Wang, Zhuo; Wang, Cheng-Wei; Qian, Jing; Li, Yang-Bo; Zhao, Quan-Zhong

    2016-10-01

    We have used femtosecond laser pulses to ablate monocrystalline silicon wafer. Raman spectroscopy and X-ray diffraction analysis of ablation surface indicates horizontally polarized laser beam shows an enhancement in amorphization efficiency by a factor of 1.6-1.7 over the circularly polarized laser ablation. This demonstrates that one can tune the amorphization efficiency through the polarization of irradiation laser.

  9. Effect of crystal plane orientation on tribochemical removal of monocrystalline silicon

    NASA Astrophysics Data System (ADS)

    Xiao, Chen; Guo, Jian; Zhang, Peng; Chen, Cheng; Chen, Lei; Qian, Linmao

    2017-01-01

    The effect of crystal plane orientation on tribochemical removal of monocrystalline silicon was investigated using an atomic force microscope. Experimental results indicated that the tribochemical removal of silicon by SiO2 microsphere presented strong crystallography-induced anisotropy. Further analysis suggested that such anisotropic tribochemical removal of silicon was not dependent on the crystallography-dependent surface mechanical properties (i.e., hardness and elastic modulus), but was mainly attributed to various atomic planar density and interplanar spacing in different crystal planes. Phenomenological results speculated that higher density of silicon atom could promote the formation of Si-O-Si bonds between the SiO2 microsphere and silicon substrate, resulting in more severe tribochemical material removal. Larger interplanar spacing with smaller energy barrier facilitated the rupture of the Si-Si network with the help of mechanical shearing stress, which caused more serious wear of the silicon surface. The results may help understand the material removal mechanism of silicon and provide useful knowledge for chemical mechanical polishing.

  10. Effect of crystal plane orientation on tribochemical removal of monocrystalline silicon

    PubMed Central

    Xiao, Chen; Guo, Jian; Zhang, Peng; Chen, Cheng; Chen, Lei; Qian, Linmao

    2017-01-01

    The effect of crystal plane orientation on tribochemical removal of monocrystalline silicon was investigated using an atomic force microscope. Experimental results indicated that the tribochemical removal of silicon by SiO2 microsphere presented strong crystallography-induced anisotropy. Further analysis suggested that such anisotropic tribochemical removal of silicon was not dependent on the crystallography-dependent surface mechanical properties (i.e., hardness and elastic modulus), but was mainly attributed to various atomic planar density and interplanar spacing in different crystal planes. Phenomenological results speculated that higher density of silicon atom could promote the formation of Si-O-Si bonds between the SiO2 microsphere and silicon substrate, resulting in more severe tribochemical material removal. Larger interplanar spacing with smaller energy barrier facilitated the rupture of the Si-Si network with the help of mechanical shearing stress, which caused more serious wear of the silicon surface. The results may help understand the material removal mechanism of silicon and provide useful knowledge for chemical mechanical polishing. PMID:28084433

  11. Targeted Sterically Stabilized Phospholipid siRNA Nanomedicine for Hepatic and Renal Fibrosis

    PubMed Central

    Khaja, Fatima; Jayawardena, Dulari; Kuzmis, Antonina; Önyüksel, Hayat

    2016-01-01

    Since its discovery, small interfering RNA (siRNA) has been considered a potent tool for modulating gene expression. It has the ability to specifically target proteins via selective degradation of messenger RNA (mRNA) not easily accessed by conventional drugs. Hence, RNA interference (RNAi) therapeutics have great potential in the treatment of many diseases caused by faulty protein expression such as fibrosis and cancer. However, for clinical application siRNA faces a number of obstacles, such as poor in vivo stability, and off-target effects. Here we developed a unique targeted nanomedicine to tackle current siRNA delivery issues by formulating a biocompatible, biodegradable and relatively inexpensive nanocarrier of sterically stabilized phospholipid nanoparticles (SSLNPs). This nanocarrier is capable of incorporating siRNA in its core through self-association with a novel cationic lipid composed of naturally occuring phospholipids and amino acids. This overall assembly protects and delivers sufficient amounts of siRNA to knockdown over-expressed protein in target cells. The siRNA used in this study, targets connective tissue growth factor (CTGF), an important regulator of fibrosis in both hepatic and renal cells. Furthermore, asialoglycoprotein receptors are targeted by attaching the galactosamine ligand to the nanocarries which enhances the uptake of nanoparticles by hepatocytes and renal tubular epithelial cells, the major producers of CTGF in fibrosis. On animals this innovative nanoconstruct, small interfering RNA in sterically stabilized phospholipid nanoparticles (siRNA-SSLNP), showed favorable pharmacokinetic properties and accumulated mostly in hepatic and renal tissues making siRNA-SSLNP a suitable system for targeting liver and kidney fibrotic diseases.

  12. Exosomes for targeted siRNA delivery across biological barriers.

    PubMed

    El Andaloussi, Samir; Lakhal, Samira; Mäger, Imre; Wood, Matthew J A

    2013-03-01

    Using oligonucleotide-based drugs to modulate gene expression has opened a new avenue for drug discovery. In particular small interfering RNAs (siRNAs) are being rapidly recognized as promising therapeutic tools, but their poor bioavailability limits the full realization of their clinical potential. In recent years, cumulating evidence has emerged for the role of membrane vesicles, secreted by most cells and found in all body fluids, as key mediators of information transmission between cells. Importantly, a sub-group of these termed exosomes, have recently been shown to contain various RNA species and to mediate their horizontal transfer to neighbouring- or distant recipient cells. Here, we provide a brief overview on membrane vesicles and their role in exchange of genetic information. We also describe how these natural carriers of genetic material can be harnessed to overcome the obstacle of poor delivery and allow efficient systemic delivery of exogenous siRNA across biological barriers such as the blood-brain barrier.

  13. ICS-283: a system for targeted intravenous delivery of siRNA.

    PubMed

    Schiffelers, Raymond M; Storm, Gert

    2006-05-01

    ICS-283 was developed within Intradigm Corporation as a system that is designed for the systemic delivery of therapeutic small interfering (siRNA) to sites of pathological angiogenesis. The non-viral siRNA delivery system is based on synthetic nanoparticles, known as Targe (Intradigm Corporation), which functions as a broad-platform technology to deliver siRNA to specific target cells in diseased tissues. The system is constructed to incorporate different functionalities that address critical needs for successful nucleic acid delivery. The TargeTran synthetic vector is a self-assembling, layered nanoparticle that protects and targets siRNA to specific cell types in pathological tissues. At present, ICS-283 is the only antiangiogenic siRNA delivery system that is designed for intravenous administration to treat angiogenesis-driven diseases.

  14. [siRNAs with high specificity to the target: a systematic design by CRM algorithm].

    PubMed

    Alsheddi, T; Vasin, L; Meduri, R; Randhawa, M; Glazko, G; Baranova, A

    2008-01-01

    'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

  15. Selecting effective siRNA target sequences by using Bayes' theorem.

    PubMed

    Takasaki, Shigeru

    2009-10-01

    Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells but varies markedly in its gene silencing efficacy. Although many design rules/guidelines for effective siRNAs based on various criteria have been reported recently, there are few consistencies among them. This makes it difficult to select effective siRNA sequences in mammalian genes. Another shortcoming of most previously reported methods is that they cannot estimate the probability that a candidate sequence will silence the target gene. The analytical prediction method proposed in the present study uses Bayes' theorem to select effective siRNA target sequences from many possible candidate sequences. It is quite different from the previous score-based siRNA design techniques and can predict the probability that a candidate siRNA sequence will be effective. The results of evaluating it by applying it to recently reported effective and ineffective siRNA sequences for various genes indicate that it would be useful for many other genes. It should therefore be useful for selecting siRNA sequences effective for mammalian genes.

  16. Silica substrate or portion formed from oxidation of monocrystalline silicon

    DOEpatents

    Matzke, Carolyn M.; Rieger, Dennis J.; Ellis, Robert V.

    2003-07-15

    A method is disclosed for forming an inclusion-free silica substrate using a monocrystalline silicon substrate as the starting material and oxidizing the silicon substrate to convert it entirely to silica. The oxidation process is performed from both major surfaces of the silicon substrate using a conventional high-pressure oxidation system. The resulting product is an amorphous silica substrate which is expected to have superior etching characteristics for microfabrication than conventional fused silica substrates. The present invention can also be used to convert only a portion of a monocrystalline silicon substrate to silica by masking the silicon substrate and locally thinning a portion the silicon substrate prior to converting the silicon portion entirely to silica. In this case, the silica formed by oxidizing the thinned portion of the silicon substrate can be used, for example, as a window to provide optical access through the silicon substrate.

  17. Mechanical instability of monocrystalline and polycrystalline methane hydrates

    PubMed Central

    Wu, Jianyang; Ning, Fulong; Trinh, Thuat T.; Kjelstrup, Signe; Vlugt, Thijs J. H.; He, Jianying; Skallerud, Bjørn H.; Zhang, Zhiliang

    2015-01-01

    Despite observations of massive methane release and geohazards associated with gas hydrate instability in nature, as well as ductile flow accompanying hydrate dissociation in artificial polycrystalline methane hydrates in the laboratory, the destabilising mechanisms of gas hydrates under deformation and their grain-boundary structures have not yet been elucidated at the molecular level. Here we report direct molecular dynamics simulations of the material instability of monocrystalline and polycrystalline methane hydrates under mechanical loading. The results show dislocation-free brittle failure in monocrystalline hydrates and an unexpected crossover from strengthening to weakening in polycrystals. Upon uniaxial depressurisation, strain-induced hydrate dissociation accompanied by grain-boundary decohesion and sliding destabilises the polycrystals. In contrast, upon compression, appreciable solid-state structural transformation dominates the response. These findings provide molecular insight not only into the metastable structures of grain boundaries, but also into unusual ductile flow with hydrate dissociation as observed during macroscopic compression experiments. PMID:26522051

  18. Method and apparatus for drawing monocrystalline ribbon from a melt

    DOEpatents

    Ciszek, Theodore F.; Schwuttke, Guenter H.

    1981-11-10

    A method and apparatus for drawing a monocrystalline ribbon or web from a melt comprising utilizing a shaping die including at least two elements spaced one from the other each having a portion thereof located below the level of the melt and another portion located above the level of the melt a distance sufficient to form a raised meniscus of melt about the corresponding element.

  19. Picosecond optical vortex pulse illumination forms a monocrystalline silicon needle

    PubMed Central

    Takahashi, Fuyuto; Miyamoto, Katsuhiko; Hidai, Hirofumi; Yamane, Keisaku; Morita, Ryuji; Omatsu, Takashige

    2016-01-01

    The formation of a monocrystalline silicon needle by picosecond optical vortex pulse illumination was demonstrated for the first time in this study. The dynamics of this silicon needle formation was further revealed by employing an ultrahigh-speed camera. The melted silicon was collected through picosecond pulse deposition to the dark core of the optical vortex, forming the silicon needle on a submicrosecond time scale. The needle was composed of monocrystalline silicon with the same lattice index (100) as that of the silicon substrate, and had a height of approximately 14 μm and a thickness of approximately 3 μm. Overlaid vortex pulses allowed the needle to be shaped with a height of approximately 40 μm without any changes to the crystalline properties. Such a monocrystalline silicon needle can be applied to devices in many fields, such as core–shell structures for silicon photonics and photovoltaic devices as well as nano- or microelectromechanical systems. PMID:26907639

  20. Dual-Functional Nanoparticles Targeting CXCR4 and Delivering Antiangiogenic siRNA Ameliorate Liver Fibrosis.

    PubMed

    Liu, Chun-Hung; Chan, Kun-Ming; Chiang, Tsaiyu; Liu, Jia-Yu; Chern, Guann-Gen; Hsu, Fu-Fei; Wu, Yu-Hsuan; Liu, Ya-Chi; Chen, Yunching

    2016-07-05

    The progression of liver fibrosis, an intrinsic response to chronic liver injury, is associated with hepatic hypoxia, angiogenesis, abnormal inflammation, and significant matrix deposition, leading to the development of cirrhosis and hepatocellular carcinoma (HCC). Due to the complex pathogenesis of liver fibrosis, antifibrotic drug development has faced the challenge of efficiently and specifically targeting multiple pathogenic mechanisms. Therefore, CXCR4-targeted nanoparticles (NPs) were formulated to deliver siRNAs against vascular endothelial growth factor (VEGF) into fibrotic livers to block angiogenesis during the progression of liver fibrosis. AMD3100, a CXCR4 antagonist that was incorporated into the NPs, served dual functions: it acted as a targeting moiety and suppressed the progression of fibrosis by inhibiting the proliferation and activation of hepatic stellate cells (HSCs). We demonstrated that CXCR4-targeted NPs could deliver VEGF siRNAs to fibrotic livers, decrease VEGF expression, suppress angiogenesis and normalize the distorted vessels in the fibrotic livers in the carbon tetrachloride (CCl4) induced mouse model. Moreover, blocking SDF-1α/CXCR4 by CXCR4-targeted NPs in combination with VEGF siRNA significantly prevented the progression of liver fibrosis in CCl4-treated mice. In conclusion, the multifunctional CXCR4-targeted NPs delivering VEGF siRNAs provide an effective antifibrotic therapeutic strategy.

  1. Synthesis of folate-functionalized RAFT polymers for targeted siRNA delivery.

    PubMed

    Benoit, Danielle S W; Srinivasan, Selvi; Shubin, Andrew D; Stayton, Patrick S

    2011-07-11

    Receptor-mediated, cell-specific delivery of siRNA enables silencing of target genes in specific tissues, opening the door to powerful therapeutic options for a multitude of diseases. However, the development of delivery systems capable of targeted and effective siRNA delivery typically requires multiple steps and the use of sophisticated, orthogonal chemistries. Previously, we developed diblock copolymers consisting of dimethaminoethyl methacrylate-b-dimethylaminoethyl methacrylate-co-butyl methacrylate-co-propylacrylic acid as potent siRNA delivery systems that protect siRNA from enzymatic degradation and enable its cytosolic delivery through pH-responsive, endosomolytic behavior. (1, 2) These architectures were polymerized using a living radical polymerization method, specifically reversible addition-fragmentation chain transfer (RAFT) polymerization, which employs a chain transfer agent (CTA) to modulate the rate of reaction, resulting in polymers with low polydispersity and telechelic chain ends reflecting the chemistry of the CTA. Here we describe the straightforward, facile synthesis of a folate receptor-targeted diblock copolymer siRNA delivery system because the folate receptor is an attractive target for tumor-selective therapies as a result of its overexpression in a number of cancers. Specifically, we detail the de novo synthesis of a folate-functionalized CTA, use the folate-CTA for controlled polymerizations of diblock copolymers, and demonstrate efficient, specific cellular folate receptor interaction and in vitro gene knockdown using the folate-functionalized polymer.

  2. Investigation of surface passivation schemes for p-type monocrystalline silicon solar cell

    NASA Astrophysics Data System (ADS)

    Rahman, Md. Momtazur; Udoy, Ariful Banna

    2016-10-01

    This paper represents an experiment to analyze the dark saturation current densities of passivated surfaces for monocrystalline silicon solar cells. The samples are diffused at peak temperatures of 800-950 °C. Basically, symmetrical lifetime samples with different doping profiles are prepared with alkaline textured and saw damage etched (planar) surfaces. After POCl3 diffusion, the phosphorous silicate glass layers are removed in a wet chemical etching step. Several designs are chosen for the determination of the sheet resistance ( R sh), the concentration profile for excess charge carrier and the minority carrier effective lifetime of the diffused surfaces. The dark saturation current densities ( J o ) and the doping profiles are determined accordingly via quasi-steady state photoconductance decay measurement and electrochemical capacitance-voltage measurement. Three different passivation schemes are investigated as follows: silicon nitride (SiN x ) deposited by plasma-enhanced chemical vapor deposition (PECVD) technique, silicon-rich oxynitride (SiriO x N y ) capped with a PECVD SiN x layer, and thin thermally grown oxide, capped with a PECVD SiN x layer.

  3. siRNA Targeting the 2Apro Genomic Region Prevents Enterovirus 71 Replication In Vitro

    PubMed Central

    Kong, Zhenzhen; Shao, Qixiang; Su, Zhaoliang; Wang, Shengjun; Chen, Jianguo

    2016-01-01

    Enterovirus 71 (EV71) is the most important etiological agent of hand, foot, and mouth disease (HFMD) in young children, which is associated with severe neurological complications and has caused significant mortalities in recent HFMD outbreaks in Asia. However, there is no effective antiviral therapy against EV71. In this study, RNA interference (RNAi) was used as an antiviral strategy to inhibit EV71 replication. Three small interfering RNAs (siRNAs) targeting the 2Apro region of the EV71 genome were designed and synthesized. All the siRNAs were transfected individually into rhabdomyosarcoma (RD) cells, which were then infected with strain EV71-2006-52-9. The cytopathic effects (CPEs) in the infected RD cells, cell viability, viral titer, and viral RNA and protein expression were examined to evaluate the specific viral inhibition by the siRNAs. The results of cytopathogenicity and MTT tests indicated that the RD cells transfected with the three siRNAs showed slight CPEs and significantly high viability. The 50% tissue culture infective dose (TCID50) values demonstrated that the viral titer of the groups treated with three siRNAs were lower than those of the control groups. qRT–PCR and western blotting revealed that the levels of viral RNA and protein in the RD cells treated with the three siRNAs were lower than those in the controls. When RD cells transfected with siRNAs were also infected with strain EV71-2008-43-16, the expression of the VP1 protein was significantly inhibited. The levels of interferon α (IFN-α) and IFN-β did not differ significantly in any group. These results suggest that siRNAs targeting the 2Apro region of the EV71 genome exerted antiviral effects in vitro. PMID:26886455

  4. Ozone cleaning of the Si-SiO2 system

    NASA Astrophysics Data System (ADS)

    Baumgärtner, H.; Fuenzalida, V.; Eisele, I.

    1987-07-01

    The cleaning of monocrystalline silicon substrates and thin thermally grown SiO2 layers on silicon by electrochemically produced ozone has been investigated. In both cases organics are removed very effectively. In comparison with other dry cleaning methods no radiation damage occurs.

  5. RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model.

    PubMed

    Lee, Tae Jin; Haque, Farzin; Shu, Dan; Yoo, Ji Young; Li, Hui; Yokel, Robert A; Horbinski, Craig; Kim, Tae Hyong; Kim, Sung-Hak; Kwon, Chang-Hyuk; Nakano, Ichiro; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M

    2015-06-20

    Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues.

  6. RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model

    PubMed Central

    Lee, Tae Jin; Haque, Farzin; Shu, Dan; Yoo, Ji Young; Li, Hui; Yokel, Robert A.; Horbinski, Craig; Kim, Tae Hyong; Kim, Sung-Hak; Kwon, Chang-Hyuk; Nakano, Ichiro; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.

    2015-01-01

    Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues. PMID:25885522

  7. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery

    NASA Astrophysics Data System (ADS)

    Lee, Hyukjin; Lytton-Jean, Abigail K. R.; Chen, Yi; Love, Kevin T.; Park, Angela I.; Karagiannis, Emmanouil D.; Sehgal, Alfica; Querbes, William; Zurenko, Christopher S.; Jayaraman, Muthusamy; Peng, Chang G.; Charisse, Klaus; Borodovsky, Anna; Manoharan, Muthiah; Donahoe, Jessica S.; Truelove, Jessica; Nahrendorf, Matthias; Langer, Robert; Anderson, Daniel G.

    2012-06-01

    Nanoparticles are used for delivering therapeutics into cells. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell-specific internalization, excretion, toxicity and efficacy. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)--a therapeutic agent that suppresses the expression of targeted genes. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, a lack of tissue specificity and potential toxicity. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer-targeting ligands (such as peptides and folate) on the nanoparticle surface can be controlled precisely. We show that at least three folate molecules per nanoparticle are required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t1/2 ~ 24.2 min) than the parent siRNA (t1/2 ~ 6 min).

  8. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery.

    PubMed

    Lee, Hyukjin; Lytton-Jean, Abigail K R; Chen, Yi; Love, Kevin T; Park, Angela I; Karagiannis, Emmanouil D; Sehgal, Alfica; Querbes, William; Zurenko, Christopher S; Jayaraman, Muthusamy; Peng, Chang G; Charisse, Klaus; Borodovsky, Anna; Manoharan, Muthiah; Donahoe, Jessica S; Truelove, Jessica; Nahrendorf, Matthias; Langer, Robert; Anderson, Daniel G

    2012-06-03

    Nanoparticles are used for delivering therapeutics into cells. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell-specific internalization, excretion, toxicity and efficacy. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)--a therapeutic agent that suppresses the expression of targeted genes. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, a lack of tissue specificity and potential toxicity. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer-targeting ligands (such as peptides and folate) on the nanoparticle surface can be controlled precisely. We show that at least three folate molecules per nanoparticle are required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t(1/2) ≈ 24.2 min) than the parent siRNA (t(1/2) ≈ 6 min).

  9. Fluorescence imaging as a diagnostic of M-band x-ray drive condition in hohlraum with fluorescent Si targets

    NASA Astrophysics Data System (ADS)

    Li, Qi; Hu, Zhimin; Yao, Li; Huang, Chengwu; Yuan, Zheng; Zhao, Yang; Xiong, Gang; Qing, Bo; Lv, Min; Zhu, Tuo; Deng, Bo; Li, Jin; Wei, Minxi; Zhan, Xiayu; Li, Jun; Yang, Yimeng; Su, Chunxiao; Yang, Guohong; Zhang, Jiyan; Li, Sanwei; Yang, Jiamin; Ding, Yongkun

    2017-01-01

    Fluorescence imaging of surrogate Si-doped CH targets has been used to provide a measurement for drive condition of high-energy x-ray (i.e. M-band x-ray) drive symmetry upon the capsule in hohlraum on Shenguang-II laser facility. A series of experiments dedicated to the study of photo-pumping and fluorescence effect in Si-plasma are presented. To investigate the feasibility of fluorescence imaging in Si-plasma, an silicon plasma in Si-foil target is pre-formed at ground state by the soft x-ray from a half-hohlraum, which is then photo-pumped by the K-shell lines from a spatially distinct laser-produced Si-plasma. The resonant Si photon pump is used to improve the fluorescence signal and cause visible image in the Si-foil. Preliminary fluorescence imaging of Si-ball target is performed in both Si-doped and pure Au hohlraum. The usual capsule at the center of the hohlraum is replaced with a solid Si-doped CH-ball (Si-ball). Since the fluorescence is proportional to the photon pump upon the Si-plasma, high-energy x-ray drive symmetry is equal to the fluorescence distribution of the Si-ball.

  10. Targeted delivery of siRNA to macrophages for anti-inflammatory treatment.

    PubMed

    Kim, Sang-Soo; Ye, Chunting; Kumar, Priti; Chiu, Isaac; Subramanya, Sandesh; Wu, Haoquan; Shankar, Premlata; Manjunath, N

    2010-05-01

    Inflammation mediated by tumor necrosis factor-alpha (TNF-alpha) and the associated neuronal apoptosis characterizes a number of neurologic disorders. Macrophages and microglial cells are believed to be the major source of TNF-alpha in the central nervous system (CNS). Here, we show that suppression of TNF-alpha by targeted delivery of small interfering RNA (siRNA) to macrophage/microglial cells dramatically reduces lipopolysaccharide (LPS)-induced neuroinflammation and neuronal apoptosis in vivo. Because macrophage/microglia express the nicotinic acetylcholine receptor (AchR) on their surface, we used a short AchR-binding peptide derived from the rabies virus glycoprotein (RVG) as a targeting ligand. This peptide was fused to nona-D-arginine residues (RVG-9dR) to enable siRNA binding. RVG-9dR was able to deliver siRNA to induce gene silencing in macrophages and microglia cells from wild type, but not AchR-deficient mice, confirming targeting specificity. Treatment with anti-TNF-alpha siRNA complexed to RVG-9dR achieved efficient silencing of LPS-induced TNF-alpha production by primary macrophages and microglia cells in vitro. Moreover, intravenous injection with RVG-9dR-complexed siRNA in mice reduced the LPS-induced TNF-alpha levels in blood as well as in the brain, leading to a significant reduction in neuronal apoptosis. These results demonstrate that RVG-9dR provides a tool for siRNA delivery to macrophages and microglia and that suppression of TNF-alpha can potentially be used to suppress neuroinflammation in vivo.

  11. Phosphorus and boron diffusion gettering of iron in monocrystalline silicon

    NASA Astrophysics Data System (ADS)

    Talvitie, H.; Vähänissi, V.; Haarahiltunen, A.; Yli-Koski, M.; Savin, H.

    2011-05-01

    We have studied experimentally the phosphorus diffusion gettering (PDG) of iron in monocrystalline silicon at the temperature range of 650-800 °C. Our results fill the lack of data at low temperatures so that we can obtain a reliable segregation coefficient for iron between a phosphorus diffused layer and bulk silicon. The improved segregation coefficient is verified by time dependent PDG simulations. Comparison of the PDG to boron diffusion gettering (BDG) in the same temperature range shows PDG to be only slightly more effective than BDG. In general, we found that BDG requires more carefully designed processing conditions than PDG to reach a high gettering efficiency.

  12. Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress.

    PubMed

    Wei, Pei-Chi; Lo, Wen-Ting; Su, Mei-I; Shew, Jin-Yuh; Lee, Wen-Hwa

    2012-01-01

    Short interfering RNAs (siRNAs) target specific mRNAs for their degradation mediated by RNA-induced silencing complex (RISC). Persistent activation of siRNA-RISC frequently leads to non-targeting toxicity. However, how cells mediate this stress remains elusive. In this communication, we found that the presence of non-targeting siRNA selectively induced the expression of an endoplasmic reticulum (ER)-resident protein, non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), but not other ER-stress proteins including GRP78, Calnexin and XBP1. Cells suffering from constant non-targeting siRNA stress grew slower and prolonged G1 phase, while NPGPx-depleted cells accumulated mature non-targeting siRNA and underwent apoptosis. Upon the stress, NPGPx covalently bound to exoribonuclease XRN2, facilitating XRN2 to remove accumulated non-targeting siRNA. These results suggest that NPGPx serves as a novel responder to non-targeting siRNA-induced stress in facilitating XRN2 to release the non-targeting siRNA accumulation.

  13. pH-responsive hybrid quantum dots for targeting hypoxic tumor siRNA delivery.

    PubMed

    Zhu, HongYan; Zhang, ShengYu; Ling, Yong; Meng, GuoLiang; Yang, Yu; Zhang, Wei

    2015-12-28

    Hypoxia is a characteristic of cancer and plays a key role in tumorigenesis, angiogenesis and resistance to cancer therapies. SiRNA treatment is effective against hypoxic tumors by gene silencing. However, siRNA delivery to the hypoxic regions of solid tumors still presents a challenge due to the distance from blood vessels and the increased presence of efflux transporters. Therefore, tumor therapies would be improved through the immediate development of an effective siRNA delivery system to hypoxic regions. To this end, we synthesized a system to deliver HIF-1α siRNA into hypoxic tumor cells. The system consists of a functional shell composed of 2-deoxyglucose (DG)-polyethylene glycol (PEG) connected with the compound of lipoic acid, lysine and 9-poly-d-arginine (LA-Lys-9R) by a hydrazone bond and a core of CdTe quantum dots (QDs). The molecular structure of DG-PEG-LA-Lys-9R was confirmed by liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The multifunctional CdTe QDs measured approximately 200 nm and showed excellent biocompatibility, perfect siRNA binding capability and enhanced hypoxic tumor targeting. Importantly, the system described here is pH-responsive with a hydrazone bond; therefore, it avoids GLUT1 receptor-mediated endocytic recycling, resulting in irreversible delivery of the siRNA. We used Western blots to confirm the superior gene silencing efficiency induced by the DG-PEG-LA-Lys-9R with hydrazone modified CdTe QDs. Here, we demonstrate high efficacy of the siRNA tumor delivery system using in vitro and in vivo experiments. In addition, these studies demonstrate that pH-responsive hybrid quantum dots show improved antitumor efficacy with decreased organ toxicity, indicating a promising siRNA delivery system for hypoxic cancer therapy.

  14. Poly-sgRNA/siRNA ribonucleoprotein nanoparticles for targeted gene disruption.

    PubMed

    Ha, Jong Seong; Lee, Jae Sung; Jeong, Jaepil; Kim, Hejin; Byun, Juyoung; Kim, Sang Ah; Lee, Hee Jae; Chung, Hak Suk; Lee, Jong Bum; Ahn, Dae-Ro

    2017-02-04

    Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) can be used for the specific disruption of a target gene to permanently suppress the expression of the protein encoded by the target gene. Efficient delivery of the system to an intracellular target site should be achieved to utilize the tremendous potential of the genome-editing tool in biomedical applications such as the knock-out of disease-related genes and the correction of defect genes. Here, we devise polymeric CRISPR/Cas9 system based on poly-ribonucleoprotein (RNP) nanoparticles consisting of polymeric sgRNA, siRNA, and Cas9 endonuclease in order to improve the delivery efficiency. When delivered by cationic lipids, the RNP nanoparticles built with chimeric poly-sgRNA/siRNA sequences generate multiple sgRNA-Cas9 RNP complexes upon the Dicer-mediated digestion of the siRNA parts, leading to more efficient disruption of the target gene in cells and animal models, compared with the monomeric sgRNA-Cas9 RNP complex.

  15. Selective Modification of HK Peptides Enhances siRNA Silencing of Tumor Targets In Vivo

    PubMed Central

    Chou, Szu-Ting; Leng, Qixin; Scaria, Puthupparampil; Woodle, Martin; Mixson, A. James

    2011-01-01

    Our research has focused on systemic delivery of small interference RNA (siRNA) by branched peptides composed of histidine and lysine, called HK peptides. After studying several HK peptides, one four-branched peptide, H3K(+H)4b, with a predominant repeating pattern of -HHHK-, was found to be an effective carrier of siRNA. Although the unmodified H3K(+H)4b carrier of siRNA targeting an oncogene was previously shown to have promise in a tumor-bearing mouse model, we sought to develop a more effective HK carrier of siRNA in the current study. Our primary goal was to determine whether different ligand (cyclic RGD)-pegylation patterns on the H3K(+H)4b peptide affect siRNA delivery in vitro and in vivo. We compared the unmodified H3K(+H)4b with two modified H3K(+H)4b peptides for their ability to deliver siRNA in a tumor-bearing mouse model; one modified HK peptide, (RGD-PEG)4-H3K(+H)4b, had four cRGD-PEG conjugated to each molecule, while the other peptide, (RGD-PEG)-H3K(+H)4b, had one cRGD-PEG per molecule. Although the modified HK peptides by themselves did not form stable nanoplexes with siRNA, combination of a highly charged unmodified HK peptide, H2K4b, with either of the modified HK peptides did form stable siRNA nanoparticles. For in vitro experiments with MDA-MB-435 cells that expressed luciferase, the H3K(+H)4b siRNA nanoplexes targeting luciferase decreased its activity by 90% compared with negligible down-regulation by the modified H3K(+H)4b nanoplexes (P<0.01). In contrast, the two modified H3K(+H)4b siRNA nanoplexes administered intravenously were more effective than the H3K(+H)4b nanoplexes in silencing luciferase in a tumor xenograft model. The luciferase activity in tumor lysates of mice administered H3K(+H)4b, (RGD-PEG)-H3K(+H)4b, and (RGD-PEG)4-H3K(+H)4b nanoplexes decreased by 18%, 35%, and 75%, respectively. Thus, the siRNA nanoplex incorporating the highly modified peptide, (RGD-PEG)4-H3K(+H)4b, was the most effective at silencing its target in vivo

  16. Soft computing model for optimized siRNA design by identifying off target possibilities using artificial neural network model.

    PubMed

    Murali, Reena; John, Philips George; Peter S, David

    2015-05-15

    The ability of small interfering RNA (siRNA) to do posttranscriptional gene regulation by knocking down targeted genes is an important research topic in functional genomics, biomedical research and in cancer therapeutics. Many tools had been developed to design exogenous siRNA with high experimental inhibition. Even though considerable amount of work has been done in designing exogenous siRNA, design of effective siRNA sequences is still a challenging work because the target mRNAs must be selected such that their corresponding siRNAs are likely to be efficient against that target and unlikely to accidentally silence other transcripts due to sequence similarity. In some cases, siRNAs may tolerate mismatches with the target mRNA, but knockdown of genes other than the intended target could make serious consequences. Hence to design siRNAs, two important concepts must be considered: the ability in knocking down target genes and the off target possibility on any nontarget genes. So before doing gene silencing by siRNAs, it is essential to analyze their off target effects in addition to their inhibition efficacy against a particular target. Only a few methods have been developed by considering both efficacy and off target possibility of siRNA against a gene. In this paper we present a new design of neural network model with whole stacking energy (ΔG) that enables to identify the efficacy and off target effect of siRNAs against target genes. The tool lists all siRNAs against a particular target with their inhibition efficacy and number of matches or sequence similarity with other genes in the database. We could achieve an excellent performance of Pearson Correlation Coefficient (R=0. 74) and Area Under Curve (AUC=0.906) when the threshold of whole stacking energy is ≥-34.6 kcal/mol. To the best of the author's knowledge, this is one of the best score while considering the "combined efficacy and off target possibility" of siRNA for silencing a gene. The proposed model

  17. Mechanical properties of monocrystalline and polycrystalline monolayer black phosphorus

    NASA Astrophysics Data System (ADS)

    Cao, Pinqiang; Wu, Jianyang; Zhang, Zhisen; Ning, Fulong

    2017-01-01

    The mechanical properties of monocrystalline and polycrystalline monolayer black phosphorus (MBP) are systematically investigated using classic molecular dynamic simulations. For monocrystalline MBP, it is found that the shear strain rate, sample dimensions, temperature, atomic vacancies and applied statistical ensemble affect the shear behaviour. The wrinkled morphology is closely connected with the direction of the in-plane shear, dimensions of the samples, and applied ensembles. Particularly, small samples subjected to loading/unloading of the shear deformation along the armchair direction demonstrate a clear mechanical hysteresis loop. For polycrystalline MBP, the maximum shear stress as a function of the average grain size follows an inverse pseudo Hall-Petch type relationship under an isothermal-isobaric (NPT) ensemble, whereas under a canonical (NVT) ensemble, the maximum shear stress of polycrystalline MBP exhibits a ‘flipped’ behaviour. Furthermore, polycrystalline MBP subjected to uniaxial tension also exhibits a strongly grain size-dependent mechanical response, and it can fail by brittle intergranular and transgranular fractures because of its weaker grain boundary structures and the direction-dependent edge energy, respectively. These findings provide useful insight into the mechanical design of BP for nanoelectronic devices.

  18. Monocrystalline CdTe solar cells with open-circuit voltage over 1 V and efficiency of 17%

    NASA Astrophysics Data System (ADS)

    Zhao, Yuan; Boccard, Mathieu; Liu, Shi; Becker, Jacob; Zhao, Xin-Hao; Campbell, Calli M.; Suarez, Ernesto; Lassise, Maxwell B.; Holman, Zachary; Zhang, Yong-Hang

    2016-06-01

    The open-circuit voltages of mature single-junction photovoltaic devices are lower than the bandgap energy of the absorber, typically by a gap of 400 mV. For CdTe, which has a bandgap of 1.5 eV, the gap is larger; for polycrystalline samples, the open-circuit voltage of solar cells with the record efficiency is below 900 mV, whereas for monocrystalline samples it has only recently achieved values barely above 1 V. Here, we report a monocrystalline CdTe/MgCdTe double-heterostructure solar cell with open-circuit voltages of up to 1.096 V. The latticed-matched MgCdTe barrier layers provide excellent passivation to the CdTe absorber, resulting in a carrier lifetime of 3.6 μs. The solar cells are made of 1- to 1.5-μm-thick n-type CdTe absorbers, and passivated hole-selective p-type a-SiCy:H contacts. This design allows CdTe solar cells to be made thinner and more efficient. The best power conversion efficiency achieved in a device with this structure is 17.0%.

  19. Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery

    PubMed Central

    Zhou, Jihan; Li, Dong; Wen, Hao; Zheng, Shuquan; Su, Cuicui; Yi, Fan; Wang, Jue; Liang, Zicai; Tang, Tao; Zhou, Demin; Zhang, Li-He; Liang, Dehai; Du, Quan

    2016-01-01

    Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications. PMID:26955887

  20. Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery

    NASA Astrophysics Data System (ADS)

    Zhou, Jihan; Li, Dong; Wen, Hao; Zheng, Shuquan; Su, Cuicui; Yi, Fan; Wang, Jue; Liang, Zicai; Tang, Tao; Zhou, Demin; Zhang, Li-He; Liang, Dehai; Du, Quan

    2016-03-01

    Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.

  1. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors.

    PubMed

    Ganesh, Shanthi; Iyer, Arun K; Morrissey, David V; Amiji, Mansoor M

    2013-04-01

    Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions.

  2. Going beyond the liver: progress and challenges of targeted delivery of siRNA therapeutics.

    PubMed

    Lorenzer, Cornelia; Dirin, Mehrdad; Winkler, Anna-Maria; Baumann, Volker; Winkler, Johannes

    2015-04-10

    Therapeutic gene silencing promises significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility for treating orphan diseases. Technological hurdles have complicated the efficient use of therapeutic oligonucleotides, and siRNA agents suffer particularly from insufficient pharmacokinetic properties and poor cellular uptake. Intense development and evolution of delivery systems have resulted in efficient uptake predominantly in liver tissue, in which practically all nanoparticulate and liposomal delivery systems show the highest accumulation. The most efficacious strategies include liposomes and bioconjugations with N-acetylgalactosamine. Both are in early clinical evaluation stages for treatment of liver-associated diseases. Approaches for achieving knockdown in other tissues and tumors have been proven to be more complicated. Selective targeting to tumors may be enabled through careful modulation of physical properties, such as particle size, or by taking advantage of specific targeting ligands. Significant barriers stand between sufficient accumulation in other organs, including endothelial barriers, cellular membranes, and the endosome. The brain, which is shielded by the blood-brain barrier, is of particular interest to facilitate efficient oligonucleotide therapy of neurological diseases. Transcytosis of the blood-brain barrier through receptor-specific docking is investigated to increase accumulation in the central nervous system. In this review, the current clinical status of siRNA therapeutics is summarized, as well as innovative and promising preclinical concepts employing tissue- and tumor-targeted ligands. The requirements and the respective advantages and drawbacks of bioconjugates and ligand-decorated lipid or polymeric particles are discussed.

  3. Calculations and First Results Obtained with a SiC Prototype of the SPES Direct Target

    SciTech Connect

    Barbui, Marina; Andrighetto, Alberto; Antonucci, C.; Biasetto, Lisa; Carturan, S.; Cervellera, F.; Cevolani, S.; Cinausero, Marco; Colombo, P.; Dainelli, A.; Di Bernardo, P.; Giacchini, Mauro; Gramegna, Fabiana; Lollo, M.; Maggioni, G.; Manzolaro, Mattia; Meneghetti, G.; Petrovich, C.; Piga, L.; Prete, Gianfranco; Re, Maurizio; Rizzi, Valentina; Stracener, Daniel W; Tonezzer, Michele; Zafiropoulos, D.; Zanonato, P.

    2008-01-01

    In the framework of the SPES project at LNL [A. Bracco, A. Pisent (Ed.), REP 181/02, LNL-INFN, 2002], the realization of a direct ISOL Target for a mid-term radioactive ion beam facility is in progress. Using a primary proton beam of energy 40 MeV and intensity 0.2 mA, a high number of fission products will be obtained in the SPES multi-foil uranium carbide target, keeping a low power density deposition in the refractory matrix [A. Andrighetto, S. Cevolani, C. Petrovich, Eur. Phys J. A 25 (2005) 41]. The exotic species produced by Uranium fission in the target are collected in the ion source after the diffusion and the effusion processes. When short lived isotopes are produced it is very important to optimize the release properties of the target. To this purpose the RIBO code (radioactive ion beam optimiser) [M. Santana Leitner, A Monte Carlo Code to Optimize the Production of Radioactive Ion Beams by the ISOL Technique, PhD. Thesis, UPC-ETSEIB/CERN] has been used in order to estimate the target release efficiency for some neutron-rich nuclei. A SiC prototype of the target was recently produced at LNL and tested at ORNL using a 42 MeV proton beam. The yield of some aluminum isotopes was measured as a function of the target temperature. Some preliminary results of the data analysis will be presented.

  4. Effects of targeted nano-delivery systems combined with hTERT-siRNA and Bmi-1-siRNA on MCF-7 cells

    PubMed Central

    Liu, Lei; Li, Huixiang; Zhang, Min; Lv, Xinquan

    2015-01-01

    The aim of this study was to evaluate the efficiency of a targeted siRNA nano-delivery system to silence the expression of Bmi-1 and hTERT, and to verify the toxicity of this delivery system in MCF-7 breast cancer cells. The most effective Bmi-1 siRNA and hTERT siRNA sequences were selected using RT-PCR and Western blotting. The polyethyleneimine (PEI)/siRNA nano-condensate was synthesized using PEI and modified using an NGR peptide fragment for targeting to tumor cells. The vector morphology, particle size and zeta potential were observed using an atomic force microscope and a laser particle size analyzer. The MCF-7 breast cancer cell line was transfected with the vector, and cytotoxicity was tested by MTT assays. The transfection efficiency was evaluated by qRT-PCR and Western blotting. Changes in gene expression and apoptosis rate were measured by flow cytometry. The size of LPN carrier and the condensate particle was between 100 and 200 nm and the potentials were close to neutral. There was maximum transfection efficiency and no significant increase in toxicity at 15 pmol/L. Bmi-1 and hTERT expression decreased, but the inhibition rate increased in the hTERT siRNA group, the hTERT+Bmi-1 siRNA group and the hTERT+Bmi-1 siRNA group compared with the scrambled siRNA group and the control group. Moreover, the hTERT+Bmi-1 siRNA group had the highest level of gene silencing. The complex, composed of Lipo, PEI and siRNA, is low toxicity and efficient transfection vectors. The expression level of Bmi-1 and hTERT was decreased by the gene silencing of either Bmi-1 or hTERT, but the effects were more significant when both were silenced simultaneously. PMID:26261549

  5. Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis

    NASA Astrophysics Data System (ADS)

    Yu-Wai-Man, Cynthia; Tagalakis, Aristides D.; Manunta, Maria D.; Hart, Stephen L.; Khaw, Peng T.

    2016-02-01

    There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye.

  6. Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.

    PubMed

    Zhou, Yinjian; Zhang, Chunling; Liang, Wei

    2014-11-10

    RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.

  7. Receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient delivery system for MRTF silencing in conjunctival fibrosis

    PubMed Central

    Yu-Wai-Man, Cynthia; Tagalakis, Aristides D.; Manunta, Maria D.; Hart, Stephen L.; Khaw, Peng T.

    2016-01-01

    There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye. PMID:26905457

  8. siRNA targeting PLK-1 induces apoptosis of synoviocytes in rheumatoid arthritis

    SciTech Connect

    Wada, Makoto; Kawahito, Yutaka . E-mail: kawahity@koto.kpu-m.ac.jp; Kimura, Shinya; Kohno, Masataka; Ishino, Hidetaka; Kimura, Mizuho; Omoto, Atsushi; Yamamoto, Aihiro; Hamaguchi, Masahide; Tsubouchi, Yasunori; Tokunaga, Daisaku; Hojo, Tatsuya; Ashihara, Eishi; Maekawa, Taira; Yoshikawa, Toshikazu

    2007-06-01

    Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly expressed in synoviocytes and some infiltrative mononuclear cells in synovial tissues from patients with rheumatoid arthritis (RA), while patients with osteoarthritis and injury show little or no expression of PLK-1 in synovial tissues. Western blot analysis shows that PLK is expressed and its expression is enhanced by IL-1{beta} in RA synoviocytes. IL-1{beta} also enhanced the cell growth of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1{beta} and suppresses the proliferation of these synoviocytes through apoptosis. These findings suggest that PLK-1 plays a critical role in the proliferation of RA synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially useful for the treatment of RA.

  9. Targeting BACE1 with siRNAs ameliorates Alzheimer disease neuropathology in a transgenic model.

    PubMed

    Singer, Oded; Marr, Robert A; Rockenstein, Edward; Crews, Leslie; Coufal, Nicole G; Gage, Fred H; Verma, Inder M; Masliah, Eliezer

    2005-10-01

    In Alzheimer disease, increased beta-secretase (BACE1) activity has been associated with neurodegeneration and accumulation of amyloid precursor protein (APP) products. Thus, inactivation of BACE1 could be important in the treatment of Alzheimer disease. In this study, we found that lowering BACE1 levels using lentiviral vectors expressing siRNAs targeting BACE1 reduced amyloid production and the neurodegenerative and behavioral deficits in APP transgenic mice, a model of Alzheimer disease. Our results suggest that lentiviral vector delivery of BACE1 siRNA can specifically reduce the cleavage of APP and neurodegeneration in vivo and indicate that this approach could have potential therapeutic value for treatment of Alzheimer disease.

  10. SiASR4, the Target Gene of SiARDP from Setaria italica, Improves Abiotic Stress Adaption in Plants

    PubMed Central

    Li, Jianrui; Dong, Yang; Li, Cong; Pan, Yanlin; Yu, Jingjuan

    2017-01-01

    Drought and other types of abiotic stresses negatively affect plant growth and crop yields. The abscisic acid-, stress-, and ripening-induced (ASR) proteins play important roles in the protection of plants against abiotic stress. However, the regulatory pathway of the gene encoding this protein remains to be elucidated. In this study, the foxtail millet (Setaria italica) ASR gene, SiASR4, was cloned and characterized. SiASR4 localized to the cell nucleus, cytoplasm and cytomembrane, and the protein contained 102 amino acids, including an ABA/WDS (abscisic acid/water-deficit stress) domain, with a molecular mass of 11.5 kDa. The abundance of SiASR4 transcripts increased after treatment with ABA, NaCl, and PEG in foxtail millet seedlings. It has been reported that the S. italica ABA-responsive DRE-binding protein (SiARDP) binds to a DNA sequence with a CCGAC core and that there are five dehydration-responsive element (DRE) motifs within the SiASR4 promoter. Our analyses demonstrated that the SiARDP protein could bind to the SiASR4 promoter in vitro and in vivo. The expression of SiASR4 increased in SiARDP-overexpressing plants. SiASR4-transgenic Arabidopsis and SiASR4-overexpressing foxtail millet exhibited enhanced tolerance to drought and salt stress. Furthermore, the transcription of stress-responsive and reactive oxygen species (ROS) scavenger-associated genes was activated in SiASR4 transgenic plants. Together, these findings show that SiASR4 functions in the adaption to drought and salt stress and is regulated by SiARDP via an ABA-dependent pathway. PMID:28127300

  11. Systemic delivery of siRNA by hyaluronan-functionalized calcium phosphate nanoparticles for tumor-targeted therapy

    NASA Astrophysics Data System (ADS)

    Qiu, Chong; Wei, Wei; Sun, Jing; Zhang, Hai-Tao; Ding, Jing-Song; Wang, Jian-Cheng; Zhang, Qiang

    2016-06-01

    In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform spherical core-shell morphology with an approximate size of 170 nm and zeta potential of -12 mV. The coating of hydrophilic HA improved the physical stability of nanoparticles over one month due to the strong interactions between phosphonate and calcium. In vitro experiments demonstrated that the negatively charged CaP-AHA/siRNA NPs could effectively deliver EGFR-targeted siRNA into A549 cells through CD44-mediated endocytosis and significantly down-regulate the level of EGFR expression. Also, the internalized CaP-AHA/siRNA NPs exhibited a pH-responsive release of siRNA, indicating that the acidification of lysosomes probably facilitated the disassembling of nanoparticles and the resultant ions sharply increased the inner osmotic pressure and thus expedited the release of siRNA from late lysosomes into the cytoplasm. Furthermore, in vivo tumor therapy demonstrated that high accumulation of CaP-AHA/siEGFR NPs in tumor led to a significant tumor growth inhibition with a specific EGFR gene silencing effect after intravenous administration in nude mice xenografted with A549 tumor, along with a negligible body weight loss. These results suggested that the CaP-AHA/siRNA NPs could be an effective and safe systemic siRNA delivery system for a RNAi-based tumor targeted therapy strategy.In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform

  12. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

    PubMed Central

    Davis, Mark E.; Zuckerman, Jonathan E.; Choi, Chung Hang J.; Seligson, David; Tolcher, Anthony; Alabi, Christopher A.; Yen, Yun; Heidel, Jeremy D.; Ribas, Antoni

    2010-01-01

    Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients.1,2 Fire et al. first demonstrated that long, double stranded RNAs mediate RNAi in Caenorhabditis elegans,3 and Elbashir et al. opened the pathway to the use of RNAi for human therapy by showing that small interfering RNAs (siRNAs: ca. 21 base pair double stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response.4 We are currently conducting the first-in-human Phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumor biopsies from melanoma patients obtained after treatment reveal: (i) the presence of intracellularly-localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is a first for systemically delivered nanoparticles of any kind), and (ii) reduction in both the specific mRNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) when compared to pre-dosing tissue. Most importantly, we detect the presence of an mRNA fragment that demonstrates siRNA mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. These data when taken in total demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action. PMID:20305636

  13. Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma

    PubMed Central

    Oh, Hea Ry; Jo, Hyun-Young; Park, James S.; Kim, Dong-Eun; Cho, Je-Yoel; Kim, Pyung-Hwan; Kim, Keun-Sik

    2016-01-01

    The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA. Previous studies have shown that Gal-DOX/siRNA-L inhibited tumor growth by combined effect of DOX and vimentin siRNA than single delivery of either DOX or vimentin siRNA. These Gal-DOX/siRNA-Ls showed stronger affinity to human hepatocellular carcinoma cells (Huh7) than other cells (lung epithelial carcinoma, A549). These liposomes also have demonstrated that novel hepatic drug/gene delivery systems composed of cationic lipid (DMKE: O,O’-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG2000-DSPE (distearoyl phosphatidyl ethanolamine) at 2:1:1:1:0.2 (moral ratios) can be used as an effective drug/gene carrier specifically targeting the liver in vivo. These results suggest that Gal-DOX-siRNA-L could effectively target tumor cells, enhance transfection efficacy and subsequently achieve the co-delivery of DOX and siRNA, demonstrating great potential for synergistic anti-tumor therapy. PMID:28335269

  14. Transparent conducting Si-codoped Al-doped ZnO thin films prepared by magnetron sputtering using Al-doped ZnO powder targets containing SiC

    SciTech Connect

    Nomoto, Jun-ichi; Miyata, Toshihiro; Minami, Tadatsugu

    2009-07-15

    Transparent conducting Al-doped ZnO (AZO) thin films codoped with Si, or Si-codoped AZO (AZO:Si), were prepared by radio-frequency magnetron sputtering using a powder mixture of ZnO, Al{sub 2}O{sub 3}, and SiC as the target; the Si content (Si/[Si+Zn] atomic ratio) was varied from 0 to 1 at. %, but the Al content (Al/[Al+Zn] atomic ratio) was held constant. To investigate the effect of carbon on the electrical properties of AZO:Si thin films prepared using the powder targets containing SiC, the authors also prepared thin films using a mixture of ZnO, Al{sub 2}O{sub 3}, and SiO{sub 2} or SiO powders as the target. They found that when AZO:Si thin films were deposited on glass substrates at about 200 degree sign C, both Al and Si doped into ZnO acted as effective donors and the atomic carbon originating from the sputtered target acted as a reducing agent. As a result, sufficient improvement was obtained in the spatial distribution of resistivity on the substrate surface in AZO:Si thin films prepared with a Si content (Si/[Si+Zn] atomic ratio) of 0.75 at. % using powder targets containing SiC. The improvement in resistivity distribution was mainly attributed to increases in both carrier concentration and Hall mobility at locations on the substrate corresponding to the target erosion region. In addition, the resistivity stability of AZO: Si thin films exposed to air for 30 min at a high temperature was found to improve with increasing Si content.

  15. Co-delivery of doxorubicin and siRNA using octreotide-conjugated gold nanorods for targeted neuroendocrine cancer therapy

    NASA Astrophysics Data System (ADS)

    Xiao, Yuling; Jaskula-Sztul, Renata; Javadi, Alireza; Xu, Wenjin; Eide, Jacob; Dammalapati, Ajitha; Kunnimalaiyaan, Muthusamy; Chen, Herbert; Gong, Shaoqin

    2012-10-01

    A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The Au NR was conjugated with (1) DOX, an anticancer drug, via a pH-labile hydrazone linkage to enable pH-controlled drug release, (2) polyarginine, a cationic polymer for complexing siRNA, and (3) octreotide (OCT), a tumor-targeting ligand, to specifically target NE cancer cells with overexpressed somatostatin receptors. The Au NR-based nanocarriers exhibited a uniform size distribution as well as pH-sensitive drug release. The OCT-conjugated Au NR-based nanocarriers (Au-DOX-OCT, targeted) exhibited a much higher cellular uptake in a human carcinoid cell line (BON cells) than non-targeted Au NR-based nanocarriers (Au-DOX) as measured by both flow cytometry and confocal laser scanning microscopy (CLSM). Moreover, Au-DOX-OCT-ASCL1 siRNA (Au-DOX-OCT complexed with ASCL1 siRNA) resulted in significantly higher gene silencing in NE cancer cells than Au-DOX-ASCL1 siRNA (non-targeted Au-DOX complexed with ASCL1 siRNA) as measured by an immunoblot analysis. Additionally, Au-DOX-OCT-ASCL1 siRNA was the most efficient nanocarrier at altering the NE phenotype of NE cancer cells and showed the strongest anti-proliferative effect. Thus, combined chemotherapy and RNA silencing using NE tumor-targeting Au NR-based nanocarriers could potentially enhance the therapeutic outcomes in treating NE cancers.A multifunctional gold (Au) nanorod (NR)-based nanocarrier capable of co-delivering small interfering RNA (siRNA) against achaete-scute complex-like 1 (ASCL1) and an anticancer drug (doxorubicin (DOX)) specifically to neuroendocrine (NE) cancer cells was developed and characterized for combined chemotherapy and siRNA-mediated gene silencing. The

  16. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    SciTech Connect

    Ying, Bo; Campbell, Robert B.

    2014-04-04

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  17. Comparing the soft x-rays transport in Si and Ge-sandwich targets by measuring transmission flux

    NASA Astrophysics Data System (ADS)

    Zhang, Lu; Li, Liling; Guo, Liang; Jing, Longfei; Lin, Zhiwei; Qing, Bo; Li, Zhichao; Li, Hang; Kuang, Longyu; Zheng, Jianhua; Zhang, Jiyan; Yang, Jiamin; Jiang, Shaoen; Ding, Yongkun

    2017-03-01

    Mid-Z dopant in ablator is very important in point design targets. In this paper, we develop a method to evaluate the soft x-ray transport of doped material with one dimensional planar target. The targets are designed as sandwich, so that the mid-layer is heated by M band, shock and thermal wave. The transmission fluxes from heated targets are measured with band-pass x-ray diodes. The Si and Ge dopants are evaluated with this method. The experimental results show that 1-1.6 keV x-ray transmission flux through Si-sandwich is higher than that through Ge-sandwich all the time. Also, the comparison of opacities shows that the opacity of Si is lower than that of Ge in the range of 1-1.6 keV, which is consistent with the experimental results.

  18. Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA and lonidamine.

    PubMed

    Zhang, Bing-Feng; Xing, Lei; Cui, Peng-Fei; Wang, Feng-Zhen; Xie, Rong-Lin; Zhang, Jia-Liang; Zhang, Mei; He, Yu-Jing; Lyu, Jin-Yuan; Qiao, Jian-Bin; Chen, Bao-An; Jiang, Hu-Lin

    2015-08-01

    The mitochondria-mediated apoptosis pathway is an effective option for cancer therapy due to the presence of cell-suicide weapons in mitochondria. However, anti-apoptotic proteins that are over-expressed in the mitochondria of many malignant tumors, such as Bcl-2 protein, could allow the cancer cells to evade apoptosis, greatly reducing the efficacy of this type of chemotherapy. Here, we constructed a hierarchical targeted delivery system that can deliver siRNA and chemotherapeutic agents sequentially to tumor cells and mitochondria. In detail, the copolymer TPP-CP-LND (TCPL) was synthesized by the mitochondria-targeting ligand triphenylphosphine (TPP) and therapeutic drug lonidamine (LND) conjugated to the polyethyleneimine in chitosan-graft-PEI (CP), and then complexed with siRNA. Followed, the complexes were coated with poly(acrylic acid)-polyethylene glycol-folic acid (PPF) copolymer to form a hierarchical targeted co-delivery system (TCPL/siRNA/PPF NPs). The TCPL/siRNA/PPF NPs had a neutral surface charge, were stable in plasma and exhibited pH-responsive shell separation. Remarkably, the TCPL/siRNA/PPF NPs simultaneously released siBcl-2 into the cytoplasm and delivered LND to mitochondria in the same cancer cell after FA-directed internalization, and even synergistically activated mitochondria apoptosis pathway. This work demonstrated the potential of RNA-interference and mitochondria-targeted chemotherapeutics to collaboratively stimulate the mitochondria apoptosis pathway for cancer therapy.

  19. Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple Negative Breast Cancer

    PubMed Central

    Mack, Margaret A.; Schiemann, William P.; Lu, Zheng-Rong

    2015-01-01

    Metastatic breast cancer is the second leading cause of cancer-related deaths amongst women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Since previous studies coupled β3 integrin to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGF-β-mediated EMT and invasion, restore TGF-β-mediated cytostasis, and inhibit 3-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden, and more importantly, significantly inhibited metastasis. Mice bearing orthotopic, TGF-β-pre-stimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse after primary tumor resection and 4 weeks after release from the treatment, in comparison to untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC. PMID:25858145

  20. In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes

    PubMed Central

    ElHefnawi, Mahmoud; Kim, TaeKyu; Kamar, Mona A.; Min, Saehong; Hassan, Nafisa M.; El-Ahwany, Eman; Kim, Heeyoung; Zada, Suher; Amer, Marwa; Windisch, Marc P.

    2016-01-01

    RNA interference (RNAi) is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs) targeting highly conserved regions of the hepatitis C virus (HCV) genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258) were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h); they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic oligonucleotide

  1. Monocrystalline silicon gradiometer for gravity experiments in space

    NASA Technical Reports Server (NTRS)

    Richard, Jean-Paul

    1987-01-01

    A very important research effort has been made in the last decade in the field of high precision measurement with laser instrumentation. The development of a space borne gradiometer operating at a high sensitivity level using laser measurement of the distance between proof mass over a short base line of order one meter is discussed. Two aspects of laser technology make it a promising tool for gradiometry measurements: quantum limited accuracy and absolute distance measurements. The quantum limit associated with laser instrumentation was formulated. The relevant quantum and classical sources of errors in laser measurements were reviewed and corresponding laser performance requirements for gradient measurements were evaluated. Some mechanical quality factor measurements were made on simple resonant monocrystalline silicon suspensions. It was discovered that the use of zero derivative restoring forces to position the gradiometer test masses will dramatically reduce the gradiometer temperature control requirements. A laser beam side injection scheme was discovered which permits rejection of common mode accelerations. These concepts are briefly discussed.

  2. Delivery of siRNA using ternary complexes containing branched cationic peptides: the role of peptide sequence, branching and targeting.

    PubMed

    Kudsiova, Laila; Welser, Katharina; Campbell, Frederick; Mohammadi, Atefeh; Dawson, Natalie; Cui, Lili; Hailes, Helen C; Lawrence, M Jayne; Tabor, Alethea B

    2016-03-01

    Ternary nanocomplexes, composed of bifunctional cationic peptides, lipids and siRNA, as delivery vehicles for siRNA have been investigated. The study is the first to determine the optimal sequence and architecture of the bifunctional cationic peptide used for siRNA packaging and delivery using lipopolyplexes. Specifically three series of cationic peptides of differing sequence, degrees of branching and cell-targeting sequences were co-formulated with siRNA and vesicles prepared from a 1 : 1 molar ratio of the cationic lipid DOTMA and the helper lipid, DOPE. The level of siRNA knockdown achieved in the human alveolar cell line, A549-luc cells, in both reduced serum and in serum supplemented media was evaluated, and the results correlated to the nanocomplex structure (established using a range of physico-chemical tools, namely small angle neutron scattering, transmission electron microscopy, dynamic light scattering and zeta potential measurement); the conformational properties of each component (circular dichroism); the degree of protection of the siRNA in the lipopolyplex (using gel shift assays) and to the cellular uptake, localisation and toxicity of the nanocomplexes (confocal microscopy). Although the size, charge, structure and stability of the various lipopolyplexes were broadly similar, it was clear that lipopolyplexes formulated from branched peptides containing His-Lys sequences perform best as siRNA delivery agents in serum, with protection of the siRNA in serum balanced against efficient release of the siRNA into the cytoplasm of the cell.

  3. Immunostimulatory motifs enhance antiviral siRNAs targeting highly pathogenic avian influenza H5N1.

    PubMed

    Stewart, Cameron R; Karpala, Adam J; Lowther, Sue; Lowenthal, John W; Bean, Andrew G

    2011-01-01

    Highly pathogenic avian influenza (HPAI) H5N1 virus is endemic in many regions around the world and remains a significant pandemic threat. To date H5N1 has claimed almost 300 human lives worldwide, with a mortality rate of 60% and has caused the death or culling of hundreds of millions of poultry since its initial outbreak in 1997. We have designed multi-functional RNA interference (RNAi)-based therapeutics targeting H5N1 that degrade viral mRNA via the RNAi pathway while at the same time augmenting the host antiviral response by inducing host type I interferon (IFN) production. Moreover, we have identified two factors critical for maximising the immunostimulatory properties of short interfering (si)RNAs in chicken cells (i) mode of synthesis and (ii) nucleoside sequence to augment the response to virus. The 5-bp nucleoside sequence 5'-UGUGU-3' is a key determinant in inducing high levels of expression of IFN-α, -β, -λ and interleukin 1-β in chicken cells. Positioning of this 5'-UGUGU-3' motif at the 5'-end of the sense strand of siRNAs, but not the 3'-end, resulted in a rapid and enhanced induction of type I IFN. An anti-H5N1 avian influenza siRNA directed against the PB1 gene (PB1-2257) tagged with 5'-UGUGU-3' induced type I IFN earlier and to a greater extent compared to a non-tagged PB1-2257. Tested against H5N1 in vitro, the tagged PB1-2257 was more effective than non-tagged PB1-2257. These data demonstrate the ability of an immunostimulatory motif to improve the performance of an RNAi-based antiviral, a finding that may influence the design of future RNAi-based anti-influenza therapeutics.

  4. Large-area monocrystalline silicon thin films by annealing of macroporous arrays: Understanding and tackling defects in the material

    NASA Astrophysics Data System (ADS)

    Depauw, Valérie; Gordon, Ivan; Beaucarne, Guy; Poortmans, Jef; Mertens, Robert; Celis, Jean-Pierre

    2009-08-01

    A concept that could provide a thin monocrystalline-silicon absorber layer without resorting to the expensive step of epitaxy would be very appealing for reducing the cost of solar cells. The empty-space-in-silicon technique by which thin films of silicon can be formed by reorganization of regular arrays of cylindrical voids at high temperature may be such a concept if the high quality of the thin film could be ensured on centimeter-large areas. While previous works mainly investigated the influence of the porous array on the final structure, this work focuses on the practical aspects of the high-temperature step and its application to large areas. An insight into the defects that may form is given and the origin of these defects is discussed, providing recommendations on how to avoid them. Surface roughening, pitting, formation of holes, and silicon pillars could be attributed to the nonuniform reactions between Si, SiO2, and SiO. Hydrogen atmospheres are therefore preferred for reorganization of macroporous arrays. Argon atmospheres, however, may provide high-quality silicon thin films as well, possibly even more easily transferable, as long as annealing is performed in controlled, clean, and oxygen-free conditions. Our experiments on large areas also highlight the importance of kinetics, which had not been considered up to now and which will require further understanding to ensure a complete reorganization over any wafer area.

  5. siRNA screen identifies QPCT as a druggable target for Huntington’s disease

    PubMed Central

    Jimenez-Sanchez, Maria; Lam, Wun; Tarditi, Alessia; Menzies, Fiona; Dami, Teresa Ed; Xu, Catherine; Gonzalez-Couto, Eduardo; Lazzeroni, Giulia; Heitz, Freddy; Diamanti, Daniela; Massai, Luisa; Satagopam, Venkata P.; Marconi, Guido; Caramelli, Chiara; Nencini, Arianna; Andreini, Matteo; Sardone, Gian Luca; Caradonna, Nicola P.; Porcari, Valentina; Scali, Carla; Schneider, Reinhard; Pollio, Giuseppe; O’Kane, Cahir J.; Caricasole, Andrea; Rubinsztein, David C.

    2015-01-01

    Huntington’s disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified novel modifiers of mutant HTT toxicity by performing a large-scale “druggable genome” siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen, and which also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone alpha B-crystallin and reduced the aggregation of diverse proteins. We generated novel QPCT inhibitors using in silico methods followed by in vitro screens, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a novel HD druggable target affecting mutant huntingtin aggregation, and provide proof-of-principle for a discovery pipeline from druggable genome screen to drug development. PMID:25848931

  6. siRNA screen identifies QPCT as a druggable target for Huntington's disease.

    PubMed

    Jimenez-Sanchez, Maria; Lam, Wun; Hannus, Michael; Sönnichsen, Birte; Imarisio, Sara; Fleming, Angeleen; Tarditi, Alessia; Menzies, Fiona; Ed Dami, Teresa; Xu, Catherine; Gonzalez-Couto, Eduardo; Lazzeroni, Giulia; Heitz, Freddy; Diamanti, Daniela; Massai, Luisa; Satagopam, Venkata P; Marconi, Guido; Caramelli, Chiara; Nencini, Arianna; Andreini, Matteo; Sardone, Gian Luca; Caradonna, Nicola P; Porcari, Valentina; Scali, Carla; Schneider, Reinhard; Pollio, Giuseppe; O'Kane, Cahir J; Caricasole, Andrea; Rubinsztein, David C

    2015-05-01

    Huntington's disease (HD) is a currently incurable neurodegenerative condition caused by an abnormally expanded polyglutamine tract in huntingtin (HTT). We identified new modifiers of mutant HTT toxicity by performing a large-scale 'druggable genome' siRNA screen in human cultured cells, followed by hit validation in Drosophila. We focused on glutaminyl cyclase (QPCT), which had one of the strongest effects on mutant HTT-induced toxicity and aggregation in the cell-based siRNA screen and also rescued these phenotypes in Drosophila. We found that QPCT inhibition induced the levels of the molecular chaperone αB-crystallin and reduced the aggregation of diverse proteins. We generated new QPCT inhibitors using in silico methods followed by in vitro screening, which rescued the HD-related phenotypes in cell, Drosophila and zebrafish HD models. Our data reveal a new HD druggable target affecting mutant HTT aggregation and provide proof of principle for a discovery pipeline from druggable genome screen to drug development.

  7. Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice

    PubMed Central

    Bogorad, Roman L; Yin, Hao; Zeigerer, Anja; Nonaka, Hidenori; Ruda, Vera; Zerial, Marino; Anderson, Daniel G; Koteliansky, Victor

    2014-01-01

    Integrins play an important role during development, regulating cell differentiation, proliferation and survival. Here we show that knockdown of integrin subunits slows down the progression of hepatocellular carcinoma (HCC). Using nanoparticulate delivery of short interfering RNAs targeting β1 and αv integrin subunits we downregulate all integrin receptors in hepatocytes. Short-term integrin knockdown (two weeks) does not cause apparent structural or functional perturbations of normal liver tissue. Alterations in liver morphology accumulate upon sustained integrin downregulation (seven weeks). The integrin knockdown leads to significant retardation of HCC progression, reducing proliferation and increasing tumour cell death. This tumour retardation is accompanied by reduced activation of MET oncogene as well as expression of its mature form on the cell surface. Our data suggest that transformed proliferating cells from HCC are more sensitive to knockdown of integrins than normal quiescent hepatocytes, highlighting the potential of siRNA-mediated inhibition of integrins as an anti-cancer therapeutic approach. PMID:24844798

  8. Noninvasive Drug Delivery Using Ultrasound: Targeting Melanoma Using siRNA Against Mutant (V600E) B-Raf

    NASA Astrophysics Data System (ADS)

    Tran, Melissa A.; Gowda, Raghavendra; Park, Eun-Joo; Adair, James; Smith, Nadine; Kester, Mark; Robertson, Gavin P.

    2009-04-01

    Melanoma is the most deadly form of skin cancer. Currently early surgical removal is the best treatment option for melanoma patients with little hope of successful treatment of late stage melanoma. Clearly new treatment options must be explored. Topical administration of drugs provides the advantage of being able to apply large quantities of drug in close proximity to the tumor without the issue of systemic side effects. However, the natural barrier formed by the skin must first be overcome for topical treatment to become a viable option. With this in mind we have sought to use low-frequency ultrasound to transiently permeabilize the stratum corneum and successfully deliver liposomal siRNA to melanoma cells residing at the basement membrane. B-Raf is one of the most frequently activated genes in melanoma, making it an ideal candidate for targeting via siRNA. The novel liposomes used in this study load siRNA, protect if from the outside environment and lead to knockdown of target message. Combining ultrasound with liposomal siRNA we show that siRNA can be delivered into melanoma cells. Additionally, we show that siRNA to mutant B-Raf can effectively inhibit melanoma growth in reconstructs and in mice by 60% and 30% respectively. Therefore, ultrasound with liposomal siRNA is a potentially valuable treatment option for melanoma patients.

  9. Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines

    NASA Astrophysics Data System (ADS)

    Wilson, D. Scott; Dalmasso, Guillaume; Wang, Lixin; Sitaraman, Shanthi V.; Merlin, Didier; Murthy, Niren

    2010-11-01

    Small interfering RNAs (siRNAs) directed against proinflammatory cytokines have the potential to treat numerous diseases associated with intestinal inflammation; however, the side-effects caused by the systemic depletion of cytokines demands that the delivery of cytokine-targeted siRNAs be localized to diseased intestinal tissues. Although various delivery vehicles have been developed to orally deliver therapeutics to intestinal tissue, none of these strategies has demonstrated the ability to protect siRNA from the harsh environment of the gastrointestinal tract and target its delivery to inflamed intestinal tissue. Here, we present a delivery vehicle for siRNA, termed thioketal nanoparticles (TKNs), that can localize orally delivered siRNA to sites of intestinal inflammation, and thus inhibit gene expression in inflamed intestinal tissue. TKNs are formulated from a polymer, poly-(1,4-phenyleneacetone dimethylene thioketal), that degrades selectively in response to reactive oxygen species (ROS). Therefore, when delivered orally, TKNs release siRNA in response to the abnormally high levels of ROS specific to sites of intestinal inflammation. Using a murine model of ulcerative colitis, we demonstrate that orally administered TKNs loaded with siRNA against the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α) diminish TNF-α messenger RNA levels in the colon and protect mice from ulcerative colitis.

  10. Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells.

    PubMed

    Yang, H; Fu, J-H; Hu, Y; Huang, W-Z; Zheng, B; Wang, G; Zhang, X; Wen, J

    2008-01-01

    We investigated the difference in survivin expression between a multidrug-resistant lung cancer cell line (H460/cDDP) and its parental counterpart (H460) and the influence of siRNA targeting survivin on the chemosensitivity of H460/cDDP. SiRNA targeting survivin was transfected into H460/cDDP cells using a liposome approach. Survivin mRNA and protein expression were significantly higher in H460/cDDP than H460 cells. The median inhibitory concentrations (IC(50)s) for cisplatin and paclitaxol in vitro against H460/cDDP cells were significantly lower in cells treated with survivin-specific siRNA than in control cells. Apoptosis and cleaved caspase-3 expression were analysed using annexin V and Western blotting, respectively, and showed a significant increase in apoptosis after treatment with the chemotherapeutic agents plus specific siRNA. Specific siRNA sensitized H460/cDDP cells to both cisplatin and paclitaxol. Thus, survivin appears to participate in the multidrug resistance mechanism of H460/cDDP cells and siRNA targeting survivin has the potential to increase the sensitivity of drug-resistant cancer cells to anticancer drugs.

  11. A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

    PubMed Central

    Bramsen, Jesper B.; Pakula, Malgorzata M.; Hansen, Thomas B.; Bus, Claus; Langkjær, Niels; Odadzic, Dalibor; Smicius, Romualdas; Wengel, Suzy L.; Chattopadhyaya, Jyoti; Engels, Joachim W.; Herdewijn, Piet; Wengel, Jesper; Kjems, Jørgen

    2010-01-01

    Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low. PMID:20453030

  12. Fabrication of Sr silicate buffer layer on Si(100) substrate by pulsed laser deposition using a SrO target

    SciTech Connect

    Imanaka, Atsuhiro; Sasaki, Tsubasa; Hotta, Yasushi Satoh, Shin-ichi

    2014-09-01

    The authors fabricated 2 × 1 Sr-reconstructed Si(100) substrates using thin SrO layers, and used them to direct growth of crystalline perovskite oxide on Si. The SrO layers used to reconstruct the Si(100) substrates were grown by pulsed laser deposition from a SrO single crystal target, followed by postdeposition-annealing (PDA) of the SrO/Si(100) structure. In situ observations of reflective high-energy electron diffraction during PDA confirmed a 2 × 1 reconstruction of the Si surface and x-ray photoemission spectroscopy of the annealed samples confirmed the existence of Sr atoms in a silicate phase, which indicated that a 2 × 1 Sr-reconstructed Si surface was achieved. The optimal fabrication conditions were annealing at 720 °C for 1 min and an equivalent SrO layer thickness (ML{sub eq}) of 2.5 ML{sub eq}. The temperature condition was very narrow, at 720 ± 20 °C, for an acceptable product. Subsequently, the authors demonstrated the growth of crystalline SrTiO{sub 3} films on the 2 × 1 Sr-reconstructed Si(100) surfaces.

  13. Tumor responsive targeted multifunctional nanosystems for cancer imaging, chemo- and siRNA therapy

    NASA Astrophysics Data System (ADS)

    Savla, Ronak

    Cancer is one of the most insidious diseases. Compromising of over 100 different types and sharing the unifying factors of uncontrolled growth and metastasis, unmet clinical needs in terms of cancer diagnosis and treatment continue to exist. It is widely accepted that most forms of cancer are treatable or even curable if detected before widespread metastasis occurs. Nearly a quarter of deaths in the United States is the result of cancer and it only trails heart disease in terms of annual mortality. Surgery, chemotherapy, and radiation therapy are the primary treatment modalities for cancer. Research in these procedures has resulted in substantial benefits for cancer patients, but there is still room for an improvement. However, a time has been reached at which it appears that the benefits from these modalities have been reached the maximum. Therefore, it is vital to develop new strategies for the diagnosis and treatment of cancer. The field of nanotechnology is concerned with structures in the nanometer size range and holds the potential to drastically impact and improve the lives of patients suffering from cancer. Not only can nanotechnology improve current methods of diagnosis and treatment, it has a possibility of introducing newer and better modalities. The overall purpose of this work is to develop novel nanotechnology-based methodologies for the diagnosis and treatment of various forms of cancers. The first aim of the project is the development of a multifunctional targeted nanosystem for the delivery of siRNA to overcome drug resistance. The second aspect is the synthesis of a quantum dot-based delivery system that releases drug in response to pH changes. The third aim is the development of a targeted, tumor environment responsive magnetic resonance nanoparticle contrast agent coupled with a nanoparticle-based treatment.

  14. pH-sensitive siRNA Nanovector for Targeted Gene Silencing and Cytotoxic Effect in Cancer Cells

    PubMed Central

    Mok, Hyejung; Veiseh, Omid; Fang, Chen; Kievit, Forrest M.; Wang, Freddy Y.; Park, James O.; Zhang, Miqin

    2010-01-01

    A small interfering RNA (siRNA) nanovector with dual targeting specificity and dual therapeutic effect is developed for targeted cancer imaging and therapy. The nanovector is comprised of an iron oxide magnetic nanoparticle core coated with three different functional molecules: polyethyleneimine (PEI), siRNA, and chlorotoxin (CTX). The primary amine group of PEI is blocked with citraconic anhydride that is removable at acidic conditions, not only to increase its biocompatibility at physiological conditions but also to elicit a pH-sensitive cytotoxic effect in the acidic tumor microenvironment. The PEI is covalently immobilized on the nanovector via a disulfide linkage that is cleavable after cellular internalization of the nanovector. CTX as a tumor-specific targeting ligand and siRNA as a therapeutic payload are conjugated on the nanovector via a flexible and hydrophilic PEG linker for targeted gene silencing in cancer cells. With a size of ~ 60 nm, the nanovector exhibits long-term stability and good magnetic property for magnetic resonance imaging. The multifunctional nanovector exhibits both significant cytotoxic and gene silencing effects at acidic pH conditions for C6 glioma cells, but not at physiological pH conditions. Our results suggest that this nanovector system could be safely used as a potential therapeutic agent for targeted treatment of glioma as well as other cancers. PMID:20722417

  15. siRNA targeting of Trop2 suppresses the proliferation and invasion of lung adenocarcinoma H460 cells.

    PubMed

    Gao, Xiao-Yan; Zhu, Ye-Han; Zhang, Li-Xin; Lu, Hui-Yu; Jiang, Ai-Gui

    2015-08-01

    The aim of the present study was to investigate the effect of the small interfering RNA (siRNA)-induced inhibition of the Trop2 gene on the proliferation and invasion of lung adenocarcinoma H460 cells. A recombinant adenovirus expression vector, which contained siRNA targeting open reading frames for Trop2 (rAd5-siTrop2), was transfected into lung adenocarcinoma H460 cells. Three groups were included in the study, namely the Ctrl (non-transfected control), rAd5-siCtrl (native control) and rAd5-siTrop2 (knockdown Trop2 gene) groups. The mRNA and protein expression levels of Trop2 were detected using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the expression levels of cyclin Dl and phospho-extracellular signal regulated kinase (p-ERK)-1 were detected using western blot analysis. The effects of Trop2 inhibition on the proliferation and invasion of lung adenocarcinoma H460 cells were investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay. Trop2-targeted siRNA recombinant plasmids were successfully constructed. The recombinant adenovirus vector, rAd5-siTrop2, significantly downregulated the mRNA and protein expression levels of Trop2 in the lung adenocarcinoma H460 cells, with cyclin D1 and p-ERK-1 expression downregulated simultaneously. In addition, following the silencing of Trop2, the proliferation and invasion rates of the lung adenocarcinoma H460 cells were reduced. Therefore, the results indicated that Trop2 serves a key function in the proliferation and invasion of lung adenocarcinoma H460 cells in vitro.

  16. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse

    PubMed Central

    Liu, Yuchen; Li, Dameng; Liu, Zhengya; Zhou, Yu; Chu, Danping; Li, Xihan; Jiang, Xiaohong; Hou, Dongxia; Chen, Xi; Chen, Yuda; Yang, Zhanzhao; Jin, Ling; Jiang, Waner; Tian, Chenfei; Zhou, Geyu; Zen, Ke; Zhang, Junfeng; Zhang, Yujing; Li, Jing; Zhang, Chen-Yu

    2015-01-01

    Cell-derived exosomes have been demonstrated to be efficient carriers of small RNAs to neighbouring or distant cells, highlighting the preponderance of exosomes as carriers for gene therapy over other artificial delivery tools. In the present study, we employed modified exosomes expressing the neuron-specific rabies viral glycoprotein (RVG) peptide on the membrane surface to deliver opioid receptor mu (MOR) siRNA into the brain to treat morphine addiction. We found that MOR siRNA could be efficiently packaged into RVG exosomes and was associated with argonaute 2 (AGO2) in exosomes. These exosomes efficiently and specifically delivered MOR siRNA into Neuro2A cells and the mouse brain. Functionally, siRNA-loaded RVG exosomes significantly reduced MOR mRNA and protein levels. Surprisingly, MOR siRNA delivered by the RVG exosomes strongly inhibited morphine relapse via the down-regulation of MOR expression levels. In conclusion, our results demonstrate that targeted RVG exosomes can efficiently transfer siRNA to the central nervous system and mediate the treatment of morphine relapse by down-regulating MOR expression levels. Our study provides a brand new strategy to treat drug relapse and diseases of the central nervous system. PMID:26633001

  17. Synthetic siRNAs effectively target cystein protease 12 and α-actinin transcripts in Trichomonas vaginalis.

    PubMed

    Ravaee, Roya; Ebadi, Parimah; Hatam, Gholamreza; Vafafar, Arghavan; Ghahramani Seno, Mohammad Mahdi

    2015-10-01

    The flagellated protozoan Trichomonas vaginalis (T. vaginalis) causes trichomoniasis, a reproductive tract infection, in humans. Trichomoniasis is the most common non-viral sexually transmitted disease worldwide. In addition to direct consequences such as infertility and abortion, there are indications that trichomoniasis favours development of prostate cancer and it has also been associated with increased risk of spreading human immunodeficiency virus and papillomavirus infections. Reports from around the world show that the rate of drug resistance in T. vaginalis is increasing, and therefore new therapeutic approaches have to be developed. Studying molecular biology of T. vaginalis will be quite helpful in identifying new drugable targets. RNAi is a powerful technique which allows biologist to specifically target gene products (i.e. mRNA) helping them in unravelling gene functions and biology of systems. However, due to lack of some parts of the required intrinsic RNAi machinery, the RNAi system is not functional in all orders of life. Here, by using synthetic siRNAs targeting two genes, i.e. α-actinin and cystein protease 12 (cp12), we demonstrate T. vaginalis cells are amenable to RNAi experiments conducted by extrinsic siRNAs. Electroporation of siRNAs targeting α-actinin or cp12 into T. vaginalis cells resulted in, respectively, 48-67% and 33-72% downregulation of the cognate transcripts compared to the T. vaginalis cells received siRNAs targeting GL2 luciferase as a control. This finding is helpful in that it demonstrates the potential of using extrinsically induced RNAi in studies on molecular biology of T. vaginalis such as those aiming at identifying new drug targets.

  18. Targeted in vivo delivery of EGFR siRNA inhibits ovarian cancer growth and enhances drug sensitivity

    PubMed Central

    Satpathy, Minati; Mezencev, Roman; Wang, Lijuan; McDonald, John F.

    2016-01-01

    A functionalized nanohydrogel siRNA delivery system and a mouse model of serous ovarian cancer were used to test predictions from previous cell line studies that knockdown of EGFR (epidermal growth factor receptor) may be of clinical significance in the treatment of epithelial tumors especially with respect to the enhancement of platinum based therapies. Our results support these predictions and suggest that targeted delivery of EGFR siRNA may be an effective strategy for the treatment of ovarian and other epithelial tumors associated with elevated levels of EGFR and especially those demonstrating resistance to platinum-based therapies. PMID:27819259

  19. Functionalized silicon quantum dots tailored for targeted siRNA delivery

    SciTech Connect

    Klein, S.; Zolk, O.; Fromm, M.F.; Schroedl, F.; Kryschi, C.

    2009-09-11

    For RNA interference (RNAi) mediated silencing of the ABCB1 gene in Caco-2 cells biocompatible luminescent silicon quantum dots (SiQDs) were developed to serve as self-tracking transfection tool for ABCB1 siRNA. While the 2-3 nm sized SiQD core exhibits green luminescence, the QD surfaces are completely saturated with covalently linked 2-vinylpyridine that may electrostatically bind siRNA. For down-regulating P-glycoprotein (Pgp) expression of the ABCB1 gene the SiQDs were complexed with siRNA. The cellular uptake and allocation of SiQD-siRNA complexes in Caco-2 cells were monitored using confocal laser scanning microscopy and transmission electron microscopy. The release of siRNA to the cytoplasm was verified through real-time PCR quantification of the reduced ABCB1 mRNA level. Additional evidence was obtained from time-resolved in situ fluorescence spectroscopic monitoring of the Pgp efflux dynamics in transfected Caco-2 cells which yielded significantly reduced transporter efficiencies for the Pgp substrate Rhodamine 123.

  20. In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles.

    PubMed

    Ganesh, Shanthi; Iyer, Arun K; Gattacceca, Florence; Morrissey, David V; Amiji, Mansoor M

    2013-12-28

    Multidrug resistance (MDR) is a significant problem in the clinical management of several cancers. Overcoming MDR generally involves multi-modal therapeutic approaches that integrate enhancement of delivery efficiency using targeted nano-platforms as well as strategies that can sensitize cancer cells to drug treatments. We recently demonstrated that tandem delivery of siRNAs that downregulate anti-apoptotic genes overexpressed in cisplatin resistant tumors followed by therapeutic challenge using cisplatin loaded CD44 targeted hyaluronic acid (HA) nanoparticle (NP) induced synergistic antitumor response CD44 expressing tumors that are resistant to cisplatin. In the current study, a near infrared (NIR) dye-loaded HA NP was employed to image the whole body localization of NPs after intravenous (i.v.) injection into live mice bearing human lung tumors that were sensitive and resistant to cisplatin. In addition, we quantified the siRNA duplexes and cisplatin dose distribution in various tissues and organs using an ultra-sensitive quantitative PCR method and inductively coupled plasma-mass spectrometry (ICP-MS), respectively, after i.v. injection of the payload loaded HA NPs in tumor bearing mice. Our findings demonstrate that the distribution pattern of the siRNA and cisplatin using specifically engineered CD44 targeting HA NPs correlated well with the tumor targeting capability as well as the activity and efficacy obtained with combination treatments.

  1. Human CD64-targeted non-viral siRNA delivery system for blood monocyte gene modulation

    PubMed Central

    Yong, Seok-Beom; Kim, Hyung Jin; Kim, Jang Kyoung; Chung, Jee Young; Kim, Yong-Hee

    2017-01-01

    A subset of phagocytes including inflammatory monocytes in blood migrate and give rise to macrophages in inflammatory tissues which generated the idea that blood monocytes are the therapeutic targets for drug delivery. Fc gamma receptor I (CD64) is a membrane receptor for the Fc region of immunoglobulin G, primarily expressed on monocyte-lineage, and H22 a monoclonal antibody for human CD64 had shown rapid blood monocyte binding and occupation in clinical studies. Small interfering RNA-mediated gene silencing as a therapeutic has been proposed and is a promising strategy in terms of its “knock-down” ability on the target gene prior to translation. However, its instability and off-targeting effect must be overcome for success in clinical studies. In this study, we developed a non-viral delivery system composed of oligo-nona-arginine (9R) and anti-human CD64 single chain antibodies (H22) for human monocyte-specific siRNA delivery. A targeted and efficient siRNA delivery mediated by anti-CD64 scFv-9R was observed in CD64 positive human leukemia cells, THP-1. With primary human blood cells, anti-CD64 scFv-9R mediated gene silencing was quantitatively confirmed representing blood monocyte selective gene delivery. These results demonstrate the potential of anti-CD64 scFv-9R mediated siRNA delivery for the treatment of human inflammatory diseases via blood monocytes gene delivery. PMID:28169353

  2. Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment

    PubMed Central

    Zhu, Xi; Xu, Yingjie; Solis, Luisa M.; Tao, Wei; Wang, Liangzhe; Behrens, Carmen; Xu, Xiaoyang; Zhao, Lili; Liu, Danny; Wu, Jun; Zhang, Ning; Wistuba, Ignacio I.; Farokhzad, Omid C.; Zetter, Bruce R.; Shi, Jinjun

    2015-01-01

    RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery. The new generation lipid–polymer hybrid NPs are small and uniform, and can efficiently encapsulate siRNA and control its sustained release. They exhibit long blood circulation (t1/2 ∼8 h), high tumor accumulation, effective gene silencing, and negligible in vivo side effects. With this RNAi NP, we delineate and validate the therapeutic role of Prohibitin1 (PHB1), a target protein that has not been systemically evaluated in vivo due to the lack of specific and effective inhibitors, in treating non-small cell lung cancer (NSCLC) as evidenced by the drastic inhibition of tumor growth upon PHB1 silencing. Human tissue microarray analysis also reveals that high PHB1 tumor expression is associated with poorer overall survival in patients with NSCLC, further suggesting PHB1 as a therapeutic target. We expect this long-circulating RNAi NP platform to be of high interest for validating potential cancer targets in vivo and for the development of new cancer therapies. PMID:26056316

  3. SiRNA Targeting mTOR Effectively Prevents the Proliferation and Migration of Human Lens Epithelial Cells

    PubMed Central

    Zhang, Chunmei; Liu, Jingjing; Jin, Na; Zhang, Guiming; Xi, Yahui; Liu, Hongling

    2016-01-01

    Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms. The mTOR-siRNA was transfected into HLE B3 cells using lipofectamine 2000. The mRNA and protein levels of mTOR were examined to confirm the efficiency of mTOR-siRNA. The levels of mRNA and protein as well as the activity of mTOR down-stream effectors p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB, AKT) were examined using real-time PCR or Western blot, respectively. The cell proliferation was determined using cell counting kit (CCK) 8 and cell growth curve assay. The cell migration was examined using Transwell system and Scratch assay. MTOR-siRNA effectively eliminated mTOR mRNA and protein. The proliferation and migration were significantly suppressed by mTOR-siRNA transfection. mTOR-siRNA reduced the mRNA of p70S6K and AKT in a time-dependent manner. Furthermore, the phosphorylation of p70S6K and AKT was decreased by mTOR-siRNA. MTOR-siRNA also eliminated the formation of mTORC1 and mTORC2 protein complex and blocked the transforming growth factor (TGF)-β-induced EMT. Our results suggested that mTOR-siRNA could effectively inhibit the proliferation, migration and EMT of HLE B3 cells through the inhibition of p70S6K and AKT. These results indicated that mTOR-siRNA might be an effective agent inhibiting HLE cells growth and EMT following cataract surgery and provide an alternative therapy for preventing

  4. Efficient siRNA-peptide conjugation for specific targeted delivery into tumor cells.

    PubMed

    Gandioso, Albert; Massaguer, Anna; Villegas, Núria; Salvans, Cándida; Sánchez, Dani; Brun-Heath, Isabelle; Marchán, Vicente; Orozco, Modesto; Terrazas, Montserrat

    2017-03-02

    Despite the broad applicability of the Huisgen cycloaddition reaction, the click functionalization of RNAs with peptides still remains a challenge. Here we describe a straightforward method for the click functionalization of siRNAs with peptides of different sizes and complexities. Among them, a promising peptide carrier for the selective siRNA delivery into HER2+ breast cancer cell lines has been reported.

  5. Nanoengineered strategies for siRNA delivery: from target assessment to cancer therapeutic efficacy.

    PubMed

    Mishra, Dinesh Kumar; Balekar, Neelam; Mishra, Pradyumna Kumar

    2017-04-01

    The promise of RNA interference (RNAi) technology in cancer therapeutics aims to deliver small interfering RNA (siRNA) for silencing of gene expression in cell type-specific pathway. However, the challenge for the delivery of stable siRNA is hindered by an immune-hostile tumor microenvironment and physiological barriers of the circulatory system. Therefore, the development and validation of safe, stable, and efficient nanoengineered delivery systems are highly essential for effective delivery of siRNA into cancer cells. This review focuses on gene-silencing mechanisms, challenges to siRNA delivery, design and delivery of nanocarrier systems, ongoing clinical trials, and translational prospects for siRNA-mediated cancer therapeutics.

  6. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer

    PubMed Central

    Liu, Hong Yan; Yu, Xiaolin; Liu, Haitao; Wu, Daqing; She, Jin-Xiong

    2016-01-01

    Current targeted therapies using small kinase inhibitors and antibodies have limited efficacy in treating prostate cancer (PCa), a leading cause of cancer death in American men. We have developed a novel strategy by engineering an RNA-based aptamer-siRNA chimera, in which a bivalent aptamer specifically binds prostate-specific membrane antigen (PSMA) via an antibody-like structure to promote siRNA internalization in PCa cells, and two siRNAs specific to EGFR and survivin are fused between two aptamers. The chimera is able to inhibit EGFR and survivin simultaneously and induce apoptosis effectively in vitro and in vivo. In the C4-2 PCa xenograft model, the treatment with the chimera significantly suppresses tumor growth and angiogenesis. The inhibition of angiogenesis is mediated by an EGFR-HIF1α-VEGF-dependent mechanism. Our results support that the bivalent aptamer-driven delivery of two siRNAs could be a new combination therapeutic strategy to effectively inhibit multiple and conventionally “undruggable” targets. PMID:27456457

  7. New therapeutic strategies in neuroblastoma: combined targeting of a novel tyrosine kinase inhibitor and liposomal siRNAs against ALK

    PubMed Central

    Di Paolo, Daniela; Yang, D.; Pastorino, Fabio; Emionite, Laura; Cilli, Michele; Daga, Antonio; Destefanis, Elisa; Di Fiore, Annarita; Piaggio, Francesca; Brignole, Chiara; Xu, Xiaobao; Liang, Chris; Gibbons, James

    2015-01-01

    Many different aberrations in the Anaplastic Lymphoma Kinase (ALK) were found to be oncogenic drivers in several cancers including neuroblastoma (NB), therefore ALK is now considered a critical player in NB oncogenesis and a promising therapeutic target. The ALK-inhibitor crizotinib has a limited activity against the various ALK mutations identified in NB patients. We tested: the activity of the novel ALK-inhibitor X-396 administered alone or in combination with Targeted Liposomes carrying ALK-siRNAs (TL[ALK-siRNA]) that are active irrespective of ALK gene mutational status; the pharmacokinetic profiles and the biodistribution of X-396; the efficacy of X-396 versus crizotinib treatment in NB xenografts; whether the combination of X-396 with the TL[ALK-siRNA] could promote long-term survival in NB mouse models. X-396 revealed good bioavailability, moderate half-life, high mean plasma and tumor concentrations. X-396 was more effective than crizotinib in inhibiting in vitro cell proliferation of NB cells and in reducing tumor volume in subcutaneous NB models in a dose-dependent manner. In orthotopic NB xenografts, X-396 significantly increased life span independently of the ALK mutation status. In combination studies, all effects were significantly improved in the mice treated with TL[ALK-siRNA] and X-396 compared to mice receiving the single agents. Our findings provide a rational basis to design innovative molecular-based treatment combinations for clinical application in ALK-driven NB tumors. PMID:26299615

  8. New therapeutic strategies in neuroblastoma: combined targeting of a novel tyrosine kinase inhibitor and liposomal siRNAs against ALK.

    PubMed

    Di Paolo, Daniela; Yang, D; Pastorino, Fabio; Emionite, Laura; Cilli, Michele; Daga, Antonio; Destafanis, Elisa; Di Fiore, Annarita; Piaggio, Francesca; Brignole, Chiara; Xu, Xiaobao; Liang, Chris; Gibbons, James; Ponzoni, Mirco; Perri, Patrizia

    2015-10-06

    Many different aberrations in the Anaplastic Lymphoma Kinase (ALK) were found to be oncogenic drivers in several cancers including neuroblastoma (NB), therefore ALK is now considered a critical player in NB oncogenesis and a promising therapeutic target. The ALK-inhibitor crizotinib has a limited activity against the various ALK mutations identified in NB patients. We tested: the activity of the novel ALK-inhibitor X-396 administered alone or in combination with Targeted Liposomes carrying ALK-siRNAs (TL[ALK-siRNA]) that are active irrespective of ALK gene mutational status; the pharmacokinetic profiles and the biodistribution of X-396; the efficacy of X-396 versus crizotinib treatment in NB xenografts; whether the combination of X-396 with the TL[ALK-siRNA] could promote long-term survival in NB mouse models. X-396 revealed good bioavailability, moderate half-life, high mean plasma and tumor concentrations. X-396 was more effective than crizotinib in inhibiting in vitro cell proliferation of NB cells and in reducing tumor volume in subcutaneous NB models in a dose-dependent manner. In orthotopic NB xenografts, X-396 significantly increased life span independently of the ALK mutation status. In combination studies, all effects were significantly improved in the mice treated with TL[ALK-siRNA] and X-396 compared to mice receiving the single agents. Our findings provide a rational basis to design innovative molecular-based treatment combinations for clinical application in ALK-driven NB tumors.

  9. siRNA delivery targeting to the lung via agglutination-induced accumulation and clearance of cationic tetraamino fullerene

    NASA Astrophysics Data System (ADS)

    Minami, Kosuke; Okamoto, Koji; Doi, Kent; Harano, Koji; Noiri, Eisei; Nakamura, Eiichi

    2014-05-01

    The efficient treatment of lung diseases requires lung-selective delivery of agents to the lung. However, lung-selective delivery is difficult because the accumulation of micrometer-sized carriers in the lung often induces inflammation and embolization-related toxicity. Here we demonstrate a lung-selective delivery system of small interfering RNA (siRNA) by controlling the size of carrier vehicle in blood vessels. The carrier is made of tetra(piperazino)fullerene epoxide (TPFE), a water-soluble cationic tetraamino fullerene. TPFE and siRNA form sub-micrometer-sized complexes in buffered solution and these complexes agglutinate further with plasma proteins in the bloodstream to form micrometer-sized particles. The agglutinate rapidly clogs the lung capillaries, releases the siRNA into lung cells to silence expression of target genes, and is then cleared rapidly from the lung after siRNA delivery. We applied our delivery system to an animal model of sepsis, indicating the potential of TPFE-based siRNA delivery for clinical applications.

  10. Fabrication of Source/Drain Electrodes for a-Si:H Thin-Film Transistors Using a Single Cu Alloy Target

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Lee, C. Y.; Nam, H. S.; Lee, J. G.; Yang, H. J.; Ho, W. J.; Jeong, J. Y.; Koo, D. H.

    2011-11-01

    A Cu alloy/Cu alloy oxide bilayer structure was formed on an n +-a-Si:H substrate using a single Cu alloy target. It was employed for the source/drain electrodes in the fabrication of a-Si:H thin-film transistors with good electrical performance, high thermal stability, and good adhesion. Transmission electron microscopy and electron energy-loss spectroscopy analyses revealed that the initial sputtering of the Cu alloy in O2/Ar allowed for preferential oxidation of Si and the formation of a SiO x /Cu-supersaturated a-Si:H bilayer at the copper oxide-a-Si:H interface. This bilayer turned into an SiO x /Cu3Si bilayer after annealing at 300°C. It provided a stable contact structure with low contact resistance.

  11. Nano-siRNA Particles and Combination Therapies for Ovarian Tumor Targeting

    DTIC Science & Technology

    2015-08-01

    ability to load LbL nanoparticles with different cargos, ranging from cisplatin to paclitaxel, with sufficient control for effective thereapies (Aim...using siRNA sensitizes COV362, Caov3, and SKOV3 ovarian cancer cells to cisplatin . a) Caov3 cells were transfected with EZH2 siRNA (siEZH2) or control...of three biological replicates. c) The fold change in cisplatin IC50 due to EZH2 depletion was determined for COV362, Caov3, and SKOV3 ovarian cancer

  12. An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress.

    PubMed

    Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

    2014-10-01

    The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants.

  13. Focused ultrasound for targeted delivery of siRNA and efficient knockdown of Htt expression.

    PubMed

    Burgess, Alison; Huang, Yuexi; Querbes, William; Sah, Dinah W; Hynynen, Kullervo

    2012-10-28

    RNA interference is a promising strategy for the treatment of Huntington's disease (HD) as it can specifically decrease the expression of the mutant Huntingtin protein (Htt). However, siRNA does not cross the blood-brain barrier and therefore delivery to the brain is limited to direct CNS delivery. Non-invasive delivery of siRNA through the blood-brain barrier (BBB) would be a significant advantage for translating this therapy to HD patients. Focused ultrasound (FUS), combined with intravascular delivery of microbubble contrast agent, was used to locally and transiently disrupt the BBB in the right striatum of adult rats. 48h following treatment with siRNA, the right (treated) and the left (control) striatum were dissected and analyzed for Htt mRNA levels. We demonstrate that FUS can non-invasively deliver siRNA-Htt directly to the striatum leading to a significant reduction of Htt expression in a dose dependent manner. Furthermore, we show that reduction of Htt with siRNA-Htt was greater when the extent of BBB disruption was increased. This study demonstrates that siRNA treatment for knockdown of mutant Htt is feasible without the surgical intervention previously required for direct delivery to the brain.

  14. Fabrication of Fe@mSiO2 nanowires with large remanence and low cytotoxicity for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Song, Meng-Meng; Bi, Hong; Zhang, Ye

    2012-04-01

    Core-shell structured Fe@mSiO2 nanowires for targeted drug delivery have been prepared through electrodeposition followed by a CTAB-template sol-gel process. The magnetic Fe nanowire core has a diameter of ˜40 nm and the mesoporous silica shell has a uniform thickness of ˜40 nm with an average pore size of ˜2.45 nm. The drug loading experiment indicates Fe@mSiO2 nanowires have a good capability for loading drug molecules due to the large surface area of the mesoporous silica shell. Furthermore, MDA-MB-231 human breast cancer cells were chosen as model cells to investigate cyototoxicity of the nanowires by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) assays. MTT results show low cytotoxicity of the nanowires, which is concentration-dependent and the cell viability is still nearly 80% while the concentration reaches as high as 250 μg/mL. Moreover, LDH assay has demonstrated that the nanowires have no influence on the integrity of the cell membrane. All results indicate that the as-prepared Fe@mSiO2 nanowires have a potential application as a drug nanocarrier for magnetic-targeted drug delivery.

  15. Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift

    NASA Astrophysics Data System (ADS)

    Zhang, Ying-Ming; Yang, Yang; Zhang, Yu-Hui; Liu, Yu

    2016-07-01

    Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host‒guest interactions of an adamantane-bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA’s diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin‒hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates.

  16. Polysaccharide Nanoparticles for Efficient siRNA Targeting in Cancer Cells by Supramolecular pKa Shift

    PubMed Central

    Zhang, Ying-Ming; Yang, Yang; Zhang, Yu-Hui; Liu, Yu

    2016-01-01

    Biomacromolecular pKa shifting is considered as one of the most ubiquitous processes in biochemical events, e.g., the enzyme-catalyzed reaction and protein conformational stabilization. In this paper, we report on the construction of biocompatible polysaccharide nanoparticle with targeting ability and lower toxicity by supramolecular pKa shift strategy. This was realized through a ternary assembly constructed by the dual host‒guest interactions of an adamantane-bis(diamine) conjugate (ADA) with cucurbit[6]uril (CB[6]) and a polysaccharide. The potential application of such biocompatible nanostructure was further implemented by the selective transportation of small interfering RNA (siRNA) in a controlled manner. It is demonstrated that the strong encapsulation of the ADA’s diammonium tail by CB[6] not only reduced the cytotoxicity of the nano-scaled vehicle but also dramatically enhanced cation density through an obvious positive macrocycle-induced pKa shift, which eventually facilitated the subsequent siRNA binding. With a targeted polysaccharide shell containing a cyclodextrin‒hyaluronic acid conjugate, macrocycle-incorporated siRNA polyplexes were specifically delivered into malignant human prostate PC-3 cells. The supramolecular polysaccharide nanoparticles, the formation of which was enabled and promoted by the complexation-assisted pKa shift, may be used as a versatile tool for controlled capture and release of biofunctional substrates. PMID:27363811

  17. EGF receptor targeted lipo-oligocation polyplexes for antitumoral siRNA and miRNA delivery

    NASA Astrophysics Data System (ADS)

    Müller, Katharina; Klein, Philipp M.; Heissig, Philipp; Roidl, Andreas; Wagner, Ernst

    2016-11-01

    Antitumoral siRNA and miRNA delivery was demonstrated by epidermal growth factor receptor (EGFR) targeted oligoaminoamide polyplexes. For this purpose, the T-shaped lipo-oligomer 454 was used to complex RNA into a core polyplex, which was subsequently functionalized with the targeting peptide ligand GE11 via a polyethylene glycol (PEG) linker. To this end, free cysteines on the surface of 454 polyplex were coupled with a maleimide-PEG-GE11 reagent (Mal-GE11). Resulting particles with sizes of 120-150 nm showed receptor-mediated uptake into EGFR-positive T24 bladder cancer cells, MDA-MB 231 breast cancer cells and Huh7 liver cancer cells. Furthermore, these formulations led to ligand-dependent gene silencing. RNA interference (RNAi) triggered antitumoral effects were observed for two different therapeutic RNAs, a miRNA-200c mimic or EG5 siRNA. Using polyplexes modified with a ratio of 0.8 molar equivalents of Mal-GE11, treatment of T24 or MDA-MB 231 cancer cells with miR-200c led to the expected decreased proliferation and migration, changes in cell cycle and enhanced sensitivity towards doxorubicin. Delivery of EG5 siRNA into Huh7 cells resulted in antitumoral activity with G2/M arrest, triggered by loss of mitotic spindle separation and formation of mono-astral spindles. These findings demonstrate the potential of GE11 ligand-containing RNAi polyplexes for cancer treatment.

  18. Microstructure and temperature coefficient of resistance of thin cermet resistor films deposited from CrSi{sub 2}-Cr-SiC targets by S-gun magnetron

    SciTech Connect

    Felmetsger, Valery V.

    2010-01-15

    Technological solutions for producing nanoscale cermet resistor films with sheet resistances above 1000 {Omega}/{open_square} and low temperature coefficients of resistance (TCR) have been investigated. 2-40 nm thick cermet films were sputter deposited from CrSi{sub 2}-Cr-SiC targets by a dual cathode dc S-gun magnetron. In addition to studying film resistance versus temperature, the nanofilm structural features and composition were analyzed using scanning electron microscopy, atomic force microscopy, high-resolution transmission electron microscopy, energy-dispersive x-ray spectroscopy, and electron energy loss spectroscopy. This study has revealed that all cermet resistor films deposited at ambient and elevated temperatures were amorphous. The atomic ratio of Si to Cr in these films was about 2 to 1. The film TCR displayed a significant increase when the deposited film thickness was reduced below 2.5 nm. An optimized sputter process consisting of wafer degassing, cermet film deposition at elevated temperature with rf substrate bias, and a double annealing in vacuum, consisting of in situ annealing following the film sputtering and an additional annealing following the exposure of the wafers to air, has been found to be very effective for the film thermal stabilization and for fine tuning the film TCR. Cermet films with thicknesses in the range of 2.5-4 nm deposited using this technique had sheet resistances ranging from 1800 to 1200 {Omega}/{open_square} and TCR values from -50 ppm/ deg. C to near zero, respectively. A possible mechanism responsible for the high efficiency of annealing the cermet films in vacuum (after preliminary exposure to air), resulting in resistance stabilization and TCR reduction, is also discussed.

  19. Disruption of Aedes aegypti Olfactory System Development through Chitosan/siRNA Nanoparticle Targeting of semaphorin-1a

    PubMed Central

    Mysore, Keshava; Flannery, Ellen M.; Tomchaney, Michael; Severson, David W.; Duman-Scheel, Molly

    2013-01-01

    Despite the devastating impact of mosquito-borne illnesses on human health, surprisingly little is known about mosquito developmental biology, including development of the olfactory system, a tissue of vector importance. Analysis of mosquito olfactory developmental genetics has been hindered by a lack of means to target specific genes during the development of this sensory system. In this investigation, chitosan/siRNA nanoparticles were used to target semaphorin-1a (sema1a) during olfactory system development in the dengue and yellow fever vector mosquito Aedes aegypti. Immunohistochemical analyses and anterograde tracing of antennal sensory neurons, which were used to track the progression of olfactory development in this species, revealed antennal lobe defects in sema1a knockdown fourth instar larvae. These findings, which correlated with a larval odorant tracking behavioral phenotype, identified previously unreported roles for Sema1a in the developing insect larval olfactory system. Analysis of sema1a knockdown pupae also revealed a number of olfactory phenotypes, including olfactory receptor neuron targeting and projection neuron defects coincident with a collapse in the structure and shape of the antennal lobe and individual glomeruli. This study, which is to our knowledge the first functional genetic analysis of insect olfactory development outside of D. melanogaster, identified critical roles for Sema1a during Ae. aegypti larval and pupal olfactory development and advocates the use of chitosan/siRNA nanoparticles as an effective means of targeting genes during post-embryonic Ae. aegypti development. Use of siRNA nanoparticle methodology to understand sensory developmental genetics in mosquitoes will provide insight into the evolutionary conservation and divergence of key developmental genes which could be exploited in the development of both common and species-specific means for intervention. PMID:23696908

  20. A new texturing technique of monocrystalline silicon surface with sodium hypochlorite

    NASA Astrophysics Data System (ADS)

    Sun, Linfeng; Tang, Jiuyao

    2009-08-01

    This work proposes a new texturing technique of monocrystalline silicon surface for solar cells with sodium hypochlorite. A mixed solution consisting of 5 wt% sodium hypochlorite and 10 vl% ethanol has been found that results in a homogeneous pyramidal structure, and an optimal size of pyramids on the silicon surface. The textured silicon surface exhibits a lower average reflectivity (about 10.8%) in the main range of solar spectrum (400-1000 nm).

  1. Growth, Characterization and Device Development in Monocrystalline Diamond Films

    DTIC Science & Technology

    1990-09-30

    silicon substrate surfaces. The aspect ratio of diamond grown on single crystals of different substrate materials correlates with their surface free ...to check the feasibility of such considerations for the present research. The surface free energy of diamond is estimated to be 3387 ergs/cm 2, [Il...while the surface free energies of Si, Ni, Mo, Ta, and W are 1457 ergs/cm2 , 2072 ergs/cm 2, 2463 ergs/cm 2 , 2628 ergs/cm 2 and 3111 ergs/cm 2

  2. Use of Monocrystalline Silicon as Tool Material for Highly Accurate Blanking of Thin Metal Foils

    SciTech Connect

    Hildering, Sven; Engel, Ulf; Merklein, Marion

    2011-05-04

    The trend towards miniaturisation of metallic mass production components combined with increased component functionality is still unbroken. Manufacturing these components by forming and blanking offers economical and ecological advantages combined with the needed accuracy. The complexity of producing tools with geometries below 50 {mu}m by conventional manufacturing methods becomes disproportional higher. Expensive serial finishing operations are required to achieve an adequate surface roughness combined with accurate geometry details. A novel approach for producing such tools is the use of advanced etching technologies for monocrystalline silicon that are well-established in the microsystems technology. High-precision vertical geometries with a width down to 5 {mu}m are possible. The present study shows a novel concept using this potential for the blanking of thin copper foils with monocrystallline silicon as a tool material. A self-contained machine-tool with compact outer dimensions was designed to avoid tensile stresses in the brittle silicon punch by an accurate, careful alignment of the punch, die and metal foil. A microscopic analysis of the monocrystalline silicon punch shows appropriate properties regarding flank angle, edge geometry and surface quality for the blanking process. Using a monocrystalline silicon punch with a width of 70 {mu}m blanking experiments on as-rolled copper foils with a thickness of 20 {mu}m demonstrate the general applicability of this material for micro production processes.

  3. Multifunctional polyglycerol-grafted Fe₃O₄@SiO₂ nanoparticles for targeting ovarian cancer cells.

    PubMed

    Wang, Liang; Neoh, Koon Gee; Kang, En-Tang; Shuter, Borys

    2011-03-01

    Ligand-mediated magnetic resonance (MR) contrast agents would be highly desirable for cancer diagnosis. In the present study, nanoparticles of Fe₃O₄ core with fluorescent SiO₂ shell were synthesized and grafted with hyperbranched polyglycerol (HPG-grafted Fe₃O₄@SiO₂ nanoparticles). These nanoparticles have a hydrodynamic diameter of 47.0 ± 4.0 nm, and are very stable in aqueous solution as well as in cell culture medium. Numerous surface hydroxyl groups of these nanoparticles were conjugated with folic acid by a thiol 'click' reaction. The successful covalent attachment of folic acid on the nanoparticles was confirmed by FTIR and XPS analyses. Both MR imaging and fluorescence microscopy show significant preferential uptake of the folic acid-conjugated polyglycerol-grafted Fe₃O₄@SiO₂ (FA-HPG-grafted Fe₃O₄@SiO₂) nanoparticles by human ovarian carcinoma cells (SKOV-3) as compared to macrophages and fibroblasts. Such nanoparticles can potentially be used to provide real-time imaging in ovarian cancer resection.

  4. Targeting Intestinal Inflammation With CD98 siRNA/PEI–loaded Nanoparticles

    PubMed Central

    Laroui, Hamed; Geem, Duke; Xiao, Bo; Viennois, Emilie; Rakhya, Poonam; Denning, Timothy; Merlin, Didier

    2014-01-01

    Intestinal CD98 expression plays a crucial role in controlling homeostatic and innate immune responses in the gut. Modulation of CD98 expression in intestinal cells therefore represents a promising therapeutic strategy for the treatment and prevention of inflammatory intestinal diseases, such as inflammatory bowel disease. Here, the advantages of nanoparticles (NPs) are used, including their ability to easily pass through physiological barriers and evade phagocytosis, high loading concentration, rapid kinetics of mixing and resistance to degradation. Using physical chemistry characterizations techniques, CD98 siRNA/polyethyleneimine (PEI)–loaded NPs was characterized (diameter of ~480 nm and a zeta potential of −5.26 mV). Interestingly, CD98 siRNA can be electrostatically complexed by PEI and thus protected from RNase. In addition, CD98 siRNA/PEI–loaded NPs are nontoxic and biocompatible with intestinal cells. Oral administration of CD98/PEI-loaded NPs encapsulated in a hydrogel reduced CD98 expression in mouse colonic tissues and decreased dextran sodium sulfate–induced colitis in a mouse model. Finally, flow cytometry showed that CD98 was effectively downregulated in the intestinal epithelial cells and intestinal macrophages of treated mice. Finally, the results collectively demonstrated the therapeutic effect of “hierarchical nano-micro particles” with colon-homing capabilities and the ability to directly release “molecularly specific” CD98 siRNA in colonic cells, thereby decreasing colitis. PMID:24025751

  5. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging.

    PubMed

    Bartlett, Derek W; Su, Helen; Hildebrandt, Isabel J; Weber, Wolfgang A; Davis, Mark E

    2007-09-25

    Targeted delivery represents a promising approach for the development of safer and more effective therapeutics for oncology applications. Although macromolecules accumulate nonspecifically in tumors through the enhanced permeability and retention (EPR) effect, previous studies using nanoparticles to deliver chemotherapeutics or siRNA demonstrated that attachment of cell-specific targeting ligands to the surface of nanoparticles leads to enhanced potency relative to nontargeted formulations. Here, we use positron emission tomography (PET) and bioluminescent imaging to quantify the in vivo biodistribution and function of nanoparticles formed with cyclodextrin-containing polycations and siRNA. Conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid to the 5' end of the siRNA molecules allows labeling with (64)Cu for PET imaging. Bioluminescent imaging of mice bearing luciferase-expressing Neuro2A s.c. tumors before and after PET imaging enables correlation of functional efficacy with biodistribution data. Although both nontargeted and transferrin-targeted siRNA nanoparticles exhibit similar biodistribution and tumor localization by PET, transferrin-targeted siRNA nanoparticles reduce tumor luciferase activity by approximately 50% relative to nontargeted siRNA nanoparticles 1 d after injection. Compartmental modeling is used to show that the primary advantage of targeted nanoparticles is associated with processes involved in cellular uptake in tumor cells rather than overall tumor localization. Optimization of internalization may therefore be key for the development of effective nanoparticle-based targeted therapeutics.

  6. Polarized 3He target and Final State Interactions in SiDIS

    DOE PAGES

    Del Dotto, Alessio; Kaptari, Leonid; Pace, Emanuele; ...

    2017-01-03

    Jefferson Lab is starting a wide experimental program aimed at studying the neutron’s structure, with a great emphasis on the extraction of the parton transverse-momentum distributions (TMDs). To this end, Semi-inclusive deep-inelastic scattering (SiDIS) experiments on polarized $^3$He will be carried out, providing, together with proton and deuteron data, a sound flavor decomposition of the TMDs. Here, given the expected high statistical accuracy, it is crucial to disentangle nuclear and partonic degrees of freedom to get an accurate theoretical description of both initial and final states. In this contribution, a preliminary study of the Final State Interaction (FSI) in themore » standard SiDIS, where a pion (or a Kaon) is detected in the final state is presented, in view of constructing a realistic description of the nuclear initial and final states.« less

  7. Polarized ^{\\varvec{3}}He Target and Final State Interactions in SiDIS

    NASA Astrophysics Data System (ADS)

    Del Dotto, Alessio; Kaptari, Leonid; Pace, Emanuele; Salmè, Giovanni; Scopetta, Sergio

    2017-01-01

    Jefferson Lab is starting a wide experimental program aimed at studying the neutron's structure, with a great emphasis on the extraction of the parton transverse-momentum distributions (TMDs). To this end, Semi-inclusive deep-inelastic scattering (SiDIS) experiments on polarized ^3He will be carried out, providing, together with proton and deuteron data, a sound flavor decomposition of the TMDs. Given the expected high statistical accuracy, it is crucial to disentangle nuclear and partonic degrees of freedom to get an accurate theoretical description of both initial and final states. In this contribution, a preliminary study of the Final State Interaction (FSI) in the standard SiDIS, where a pion (or a Kaon) is detected in the final state is presented, in view of constructing a realistic description of the nuclear initial and final states.

  8. Nano-siRNA Particles and Combination Therapies for Ovarian Tumor Targeting

    DTIC Science & Technology

    2014-08-01

    TEM reveals a filamentous particle structure (Figure 2c). In contrast, even at high N/P ratios (i.e., 5-10), monomeric siRNA does not form detectable...indicate for the first time that systems with optimized 3D clustering of ligand groups can lead to significantly higher intracellular uptake, as...polymeric ODNs were significantly more resistant to DNase enzyme degradation (Fig 3D and Supplementary Fig. 7). To further explore the systemic delivery of

  9. Thermodynamic stability and Watson-Crick base pairing in the seed duplex are major determinants of the efficiency of the siRNA-based off-target effect.

    PubMed

    Ui-Tei, Kumiko; Naito, Yuki; Nishi, Kenji; Juni, Aya; Saigo, Kaoru

    2008-12-01

    Short interfering RNA (siRNA) may down-regulate many unintended genes whose transcripts possess complementarity to the siRNA seed region, which contains 7 nt. The capability of siRNA to induce this off-target effect was highly correlated with the calculated melting temperature or standard free-energy change for formation of protein-free seed duplex, indicating that thermodynamic stability of seed duplex formed between the seed and target is one of the major factor in determining the degree of off-target effects. Furthermore, unlike intended gene silencing (RNA interference), off-target effect was completely abolished by introduction of a G:U pair into the seed duplex, and this loss in activity was completely recovered by a second mutation regenerating Watson-Crick pairing, indicating that seed duplex Watson-Crick pairing is also essential for off-target gene silencing. The off-target effect was more sensitive to siRNA concentration compared to intended gene silencing, which requires a near perfect sequence match between the siRNA guide strand and target mRNA.

  10. Preparation of soft magnetic films of nanocrystalline Fe-Cu-Nb-Si-B alloy by facing targets sputtering

    NASA Astrophysics Data System (ADS)

    Naoe, Masahiko; Matsumiya, Hiroaki; Ichihara, Takayuki; Nakagawa, Shigeki

    1998-06-01

    Soft magnetic thin films of nanocrystalline Fe-Cu-Nb-Si-B alloy were deposited using the facing targets sputtering (FTS) apparatus. It was found that the Fe-Cu-Nb-Si-B single layers thinner than 100 nm revealed good soft magnetic properties, of which the saturation magnetization 4πMs and the relative permeability μr were 11.3 kG and 500, respectively. However, when these films were thicker than 100 nm, their soft magnetic properties degraded due to the perpendicular magnetic anisotropy. On the other hand, the soft magnetic properties of the post-annealed films were improved owing to the release of stress in the films. Especially, μr of the post-annealed films with thickness of 120 nm increased drastically up to around 6200. Furthermore, Fe-Cu-Nb-Si-B/Al multilayers revealed superior soft magnetic properties due to the magnetostatic coupling between the two ferromagnetic layers. These multilayers post-annealed at 300 °C revealed softer magnetic properties than single layers. They exhibited very low coercivity Hc of 0.63 Oe, large 4πMs of 13.2 kG and high μr of 4600.

  11. In Vitro and In Vivo Tumor-Targeting siRNA Delivery Using Folate-PEG-appended Dendrimer (G4)/α-Cyclodextrin Conjugates.

    PubMed

    Ohyama, Ayumu; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi

    2016-03-16

    We previously reported that folate-polyethylene glycol (PEG)-appended dendrimer (generation 3)/α-cyclodextrin conjugate (Fol-PαC (G3)) shows folate receptor-α (FR-α)-overexpressing tumor cell-selective in vitro siRNA transfer activity. However, Fol-PαC (G3)/siRNA complex did not induce a significant in vivo RNAi effect after intravenous administration to tumor-bearing mice, possibly resulting from immediate dissociation of the complex in blood. Herein, to develop the novel siRNA carrier having high blood circulating ability, high in vivo siRNA transfer activity, and high safety profile, we newly prepared Fol-PαCs with higher generation (G4) and evaluated their potential as tumor-targeting siRNA carriers in vitro and in vivo. Fol-PαC (G4, average degree of substitution of α-cyclodextrin (DSC) 2.9, average degree of substitution of folate-PEG (DSF) 2)/siRNA complex had the prominent RNAi effect through adequate physicochemical properties, FR-α-mediated endocytosis, efficient endosomal escape, and siRNA delivery to cytoplasm with negligible cytotoxicity. Importantly, Fol-PαC (G4, DSC2.9, DSF2) improved the serum stability, blood circulating ability, and in vivo RNAi effects of siRNA, compared to Fol-PαC (G3). Furthermore, Fol-PαC (G4, DSC2.9, DSF2) complex with siRNA against Polo-like kinase 1 (siPLK1) suppressed the tumor growth compared to control siRNA complex. These results suggest that Fol-PαC (G4, DSC2.9, DSF2) has the potential as a novel tumor-targeting siRNA carrier in vitro and in vivo.

  12. An ABA-responsive DRE-binding protein gene from Setaria italica, SiARDP, the target gene of SiAREB, plays a critical role under drought stress

    PubMed Central

    Li, Cong; Yue, Jing; Wu, Xiaowei; Xu, Cong; Yu, Jingjuan

    2014-01-01

    The DREB (dehydration-responsive element binding)-type transcription factors regulate the expression of stress-inducible genes by binding the DRE/CRT cis-elements in promoter regions. The upstream transcription factors that regulate the transcription of DREB transcription factors have not been clearly defined, although the function of DREB transcription factors in abiotic stress is known. In this study, an abscisic acid (ABA)-responsive DREB-binding protein gene (SiARDP) was cloned from foxtail millet (Setaria italica). The transcript level of SiARDP increased not only after drought, high salt, and low temperature stresses, but also after an ABA treatment in foxtail millet seedlings. Two ABA-responsive elements (ABRE1: ACGTGTC; ABRE2: ACGTGGC) exist in the promoter of SiARDP. Further analyses showed that two ABA-responsive element binding (AREB)-type transcription factors, SiAREB1 and SiAREB2, could physically bind to the ABRE core element in vitro and in vivo. The constitutive expression of SiARDP in Arabidopsis thaliana enhanced drought and salt tolerance during seed germination and seedling development, and overexpression of SiARDP in foxtail millet improved drought tolerance. The expression levels of target genes of SiARDP were upregulated in transgenic Arabidopsis and foxtail millet. These results reveal that SiARDP, one of the target genes of SiAREB, is involved in ABA-dependent signal pathways and plays a critical role in the abiotic stress response in plants. PMID:25071221

  13. Thin-film monocrystalline-silicon solar cells based on a seed layer approach with 11% efficiency

    NASA Astrophysics Data System (ADS)

    Gordon, I.; Qiu, Y.; Van Gestel, D.; Poortmans, J.

    2010-09-01

    Solar modules made from thin-film crystalline-silicon layers of high quality on glass substrates could lower the price of photovoltaic electricity substantially. Almost half of the price of wafer-based silicon solar modules is currently due to the cost of the silicon wafers themselves. Using crystalline-silicon thin-film as the active material would substantially reduce the silicon consumption while still ensuring a high cell-efficiency potential and a stable cell performance. One way to create a crystalline-silicon thin film on glass is by using a seed layer approach in which a thin crystalline-silicon layer is first created on a non-silicon substrate, followed by epitaxial thickening of this layer. In this paper, we present new solar cell results obtained on 10-micron thick monocrystalline-silicon layers, made by epitaxial thickening of thin seed layers on transparent glass-ceramic substrates. We used thin (001)-oriented silicon single-crystal seed layers on glass-ceramic substrates provided by Corning Inc. that are made by a process based on anodic bonding and implant-induced separation. Epitaxial thickening of these seed layers was realized in an atmospheric-pressure chemical vapor deposition system. Simple solar cell structures in substrate configuration were made from the epitaxial mono-silicon layers. The Si surface was plasma-textured to reduce the front-side reflection. No other light trapping features were incorporated. Efficiencies of up to 11% were reached with Voc values above 600 mV indicating the good electronic quality of the material. We believe that by further optimizing the material quality and by integrating an efficient light trapping scheme, the efficiency potential of these single-crystal silicon thin films on glass-ceramics should be higher than 15%.

  14. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    PubMed Central

    Yang, Xiaoqian; lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-01-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer. PMID:25687880

  15. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    NASA Astrophysics Data System (ADS)

    Yang, Xiaoqian; Lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-02-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

  16. Silencing β3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple-Negative Breast Cancer.

    PubMed

    Parvani, Jenny G; Gujrati, Maneesh D; Mack, Margaret A; Schiemann, William P; Lu, Zheng-Rong

    2015-06-01

    Metastatic breast cancer is the second leading cause of cancer-related deaths among women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Because previous studies coupled β3 integrin (ITGB3) to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGFβ-mediated EMT and invasion, restore TGFβ-mediated cytostasis, and inhibit three-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden and, more importantly, significantly inhibited metastasis. In the span of 16 weeks of the experiments and observations, including primary tumor resection at week 9 and release from the treatment for 4 weeks, the mice bearing orthotopic, TGFβ-prestimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse, in comparison with untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC.

  17. In vitro study of color stability of polycrystalline and monocrystalline ceramic brackets

    PubMed Central

    de Oliveira, Cibele Braga; Maia, Luiz Guilherme Martins; Santos-Pinto, Ary; Gandini Júnior, Luiz Gonzaga

    2014-01-01

    Objective The aim of this in vitro study was to analyze color stability of monocrystalline and polycrystalline ceramic brackets after immersion in dye solutions. Methods Seven ceramic brackets of four commercial brands were tested: Two monocrystalline and two polycrystalline. The brackets were immersed in four dye solutions (coffee, red wine, Coke and black tea) and in artificial saliva for the following times: 24 hours, 7, 14 and 21 days, respectively. Color changes were measured by a spectrophotometer. Data were assessed by Multivariate Profile Analysis, Analysis of Variance (ANOVA) and Multiple Comparison Tests of means. Results There was a perceptible change of color in all ceramic brackets immersed in coffee (ΔE* Allure = 7.61, Inspire Ice = 6.09, Radiance = 6.69, Transcend = 7.44), black tea (ΔE* Allure = 6.24, Inspire Ice = 5.21, Radiance = 6.51, Transcend = 6.14) and red wine (ΔE* Allure = 6.49, Inspire Ice = 4.76, Radiance = 5.19, Transcend = 5.64), but no change was noticed in Coke and artificial saliva (ΔE < 3.7). Conclusion Ceramic brackets undergo color change when exposed to solutions of coffee, black tea and red wine. However, the same crystalline structure, either monocrystalline or polycrystalline, do not follow the same or a similar pattern in color change, varying according to the bracket fabrication, which shows a lack of standardization in the manufacturing process. Coffee dye produced the most marked color changes after 21 days of immersion for most ceramic brackets evaluated. PMID:25279530

  18. Destruction of monocrystalline silicon with nanosecond pulsed fiber laser accompanied by the oxidation of ablation microparticles

    NASA Astrophysics Data System (ADS)

    Veiko, V. P.; Skvortsov, A. M.; Huynh, C. T.; Petrov, A. A.

    2013-11-01

    In this work, we report an observation of process of local destruction monocrystalline silicon with a scanning beam irradiation of pulse ytterbium fiber laser with a wavelength λ= 1062 nm, accompanied by the oxidation of ablation microparticles. It is shown that depending on the power density of irradiation was observed a large scatter size of the microparticles. From a certain average power density is observed beginning oxidation particulate emitted from the surface of the irradiated area. By varying the parameters of the laser beam such as scanning speed, pulse repetition rate, overlap of laser spot, radiation dose can be achieved almost complete oxidation of all formed during the ablation of microparticles.

  19. Analysis of Laser-Imprinting Reduction in Spherical-RT Experiments with Si-Doped Plastic Targets

    NASA Astrophysics Data System (ADS)

    Hu, S. X.; Fiksel, G.; Goncharov, V. N.; Skupsky, S.

    2011-10-01

    Nonuniformities seeded by both long- and short-wavelength laser perturbations grow during shell implosion as a result of the RT instability, affecting the target performance. To study the effect of high- Z dopants in the ablator material on laser imprint, spherical-RT experiments have been performed at the Omega Laser Facility using Si-doped plastic targets in the cone-in-shell configuration. Compared to the pure plastic target, radiation preheating from the dopant is expected to decrease the mass density at the ablation front and increase the stand-off distance between the ablation front and laser-deposition region, reducing the imprinting efficiency and the RT growth. Analyses of experimental data using two-dimensional DRACO simulations for cases with and without dopants will be presented. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC52-08NA28302. V. N. Goncharovet al., Phys. Plasmas 10, 1906 (2003).

  20. Lipid nanoparticles for targeted siRNA delivery – going from bench to bedside

    PubMed Central

    Zatsepin, Timofei S; Kotelevtsev, Yuri V; Koteliansky, Victor

    2016-01-01

    This review covers the basic aspects of small interfering RNA delivery by lipid nano-particles (LNPs) and elaborates on the current status of clinical trials for these systems. We briefly describe the roles of all LNP components and possible strategies for their improvement. We also focus on the current clinical trials using LNP-formulated RNA and the possible outcomes for therapy in the near future. Also, we present a critical analysis of selected clinical trials that reveals the common logic behind target selection. We address this review to a wide audience, especially to medical doctors who are interested in the application of RNA interference–based treatment platforms. We anticipate that this review may spark interest in this particular audience and generate new ideas in target selection for the disorders they are dealing with. PMID:27462152

  1. Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE-1 blocks cell proliferation.

    PubMed

    Awano, Shuji; Dawson, Louise A; Hunter, Alison R; Turner, Anthony J; Usmani, Badar A

    2006-04-01

    The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin-1 (ET-1), its receptors (endothelin-A receptor (ET(A)R) and endothelin-B receptor (ET(B)R)) and isoforms of its specific converting enzyme (ECE-1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE-specific inhibitor (ECE-i) and siRNA targeting of the ECE-1 gene on SCC cell proliferation. We observed the expression of ET-1, ET(A)R, ET(B)R and all endothelin-converting enzyme-1 (ECE-1) isoforms in oral SCC cells, but only the expression of ET-1, ET(B)R and ECE-1 was increased when compared to normal human epidermal keratinocytes. ET-1 alone stimulated proliferation of oral SCC cells. Antagonists of either ET(A)R or ET(B)R inhibited ET-1-mediated proliferation. Decreased ECE-1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE-i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer.

  2. Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells.

    PubMed

    Trembley, Janeen H; Unger, Gretchen M; Korman, Vicci L; Tobolt, Diane K; Kazimierczuk, Zygmunt; Pinna, Lorenzo A; Kren, Betsy T; Ahmed, Khalil

    2012-02-01

    CK2, a pleiotropic Ser/Thr kinase, is an important target for cancer therapy. We tested our novel tenfibgen-based nanocapsule for delivery of the inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and an siRNA directed against both CK2α and α' catalytic subunits to prostate cancer cells. We present data on the TBG nanocapsule itself and on CK2 inhibition or downregulation in treated cells, including effects on Nuclear Factor-kappa B (NF-κB) p65. By direct comparison of two CK2-directed cargos, our data provide proof that the TBG encapsulation design for delivery of drugs specifically to cancer cells has strong potential for small molecule- and nucleic acid-based cancer therapy.

  3. 5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice

    PubMed Central

    Tang, Haiying; Xiang, Dan; Wang, Feng; Mao, Jingwei; Tan, Xiaoyan; Wang, Yingde

    2017-01-01

    The targeting of 5-aminosalicylic acid (5-ASA), a first-line therapeutic agent for mild to moderate active ulcerative colitis (UC), to the site of inflammation has remained a challenge and an unmet requirement in the treatment of UC. However, nanoscale carriers for targeted drug delivery are promising for pharmacotherapy, and nanoparticles improve the pharmacokinetics of the loaded therapeutics based on their physical properties. To design and prepare 5-ASA-loaded silicon dioxide nanoparticles (5-ASA-SiO2 NPs), a micro-emulsion method was conducted, and their respective therapeutic effects were validated in a mouse model of UC. Cytotoxicity of 5-ASA-SiO2 NPs was detected in vitro using the Cell Counting Kit-8 method. The therapeutic effect of 5-ASA-SiO2 NPs was assessed based on their disease activity index (DAI), colon histopathology, myeloperoxidase (MPO) and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SiO2 NPs were successfully prepared, and cytotoxicity of 5-ASA-SiO2 NPs was identified as being similar to 5-ASA and SiO2 NPs. DAI and colonic histopathology scores in the normal dosage, high dosage and the 5-ASA-SiO2 NP groups demonstrated a significant improvement when compared with the model group. DAI in the high dosage and 5-ASA-SiO2 NP groups also demonstrated a significant improvement when compared with the normal dosage group. However, MPO, serum IL-6 and TNF-α levels in normal dosage, high dosage and 5-ASA-SiO2 NPs groups were significantly lower than in the model group, and these indexes in the high dosage group and 5-ASA-SiO2 NP group were significantly lower than that in the normal dosage group. Expression of IL-6 and TNF-α mRNA in colonic mucosa in the normal dosage, high dosage and 5-ASA-SiO2 NP group was significantly lower than that in the model group. Colonic mucosal IL-6 and TNF-α mRNA expression in the high dosage and 5-ASA-SiO2 NP groups was significantly lower than that in the normal dosage group (P<0.05). In

  4. RIsearch2: suffix array-based large-scale prediction of RNA-RNA interactions and siRNA off-targets.

    PubMed

    Alkan, Ferhat; Wenzel, Anne; Palasca, Oana; Kerpedjiev, Peter; Rudebeck, Anders Frost; Stadler, Peter F; Hofacker, Ivo L; Gorodkin, Jan

    2017-01-20

    Intermolecular interactions of ncRNAs are at the core of gene regulation events, and identifying the full map of these interactions bears crucial importance for ncRNA functional studies. It is known that RNA-RNA interactions are built up by complementary base pairings between interacting RNAs and high level of complementarity between two RNA sequences is a powerful predictor of such interactions. Here, we present RIsearch2, a large-scale RNA-RNA interaction prediction tool that enables quick localization of potential near-complementary RNA-RNA interactions between given query and target sequences. In contrast to previous heuristics which either search for exact matches while including G-U wobble pairs or employ simplified energy models, we present a novel approach using a single integrated seed-and-extend framework based on suffix arrays. RIsearch2 enables fast discovery of candidate RNA-RNA interactions on genome/transcriptome-wide scale. We furthermore present an siRNA off-target discovery pipeline that not only predicts the off-target transcripts but also computes the off-targeting potential of a given siRNA. This is achieved by combining genome-wide RIsearch2 predictions with target site accessibilities and transcript abundance estimates. We show that this pipeline accurately predicts siRNA off-target interactions and enables off-targeting potential comparisons between different siRNA designs. RIsearch2 and the siRNA off-target discovery pipeline are available as stand-alone software packages from http://rth.dk/resources/risearch.

  5. Enhanced cooling in mono-crystalline ultra-thin silicon by embedded micro-air channels

    NASA Astrophysics Data System (ADS)

    Ghoneim, Mohamed T.; Fahad, Hossain M.; Hussain, Aftab M.; Rojas, Jhonathan P.; Torres Sevilla, Galo A.; Alfaraj, Nasir; Lizardo, Ernesto B.; Hussain, Muhammad M.

    2015-12-01

    In today's digital world, complementary metal oxide semiconductor (CMOS) technology enabled scaling of bulk mono-crystalline silicon (100) based electronics has resulted in their higher performance but with increased dynamic and off-state power consumption. Such trade-off has caused excessive heat generation which eventually drains the charge of battery in portable devices. The traditional solution utilizing off-chip fans and heat sinks used for heat management make the whole system bulky and less mobile. Here we show, an enhanced cooling phenomenon in ultra-thin (>10 μm) mono-crystalline (100) silicon (detached from bulk substrate) by utilizing deterministic pattern of porous network of vertical "through silicon" micro-air channels that offer remarkable heat and weight management for ultra-mobile electronics, in a cost effective way with 20× reduction in substrate weight and a 12% lower maximum temperature at sustained loads. We also show the effectiveness of this event in functional MOS field effect transistors (MOSFETs) with high-κ/metal gate stacks.

  6. Solution-Phase Epitaxial Growth of Quasi-Monocrystalline Cuprous Oxide on Metal Nanowires

    PubMed Central

    2014-01-01

    The epitaxial growth of monocrystalline semiconductors on metal nanostructures is interesting from both fundamental and applied perspectives. The realization of nanostructures with excellent interfaces and material properties that also have controlled optical resonances can be very challenging. Here we report the synthesis and characterization of metal–semiconductor core–shell nanowires. We demonstrate a solution-phase route to obtain stable core–shell metal–Cu2O nanowires with outstanding control over the resulting structure, in which the noble metal nanowire is used as the nucleation site for epitaxial growth of quasi-monocrystalline Cu2O shells at room temperature in aqueous solution. We use X-ray and electron diffraction, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, photoluminescence spectroscopy, and absorption spectroscopy, as well as density functional theory calculations, to characterize the core–shell nanowires and verify their structure. Metal–semiconductor core–shell nanowires offer several potential advantages over thin film and traditional nanowire architectures as building blocks for photovoltaics, including efficient carrier collection in radial nanowire junctions and strong optical resonances that can be tuned to maximize absorption. PMID:25233392

  7. Solution-phase epitaxial growth of quasi-monocrystalline cuprous oxide on metal nanowires.

    PubMed

    Sciacca, Beniamino; Mann, Sander A; Tichelaar, Frans D; Zandbergen, Henny W; van Huis, Marijn A; Garnett, Erik C

    2014-10-08

    The epitaxial growth of monocrystalline semiconductors on metal nanostructures is interesting from both fundamental and applied perspectives. The realization of nanostructures with excellent interfaces and material properties that also have controlled optical resonances can be very challenging. Here we report the synthesis and characterization of metal-semiconductor core-shell nanowires. We demonstrate a solution-phase route to obtain stable core-shell metal-Cu2O nanowires with outstanding control over the resulting structure, in which the noble metal nanowire is used as the nucleation site for epitaxial growth of quasi-monocrystalline Cu2O shells at room temperature in aqueous solution. We use X-ray and electron diffraction, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, photoluminescence spectroscopy, and absorption spectroscopy, as well as density functional theory calculations, to characterize the core-shell nanowires and verify their structure. Metal-semiconductor core-shell nanowires offer several potential advantages over thin film and traditional nanowire architectures as building blocks for photovoltaics, including efficient carrier collection in radial nanowire junctions and strong optical resonances that can be tuned to maximize absorption.

  8. Enhanced delivery of PEAL nanoparticles with ultrasound targeted microbubble destruction mediated siRNA transfection in human MCF-7/S and MCF-7/ADR cells in vitro

    PubMed Central

    Teng, Yanwei; Bai, Min; Sun, Ying; Wang, Qi; Li, Fan; Xing, Jinfang; Du, Lianfang; Gong, Tao; Duan, Yourong

    2015-01-01

    The gene knockdown activity of small interfering RNA (siRNA) has led to their use as potential therapeutics for a variety of diseases. However, successful gene therapy requires safe and efficient delivery systems. In this study, we choose mPEG-PLGA-PLL nanoparticles (PEAL NPs) with ultrasound targeted microbubble destruction (UTMD) to efficiently deliver siRNA into cells. An emulsification-solvent evaporation method was used to prepare siRNA-loaded PEAL NPs. The NPs possessed an average size of 132.6±10.3 nm (n=5), with a uniform spherical shape, and had an encapsulation efficiency (EE) of more than 98%. As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations. The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells. Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics. PMID:26346350

  9. Task-dependent modulation of SI physiological responses to targets and distractors.

    PubMed

    Spingath, Elsie; Kang, Hyun-Sug; Blake, David T

    2013-02-01

    Selective attention experimental designs have shown that neural responses to stimuli in primary somatosensory cortex are stronger when the sensory stimuli are task relevant. Other studies have used animals under no task demands for data collection. The relationship between neural responses in the brain during behavior, and while an animal has no task demands, remains underexplored. We trained two animals to perform somatosensory detection for several weeks, followed by somatosensory discrimination for several weeks. Data in response to physically identical stimuli were collected from cortical implants while the animal was under no task demands before each behavioral session and also during that behavioral session. The Fourier spectra of the field potentials during detection or discrimination compared with the no task condition demonstrated suppression of the somatosensory μ-rhythm that is associated with readiness and anticipation of cognitive use of somatosensory and motor inputs. Responses to the task target were stronger during detection and discrimination than in the no task condition. The amplitude normalized time course of the target evoked response was similar in both cases. Evoked responses to the task distractor were not significantly stronger during behavior than in recordings under no task demands. The normalized time course of the distractor responses showed a suppression that peaks 30-35 ms after the onset of the response. The selectivity of this within trial suppression is the same as the selectivity of enduring suppression evident in studies of sensory cortical plasticity, which suggests the same neural process may be responsible for both.

  10. Targeted si-RNA with liposomes and exosomes (extracellular vesicles): How to unlock the potential.

    PubMed

    Antimisiaris, Sophia; Mourtas, Spyridon; Papadia, Konstantina

    2017-02-02

    The concept of RNA interference therapeutics has been initiated 18 years ago, and the main bottleneck for translation of the technology into therapeutic products remains the delivery of functional RNA molecules into the cell cytoplasm. In the present review article after an introduction about the theoretical basis of RNAi therapy and the main challenges encountered for its realization, an overview of the different types of delivery systems or carriers, used as potential systems to overcome RNAi delivery issues, will be provided. Characteristic examples or results obtained with the most promising systems will be discussed. Focus will be given mostly on the applications of liposomes or other types of lipid carriers, such as exosomes, towards improved delivery of RNAi to therapeutic targets. Finally the approach of integrating the advantages of these two vesicular systems, liposomes and exosomes, as a potential solution to realize RNAi therapy, will be proposed.

  11. Intracellular siRNA delivery dynamics of integrin-targeted, PEGylated chitosan-poly(ethylene imine) hybrid nanoparticles: A mechanistic insight.

    PubMed

    Ragelle, Héloïse; Colombo, Stefano; Pourcelle, Vincent; Vanvarenberg, Kevin; Vandermeulen, Gaëlle; Bouzin, Caroline; Marchand-Brynaert, Jacqueline; Feron, Olivier; Foged, Camilla; Préat, Véronique

    2015-08-10

    Integrin-targeted nanoparticles are promising for the delivery of small interfering RNA (siRNA) to tumor cells or tumor endothelium in cancer therapy aiming at silencing genes essential for tumor growth. However, during the process of optimizing and realizing their full potential, it is pertinent to gain a basic mechanistic understanding of the bottlenecks existing for nanoparticle-mediated intracellular delivery. We designed αvβ3 integrin-targeted nanoparticles by coupling arginine-glycine-aspartate (RGD) or RGD peptidomimetic (RGDp) ligands to the surface of poly(ethylene glycol) (PEG) grafted chitosan-poly(ethylene imine) hybrid nanoparticles. The amount of intracellular siRNA delivered by αvβ3-targeted versus non-targeted nanoparticles was quantified in the human non-small cell lung carcinoma cell line H1299 expressing enhanced green fluorescent protein (EGFP) using a stem-loop reverse transcription quantitative polymerase chain reaction (RT-qPCR) approach. Data demonstrated that the internalization of αvβ3-targeted nanoparticles was highly dependent on the surface concentration of the ligand. Above a certain threshold concentration, the use of targeted nanoparticles provided a two-fold increase in the number of siRNA copies/cell, subsequently resulting in as much as 90% silencing of EGFP at well-tolerated carrier concentrations. In contrast, non-targeted nanoparticles mediated low levels of gene silencing, despite relatively high intracellular siRNA concentrations, indicating that these nanoparticles might end up in late endosomes or lysosomes without releasing their cargo to the cell cytoplasm. Thus, the silencing efficiency of the chitosan-based nanoparticles is strongly dependent on the uptake and the intracellular trafficking in H1299 EGFP cells, which is critical information towards a more complete understanding of the delivery mechanism that can facilitate the future design of efficient siRNA delivery systems.

  12. Dynamic Contrast Enhanced MRI Assessing the Antiangiogenic Effect of Silencing HIF-1α with Targeted Multifunctional ECO/siRNA Nanoparticles.

    PubMed

    Malamas, Anthony S; Jin, Erlei; Gujrati, Maneesh; Lu, Zheng-Rong

    2016-07-05

    Stabilization of hypoxia inducible factor 1α (HIF-1α), a biomarker of hypoxia, in hypoxic tumors mediates a variety of downstream genes promoting tumor angiogenesis and cancer cell survival as well as invasion, and compromising therapeutic outcome. In this study, dynamic contrast enhanced MRI (DCE-MRI) with a biodegradable macromolecular MRI contrast agent was used to noninvasively assess the antiangiogenic effect of RGD-targeted multifunctional lipid ECO/siHIF-1α nanoparticles in a mouse HT29 colon cancer model. The RGD-targeted ECO/siHIF-1α nanoparticles resulted in over 50% reduction in tumor size after intravenous injection at a dose of 2.0 mg of siRNA/kg every 3 days for 3 weeks compared to a saline control. DCE-MRI revealed significant decline in vascularity and over a 70% reduction in the tumor blood flow, permeability-surface area product, and plasma volume fraction vascular parameters in the tumor treated with the targeted ECO/siHIF-1α nanoparticles. The treatment with targeted ECO/siRNA nanoparticles resulted in significant silencing of HIF-1α expression at the protein level, which also significantly suppressed the expression of VEGF, Glut-1, HKII, PDK-1, LDHA, and CAIX, which are all important players in tumor angiogenesis, glycolytic metabolism, and pH regulation. By possessing the ability to elicit a multifaceted effect on tumor biology, silencing HIF-1α with RGD-targeted ECO/siHIF-1α nanoparticles has great promise as a single therapy or in combination with traditional chemotherapy or radiation strategies to improve cancer treatment.

  13. Measurement of proton induced thick target γ-ray yields on B, N, Na, Al and Si from 2.5 to 4.1 MeV

    NASA Astrophysics Data System (ADS)

    Chiari, M.; Ferraccioli, G.; Melon, B.; Nannini, A.; Perego, A.; Salvestrini, L.; Lagoyannis, A.; Preketes-Sigalas, K.

    2016-01-01

    Thick target yields for proton induced γ-ray emission (PIGE) on low-Z nuclei, namely B, N, Na, Al and Si, were measured for proton energies from 2.5 to 4.1 MeV and emission angles of 0°, 45° and 90°, at the 3 MV Tandetron laboratory of INFN-LABEC in Florence. The studied reactions were: 10B(p,α‧γ)7Be (Eγ = 429 keV), 10B(p,p‧γ)10B (Eγ = 718 keV) and 11B(p,p‧γ)11B (Eγ = 2125 keV) for boron; 14N(p,p‧γ)14N (Eγ = 2313 keV) for nitrogen; 23Na(p,p‧γ)23Na (Eγ = 441 and 1636 keV) and 23Na(p,α‧γ)20Ne (Eγ = 1634 keV) for sodium; 27Al(p,p‧γ)27Al (Eγ = 844 and 1014 keV) and 27Al(p,α‧γ)24Mg (Eγ = 1369 keV) for aluminum; 28Si(p,p‧γ)28Si (Eγ = 1779 keV) and 29Si(p,p‧γ)29Si (Eγ = 1273 keV) for silicon. The PIGE thick target yields have been measured with an overall uncertainty typically better than 10%. The use of the measured thick target yield to benchmark and validate experimental cross sections available in the literature is demonstrated.

  14. Screening target specificity of siRNAs by rapid amplification of cDNA ends (RACE) for non-sequenced species.

    PubMed

    Sabirzhanov, Boris; Sabirzhanova, Inna B; Keifer, Joyce

    2011-05-01

    RNA interference (RNAi) is the process of sequence-specific posttranslational gene silencing triggered by double-stranded RNAs (dsRNAs). RNAi is a widely used approach for studying gene function. However, studies have shown that using siRNA can lead to off-target effects when the siRNA contains sufficient sequence identity to non-target mRNA sequences. One of the important steps in designing dsRNA is verification that it has sequence identity to only the target mRNA. In this report, we propose an approach for primary screening dsRNAs for potential off-target effects by using rapid amplification of cDNA ends. This method can be especially useful for model systems using species that have limited availability of sequence data.

  15. Folate conjugated Mn{sub 3}O{sub 4}@SiO{sub 2} nanoparticles for targeted magnetic resonance imaging in vivo

    SciTech Connect

    Yang, Xinyi; Zhou, Zhiguo; Wang, Li; Tang, Caizhi; Yang, Hong; Yang, Shiping

    2014-09-15

    Graphical abstract: The Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA has been used as a T{sub 1}-MRI probe for in vivo. - Highlights: • The PEG and FA modified Mn{sub 3}O{sub 4}@SiO{sub 2} nanoparticles (Mn{sub 3}O{sub 4}@SiO{sub 2}–FA) were prepared. • Mn{sub 3}O{sub 4}@SiO{sub 2}–FA exhibited the good colloidal stability in the simulated biological medium. • Mn{sub 3}O{sub 4}@SiO{sub 2}–FA showed the targeting ability to HeLa cells overexpressed the FA receptor. • The T{sub 1}-weighted magnetic resonance (MR) imaging demonstrated the targeting ability of Mn{sub 3}O{sub 4}@SiO{sub 2}–FA in vivo tumor. - Abstract: The monodisperse silica-coated manganese oxide nanoparticles (Mn{sub 3}O{sub 4}@SiO{sub 2} NPs) were synthesized via the high temperature pyrolysis approach and were aminated through silanization. The amine-functionalized Mn{sub 3}O{sub 4} NPs enabled the covalent conjugation of hydrophilic methoxypoly(ethylene glycol) (PEG) and the targeting ligand of folate (FA) onto their surface. The formed PEG and FA modified Mn{sub 3}O{sub 4} NPs (Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA) exhibited the good colloidal stability in the simulated biological medium and the targeting ability to HeLa cells overexpressed the FA receptor. The T{sub 1}-weighted magnetic resonance (MR) imaging and inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis of Mn{sub 3}O{sub 4}@SiO{sub 2}(PEG)–FA NPs further demonstrated their targeting ability in tumor.

  16. Construction of simple and efficient siRNA validation systems for screening and identification of effective RNAi-targeted sequences from mammalian genes.

    PubMed

    Tsai, Wen-Hui; Chang, Wen-Tsan

    2014-01-01

    RNA interference (RNAi) is an evolutionarily conserved mechanism of gene silencing induced by double-stranded RNAs (dsRNAs). Among the widely used dsRNAs, small interfering RNAs (siRNAs) and short hairpin RNAs have evolved as extremely powerful and the most popular gene silencing reagents. The key challenge to achieving efficient gene silencing especially for the purpose of therapeutics is mainly dependent on the effectiveness and specificity of the selected RNAi-targeted sequences. Practically, only a small number of dsRNAs are capable of inducing highly effective and sequence-specific gene silencing via RNAi mechanism. In addition, the efficiency of gene silencing induced by dsRNAs can only be experimentally examined based on inhibition of the target gene expression. Therefore, it is essential to develop a fully robust and comparative validation system for measuring the efficacy of designed dsRNAs. In this chapter, we focus our discussion on a reliable and quantitative reporter-based siRNA validation system that has been previously established in our laboratory. The system consists of a short synthetic DNA fragment containing an RNAi-targeted sequence of interest and two expression vectors for targeting reporter and triggering siRNA expressions. The efficiency of siRNAs is determined by their abilities to inhibit expression of the targeting reporters with easily quantified readouts including enhanced green fluorescence protein and firefly luciferase. Since only a readily available short synthetic DNA fragment is needed for constructing this reliable and efficient reporter-based siRNA validation system, this system not only provides a powerful strategy for screening highly effective RNAi-targeted sequences from mammalian genes but also implicates the use of RNAi-based dsRNA reagents for reverse functional genomics and molecular therapeutics.

  17. Ovarian cancer immunotherapy using PD-L1 siRNA targeted delivery from folic acid-functionalized polyethylenimine: strategies to enhance T cell killing.

    PubMed

    Teo, Pei Yun; Yang, Chuan; Whilding, Lynsey M; Parente-Pereira, Ana C; Maher, John; George, Andrew J T; Hedrick, James L; Yang, Yi Yan; Ghaem-Maghami, Sadaf

    2015-06-03

    Adoptive T cell immunotherapy is a promising treatment strategy for epithelial ovarian cancer (EOC). However, programmed death ligand-1 (PD-L1), highly expressed on EOC cells, interacts with programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. This study aims to block PD-1/PD-L1 interactions by delivering PD-L1 siRNA, using various folic acid (FA)-functionalized polyethylenimine (PEI) polymers, to SKOV-3-Luc EOC cells, and investigate the sensitization of the EOC cells to T cell killing. To enhance siRNA uptake into EOC cells, which over express folate receptors, PEI is modified with FA or PEG-FA so that siRNA is complexed into nanoparticles with folate molecules on the surface. PEI modification with a single functional group lowers the polymer cytotoxicity compared to unmodified PEI. FA-conjugated polymers increase siRNA uptake into SKOV-3-luc cells and decrease unspecific uptake into monocytes. All polymers result in 40% to 50% PD-L1 protein knockdown. Importantly, SKOV-3-Luc cells treated with either PEI-FA or PEI- polyethylene glycol (PEG)-FA/PD-L1 siRNA complexes are up to twofold more sensitive to T cell killing compared to scrambled siRNA treated controls. These findings are the first to demonstrate that PD-L1 knockdown in EOC cells, via siRNA/FA-targeted delivery, are able to sensitize cancer cells to T cell killing.

  18. NIR light controlled photorelease of siRNA and its targeted intracellular delivery based on upconversion nanoparticles

    NASA Astrophysics Data System (ADS)

    Yang, Yanmei; Liu, Fang; Liu, Xiaogang; Xing, Bengang

    2012-12-01

    The most notable role of small interfering RNA (siRNA) is in RNA interference (RNAi) and post-transcriptional gene silencing, which leads to a surge of interest in RNAi for both biomedical research and therapeutic applications. However, ``naked'' siRNA cannot cross cellular membranes freely because of highly negative charges which limits its utility for gene therapy. In this work, a system of near-infrared (NIR) light-induced siRNA release from silica coated upconversion nanoparticles (Si-UCNPs) is presented. These Si-UCNPs were functionalized with cationic photocaged linkers through covalent bonding, which could effectively adsorb anionic siRNA through electrostatic attractions and were easily internalized by living cells. Upon NIR light irradiation, the photocaged linker on the Si-UCNPs surface could be cleaved by the upconverted UV light and thus initiated the intracellular release of the siRNA. The in vitro agarose gel electrophoresis and intracellular imaging results indicated that the Si-UCNPs-based gene carrier system allowed effective siRNA delivery and the applications of NIR light instead of direct high energy UV irradiation may greatly guarantee less cell damage.The most notable role of small interfering RNA (siRNA) is in RNA interference (RNAi) and post-transcriptional gene silencing, which leads to a surge of interest in RNAi for both biomedical research and therapeutic applications. However, ``naked'' siRNA cannot cross cellular membranes freely because of highly negative charges which limits its utility for gene therapy. In this work, a system of near-infrared (NIR) light-induced siRNA release from silica coated upconversion nanoparticles (Si-UCNPs) is presented. These Si-UCNPs were functionalized with cationic photocaged linkers through covalent bonding, which could effectively adsorb anionic siRNA through electrostatic attractions and were easily internalized by living cells. Upon NIR light irradiation, the photocaged linker on the Si-UCNPs surface

  19. Photoconductivities in monocrystalline layered V2O5 nanowires grown by physical vapor deposition

    NASA Astrophysics Data System (ADS)

    Chen, Ruei-San; Wang, Wen-Chun; Chan, Ching-Hsiang; Hsu, Hung-Pin; Tien, Li-Chia; Chen, Yu-Jyun

    2013-10-01

    Photoconductivities of monocrystalline vanadium pentoxide (V2O5) nanowires (NWs) with layered orthorhombic structure grown by physical vapor deposition (PVD) have been investigated from the points of view of device and material. Optimal responsivity and gain for single-NW photodetector are at 7,900 A W-1 and 30,000, respectively. Intrinsic photoconduction (PC) efficiency (i.e., normalized gain) of the PVD-grown V2O5 NWs is two orders of magnitude higher than that of the V2O5 counterpart prepared by hydrothermal approach. In addition, bulk and surface-controlled PC mechanisms have been observed respectively by above- and below-bandgap excitations. The coexistence of hole trapping and oxygen sensitization effects in this layered V2O5 nanostructure is proposed, which is different from conventional metal oxide systems, such as ZnO, SnO2, TiO2, and WO3.

  20. Photoconductivities in monocrystalline layered V2O5 nanowires grown by physical vapor deposition

    PubMed Central

    2013-01-01

    Photoconductivities of monocrystalline vanadium pentoxide (V2O5) nanowires (NWs) with layered orthorhombic structure grown by physical vapor deposition (PVD) have been investigated from the points of view of device and material. Optimal responsivity and gain for single-NW photodetector are at 7,900 A W-1 and 30,000, respectively. Intrinsic photoconduction (PC) efficiency (i.e., normalized gain) of the PVD-grown V2O5 NWs is two orders of magnitude higher than that of the V2O5 counterpart prepared by hydrothermal approach. In addition, bulk and surface-controlled PC mechanisms have been observed respectively by above- and below-bandgap excitations. The coexistence of hole trapping and oxygen sensitization effects in this layered V2O5 nanostructure is proposed, which is different from conventional metal oxide systems, such as ZnO, SnO2, TiO2, and WO3. PMID:24160337

  1. Numerical analysis of monocrystalline silicon solar cells with fine nanoimprinted textured surface

    NASA Astrophysics Data System (ADS)

    Yoshinaga, Seiya; Ishikawa, Yasuaki; Araki, Shinji; Honda, Tatsuki; Jiang, Yunjiang; Uraoka, Yukiharu

    2017-02-01

    We investigated the surface reflectance of nanoimprinted textures on silicon. Zirconium oxide, which is a wide-bandgap inorganic dielectric material, was used as the texturing material. We performed several calculations to optimize the textures for the production of high-efficiency bulk-type monocrystalline silicon solar cells. Our analysis revealed that nanoimprinted textured solar cells exhibit a lower reverse saturation current density than a solar cell with a conventional etched texture. It was also confirmed that the photocarrier generation rate for a solar cell with a submicron-scale nanoimprinted texture has little dependence on the texture shape. Furthermore, the weighted average reflectance of an optimized nanoimprinted textured solar cell was substantially reduced to 3.72%, suggesting that texture formation by nanoimprint lithography is an extremely effective technology for producing high-efficiency solar cells at a low cost.

  2. Progress on the fabrication of high resolution and lightweight monocrystalline silicon x-ray mirrors

    NASA Astrophysics Data System (ADS)

    Riveros, Raul E.; Biskach, Michael P.; Allgood, Kim D.; Mazzarella, James R.; Sharpe, Marton V.; Zhang, William W.

    2016-07-01

    Monocrystalline silicon is an excellent X-ray mirror substrate material due to its high stiffness, low density, high thermal conductivity, zero internal stress, and commercial availability. Our work at NASA Goddard Space Flight Center focuses on identifying and developing a manufacturing process to produce high resolution and lightweight X-ray mirror segments in a cost and time effective manner. Previous efforts focused on demonstrating the feasibility of cylindrical silicon mirror polishing and lightweighting. Present efforts are aimed towards producing true paraboloidal and hyperboloidal mirror surfaces on the lightweight silicon segments. This paper presents results from these recent investigations, including a mirror which features a surface quality sufficient for a 3 arcsecond telescope.

  3. Animal models for target diseases in gene therapy--using DNA and siRNA delivery strategies.

    PubMed

    Blagbrough, Ian S; Zara, Chiara

    2009-01-01

    Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmacokinetics within the setting of the wide variety of in vivo animal models now used. This critical appraisal of the recent literature sets out the different models that are currently being investigated to bridge from studies in cell lines through towards clinical reality. Whilst many scientists will be familiar with rodent (murine, fecine, cricetine, and musteline) models, few probably think of fish as a clinically relevant animal model, but zebrafish, madake, and rainbow trout are all being used. Larger animal models include rabbit, cat, dog, and cow. Pig is used both for the prevention of foot-and-mouth disease and human diseases, sheep is a model for corneal transplantation, and the horse naturally develops arthritis. Non-human primate models (macaque, common marmoset, owl monkey) are used for preclinical gene vector safety and efficacy trials to bridge the gap prior to clinical studies. We aim for the safe development of clinically effective delivery systems for DNA and RNAi technologies.

  4. Photomechanical Wave-Driven Delivery of siRNAs Targeting Intermediate Filament Proteins Promotes Functional Recovery after Spinal Cord Injury in Rats

    PubMed Central

    Ando, Takahiro; Sato, Shunichi; Toyooka, Terushige; Kobayashi, Hiroaki; Nawashiro, Hiroshi; Ashida, Hiroshi; Obara, Minoru

    2012-01-01

    The formation of glial scars after spinal cord injury (SCI) is one of the factors inhibiting axonal regeneration. Glial scars are mainly composed of reactive astrocytes overexpressing intermediate filament (IF) proteins such as glial fibrillary acidic protein (GFAP) and vimentin. In the current study, we delivered small interfering RNAs (siRNAs) targeting these IF proteins to SCI model rats using photomechanical waves (PMWs), and examined the restoration of motor function in the rats. PMWs are generated by irradiating a light-absorbing material with 532-nm nanosecond laser pulses from a Q-switched Nd:YAG laser. PMWs can site-selectively increase the permeability of the cell membrane for molecular delivery. Rat spinal cord was injured using a weight-drop device and the siRNA(s) solutions were intrathecally injected into the vicinity of the exposed SCI, to which PMWs were applied. We first confirmed the substantial uptake of fluorescence-labeled siRNA by deep glial cells; then we delivered siRNAs targeting GFAP and vimentin into the lesion. The treatment led to a significant improvement in locomotive function from five days post-injury in rats that underwent PMW-mediated siRNA delivery. This was attributable to the moderate silencing of the IF proteins and the subsequent decrease in the cavity area in the injured spinal tissue. PMID:23272155

  5. Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation

    PubMed Central

    Takahashi, Hironobu; Wang, Yuwei; Grainger, David W.

    2010-01-01

    Fibrous encapsulation of surgically implant devices is associated with elevated proliferation and activation of fibroblasts in tissues surrounding these implants, frequently causing foreign body complications. Here we test the hypothesis that inhibition of the expression of mammalian target of rapamycin (mTOR) in fibroblasts can mitigate the soft tissue implant foreign body response by suppressing fibrotic responses around implants. In this study, mTOR was knocked down using small interfering RNA conjugated with branched cationic polyethylenimine (bPEI) in fibroblastic lineage cells in serum-based cell culture as shown by both gene and protein analysis. This mTOR knockdown led to an inhibition in fibroblast proliferation by 70% and simultaneous down-regulation in the expression of type I collagen in fibroblasts in vitro. These siRNA/bPEI complexes were released from poly(ethylene glycol) (PEG)-based hydrogel coatings surrounding model polymer implants in a subcutaneous rodent model in vivo. No significant reduction in fibrous capsule thickness and mTOR expression in the foreign body capsules was observed. Observed siRNA inefficacy in this in vivo implant model was attributed to siRNA dosing limitations in the gel delivery system, and lack of targeting ability of the siRNA complex specifically to fibroblasts. While in vitro data supported mTOR knock-down in fibroblast cultures, in vivo siRNA delivery must be further improved to produce clinically relevant effects on fibrotic encapsulation around implants. PMID:20727922

  6. Core-interlayer-shell Fe3O4@mSiO2@lipid-PEG-methotrexate nanoparticle for multimodal imaging and multistage targeted chemo-photodynamic therapy.

    PubMed

    Liu, Guihua; Ma, Jinyuan; Li, Yang; Li, Qi; Tan, Chunhua; Song, Hua; Cai, Shuhui; Chen, Dengyue; Hou, Zhenqing; Chen, Qing; Zhu, Xuan

    2017-02-03

    Multimodal imaging-guided multistage targeted synergistic combination therapy possesses many advantages including increased tumoricidal effect, reduced toxicity, and retarded drug resistance. Herein, we have elaborately developed a core-interlayer-shell structure Fe3O4@mSiO2@lipid-PEG-methotrexatenanoparticle(FMLM), in which the Fe3O4 core could be used for magnet-stimulate-response drug release, magnetic resonance imaging, and early-phase magnet targeting ability; the mSiO2 layer could encapsulate anticancer drug doxorubicin (Dox) for chemotherapy; and the protective shell of lipid-PEG and lipid-PEG-methotrexate offered later-phase specific cellular targeting ability, good water dispersibility, and loading of photosensitizer zinc phthalocyanine (ZnPc) for simultaneous near-infrared fluorescence imaging and photodynamic therapy. Both in vitro and in vivo studies indicated that the both Dox and ZnPc-loaded FMLM (Dox/ZnPc-FMLM) exhibited the enhanced tumor accumulation, increased cellular uptake, improved anticancer activity, and weaked side effects compared with Dox/ZnPc-Fe3O4@mSiO2@lipid-PEG nanoparticle (Dox/ZnPc-FML) and free drug. For the first time, magnet targeting cooperative with methotrexate macromolecular prodrug targeting is successfully exploited to develop a promising versatile theranostic nanoplatform for dual-modal fluorescence and magnetic resonance imaging-guided combined chemo-photodynamic cancer therapy.

  7. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis

    PubMed Central

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    2016-01-01

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis. PMID:27729789

  8. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

    PubMed

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

  9. Targeted therapy with MXD3 siRNA, anti-CD22 antibody and nanoparticles for precursor B-cell acute lymphoblastic leukaemia.

    PubMed

    Satake, Noriko; Duong, Connie; Chen, Cathy; Barisone, Gustavo A; Diaz, Elva; Tuscano, Joseph; Rocke, David M; Nolta, Jan; Nitin, Nitin

    2014-11-01

    Conventional chemotherapy for precursor B-cell (preB) acute lymphoblastic leukaemia (ALL) has limitations that could be overcome by targeted therapy. Previously, we discovered a potential therapeutic molecular target, MDX3 (MAX dimerization protein 3), in preB ALL. In this study, we hypothesize that an effective siRNA therapy for preB ALL can be developed using antiCD22 antibody (αCD22 Ab) and nanoparticles. We composed nanocomplexes with super paramagnetic iron oxide nanoparticles (SPIO NPs), αCD22 Abs and MXD3 siRNA molecules based on physical interactions between the molecules. We demonstrated that the MXD3 siRNA-αCD22 Ab-SPIO NP complexes entered leukaemia cells and knocked down MXD3, leading the cells to undergo apoptosis and resulting in decreased live cell counts in the cell line Reh and in primary preB ALL samples in vitro. Furthermore, the cytotoxic effects of the MXD3 siRNA-αCD22 Ab-SPIO NP complexes were significantly enhanced by addition of the chemotherapy drugs vincristine or doxorubicin. We also ruled out potential cytotoxic effects of the MXD3 siRNA-αCD22 Ab-SPIO NP complexes on normal primary haematopoietic cells. Normal B cells were affected while CD34-positive haematopoietic stem cells and non-B cells were not. These data suggest that MXD3 siRNA-αCD22 Ab-SPIO NP complexes have the potential to be a new targeted therapy for preB ALL.

  10. Fab'-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis.

    PubMed

    Laroui, Hamed; Viennois, Emilie; Xiao, Bo; Canup, Brandon S B; Geem, Duke; Denning, Timothy L; Merlin, Didier

    2014-07-28

    Patients suffering from inflammatory bowel disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab' portion of the F4/80 Ab (Fab'-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab'-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab'-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab'-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab'-bearing NPs loaded with TNFα siRNA than without the Fab'-bearing. Grafting the Fab'-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab'-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages.

  11. Fab’-bearing siRNA TNFα-loaded nanoparticles targeted to colonic macrophages offer an effective therapy for experimental colitis

    PubMed Central

    Hamed, Laroui; Emilie, Viennois; Xiao, Bo; Canup, Brandon S.; Duke, Geem; Denning, Timothy L.; Didier, Merlin

    2014-01-01

    Patients suffering from Inflammatory Bowel Disease (IBD) are currently treated by systemic drugs that can have significant side effects. Thus, it would be highly desirable to target TNFα siRNA (a therapeutic molecule) to the inflamed tissue. Here, we demonstrate that TNFα siRNA can be efficiently loaded into nanoparticles (NPs) made of poly (lactic acid) poly (ethylene glycol) block copolymer (PLA-PEG), and that grafting of the Fab’ portion of the F4/80 Ab (Fab’-bearing) onto the NP surface via maleimide/thiol group-mediated covalent bonding improves the macrophage (MP)-targeting kinetics of the NPs to RAW264.7 cells in vitro. Direct binding was shown between MPs and the Fab’-bearing NPs. Next, we orally administered hydrogel (chitosan/alginate)-encapsulated Fab’-bearing TNFα-siRNA-loaded NPs to 3% dextran sodium sulfate (DSS)-treated mice and investigated the therapeutic effect on colitis. In vivo, the release of TNFα-siRNA-loaded NPs into the mouse colon attenuated colitis more efficiently when the NPs were covered with Fab’-bearing, compared to uncovered NPs. All DSS-induced parameters of colonic inflammation (e.g., weight loss, myeloperoxidase activity, and Iκbα accumulation) were more attenuated Fab’-bearing NPs loaded with TNFα siRNA than without the Fab’-bearing. Grafting the Fab’-bearing onto the NPs improved the kinetics of endocytosis as well as the MP-targeting ability, as indicated by flow cytometry. Collectively, our results show that Fab’-bearing PLA-PEG NPs are powerful and efficient nanosized tools for delivering siRNAs into colonic macrophages. PMID:24810114

  12. Antibody h-R3-dendrimer mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion

    PubMed Central

    Li, Jun; Liu, Jing; Li, Shengnan; Hao, Yanli; Chen, Lei; Zhang, Xiaoning

    2016-01-01

    The major obstacle to developing siRNA delivery is their extracellular and intracellular barriers. Herein, a humanized anti-EGFR monoclonal antibody h-R3 was developed to modify the self-assembled binary complexes (dendriplexes) of PAMAM and siRNA via electrostatic interactions, and two common ligands HSA and EGF were used as a control. Compared to dendriplexes, h-R3/EGF/HSA-dendriplexes showed increased particle size, decreased zeta potentials and lower cytotoxicity. Moreover, h-R3-dendriplexes presented greater cellular uptake and excellent endosomal escape ability in HepG2 cells. Ex vivo fluorescence imaging revealed that h-R3-dendriplexes showed higher targeted delivery and gene expression in the tumors than dendriplexes, HSA-dendriplexes and EGF-dendriplexes, which was in agreement with confocal results of cryosections. Furthermore, h-R3-dendriplexes for siPLK1 delivery indicated efficient gene silencing, potentiated cell growth inhibition and cell apoptosis, and suppressed cellular migration/invasion. These results indicate that h-R3-dendriplexes represent a great potential to be used as efficient targeted siRNA delivery carriers. PMID:26883109

  13. Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo.

    PubMed

    Chen, Zhenhua; Yu, Ting; Zhou, Bangfen; Wei, Jinhuan; Fang, Yong; Lu, Jun; Guo, Ling; Chen, Wei; Liu, Zhi-Ping; Luo, Junhang

    2016-03-01

    Emerging evidence indicates that combination of two or more therapeutic strategies can synergistically enhance antitumor activity in cancer therapy. Here, we established a green method of generating nanocomposite particles that can be fabricated using catechin, a natural anti-cancer compound from green tea, and Mg(2+) in an easy one-step approach at room temperature. We show that Mg(II)-Catechin nanocomposite particles (Mg(II)-Cat NPs) have good biocompatibility and high cellular uptake also can load and effectively deliver small interfering RNA (siRNA) into cells in vitro and to tumor site in vivo. Mg(II)-Cat NPs by themselves had tumor-suppression effects. When complexed with siRNA that targets oncogene eukaryotic translation initiation factor 5A2 (EIF5A2), Mg(II)-Cat/siEIF5A2 complex had further enhanced anti-tumor activity. Mechanistically, we show that Mg(II)-Cat/siEIF5A2 inhibits oncogenic PI3K/Akt signal pathway. More importantly, Mg(II)-Cat/siEIF5A2 had tumor suppression effect in a clinically-relevant rat in-situ bladder cancer model. Our studies demonstrated that combination of Mg(II)-Cat NPs and siRNA is a promising therapeutic modality of combining chemotherapy with gene therapy in order to afford higher therapeutic efficacy and provided a proof of principle for such modality in a pre-clinical setting.

  14. Detection of siRNA Mediated Target mRNA Cleavage Activities in Human Cells by a Novel Stem-Loop Array RT-PCR Analysis

    DTIC Science & Technology

    2016-09-07

    sequences at the 3′- termini of cleaved mRNA fragments in human cells under physiological conditions. Our results demonstrated the great potential...siRNA action in mul- ticellular organisms under physiological conditions. In this study, we used a novel stem-loop array RT-PCR (SLA-RT-PCR) assay to... physiological condition in human cells. We used the synthetic siRNAs with an ectopically expressed mRNA target templates as testing models, and the wild-type

  15. (Si){sub 5-2y}(AlP){sub y} alloys assembled on Si(100) from Al-P-Si{sub 3} building units

    SciTech Connect

    Watkins, T.; Chizmeshya, A. V. G.; Kouvetakis, J.; Jiang, L.; Xu, C.; Smith, D. J.; Menendez, J.

    2012-01-09

    An original class of IV/III-V hybrid (Si){sub 5-2y}(AlP){sub y}/Si(100) semiconductors have been produced via tailored interactions of molecular P(SiH{sub 3}){sub 3} and atomic Al yielding tetrahedral ''Al-P-Si{sub 3}'' building blocks. Extensive structural, optical, and vibrational characterization corroborates that these units condense to assemble single-phase, monocrystalline alloys containing 60%-90% Si (y = 0.3-1.0) as nearly defect-free layers lattice-matched to Si. Spectroscopic ellipsometry and density functional theory band structure calculations indicate mild compositional bowing of the band gaps, suggesting that the tuning needed for optoelectronic applications should be feasible.

  16. In vivo efficacy and off-target effects of locked nucleic acid (LNA) and unlocked nucleic acid (UNA) modified siRNA and small internally segmented interfering RNA (sisiRNA) in mice bearing human tumor xenografts.

    PubMed

    Mook, Orf; Vreijling, Jeroen; Wengel, Suzy L; Wengel, Jesper; Zhou, Chuanzheng; Chattopadhyaya, Jyoti; Baas, Frank; Fluiter, Kees

    2010-07-01

    The clinical use of small interfering RNA (siRNA) is hampered by poor uptake by tissues and instability in circulation. In addition, off-target effects pose a significant additional problem for therapeutic use of siRNA. Chemical modifications of siRNA have been reported to increase stability and reduce off-target effects enabling possible therapeutic use of siRNA. Recently a large scale direct comparison of the impact of 21 different types of novel chemical modifications on siRNA efficiency and cell viability was published.1 It was found that several types of chemical modifications could enhance siRNA activity beyond that of an unmodified siRNA in vitro. In addition, a novel siRNA design, termed small internally segmented interfering RNA (sisiRNA), composed of an intact antisense strand and segmented guide strand stabilized using LNA was shown to be effective in cell based assays. In the present study we examined the in vivo efficacy of the LNA and UNA modified siRNA and sisiRNA in a mouse model bearing human tumor xenografts. We studied the biodistribution and efficacy of target knockdown in the mouse model. In addition we used whole genome profiling to assess the off-target effects in the liver of the mouse and the tumor xenografts. We report that LNA and UNA modified siRNA and sisiRNA improve the efficacy in target knockdown as compared with unmodified siRNA in the tumor xenografts without formulation. However, the level of off-target gene regulation in both the tumor and the liver correlated with the increase in efficacy in target knockdown, unless the seed region of the siRNA was modified.

  17. Synthetic siRNA targeting the breakpoint of EWS/Fli-1 inhibits growth of Ewing sarcoma xenografts in a mouse model.

    PubMed

    Takigami, Iori; Ohno, Takatoshi; Kitade, Yukio; Hara, Akira; Nagano, Akihito; Kawai, Gou; Saitou, Mitsuru; Matsuhashi, Aya; Yamada, Kazunari; Shimizu, Katsuji

    2011-01-01

    The EWS/Fli-1 fusion gene, a product of the translocation t(11;22, q24;q12), is detected in 85% of Ewing sarcomas and primitive neuroectodermal tumors. It is thought to be a transcriptional activator that plays a significant role in tumorigenesis. In this study, we developed a novel EWS/Fli-1 blockade system using RNA interference and tested its application for inhibiting the proliferation of Ewing sarcoma cells in vitro and the treatment of mouse tumor xenografts in vivo. We designed and synthesized a small interfering RNA (siRNA) possessing an aromatic compound at the 3'-end targeting the breakpoint of EWS/Fli-1. As this sequence is present only in tumor cells, it is a potentially relevant target. We found that the siRNA targeting EWS/Fli-1 significantly suppressed the expression of EWS/Fli-1 protein sequence specifically and also reduced the expression of c-Myc protein in Ewing sarcoma cells. We further demonstrated that inhibition of EWS/Fli-1 expression efficiently inhibited the proliferation of the transfected cells but did not induce apoptotic cell death. In addition, the siRNA possessing the aromatic compound at the 3'-end was more resistant to nucleolytic degradation than the unmodified siRNA. Administration of the siRNA with atelocollagen significantly inhibited the tumor growth of TC-135, a Ewing sarcoma cell line, which had been subcutaneously xenografted into mice. Moreover, modification of the 3'-end with an aromatic compound improved its efficiency in vivo. Our data suggest that specific downregulation of EWS/Fli-1 by RNA interference is a possible approach for the treatment of Ewing sarcoma.

  18. Folic acid-conjugated GdPO4:Tb3+@SiO2 Nanoprobe for folate receptor-targeted optical and magnetic resonance bi-modal imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xianzhu; Zhang, Xiaoying; Wu, Yanli

    2016-11-01

    Both fluorescent and magnetic nanoprobes have great potential applications for diagnostics and therapy. In the present work, a folic acid-conjugated and silica-modified GdPO4:Tb3+ (GdPO4:Tb3+@SiO2-FA) dual nanoprobe was strategically designed and synthesized for the targeted dual-modality optical and magnetic resonance (MR) imaging via a facile aqueous method. Their structural, optical, and magnetic properties were determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), ultraviolet-visible spectra (UV-Vis), photoluminescence (PL), and superconducting quantum interference device (SQUID). These results indicated that GdPO4:Tb3+@SiO2-FA were uniform monodisperse core-shell structured nanorods (NRs) with an average length of 200 nm and an average width of 25 nm. The paramagnetic property of the synthesized GdPO4:Tb3+@SiO2-FA NRs was confirmed with its linear hysteresis plot (M-H). In addition, the NRs displayed an obvious T1-weighted effect and thus it could potentially serve as a T1-positive contrast agent. The NRs emitted green lights due to the 5D4 → 7F5 transition of the Tb3+. The in vitro assays with NCI-H460 lung cancer cells and human embryonic kidney cell line 293T cells indicated that the GdPO4:Tb3+@SiO2-FA nanoprobe could specifically bind the cells bearing folate receptors (FR). The MTT assay of the NRs revealed that its cytotoxicity was very low. Further in vivo MRI experiments distinctively depict enhanced anatomical features in a xenograft tumor. These results suggest that the GdPO4:Tb3+@SiO2-FA NPs have excellent imaging and cell-targeting abilities for the folate receptor-targeted dual-modality optical and MR imaging and can be potentially used as the nanoprobe for bioimaging.

  19. Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Wang, Lei; Hao, Yongwei; Li, Haixia; Zhao, Yalin; Meng, Dehui; Li, Dong; Shi, Jinjin; Zhang, Hongling; Zhang, Zhenzhong; Zhang, Yun

    2015-01-01

    It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.

  20. CONDENSED MATTER: STRUCTURE, THERMAL AND MECHANICAL PROPERTIES: SiC based Si/SiC heterojunction and its rectifying characteristics

    NASA Astrophysics Data System (ADS)

    Zhu, Feng; Chen, Zhi-Ming; Li, Lian-Bi; Zhao, Shun-Feng; Lin, Tao

    2009-11-01

    The Si on SiC heterojunction is still poorly understood, although it has a number of potential applications in electronic and optoelectronic devices, for example, light-activated SiC power switches where Si may play the role of an light absorbing layer. This paper reports on Si films heteroepitaxially grown on the Si face of (0001) n-type 6H-SiC substrates and the use of B2H6 as a dopant for p-Si grown at temperatures in a range of 700-950 °C. X-ray diffraction (XRD) analysis and transmission electron microscopy (TEM) tests have demonstrated that the samples prepared at the temperatures ranged from 850 °C to 900 °C are characterized as monocrystalline silicon. The rocking XRD curves show a well symmetry with FWHM of 0.4339° Omega. Twin crystals and stacking faults observed in the epitaxial layers might be responsible for widening of the rocking curves. Dependence of the crystal structure and surface topography on growth temperature is discussed based on the experimental results. The energy band structure and rectifying characteristics of the Si/SiC heterojunctions are also preliminarily tested.

  1. siRNAs targeting PB2 and NP genes potentially inhibit replication of Highly Pathogenic H5N1 Avian Influenza Virus.

    PubMed

    Behera, Padmanava; Nagarajan, Shanmugasundaram; Murugkar, Harshad V; Kalaiyarasu, Semmannan; Prakash, Anil; Gothalwal, Ragini; Dubey, Shiv Chandra; Kulkarni, Diwakar D; Tosh, Chakradhar

    2015-06-01

    Highly Pathogenic Avian Influenza (HPAI) H5N1 virus is a threat to animal and public health worldwide. Till date, the H5N1 virus has claimed 402 human lives, with a mortality rate of 58 percent and has caused the death or culling of millions of poultry since 2003. In this study, we have designed three siRNAs (PB2-2235, PB2-479 and NP-865) targeting PB2 and NP genes of avian influenza virus and evaluated their potential, measured by hemagglutination (HA), plaque reduction and Real time RT-PCR assay, in inhibiting H5N1 virus (A/chicken/Navapur/7972/2006) replication in MDCK cells. The siRNAs caused 8- to 16-fold reduction in virus HA titers at 24 h after challenged with 100TCID50 of virus. Among these siRNAs, PB2-2235 offered the highest inhibition of virus replication with 16-fold reduction in virus HA titer, 80 percent reduction in viral plaque counts and 94 percent inhibition in expression of specific RNA at 24 h. The other two siRNAs had 68-73 percent and 87-88 percent reduction in viral plaque counts and RNA copy number, respectively. The effect of siRNA on H5N1 virus replication continued till 48h (maximum observation period). These findings suggest that PB2-2235 could efficiently inhibit HPAI H5N1 virus replication.

  2. Targeted systemic delivery of siRNA to cervical cancer model using cyclic RGD-installed unimer polyion complex-assembled gold nanoparticles.

    PubMed

    Yi, Yu; Kim, Hyun Jin; Mi, Peng; Zheng, Meng; Takemoto, Hiroyasu; Toh, Kazuko; Kim, Beob Soo; Hayashi, Kotaro; Naito, Mitsuru; Matsumoto, Yu; Miyata, Kanjiro; Kataoka, Kazunori

    2016-12-28

    For systemic delivery of small interfering RNA (siRNA) to solid tumors, we developed an actively-targeted unimer polyion complex-assembled gold nanoparticle (uPIC-AuNP) by a two-step assembling process. First is the monodispersed uPIC formation from the single molecules of therapeutic siRNA and the block catiomer, cyclic RGD (cRGD) peptide-installed poly(ethylene glycol)-block-poly(l-lysine) modified with lipoic acid (LA) at the ω-end (cRGD-PEG-PLL-LA). Second is the surface decoration of a 20nm-sized AuNP with uPICs. The cRGD-installed uPIC-AuNPs (cRGD-uPIC-AuNP) provided the targetability for selective binding to the cancer and cancer-related endothelial cellular surface, while regulating their size <50nm with a quite narrow distribution. The targeting efficacy of the cRGD-uPIC-AuNP was confirmed by in vitro cellular uptake in cultured cervical cancer (HeLa) cells and in vivo tumor accumulation in a subcutaneous HeLa model after systemic administration, compared with a non-targeted control uPIC-AuNP. Due to the targetability of the ligand, the cRGD-uPIC-AuNP achieved the significantly enhanced gene silencing ability in the subcutaneous HeLa tumor. Ultimately, the systemic delivery of siRNA targeted for papilloma virus-derived E6 oncogene by cRGD-uPIC-AuNP significantly inhibited the growth of subcutaneous HeLa tumor. This research demonstrates that the bottom-up construction of nanocarriers using monodispersed building blocks can be employed as delivery platforms for RNA interference-based cancer therapy.

  3. VRP09 Reduction of Corneal Scarring Following Blast and Burn Injuries to Cornea Using siRNAs Targeting TGFb and CTGF

    DTIC Science & Technology

    2013-03-01

    aSMA ) synthesis. Second, we proposed to develop an advanced ex vivo organ culture system using viable explants of rabbit corneas, and assess the...effect of the most effective triple siRNA combination for reduction of target genes, collagen and alpha smooth muscle actin ( aSMA ) in rabbit corneas...targeting three key genes (TGFb, TGFbRII, and CTGF) that synergistically reduces the level of mRNAs for type I collagen gene and aSMA by >95% without

  4. ICAM-1-Targeted, Lcn2 siRNA-Encapsulating Liposomes are Potent Anti-angiogenic Agents for Triple Negative Breast Cancer

    PubMed Central

    Guo, Peng; Yang, Jiang; Jia, Di; Moses, Marsha A.; Auguste, Debra T.

    2016-01-01

    Lipocalin 2 (Lcn2) is a promising therapeutic target as well as a potential diagnostic biomarker for breast cancer. It has been previously shown to promote breast cancer progression by inducing the epithelial to mesenchymal transition in breast cancer cells as well as by enhancing angiogenesis. Lcn2 levels in urine and tissue samples of breast cancer patients has also been correlated with breast cancer status and poor patient prognosis. In this study, we have engineered a novel liposomal small interfering RNA (siRNA) delivery system to target triple negative breast cancer (TNBC) via a recently identified molecular target, intercellular adhesion molecule-1 (ICAM-1). This ICAM-1-targeted, Lcn2 siRNA- encapsulating liposome (ICAM-Lcn2-LP) binds human TNBC MDA-MB-231cells significantly stronger than non-neoplastic MCF-10A cells. Efficient Lcn2 knockdown by ICAM-Lcn2-LPs led to a significant reduction in the production of vascular endothelial growth factor (VEGF) from MDA-MB-231 cells, which, in turn, led to reduced angiogenesis both in vitro and in vivo. Angiogenesis (neovascularization) is a requirement for solid tumor growth and progression, and its inhibition is an important therapeutic strategy for human cancers. Our results indicate that a tumor-specific strategy such as the TNBC-targeted, anti-angiogenic therapeutic approach developed here, may be clinically useful in inhibiting TNBC progression. PMID:26722369

  5. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.

    PubMed

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong; Li, He; Li, Yaogang; Duan, Yourong

    2016-01-19

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately -16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy.

  6. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors

    PubMed Central

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong

    2016-01-01

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately −16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy. PMID:26625203

  7. Targeted Nanomedicine for Suppression of CD44 and Simultaneous Cell Death Induction in Ovarian Cancer: an Optimal Delivery of siRNA and Anticancer Drug

    PubMed Central

    Shah, Vatsal; Taratula, Oleh; Garbuzenko, Olga B.; Taratula, Olena R.; Rodriguez-Rodriguez, Lorna; Minko, Tamara

    2013-01-01

    Purpose: The proposed project is aimed at enhancing the efficiency of epithelial ovarian cancer treatment and reducing adverse side effects of chemotherapy using nanotechnology. Overexpression of the CD44 membrane receptor results in tumor initiation, growth, tumor stem cells specific behavior, development of drug resistance, and metastases. We hypothesize that a developed cancer targeted delivery system which combines CD44 siRNA with paclitaxel would successfully deliver its payload inside cancer cells, effectively induce cell death, and prevent metastases. Experimental Design: We synthesized, characterized, and tested a nanoscale-based drug delivery system containing a modified Polypropylenimine (PPI) dendrimer as a carrier; anticancer drug paclitaxel as a cell death inducer; a synthetic analog of luteinizing hormone-releasing hormone (LHRH) peptide as a tumor targeting moiety, and siRNA targeted to CD44 mRNA. The proposed NDDS was tested in vitro and in vivo using metastatic ovarian cancer cells isolated from patients with malignant ascites. Results: We found that in contrast to cells isolated from primary tumors, CD44 was highly overexpressed in metastatic cancer cells. Treatment with the proposed tumor-targeted nanoscale-based nucleic acid and drug delivery system led to the suppression of CD44 mRNA and protein, efficient induction of cell death, effective tumor shrinkage, and prevention of adverse side effects on healthy organs. Conclusion: We show a high therapeutic potential for combinatorial treatment of ovarian carcinoma with a novel drug delivery system that effectively transports siRNA targeting to CD44 mRNA simultaneously with cytotoxic agents. PMID:24036854

  8. Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system.

    PubMed

    Pan, Yuqin; He, Bangshun; Chen, Jie; Sun, Huiling; Deng, Qiwen; Wang, Feng; Ying, Houqun; Liu, Xian; Lin, Kang; Peng, Hongxin; Xie, Hongguang; Wang, Shukui

    2015-11-01

    Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality phenomenon in CRC. Recently observed association of CRC with cluster of differentiation 147 (CD147) could provide a novel approach for gene therapy. In the present study, we investigated the feasibility of using adenovirus‑mediated siRNA targeting CD147 based on the IGF2 LOI system for targeted gene therapy of CRC. A novel adenovirus-mediated siRNA targeting CD147, rAd-H19-CD147mirsh, which was driven by the IGF2 imprinting system, was constructed. The results showed that the EGFP expression was detected only in the IGF2 LOI cell lines (HT-29 and HCT-8), but that no EGFP was produced in cell lines with maintenance of imprinting (MOI) (HCT116). Moreover, rAd-H19-CD147mirsh significantly inhibited the expression of CD147, decreased cell viability and invasive ability, and increased sensitivity to chemotherapeutic drugs only in the LOI cell lines in vitro. Furthermore, mice bearing HT-29 xenografted tumors, which received intratumoral administration of the rAd-H19-CD147mirsh, showed significantly reduced tumor growth and enhanced survival. We conclude that recombinant adenovirus-mediated siRNA targeting CD147 based on the IGF2 LOI system inhibited the growth of the LOI cells in vitro and in vivo, which would provide a novel approach for targeted CRC gene therapy.

  9. Microbeam synchrotron radiation diffraction study of a monocrystalline nickel-base turbine blade after service

    SciTech Connect

    Biermann, H.; Grossmann, B.V.; Mechsner, S.

    1997-11-01

    In turbine blades subjected to service, the hot regions near the leading and trailing edges are subjected to temperatures up to 1,100 C, whereas the regions near the cooling channels are subjected to temperatures of about 800 C. These temperature gradients cause strong inhomogeneities in the local thermal and mechanical loads. In the present paper a monocrystalline turbine blade of the nickel-base superalloy CMSX-6 with an orientation near [001] from a developmental turbine was investigated with high lateral resolution using a Bragg-Fresnel focusing optics in combination with synchrotron radiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble. The blade had been exposed to service in so-called accelerated mission tests for several hundred hours in two test turbines. In the bulk of the material, a {gamma}/{gamma}{prime} raft structure perpendicular to the [001]-direction is observed. At the surface, the protective aluminide coating is visible. Between these two regions, a {gamma}{prime}-enriched zone exists.

  10. Preparation of dendritic-like Ag crystals using monocrystalline silicon as template

    SciTech Connect

    Wei, Yanlin; Chen, Yashao; Ye, Linjing; Chang, Pengmei

    2011-06-15

    Research highlights: {yields} Template-assisted method for synthesis of dendritic silver. {yields} Unique dendritic silver structure with stems, branches, and leaves. {yields} The morphology of silver depends on silicon surface roughness. {yields} Both diffusion and oriented attachment dominating the dendritic structure formation. -- Abstract: Symmetric dendritic silver structures with controlled morphology were successfully synthesized by a solvothermal method with the assistance of monocrystalline silicon. The morphology and structure of the dendritic silver were characterized by transmission electron microscopy (TEM), powder X-ray diffraction (XRD), and scanning electron microscopy (SEM). It was found that the architecture of silver crystals could be controlled via simply adjusting the experiment parameters: AgNO{sub 3} concentration, reaction time and temperature. Moreover, structural characterizations suggested that the dendritic silver structures preferentially grew along (1 1 1) and (2 0 0) directions, leading to the formation of dendritic structures with 1-2 {mu}m in stem diameter and 10-50 {mu}m in length. Additionally, the formation process of the dendritic silver structures was studied, and a possible formation mechanism was proposed based on the experimental results.

  11. EFFECT OF SHOCK COMPRESSION METHOD ON THE DEFECT SUBSTRUCTURE IN MONOCRYSTALLINE COPPER

    SciTech Connect

    Cao, B Y; Lassila, D H; Schneider, M S; Kad, B K; Huang, C X; Xu, Y B; Kalantar, D H; Remington, B A; Meyers, M A

    2005-09-23

    Monocrystalline copper samples with orientations of [001] and [221] were shocked at pressures ranging from 20 GPa to 60 GPa using two techniques: direct drive lasers and explosively driven flyer plates. The pulse duration for these techniques differed substantially: 40 ns for the laser experiments at 0.5 mm into the sample and 1.1 {approx} 1.4 {micro}s for the flyer-plate experiments at 5 mm into the sample. The residual microstructures were dependent on orientation, pressure, and shocking method. The much shorter pulse duration in the laser driven shock yielded microstructures closer to the ones generated at the shock front. For the flyer-plate experiments, the longer pulse duration allows shock-generated defects to reorganize into lower energy configurations. Calculations show that the post-shock cooling for the laser driven shock is 10{sup 3} {approx} 10{sup 4} faster than that for plate-impact shock, propitiating recovery and recrystallization conditions for the latter. At the higher pressure level, extensive recrystallization was observed in the plate-impact samples, while it was absent in the laser driven shock. An effect that is proposed to contribute significantly to the formation of recrystallized regions is the existence of micro-shear-bands, which increase the local temperature beyond the prediction from adiabatic compression.

  12. Effect of Shock Compression Method on the Defect Substructure in Monocrystalline Copper

    SciTech Connect

    Cao, B Y; Meyers, M A; Lassila, D H; Schneider, M S; Kad, B K; Huang, C X; Xu, Y B; Kalantar, D H; Remington, B A

    2005-02-17

    Monocrystalline copper samples with orientations of [001] and [221] were shocked at pressures ranging from 20 GPa to 60 GPa using two techniques: direct drive lasers and explosively driven flyer plates. The pulse duration for these techniques differed substantially: 2 ns for the laser experiments and 1.1-1.4 {micro}s for the flyer-plate experiments. The residual microstructures were dependent on orientation, pressure, and shocking method. The much shorter pulse duration in laser shock yielded recovery microstructures with no or limited dislocation motion. For the flyer-plate experiments, the longer pulse duration allow shock-generated defects to reorganize into lower energy configurations. Calculations show that the post shock cooling occurs in a time scale of 0.2 s for laser shock and 1000 s for plate-impact shock, propitiating recovery and recrystallization conditions for the latter. At the higher pressure level extensive recrystallization was observed in the plate-impact samples, while it was absent in laser shock. An effect that is proposed to contribute significantly to the formation of recrystallized regions is the existence of micro-shearbands, which increase the local temperature.

  13. The effect of surface microstructure on the optical reflectance of monocrystalline silicon

    NASA Astrophysics Data System (ADS)

    Wang, Quanji; Zhou, Weidong; Chen, Fangfang; Yang, Ruizhao

    2016-12-01

    Surface texturing is an important technique used to enhance the light absorption by forming certain microstructures on silicon surface. In this article, four different microstructures, based on repeat units of triangles, perpendicular grooves, hexagons and parallel grooves respectively, were fabricated directly on the surface of monocrystalline silicon wafers by using femtosecond laser texturing technique. Compare to the silicon wafers that were not treated by laser, a significant decrease of light reflectance can be observed for those laser etched silicon surfaces. And the treated silicon surface with triangles texture was found to have the lowest relative reflectance of ∼20% in the wavelength range from 400 to 1000 nm, if the textured surfaces were irradiated using the same laser fabrication condition. In addition, the relative reflectance of laser etched silicon surfaces with similar repeat unit but different structural period was investigated as well. The results show that the relative reflectance of the treated surface increases along with the increase of structural period size. These results obtained here can provide a useful guide for fabricating silicon-based optoelectronic devices with a more excellent anti-reflective performance.

  14. A molecular dynamics study of void initiation and growth in monocrystalline and nanocrystalline copper

    NASA Astrophysics Data System (ADS)

    Traiviratana, Sirirat

    MD simulations in monocrystalline and nanocrystalline copper were carried out with LAMMPS to reveal void growth mechanisms. The specimens were subjected to both tensile uniaxial and hydrostatic strains; the results confirm that the emission of (shear) loops is the primary mechanism of void growth. The expansion of the loops and their cross slip leads to the severely work hardened layer surrounding a growing void. Calculations were carried out on voids with different sizes, and a size dependence of the stress response to emitted dislocations was observed, in disagreement with the Gurson model [1] which is scale independent. The growth of voids simulated by MD is compared with the Cocks-Ashby constitutive model and significant agreement is found. The density of geometrically-necessary dislocations as a function of void size is calculated based on the emission of shear loops and their outward propagation. Calculations were also carried out for a void at the interface between two grains sharing a tilt boundary. The results show similar dislocation behaviors. A code that uses Voronoi tessellation for constructing nanocrystalline structures was developed and used to prepare the structures for simulations. Nanocrystal simulations reveal grain sliding and grain rotation as the nanocrystal deformed. Voids were nucleated at grain junctions and grew to coalescence as dislocations accommodated the material transfer. A code that can be used during post-processing to extract useful dislocation information from MD simulation data was partially developed and proved the feasibility of automatically analyzing dislocations.

  15. Improvement of corrosion protection property of Mg-alloy by DLC and Si-DLC coatings with PBII technique and multi-target DC-RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Masami, Ikeyama; Setsuo, Nakao; Tsutomu, Sonoda; Junho, Choi

    2009-05-01

    Magnesium alloys have been considered as one of the most promising light weight materials with potential applications for automobile and aircraft components. Their poor corrosion resistance, however, has to date prevented wider usage. Diamond-like carbon (DLC) and silicon-incorporated DLC (Si-DLC) coatings are known to provide a high degree of corrosion protection, and hold accordingly promise for enhancing the corrosion resistance of the magnesium alloys. In this work we have studied the effect of coating conditions of DLC coatings as well as Si incorporation into coating on corrosion resistance, deposited onto AZ91 magnesium alloy substrates by plasma based ion implantation (PBII). The influences of a Ti interlayer beneath the DLC, Si-DLC and Ti incorporated DLC (Ti-DLC) coatings fabricated by multi-target direct-current radio-frequency (DC-RF) magnetron sputtering were also examined on both the adhesion strength and corrosion resistance of the materials. We have also examined the effect of the Si content in the Si-DLC coatings made by magnetron sputtering on the alloys' corrosion resistance. The results of potentiodynamic polarization measurements demonstrate that Si-DLC coating deposited by PBII exhibits the highest corrosion resistance in an aqueous 0.05 M NaCl solution. Although Ti layer is helpful in increasing adhesion between DLC coating and AZ91 substrate, it also influences adversely corrosion protection. The ozone treatment of the magnesium alloy's surface before the formation of coatings has been found to improve both adhesion strength and corrosion resistance.

  16. Effect of combination therapy of siRNA targeting growth hormone receptor and 5-fluorouracil in hepatic metastasis of colon cancer

    PubMed Central

    ZHOU, DONG; ZHANG, YI; LIANG, DAOMING; YUAN, YONG; ZENG, DEMIAO; CHEN, JIAYONG; YANG, JIE

    2015-01-01

    The aim of this study was to investigate the effects of small interfering RNA (siRNA) targeting human growth hormone receptor (hGHR) combined with 5-fluorouracil (5-FU) on the hepatic metastasis of colon cancer. The animal model of liver metastases using human SW480 colon cancer cells was established on BALB/c mice and the siRNA interfering plasmid targeting hGHR gene was constructed. The tumor-bearing mice were randomly divided into the saline control, plasmid, growth hormone (GH), 5-FU, 5-FU+plasmid and 5-FU+plasmid+GH groups. The liver metastasis in each group was observed. All the animals showed liver metastases and using siRNA-interfering plasmid treatment the incidence of liver metastases was significantly reduced in the tumor groups compared to the saline or GH group. The combined treatment of interfering plasmid and 5-FU slightly decreased the incidence of liver metastases in the tumor groups compared to the plasmid alone or 5-FU alone treatment, although the findings were not statistically significant. On the basis of the combination of interfering plasmid and 5-FU, the additional GH did not increase the incidence of liver metastases (P>0.05), but improved the weight loss of the mice (P<0.05) induced by the inhibition of GHR and toxicity of 5-FU. The present results showed that siRNA targeting hGHR is able to reduce the incidence of liver metastases of human SW480 colon cancer cells in mice. Thus, GHR may be important in tumor metastasis. PMID:26788158

  17. Gradient nanostructured coatings obtained by magnetron sputtering of a multiphase AlN-TiB2-TiSi2 target

    NASA Astrophysics Data System (ADS)

    Pogrebnjak, A. D.; Pshyk, A. V.; Coy, E.; Zaleski, K.; Peplinska, B.; Nowaczyk, G.; Kupchishin, A. I.; Beresnev, V. M.; Kassenova, L. G.; Kravchenko, Ya. O.

    2016-10-01

    The preparation and analysis of gradient nanostructured coatings obtained by the method of the magnetron sputtering of a multiphase composite AlN-TiB2-TiSi2 target are described. The structure and phase and elemental compositions have been investigated by the methods of X-ray diffraction (XRD), atomic force microscopy (AFM), and electron microscopy (SEM and TEM, with energy-dispersive analysis). The mechanical properties of coatings were characterized by the method of nanoindentation. The coating formed consisted of three layers different in the elemental composition and structure, which determined its mechanical properties. The formation of structurally inhomogeneous coating is explained by the fact that the target to be sputtered consisted of three different components (AlN, 50 wt %; TiB2, 35 wt %; TiSi2, 15 wt %) inhomogeneously distributed over the volume of the target. The influence of different processes that occur upon the sputtering of multiphase targets by ions of inert gases on the formation of nanocomposite coatings with a gradient structure is discussed.

  18. Multilayered polyion complexes with dissolvable silica layer covered by controlling densities of cRGD-conjugated PEG chains for cancer-targeted siRNA delivery.

    PubMed

    Naito, Mitsuru; Azuma, Ryota; Takemoto, Hiroyasu; Hori, Mao; Yoshinaga, Naoto; Osawa, Shigehito; Kamegawa, Rimpei; Kim, Hyun Jin; Ishii, Takehiko; Nishiyama, Nobuhiro; Miyata, Kanjiro; Kataoka, Kazunori

    2017-03-12

    Surface functionalization of nanoparticles is a crucial factor for nanoparticle-mediated drug and nucleic acid delivery. Particularly, the density of targeting ligands on nanoparticle significantly affects the affinity of nanoparticles to specific cellular surface (or receptor) through the multivalent binding effect. Herein, multilayered polyion complexes (mPICs) are prepared to possess varying densities of cyclic RGD peptide (cRGD) ligands for cancer-targeted small interfering RNA (siRNA) delivery. A template PIC is first prepared by mixing siRNAs with homo catiomers of N-substituted polyaspartamide bearing tetraethylenepentamine (PAsp(TEP)) in aqueous solution, followed by silica-coating through silicate condensation reaction. Then, silica-coated PICs (sPICs) are further covered with block catiomers of PAsp(TEP) and poly(ethylene glycol) (PEG) equipped with cRGD ligand. Successful preparation of targeted mPICs is confirmed from the changes in size and ζ-potential and the elemental analysis by transmission electron microscopy. Notably, the number of cRGD ligands per mPIC is regulated by altering the silicate concentration upon preparation of sPICs, which is confirmed by fluorescence correlation spectroscopy using fluorescent-labeled block catiomers. Ultimately, the targeted mPICs with a higher number of cRGD ligands demonstrate more efficient cellular uptake in cultured cancer cells, leading to enhanced gene silencing activity.

  19. Deposition of copper coatings in a magnetron with liquid target

    SciTech Connect

    Tumarkin, A. V. Kaziev, A. V.; Kolodko, D. V.; Pisarev, A. A.; Kharkov, M. M.; Khodachenko, G. V.

    2015-12-15

    Copper coatings were deposited on monocrystalline Si substrates using a magnetron discharge with a liquid cathode in the metal vapour plasma. During the deposition, the bias voltage in the range from 0 V to–400 V was applied to the substrate. The prepared films were investigated by a scanning electron microscope, and their adhesive properties were studied using a scratch tester. It was demonstrated that the adhesion of the deposited films strongly depends on the bias voltage and varies in a wide range.

  20. Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown

    PubMed Central

    Srikar, R.; Suresh, Dhananjay; Zambre, Ajit; Taylor, Kristen; Chapman, Sarah; Leevy, Matthew; Upendran, Anandhi; Kannan, Raghuraman

    2016-01-01

    A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation. PMID:27530552

  1. Targeted nanoconjugate co-delivering siRNA and tyrosine kinase inhibitor to KRAS mutant NSCLC dissociates GAB1-SHP2 post oncogene knockdown

    NASA Astrophysics Data System (ADS)

    Srikar, R.; Suresh, Dhananjay; Zambre, Ajit; Taylor, Kristen; Chapman, Sarah; Leevy, Matthew; Upendran, Anandhi; Kannan, Raghuraman

    2016-08-01

    A tri-block nanoparticle (TBN) comprising of an enzymatically cleavable porous gelatin nanocore encapsulated with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA conjugate has been synthesized. Targeted delivery of siRNA to undruggable KRAS mutated non-small cell lung cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating cancer; however, efficient delivery of siRNA and releasing it in cytoplasm remains a major challenge. We have shown TBN can efficiently deliver siRNA to cytoplasm of KRAS mutant H23 Non-Small Cell Lung Cancer (NSCLC) cells for oncogene knockdown; subsequently, sensitizing it to TKI. In the absence of TKI, the nanoparticle showed minimal toxicity suggesting that the cells adapt a parallel GAB1 mediated survival pathway. In H23 cells, activated ERK results in phosphorylation of GAB1 on serine and threonine residues to form GAB1-p85 PI3K complex. In the absence of TKI, knocking down the oncogene dephosphorylated ERK, and negated the complex formation. This event led to tyrosine phosphorylation at Tyr627 domain of GAB1 that regulated EGFR signaling by recruiting SHP2. In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell death. The outcome of this study provides a promising platform for treating NSCLC patients harboring KRAS mutation.

  2. Tailoring Lipid and Polymeric Nanoparticles as siRNA Carriers towards the Blood-Brain Barrier - from Targeting to Safe Administration.

    PubMed

    Gomes, Maria João; Fernandes, Carlos; Martins, Susana; Borges, Fernanda; Sarmento, Bruno

    2017-03-01

    Blood-brain barrier is a tightly packed layer of endothelial cells surrounding the brain that acts as the main obstacle for drugs enter the central nervous system (CNS), due to its unique features, as tight junctions and drug efflux systems. Therefore, since the incidence of CNS disorders is increasing worldwide, medical therapeutics need to be improved. Consequently, aiming to surpass blood-brain barrier and overcome CNS disabilities, silencing P-glycoprotein as a drug efflux transporter at brain endothelial cells through siRNA is considered a promising approach. For siRNA enzymatic protection and efficient delivery to its target, two different nanoparticles platforms, solid lipid (SLN) and poly-lactic-co-glycolic (PLGA) nanoparticles were used in this study. Polymeric PLGA nanoparticles were around 115 nm in size and had 50 % of siRNA association efficiency, while SLN presented 150 nm and association efficiency close to 52 %. Their surface was functionalized with a peptide-binding transferrin receptor, in a site-oriented manner confirmed by NMR, and their targeting ability against human brain endothelial cells was successfully demonstrated by fluorescence microscopy and flow cytometry. The interaction of modified nanoparticles with brain endothelial cells increased 3-fold compared to non-modified lipid nanoparticles, and 4-fold compared to non-modified PLGA nanoparticles, respectively. These nanosystems, which were also demonstrated to be safe for human brain endothelial cells, without significant cytotoxicity, bring a new hopeful breath to the future of brain diseases therapies.

  3. Porous silicon carbide (SiC) semiconductor device

    NASA Technical Reports Server (NTRS)

    Shor, Joseph S. (Inventor); Kurtz, Anthony D. (Inventor)

    1994-01-01

    A semiconductor device employs at least one layer of semiconducting porous silicon carbide (SiC). The porous SiC layer has a monocrystalline structure wherein the pore sizes, shapes, and spacing are determined by the processing conditions. In one embodiment, the semiconductor device is a p-n junction diode in which a layer of n-type SiC is positioned on a p-type layer of SiC, with the p-type layer positioned on a layer of silicon dioxide. Because of the UV luminescent properties of the semiconducting porous SiC layer, it may also be utilized for other devices such as LEDs and optoelectronic devices.

  4. A general approach to prepare conjugated polymer dot embedded silica nanoparticles with a SiO2@CP@SiO2 structure for targeted HER2-positive cellular imaging

    NASA Astrophysics Data System (ADS)

    Geng, Junlong; Liu, Jie; Liang, Jing; Shi, Haibin; Liu, Bin

    2013-08-01

    We report on a one-step synthesis of conjugated polymer (CP) embedded silica nanoparticles (NPs) with a SiO2@CP@SiO2 structure by combination of a precipitation method and a modified Stöber approach. Four types of CPs are employed to demonstrate the versatility of the developed strategy, yielding fluorescent silica NPs with emission across the visible spectrum. Field emission transmission electron microscopy investigation reveals that the entanglement between hydrophobic CPs and the aminopropyl groups of 3-aminopropyl triethoxysilane contributes to the successful encapsulation of CPs into a silica matrix. The synthesized NPs exhibit excellent physical stability and good photostability. In addition, they have amine groups on surfaces, which benefit further conjugation for biological applications. Through reaction with a peptide (GGHAHFG) that is specific to the HER2 receptor, the synthesized NPs have been successfully applied for targeted cellular imaging of HER2-overexpressed SKBR-3 breast cancer cells. Along with its high quantum yield and benign biocompatibility, the developed CP embedded silica NPs have great potential for applications in biological imaging.We report on a one-step synthesis of conjugated polymer (CP) embedded silica nanoparticles (NPs) with a SiO2@CP@SiO2 structure by combination of a precipitation method and a modified Stöber approach. Four types of CPs are employed to demonstrate the versatility of the developed strategy, yielding fluorescent silica NPs with emission across the visible spectrum. Field emission transmission electron microscopy investigation reveals that the entanglement between hydrophobic CPs and the aminopropyl groups of 3-aminopropyl triethoxysilane contributes to the successful encapsulation of CPs into a silica matrix. The synthesized NPs exhibit excellent physical stability and good photostability. In addition, they have amine groups on surfaces, which benefit further conjugation for biological applications. Through

  5. Triple-Layered pH-Responsive Micelleplexes Loaded with siRNA and Cisplatin Prodrug for NF-Kappa B Targeted Treatment of Metastatic Breast Cancer

    PubMed Central

    Yu, Haijun; Guo, Chengyue; Feng, Bing; Liu, Jianping; Chen, Xianzhi; Wang, Dangge; Teng, Lesheng; Li, Youxin; Yin, Qi; Zhang, Zhiwen; Li, Yaping

    2016-01-01

    The combination of chemotherapy and RNA interference is a promising approach for efficient cancer therapy. However, the success of such a strategy is hampered by the lack of suitable vectors to coordinate small interfering RNA (siRNA) and chemotherapeutic drug into one single platform. We herein report a novel triple-layered pH-responsive micelleplex loading siRNA and alkylated cisplatin prodrug for NF-Kappa B targeted treatment of metastatic breast cancer. The micelles were self-assembled from poly(ethylene glycol)-block-poly(aminolated glycidyl methacrylate)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-b-PAGA-b-PDPA) triblock copolymers. At pH 7.4, the cisplatin prodrug was encapsulated in the hydrophobic PDPA core and siRNA was loaded on the positively charged PAGA interlayer to form the micelleplexes. The PEG corona can prevent protein absorption during blood circulation, minimize non-specific interaction with the reticuloendothelial system, and prolong the systemic circulation of the micelleplexes. The positively charged PAGA interlayer can facilitate deep tumor penetration of the micelleplexes, which, upon cellular uptake, are dissociated in the early endosomes to release anticancer drug payload due to protonation of the PDPA core. Using a 4T1 breast cancer model, we demonstrate that this novel micelleplex co-loaded with cisplatin prodrug and siRNA-p65 is able to simultaneously inhibit tumor growth and suppress distant metastasis of the cancer cells by downregulating NF-kappa B expression. The results reported in this study suggest that siRNA and anticancer drug co-delivery using pH-responsive micelleplexes is a promising strategy for efficient treatment of metastatic cancer. PMID:26722370

  6. Targeting L1 cell adhesion molecule expression using liposome-encapsulated siRNA suppresses prostate cancer bone metastasis and growth

    PubMed Central

    Sung, Shian-Ying; Petros, John A.; Wu, Hsi-Chin; Zeng, Hong-Jie; Huang, Wei-Chien; Chung, Leland W. K.; Hsieh, Chia-Ling

    2014-01-01

    The L1 cell adhesion molecule (L1CAM) has been implicated in tumor progression of many types of cancers, but its role in prostate cancer and its application in targeted gene therapy have not been investigated. Herein, we demonstrated that the L1CAM was expressed in androgen-insensitive and highly metastatic human prostate cancer cell lines. The correlation between L1CAM expression and prostate cancer metastasis was also validated in serum samples of prostate cancer patients. Knockdown of L1CAM expression in prostate cancer cells by RNA interference significantly decreased their aggressive behaviors, including colony formation, migration and invasion in vitro, and tumor formation in a metastatic murine model. These anti-malignant phenotypes of L1CAM-knockdown cancer cells were accompanied by G0/G1 cell cycle arrest and suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression and nuclear factor NF-κB activation. In vivo targeting of L1CAM expression using liposome-encapsulated L1CAM siRNAs effectively inhibited prostate cancer growth in mouse bone, which was associated with decreased L1CAM expression and cell proliferation by tumor cells. These results provide the first evidence for L1CAM being a major contributor to prostate cancer metastasis and translational application of siRNA-based L1CAM-targeted therapy. PMID:25294816

  7. Photoionization of monocrystalline CVD diamond irradiated with ultrashort intense laser pulse

    NASA Astrophysics Data System (ADS)

    Lagomarsino, Stefano; Sciortino, Silvio; Obreshkov, Boyan; Apostolova, Tzveta; Corsi, Chiara; Bellini, Marco; Berdermann, Eleni; Schmidt, Christian J.

    2016-02-01

    Direct laser writing of conductive paths in synthetic diamond is of interest for implementation in radiation detection and clinical dosimetry. Unraveling the microscopic processes involved in laser irradiation of diamond below and close to the graphitization threshold under the same conditions as the experimental procedure used to produce three-dimensional devices is necessary to tune the laser parameters to optimal results. To this purpose a transient currents technique has been used to measure laser-induced current signals in monocrystalline diamond detectors in a wide range of laser intensities and at different bias voltages. The current transients vs time and the overall charge collected have been compared with theoretical simulations of the carrier dynamics along the duration and after the conclusion of the 30 fs laser pulse. The generated charge has been derived from the collected charge by evaluation of the lifetime of the carriers. The plasma volume has also been evaluated by measuring the modified region. The theoretical simulation has been implemented in the framework of the empirical pseudopotential method extended to include time-dependent couplings of valence electrons to the radiation field. The simulation, in the low-intensity regime, I ˜1 TW /cm2 , predicts substantial deviation from the traditional multiphoton ionization, due to nonperturbative effects involving electrons from degenerate valence bands. For strong field with intensity of about 50 TW /cm2, nonadiabatic effects of electron-hole pair excitation become prominent with high carrier densities eventually causing the optical breakdown of diamond. The comparison of theoretical prediction with experimental data of laser-generated charge vs laser energy density yields a good quantitative agreement over six orders of magnitude. At the highest intensities the change of slope in the trend is explained taking into account the dependence of the optical parameters and the carrier mobility on plasma

  8. In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody

    PubMed Central

    Liu, Fang; Le, Wenjun; Mei, Tianxiao; Wang, Tiegong; Chen, Luguang; Lei, Yi; Cui, Shaobin; Chen, Bingdi; Cui, Zheng; Shao, Chengwei

    2016-01-01

    Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by −61.233±33.9 and −58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer. PMID:27274243

  9. Cationic Si−H−Si Bridges in Polysilanes: Their Detection and Targeted Formation in Stable Ion Studies

    PubMed Central

    Albers, Lena

    2016-01-01

    Abstract The ionization of 1,1‐dihydridocyclopentasilane 7 has been found to yield the cyclic polysilanylsilyl cation 8 instead of the expected hydrogen‐substituted silylium ion 6. The silyl cation 8 is stabilized by the formation of an intramolecular Si−H−Si bridge, which also provides the thermodynamic driving force for its formation. In general, the preference for the formation of Si−H−Si bridges can be used to scavenge and identify transient intermediates in the Lewis acid induced rearrangement of polysilanes. The validity of this concept has been demonstrated for one central step in this chemistry, the ring‐contraction reaction of cyclohexasilanes to form silylcyclopentasilanes. PMID:27105609

  10. siRNA targeting vaccinia virus double-stranded RNA binding protein [E3L] exerts potent antiviral effects.

    PubMed

    Dave, Rajnish S; McGettigan, James P; Qureshi, Tazeen; Schnell, Matthias J; Nunnari, Giuseppe; Pomerantz, Roger J

    2006-05-10

    The Vaccinia virus gene, E3L, encodes a double-stranded RNA [dsRNA]-binding protein. We hypothesized that, owing to the critical nature of dsRNA in triggering host innate antiviral responses, E3L-specific small-interfering RNAs [siRNAs] should be effective antiviral agents against pox viruses, for which Vaccinia virus is an appropriate surrogate. In this study, we have utilized two human cell types, namely, HeLa and 293T, one which responds to interferon [IFN]-beta and the other produces and responds to IFN-beta, respectively. The antiviral effects were equally robust in HeLa and 293T cells. However, in the case of 293T cells, several distinct features were observed, when IFN-beta is activated in these cells. Vaccinia virus replication was inhibited by 97% and 98% as compared to control infection in HeLa and 293T cells transfected with E3L-specific siRNAs, respectively. These studies demonstrate the utility of E3L-specific siRNAs as potent antiviral agents for small pox and related pox viruses.

  11. Study of Nickel Silicide as a Copper Diffusion Barrier in Monocrystalline Silicon Solar Cells

    SciTech Connect

    Kale, Abhijit; Beese, Emily; Saenz, Theresa; Warren, Emily; Nemeth, William; Young, David; Marshall, Alexander; Florent, Karine; Kurinec, Santosh K.; Agarwal, Sumit; Stradins, Pauls

    2016-11-21

    NiSi as a conductive diffusion barrier to silicon has been studied. We demonstrate that the NiSi films formed using the single step annealing process are as good as the two step process using XRD and Raman. Quality of NiSi films formed using e-beam Ni and electroless Ni process has been compared. Incomplete surface coverage and presence of constituents other than Ni are the main challenges with electroless Ni. We also demonstrate that Cu reduces the thermal stability of NiSi films. The detection of Cu has proven to be difficult due to temperature limitations.

  12. siRNA screen for genes that affect Junín virus entry uncovers voltage-gated calcium channels as a therapeutic target

    PubMed Central

    Lavanya, Madakasira; Cuevas, Christian D.; Thomas, Monica; Cherry, Sara; Ross, Susan R.

    2014-01-01

    New world hemorrhagic fever arenaviruses infection of humans results in 15–30% mortality. We performed a high throughput siRNA screen with Junín virus glycoprotein-pseudotyped viruses to find potential host therapeutic targets. Voltage-gated calcium channels (VGCC) subunits, for which there are FDA-approved drugs, were identified in the screen. Knockdown of VGCC subunits or treatment with channel blockers diminished Junín virus-cell fusion and entry into cells and thereby decreased infection. Gabapentin, an FDA-approved drug used to treat neuropathic pain that targets the α2δ2 subunit, inhibited infection of mice by the Candid 1 vaccine strain of the virus. These findings demonstrate that VGCCs play a role in virus infection and have the potential to lead to therapeutic intervention of new world arenavirus infection. PMID:24068738

  13. Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

    NASA Astrophysics Data System (ADS)

    Liu, C. W.; Lin, W. J.

    2013-10-01

    This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly( d, l-lactic-co-glycolic acid)-poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 ± 32.5 and 184.0 ± 52.9 nm, respectively, with zeta potential -21.3 ± 3.8 and -15.3 ± 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC50 of doxorubicin-loaded peptide-conjugated NPs (0.09 ± 0.06 μM) was significantly lower than peptide-free NPs (5.72 ± 2.64 μM). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

  14. Target RNA-directed tailing and trimming purifies the sorting of endo-siRNAs between the two Drosophila Argonaute proteins.

    PubMed

    Ameres, Stefan L; Hung, Jui-Hung; Xu, Jia; Weng, Zhiping; Zamore, Phillip D

    2011-01-01

    In flies, 22-23-nucleotide (nt) microRNA duplexes typically contain mismatches and begin with uridine, so they bind Argonaute1 (Ago1), whereas 21-nt siRNA duplexes are perfectly paired and begin with cytidine, promoting their loading into Ago2. A subset of Drosophila endogenous siRNAs-the hairpin-derived hp-esiRNAs-are born as mismatched duplexes that often begin with uridine. These would be predicted to load into Ago1, yet accumulate at steady-state bound to Ago2. In vitro, such hp-esiRNA duplexes assemble into Ago1. In vivo, they encounter complementary target mRNAs that trigger their tailing and trimming, causing Ago1-loaded hp-esiRNAs to be degraded. In contrast, Ago2-associated hp-esiRNAs are 2'-O-methyl modified at their 3' ends, protecting them from tailing and trimming. Consequently, the steady-state distribution of esiRNAs reflects not only their initial sorting between Ago1 and Ago2 according to their duplex structure, length, and first nucleotide, but also the targeted destruction of the single-stranded small RNAs after their loading into an Argonaute protein.

  15. Selective epitaxial growth of graphene on SiC

    NASA Astrophysics Data System (ADS)

    Camara, N.; Rius, G.; Huntzinger, J.-R.; Tiberj, A.; Mestres, N.; Godignon, P.; Camassel, J.

    2008-09-01

    We present a method of selective epitaxial growth of few layers graphene (FLG) on a "prepatterned" silicon carbide (SiC) substrate. The methods involves, successively, the sputtering of a thin aluminium nitride (AlN) layer on top of a monocrystalline SiC substrate and, then, patterning it with e-beam lithography and wet etching. The sublimation of few atomic layers of Si from the SiC substrate occurs only through the selectively etched AlN layer. The presence of the Raman G-band at ˜1582cm-1 in the AlN-free areas is used to validate the concept. It gives absolute evidence of selective FLG growth.

  16. Selective epitaxial growth of graphene on SiC

    SciTech Connect

    Camara, N.; Rius, G.; Godignon, P.; Huntzinger, J.-R.; Tiberj, A.; Camassel, J.

    2008-09-22

    We present a method of selective epitaxial growth of few layers graphene (FLG) on a ''prepatterned'' silicon carbide (SiC) substrate. The methods involves, successively, the sputtering of a thin aluminium nitride (AlN) layer on top of a monocrystalline SiC substrate and, then, patterning it with e-beam lithography and wet etching. The sublimation of few atomic layers of Si from the SiC substrate occurs only through the selectively etched AlN layer. The presence of the Raman G-band at {approx}1582 cm{sup -1} in the AlN-free areas is used to validate the concept. It gives absolute evidence of selective FLG growth.

  17. Intensity analysis of XPS spectra to determine oxide uniformity - Application to SiO2/Si interfaces

    NASA Technical Reports Server (NTRS)

    Vasquez, R. P.; Grunthaner, F. J.

    1980-01-01

    A simple method of determining oxide uniformity is derived which requires no knowlege of film thickness, escape depth, or film composition. The method involves only the measurement of oxide and substrate intensities and is illustrated by analysis of XPS spectral data for thin SiO2 films grown both thermally and by low-temperature chemical vapor deposition on monocrystalline Si. A region 20-30 A thick is found near the SiO2/Si interface on thermally oxidized samples which has an inelastic mean free path 35% less than that found in the bulk oxide. This is interpreted as being due to lattice mismatch resulting in a strained region which is structurally, but not stoichiometrically, distinct from the bulk oxide.

  18. Multifunctional NaYF4:Yb, Er@mSiO2@Fe3O4-PEG nanoparticles for UCL/MR bioimaging and magnetically targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Liu, Bei; Li, Chunxia; Ma, Ping'an; Chen, Yinyin; Zhang, Yuanxin; Hou, Zhiyao; Huang, Shanshan; Lin, Jun

    2015-01-01

    A low toxic multifunctional nanoplatform, integrating both mutimodal diagnosis methods and antitumor therapy, is highly desirable to assure its antitumor efficiency. In this work, we show a convenient and adjustable synthesis of multifunctional nanoparticles NaYF4:Yb, Er@mSiO2@Fe3O4-PEG (MFNPs) based on different sizes of up-conversion nanoparticles (UCNPs). With strong up-conversion fluorescence offered by UCNPs, superparamagnetism properties attributed to Fe3O4 nanoparticles and porous structure coming from the mesoporous SiO2 shell, the as-obtained MFNPs can be utilized not only as a contrast agent for dual modal up-conversion luminescence (UCL)/magnetic resonance (MR) bio-imaging, but can also achieve an effective magnetically targeted antitumor chemotherapy both in vitro and in vivo. Furthermore, the UCL intensity of UCNPs and the magnetic properties of Fe3O4 in the MFNPs were carefully balanced. Silica coating and further PEG modifying can improve the hydrophilicity and biocompatibility of the as-synthesized MFNPs, which was confirmed by the in vitro/in vivo biocompatibility and in vivo long-time bio-distributions tests. Those results revealed that the UCNPs based magnetically targeted drug carrier system we synthesized has great promise in the future for multimodal bio-imaging and targeted cancer therapy.A low toxic multifunctional nanoplatform, integrating both mutimodal diagnosis methods and antitumor therapy, is highly desirable to assure its antitumor efficiency. In this work, we show a convenient and adjustable synthesis of multifunctional nanoparticles NaYF4:Yb, Er@mSiO2@Fe3O4-PEG (MFNPs) based on different sizes of up-conversion nanoparticles (UCNPs). With strong up-conversion fluorescence offered by UCNPs, superparamagnetism properties attributed to Fe3O4 nanoparticles and porous structure coming from the mesoporous SiO2 shell, the as-obtained MFNPs can be utilized not only as a contrast agent for dual modal up-conversion luminescence (UCL

  19. A targeted siRNA screen identifies regulators of Cdc42 activity at the natural killer cell immunological synapse.

    PubMed

    Carlin, Leo M; Evans, Rachel; Milewicz, Hanna; Fernandes, Luis; Matthews, Daniel R; Perani, Michela; Levitt, James; Keppler, Melanie D; Monypenny, James; Coolen, Ton; Barber, Paul R; Vojnovic, Borivoj; Suhling, Klaus; Fraternali, Franca; Ameer-Beg, Simon; Parker, Peter J; Thomas, N Shaun B; Ng, Tony

    2011-11-29

    Natural killer (NK) cells kill tumor cells and virally infected cells, and an effective NK cell response requires processes, such as motility, recognition, and directional secretion, that rely on cytoskeletal rearrangement. The Rho guanosine triphosphatase (GTPase) Cdc42 coordinates cytoskeletal reorganization downstream of many receptors. The Rho-related GTPase from plants 1 (ROP1) exhibits oscillatory activation behavior at the apical plasma membrane of growing pollen tubes; however, a similar oscillation in Rho GTPase activity has so far not been demonstrated in mammalian cells. We hypothesized that oscillations in Cdc42 activity might occur within NK cells as they interact with target cells. Through fluorescence lifetime imaging of a Cdc42 biosensor, we observed that in live NK cells forming immunological synapses with target cells, Cdc42 activity oscillated after exhibiting an initial increase. We used protein-protein interaction networks and structural databases to identify candidate proteins that controlled Cdc42 activity, leading to the design of a targeted short interfering RNA screen. The guanine nucleotide exchange factors RhoGEF6 and RhoGEF7 were necessary for Cdc42 activation within the NK cell immunological synapse. In addition, the kinase Akt and the p85α subunit of phosphoinositide 3-kinase (PI3K) were required for Cdc42 activation, the periodicity of the oscillation in Cdc42 activity, and the subsequent polarization of cytotoxic vesicles toward target cells. Given that PI3Ks are targets of tumor therapies, our findings suggest the need to monitor innate immune function during the course of targeted therapy against these enzymes.

  20. Fabrication of Double Shell Targets with a Glass Inner Capsule Supported by SiO2 Aerogel for Shots on the Omega Laser in 2006

    SciTech Connect

    Bono, M; Bennett, D; Castro, C; Satcher, J; Poco, J; Brown, W; Martz, H; Teslich, N; Hibbard, R; Hamza, A; Amendt, P; Robey, H; Milovich, J; Wallace, R

    2006-10-26

    Indirectly driven double shell implosions are being investigated as a possible noncryogenic path to ignition on the National Ignition Facility. Lawrence Livermore National Laboratory has made several technological advances that have produced double shell targets that represent a significant improvement to previously fielded targets. The inner capsule is supported inside the ablator shell by SiO{sub 2} aerogel with a nominal density of 50 mg/cm{sup 3}. The aerogel is cast around the inner capsule and then machined concentric to it. The seamless sphere of aerogel containing the embedded capsule is then assembled between the two halves of the ablator shell. The concentricity between the two shells has been improved to less than 1.5 {micro}m. The ablator shell consists of two hemispherical shells that mate at a step joint that incorporates a gap with a nominal thickness of 0.1 {micro}m. Using a new flexure-based tool holder that precisely positions the diamond cutting tool on the diamond turning machine, step discontinuities on the inner surface of the ablator of less than 0.5 {micro}m have been achieved. New methods have been used to comprehensively characterize each of the targets using high-resolution x-ray imaging systems.

  1. High performance LWIR microbolometer with Si/SiGe quantum well thermistor and wafer level packaging

    NASA Astrophysics Data System (ADS)

    Roer, Audun; Lapadatu, Adriana; Bring, Martin; Wolla, Erik; Hohler, Erling; Kittilsland, Gjermund

    2011-11-01

    An uncooled microbolometer with peak responsivity in the long wave infrared region of the electromagnetic radiation is developed at Sensonor Technologies. It is a 384 x 288 focal plane array with a pixel pitch of 25μm, based on monocrystalline Si/SiGe quantum wells as IR sensitive material. The high sensitivity (TCR) and low 1/f noise are the main performance characteristics of the product. The frame rate is maximum 60Hz and the output interface is digital (LVDS). The quantum well thermistor material is transferred to the read-out integrated circuit (ROIC) by direct wafer bonding. The ROIC wafer containing the released pixels is bonded in vacuum with a silicon cap wafer, providing hermetic encapsulation at low cost. The resulting wafer stack is mounted in a standard ceramic package. In this paper the architecture of the pixels and the ROIC, the wafer packaging and the electro-optical measurement results are presented.

  2. Fabrication of Polyvalent Therapeutic RNA Nanoparticles for Specific Delivery of siRNA, Ribozyme and Drugs to Targeted Cells for Cancer Therapy

    PubMed Central

    Shu, Yi; Shu, Dan; Diao, Zhijuan; Shen, Guanxin; Guo, Peixuan

    2010-01-01

    Bacteriophage phi29 DNA packaging motor is geared by a six-pRNA ring. pRNA is able to form a multimeric complex and patterned superstructures via the interaction of two reengineered interlocking loops. This unique feature makes it an ideal polyvalent vehicle for nanomachine fabrication, pathogen detection, and the delivery of therapeutics. This report describes novel approaches for the fabrication of polyvalent therapeutic pRNA nanoparticles, especially tetramers for specific siRNA delivery to cancer cells and for the silencing of targeted genes. RNA 3-D design, circular permutation, folding energy alteration, and nucleotide modification were applied to generate stable RNA nanoparticles with low toxicity. Animal trials demonstrated the high efficiency of the polyvalent RNA nanoparticles in the prevention and treatment of cancer. Using such protein-free nanoparticles as therapeutic reagents would allow for long-term administration to avoid the induction of antibody due to repeated treatment for chronic diseases. PMID:21243099

  3. Targeted Dual pH-Sensitive Lipid ECO/siRNA Self-Assembly Nanoparticles Facilitate In Vivo Cytosolic sieIF4E Delivery and Overcome Paclitaxel Resistance in Breast Cancer Therapy.

    PubMed

    Gujrati, Maneesh; Vaidya, Amita M; Mack, Margaret; Snyder, Dayton; Malamas, Anthony; Lu, Zheng-Rong

    2016-11-01

    RNAi-mediated knockdown of oncogenes associated with drug resistance can potentially enhance the efficacy of chemotherapy. Here, we have designed and developed targeted dual pH-sensitive lipid-siRNA self-assembly nanoparticles, RGD-PEG(HZ)-ECO/siRNA, which can efficiently silence the oncogene, eukaryotic translation initiation factor 4E (eIF4E), and consequently resensitize triple-negative breast tumors to paclitaxel. The dual pH-sensitive function of these nanoparticles facilitates effective cytosolic siRNA delivery in cancer cells, both in vitro and in vivo. Intravenous injection of RGD-PEG(HZ)-ECO/siRNA nanoparticles (1.0 mg-siRNA/kg) results in effective gene silencing for at least one week in MDA-MB-231 tumors. In addition, treatment of athymic nude mice with RGD-PEG(HZ)-ECO/sieIF4E every 6 days for 6 weeks down-regulates the overexpression of eIF4E and resensitizes paclitaxel-resistant MDA-MB-231 tumors to paclitaxel, resulting in significant tumor regression at a low dose, with negligible side effects. Moreover, repeated injections of the RGD-PEG(HZ)-ECO/siRNA nanoparticles in immunocompetent mice result in minimal immunogenicity, demonstrating their safety and low toxicity. These multifunctional lipid/siRNA nanoparticles constitute a versatile platform of delivery of therapeutic siRNA for treating cancer and other human diseases.

  4. Atomistic simulations of the effect of embedded hydrogen and helium on the tensile properties of monocrystalline and nanocrystalline tungsten

    NASA Astrophysics Data System (ADS)

    Chen, Zhe; Kecskes, Laszlo J.; Zhu, Kaigui; Wei, Qiuming

    2016-12-01

    Uniaxial tensile properties of monocrystalline tungsten (MC-W) and nanocrystalline tungsten (NC-W) with embedded hydrogen and helium atoms have been investigated using molecular dynamics (MD) simulations in the context of radiation damage evolution. Different strain rates have been imposed to investigate the strain rate sensitivity (SRS) of the samples. Results show that the plastic deformation processes of MC-W and NC-W are dominated by different mechanisms, namely dislocation-based for MC-W and grain boundary-based activities for NC-W, respectively. For MC-W, the SRS increases and a transition appears in the deformation mechanism with increasing embedded atom concentration. However, no obvious embedded atom concentration dependence of the SRS has been observed for NC-W. Instead, in the latter case, the embedded atoms facilitate GB sliding and intergranular fracture. Additionally, a strong strain enhanced He cluster growth has been observed. The corresponding underlying mechanisms are discussed.

  5. Nearly zero reflectance of nano-pyramids and dual-antireflection coating structure for monocrystalline silicon solar cells.

    PubMed

    Chang, Hyo Sik; Jung, Hyun-Chul

    2011-04-01

    The effect of two-step surface treatment on monocrystalline silicon solar cells was investigated. We changed the nanostructure on pyramidal surfaces by wet nano-texturing so that less light is reflected. The two-step nano-texturing process reduces the average reflectance to about 4% in the 300-1100 nm wavelength region. The use of an antireflection coating resulted in an effective reflectance of 1%. We found that the reflectance obtained by wet nano-texturing was lower than that obtained by conventional alkaline texturing. Thus, we can expect a further increase in the efficiency of silicon solar cells with two-step nano-texturing by a wet chemical process.

  6. Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform

    PubMed Central

    Di Rocco, Giuliana; Verdina, Alessandra; Gatti, Veronica; Virdia, Ilaria; Toietta, Gabriele; Todaro, Matilde; Stassi, Giorgio; Soddu, Silvia

    2016-01-01

    Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-Δe8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a specific siRNA that spares the Hipk2-Δe8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant-negative effect of Hipk2-FL over the Δe8 isoform. From this observation, we sought to take advantage and assessed the therapeutic potential of generating Hipk2 isoform unbalance in tumor-initiating cells derived from colorectal cancer patients. Strong reduction of cell viability was induced in vitro and in vivo by the originally described exon 8-specific siRNA, supporting a potential therapeutic application. However, validation analyses performed with additional exon8-specific siRNAs with different stabilities showed that all exon8-targeting siRNAs can induce comparable Hipk2 isoform unbalance but only the originally reported e8-siRNA promotes cell death. These data show that loss of viability does not depend on the prevalence of Hipk2-Δe8 isoform but it is rather due to microRNA-like off-target effects. PMID:26625198

  7. Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell-mediated cell death.

    PubMed

    Kim, Jin Hee; Kang, Tae Heung; Noh, Kyung Hee; Bae, Hyun Cheol; Kim, Seok-Ho; Yoo, Young Do; Seong, Seung-Yong; Kim, Tae Woo

    2009-01-29

    Dendritic cells (DCs) have become an important measure for the treatment of malignancies. Current DC preparations, however, generate short-lived DCs because they are subject to cell death from various apoptotic pressures. Antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) is one of the main obstacles to limit the DC-mediated immune priming since CTLs can recognize the target antigen expressing DCs as target cells and kill the DCs. CTLs secret perforin and serine protease granzymes during CTL killing. Perforin and serine protease granzymes induce the release of a number of mitochondrial pro-apoptotic factors, which are controlled by members of the BCL-2 family, such as BAK, BAX and BIM. FasL linking to Fas on DCs triggers the activation of caspase-8, which eventually leads to mitochondria-mediated apoptosis via truncation of BID. In this study, we tried to enhance the DC priming capacity by prolonging DC survival using anti-apoptotic siRNA targeting these key pro-apoptotic molecules in CTL killing. Human papillomavirus (HPV)-16 E7 antigen presenting DCs that were transfected with these anti-apoptotic siRNAs showed increased resistance to T cell-mediated death, leading to enhanced E7-specific CD8(+) T cell activation in vitro and in vivo. Among them, siRNA targeting BIM (siBIM) generated strongest E7-specific E7-specific CD8(+) T cell immunity. More importantly, vaccination with E7 presenting DCs transfected with siBIM was capable of generating a marked therapeutic effect in vaccinated mice. Our data indicate that ex vivo manipulation of DCs with siBIM may represent a plausible strategy for enhancing dendritic cell-based vaccine potency.

  8. Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

    PubMed Central

    Liu, Tao; Wu, Xidong; Wang, Yigang; Zhang, Tao; Wu, Ting; Liu, Fang; Wang, Wansong; Jiang, Gang; Xie, Minqiang

    2016-01-01

    The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored. PMID:27259274

  9. Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

    PubMed Central

    Zuckerman, Jonathan E.; Gritli, Ismael; Tolcher, Anthony; Heidel, Jeremy D.; Lim, Dean; Morgan, Robert; Chmielowski, Bartosz; Ribas, Antoni; Davis, Mark E.; Yen, Yun

    2014-01-01

    Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)–based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase I clinical trial where 24 patients with different cancers were treated with CALAA-01 and compare those results to data obtained from multispecies animal studies to provide a detailed example of translating this class of nanoparticles from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys, and humans show fast elimination and reveal that the maximum concentration obtained in the blood after i.v. administration correlates with body weight across all species. The safety profile of CALAA-01 in animals is similarly obtained in humans except that animal kidney toxicities are not observed in humans; this could be due to the use of a predosing hydration protocol used in the clinic. Taken in total, the animal models do appear to predict the behavior of CALAA-01 in humans. PMID:25049380

  10. Novel targeting of PEGylated liposomes for codelivery of TGF-β1 siRNA and four antitubercular drugs to human macrophages for the treatment of mycobacterial infection: a quantitative proteomic study

    PubMed Central

    Niu, Ning-Kui; Yin, Juan-Juan; Yang, Yin-Xue; Wang, Zi-Li; Zhou, Zhi-Wei; He, Zhi-Xu; Chen, Xiao-Wu; Zhang, Xueji; Duan, Wei; Yang, Tianxin; Zhou, Shu-Feng

    2015-01-01

    Tuberculosis (TB) is still a major public health issue in developing countries, and its chemotherapy is compromised by poor drug compliance and severe side effects. This study aimed to synthesize and characterize new multimodal PEGylated liposomes encapsulated with clinically commonly used anti-TB drugs with linkage to small interfering RNA (siRNA) against transforming growth factor-β1 (TGF-β1). The novel NP-siRNA liposomes could target THP-1-derived human macrophages that were the host cells of mycobacterium infection. The biological effects of the NP-siRNA liposomes were evaluated on cell cycle distribution, apoptosis, autophagy, and the gene silencing efficiency of TGF-β1 siRNA in human macrophages. We also explored the proteomic responses to the newly synthesized NP-siRNA liposomes using the stable isotope labeling with amino acids in cell culture approach. The results showed that the multifunctional PEGylated liposomes were successfully synthesized and chemically characterized with a mean size of 265.1 nm. The novel NP-siRNA liposomes functionalized with the anti-TB drugs and TGF-β1 siRNA were endocytosed efficiently by human macrophages as visualized by transmission electron microscopy and scanning electron microscopy. Furthermore, the liposomes showed a low cytotoxicity toward human macrophages. There was no significant effect on cell cycle distribution and apoptosis in THP-1-derived macrophages after drug exposure at concentrations ranging from 2.5 to 62.5 μg/mL. Notably, there was a 6.4-fold increase in the autophagy of human macrophages when treated with the NP-siRNA liposomes at 62.5 μg/mL. In addition, the TGF-β1 and nuclear factor-κB expression levels were downregulated by the NP-siRNA liposomes in THP-1-derived macrophages. The Ingenuity Pathway Analysis data showed that there were over 40 signaling pathways involved in the proteomic responses to NP-siRNA liposome exposure in human macrophages, with 160 proteins mapped. The top five canonical

  11. Crystal structure of laser-induced subsurface modifications in Si

    DOE PAGES

    Verburg, P. C.; Smillie, L. A.; Römer, G. R. B. E.; ...

    2015-06-04

    Laser-induced subsurface modification of dielectric materials is a well-known technology. Applications include the production of optical components and selective etching. In addition to dielectric materials, the subsurface modification technology can be applied to silicon, by employing near to mid-infrared radiation. An application of subsurface modifications in silicon is laser-induced subsurface separation, which is a method to separate wafers into individual dies. Other applications for which proofs of concept exist are the formation of waveguides and resistivity tuning. However, limited knowledge is available about the crystal structure of subsurface modifications in silicon. In this paper, we investigate the geometry and crystalmore » structure of laser-induced subsurface modifications in monocrystalline silicon wafers. Finally, in addition to the generation of lattice defects, we found that transformations to amorphous silicon and Si-iii/Si-xii occur as a result of the laser irradiation.« less

  12. Crystal structure of laser-induced subsurface modifications in Si

    SciTech Connect

    Verburg, P. C.; Smillie, L. A.; Römer, G. R. B. E.; Haberl, B.; Bradby, J. E.; Williams, J. S.; Huis in ’t Veld, A. J.

    2015-06-04

    Laser-induced subsurface modification of dielectric materials is a well-known technology. Applications include the production of optical components and selective etching. In addition to dielectric materials, the subsurface modification technology can be applied to silicon, by employing near to mid-infrared radiation. An application of subsurface modifications in silicon is laser-induced subsurface separation, which is a method to separate wafers into individual dies. Other applications for which proofs of concept exist are the formation of waveguides and resistivity tuning. However, limited knowledge is available about the crystal structure of subsurface modifications in silicon. In this paper, we investigate the geometry and crystal structure of laser-induced subsurface modifications in monocrystalline silicon wafers. Finally, in addition to the generation of lattice defects, we found that transformations to amorphous silicon and Si-iii/Si-xii occur as a result of the laser irradiation.

  13. High-performance LWIR microbolometer with Si/SiGe quantum well thermistor and wafer level packaging

    NASA Astrophysics Data System (ADS)

    Roer, Audun; Lapadatu, Adriana; Wolla, Erik; Kittilsland, Gjermund

    2013-06-01

    An uncooled microbolometer with peak responsivity in the long wave infrared region of the electromagnetic radiation is developed at Sensonor AS. It is a 384 x 288 focal plane array with a pixel pitch of 25µm, based on monocrystalline Si/SiGe quantum wells as IR sensitive material. The high sensitivity (TCR) and low 1/f-noise are the main performance characteristics of the product. The frame rate is maximum 60Hz and the output interface is digital (LVDS). The quantum well thermistor material is transferred to the read-out integrated circuit (ROIC) by direct wafer bonding. The ROIC wafer containing the released pixels is bonded in vacuum with a silicon cap wafer, providing hermetic encapsulation at low cost. The resulting wafer stack is mounted in a standard ceramic package. In this paper the architecture of the pixels and the ROIC, the wafer packaging and the electro-optical measurement results are presented.

  14. Competitive diffusion of gold and copper atoms in Cu/Au/Si and Au/Cu/Si annealed systems

    NASA Astrophysics Data System (ADS)

    Benazzouz, C.; Benouattas, N.; Bouabellou, A.

    2005-04-01

    Thermal evaporation is used to deposit Au/Cu and Cu/Au bilayers on (1 1 1) monocrystalline silicon substrates. The layers composition and surface morphology are performed as function of annealing temperature at 200 and 400 °C using X-ray diffraction, Rutherford backscattering spectroscopy and scanning electron microscopy. Independently to the sequence of copper and gold deposition, Cu3Si and Cu4Si copper silicides result to the reaction and interdiffusion at the different interfaces. The 1000 and 1200 Å thickness of gold and copper diffusion barriers are insufficient to prevent the diffusion of copper and gold atoms respectively, after an annealing of only 200 °C. The fitting of concentration profiles of RBS spectra by using the RUMP software revealed a growth of silicides layers not uniform laterally and in depth.

  15. Behavior of oxygen doped SiC thin films: An x-ray photoelectron spectroscopy study

    NASA Astrophysics Data System (ADS)

    Avila, A.; Montero, I.; Galán, L.; Ripalda, J. M.; Levy, R.

    2001-01-01

    Thin silicon carbide films have been deposited by chemical vapor deposition on p-type (100) silicon substrates. The composition and bonds formed in these films have been analyzed by x-ray photoelectron spectroscopy (XPS) and infrared spectroscopy. The native surface oxide on the silicon carbide surface induced by air exposure has also been studied. Several phases are detected in the near-surface region: elemental Si, Si oxides (mainly SiO2), Si carbide (SiC) and Si oxicarbides (SiOxCy). Quantitative XPS analysis results indicate that, for atomic oxygen fractions <0.15, the Si-C phases are dominant in the films. Above this value no silicon oxicarbide is observed, but a multiphase material formed by elemental Si, Si oxides and Si carbides is observed. In spite of the film being a complex phase mixture, a simple relationship is found between the overall carbon and oxygen compositions. The carbon atomic fraction in the film decreases quasilinearly as the oxygen content increases, with a slope of about -1. An overall composition of SiOxC3-x in the 0.5monocrystalline silicon is made.

  16. Nonlinear phenomenon in monocrystalline silicon based PV module for low power system: Lead acid battery for low energy storage

    NASA Astrophysics Data System (ADS)

    El Amrani, A.; El Amraoui, M.; El Abbassi, A.; Messaoudi, C.

    2014-11-01

    In the present work, we report the indoor photo-electrical measurements of monocrystalline silicon based photovoltaic (PV) module associated with 4 Ah lead acid battery as a storage unit for low power PV system applications. Concerning the PV module, our measurements show, at low illumination regime, that the short circuit current ISC increases linearly with the illumination power levels. Moreover, for high illumination levels, the mechanism of bimolecular recombination and space charge limitation may be intensified and hence the short current of the PV module ISCMod depends sublinearly on the incident optical power; the behavior is nonlinear. For the open circuit voltage of the PV module VOCMod measurements, a linear variation of the VOCMod versus the short circuit current in semi-logarithmic scale has been noticed. The diode ideality factor n and diode saturation current Is have been investigated; the values of n and Is are approximately of 1.3 and 10-9 A, respectively. In addition, we have shown, for different discharging-charging currents rates (i.e. 0.35 A, 0.2 A and 0.04 A), that the battery voltage decreases with discharging time as well as discharging battery capacity, and on the other hand it increases with the charging time and will rise up until it maximized value. The initial result shows the possibility to use such lead acid battery for low power PV system, which is generally designed for the motorcycle battery.

  17. Development of targeted recombinant polymers that can deliver siRNA to the cytoplasm and plasmid DNA to the cell nucleus.

    PubMed

    Canine, Brenda F; Wang, Yuhua; Ouyang, Wenyun; Hatefi, Arash

    2011-04-10

    One of the major limitations to effective siRNA delivery is the lack of a siRNA-specific delivery system. Currently, the same delivery systems that are used for plasmid DNA (pDNA) delivery to the cell nucleus are used for siRNA delivery to the cytoplasm. To fill this gap, the objective of this study was to design a biopolymer that can be programmed via its amino acid sequence to deliver siRNA specifically to cytoplasm. For pDNA delivery, a nuclear localization signal (NLS) was added to the biopolymer structure to facilitate active translocation of the genetic material towards nucleus. The biopolymers were complexed with pEGFP and GFP-siRNA and used to transfect SKOV-3 (HER2+) cells. The intracellular trafficking of the nanoparticles was also monitored in real-time and live cells. The results demonstrated that the biopolymer with NLS is a suitable carrier for pDNA delivery but not siRNA delivery. Conversely, the biopolymer without NLS was suitable for siRNA delivery to the cytoplasm but not pDNA to the cell nucleus. The potential use of the designed biopolymer for combination therapy of cancer cells with gene (thymidine kinase) and siRNA (BCL2) was also examined in SKOV-3 cancer cells.

  18. Efficient siRNA delivery and tumor accumulation mediated by ionically cross-linked folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate nanoparticles: for the potential targeted ovarian cancer gene therapy.

    PubMed

    Li, Tony Shing Chau; Yawata, Toshio; Honke, Koichi

    2014-02-14

    For effective ovarian cancer gene therapy, systemic administrated tumor-targeting siRNA/folic acid-poly(ethylene glycol)-chitosan oligosaccharide lactate (FA-PEG-COL) nanoparticles is vital for delivery to cancer site(s). siRNA/FA-PEG-COL nanoparticles were prepared by ionic gelation for effective FA receptor-expressing ovarian cancer cells transfection and in vivo accumulation. The chemical structure of FA-PEG-COL conjugate was characterized by MALDI-TOF-MS, FT-IR and (1)H NMR. The average size of siRNA/FA-PEG-COL nanoparticles was approximately 200 nm, and the surface charge was +8.4 mV compared to +30.5 mV with siRNA/COL nanoparticles. FA-PEG-COL nanoparticles demonstrated superior compatibility with erythrocytes in terms of degree of aggregation and haemolytic activity and also effects on cell viability was lower when compared with COL nanoparticles. FA grafting significantly facilitated the uptake of nanoparticles via receptor mediated endocytosis as demonstrated by flow cytometry. The in vitro transfection and gene knockdown efficiency of HIF-1α were superior to COL nanoparticles (76-62%, respectively) and was comparable to Lipofectamine 2000 (79%) as demonstrated by RT-qPCR and Western blot. Gene knockdown at the molecular level translated into effective inhibition of proliferation in vitro. Accumulation efficiency of FA-PEG-COL nanoparticles was investigated in BALB/c mice bearing OVK18 #2 tumor xenograft using in vivo imaging. The active targeting FA-PEG-COL nanoparticles showed significantly greater accumulation than the passive targeting COL nanoparticles. Based on the results obtained, siRNA/FA-PEG-COL nanoparticles show much potential for effective ovarian cancer treatment via gene therapy.

  19. CVD-Based Valence-Mending Passivation for Crystalline-Si Solar Cells

    SciTech Connect

    Tao, Meng

    2015-03-01

    The objective of this project is to investigate a new surface passivation technique, valence-mending passivation, for its applications in crystalline-Si solar cells to achieve significant efficiency improvement and cost reduction. As the enabling technique, the project includes the development of chemical vapor deposition recipes to passivate textured Si(100) and multicrystalline-Si surfaces by sulfur and the characterization of the passivated Si surfaces, including thermal stability, Schottky barrier height, contact resistance and surface recombination. One important application is to replace the Ag finger electrode in Si cells with Al to reduce cost, by ~$0.1/Wp, and allow terawatt-scale deployment of crystalline-Si solar cells. These all-Al Si cells require a low-temperature metallization process for the Al electrode, to be compatible with valence-mending passivation and to prevent Al diffusion into n-type Si. Another application is to explore valence-mending passivation of grain boundaries in multicrystalline Si by diffusing sulfur into grain boundaries, to reduce the efficiency gas between monocrystalline-Si solar cells and multicrystalline-Si cells. The major accomplishments of this project include: 1) Demonstration of chemical vapor deposition processes for valence-mending passivation of both monocrystalline Si(100) and multicrystalline Si surfaces. Record Schottky barriers have been demonstrated, with the new record-low barrier of less than 0.08 eV between Al and sulfur-passivated n-type Si(100) and the new record-high barrier of 1.14 eV between Al and sulfur-passivated p-type Si(100). On the textured p-type monocrystalline Si(100) surface, the highest barrier with Al is 0.85 eV by valence-mending passivation. 2) Demonstration of a low-temperature metallization process for Al in crystalline-Si solar cells. The new metallization process is based on electroplating of Al in a room-temperature ionic liquid. The resistivity of the electroplated Al is ~7×10–6

  20. A small interfering RNA targeting vascular endothelial growth factor efficiently inhibits growth of VX2 cells and VX2 tumor model of hepatocellular carcinoma in rabbit by transarterial embolization-mediated siRNA delivery

    PubMed Central

    Zou, Yu; Guo, Chuan-Gen; Yang, Zheng-Gang; Sun, Jun-Hui; Zhang, Min-Ming; Fu, Cai-Yun

    2016-01-01

    -mediated VEGF-siRNA had no toxicity to the livers and kidneys of rabbits, and VEGF-siRNA had the ability to protect liver damage induced by tumor growth. Conclusion This is the first study to demonstrate that targeting VEGF via TAE-mediated siRNA delivery may become a powerful new option for effective treatment of hepatocellular carcinoma in the clinic. PMID:27069355

  1. Study by simulation of the SnO2 and ZnO anti-reflection layers in n-SiC/p-SiC solar cells

    NASA Astrophysics Data System (ADS)

    Zerfaoui, Hana; Dib, Djalel; Rahmani, Mohamed; Benyelloul, Kamel; Mebarkia, Chafia

    2016-07-01

    Recently, Two technologies of the photovoltaic cells are present today namely the cells crystalline (polycrystalline and monocrystalline) and the cell thin layers. The development of the solar cells requires a technological change of materials used in their manufacturing. The thin layers are parts of these materials and which announced their effectiveness and growth of output of the solar cell. The aim of this paper article is to the study and simulation of photovoltaic cells containing SiC materials. This material is have important having a part in the development of renewable energies. Based on the SCAPS (a Solar Cell Capacitance Simulator) simulation, the obtained results are Vco, Jsc, FF and the output energy of conversion of a solar cell n-SiC/p-SiC with different materials for the anti-reflecting layer ZnO and SnO2.with the SCAPS (a Solar Cell Capacitance Simulator) computer code in one dimension, the results obtained after optimization.

  2. Boron diffusion in nanocrystalline 3C-SiC

    SciTech Connect

    Schnabel, Manuel; Weiss, Charlotte; Rachow, Thomas; Löper, Philipp; Janz, Stefan; Canino, Mariaconcetta; Summonte, Caterina; Mirabella, Salvo; Wilshaw, Peter R.

    2014-05-26

    The diffusion of boron in nanocrystalline silicon carbide (nc-SiC) films with a grain size of 4–7 nm is studied using a poly-Si boron source. Diffusion is found to be much faster than in monocrystalline SiC as it takes place within the grain boundary (GB) network. Drive-in temperatures of 900–1000°C are suitable for creating shallow boron profiles up to 100 nm deep, while 1100°C is sufficient to flood the 200 nm thick films with boron. From the resulting plateau at 1100 °C a boron segregation coefficient of 28 between nc-SiC and the Si substrate, as well as a GB boron solubility limit of 0.2 nm{sup −2} is determined. GB diffusion in the bulk of the films is Fickian and thermally activated with D{sub GB}(T)=(3.1−5.6)×10{sup 7}exp(−5.03±0.16  eV/k{sub B}T) cm{sup 2}s{sup −1}. The activation energy is interpreted in terms of a trapping mechanism at dangling bonds. Higher boron concentrations are present at the nc-SiC surface and are attributed to immobilized boron.

  3. Formation Monocrystalline Carbon Micro-and Nanostructures Under Femtosecond Laser Irradiation of graphite in Liquid Nitrogen

    NASA Astrophysics Data System (ADS)

    Khorkov, Kirill S.; Abramov, Dmitrii V.; Kochuev, Dmitriy A.; Arakelian, Sergey M.; Prokoshev, Valery G.

    The combination of high energy and ultra short duration of femtosecond laser pulses allow to reach in the area of impact the local conditions which can change the phase composition of irradiated material. Traditional methods of structural phase transformation of the graphite at high pressures do not provide the abrupt simultaneous cancellation of the applied pressure and temperature. As a result, some of the synthesized nanostructures and metastable forms of carbon are destroyed. The suggested method allows to eliminate this disadvantage. Femtosecond laser radiation provides ultrafast heating of the target material, and the use of liquid nitrogen dramatically accelerates the process of it cooling. The formation of new carbon micro- and nanostructures has been registered at experimental approbation of the proposed method. The check of elemental composition of the created crystals showed that they are formed solely of carbon. The experimental results show the possibility of creation of new (less studied) carbon forms with a variety of properties.

  4. Magnetically targeted delivery of DOX loaded Cu9S5@mSiO2@Fe3O4-PEG nanocomposites for combined MR imaging and chemo/photothermal synergistic therapy

    NASA Astrophysics Data System (ADS)

    Liu, Bei; Zhang, Xinyang; Li, Chunxia; He, Fei; Chen, Yinyin; Huang, Shanshan; Jin, Dayong; Yang, Piaoping; Cheng, Ziyong; Lin, Jun

    2016-06-01

    The combination of multi-theranostic modes in a controlled fashion has received tremendous attention for the construction of cooperative therapeutic systems in nanomedicine. Herein, we have synthesized a smart magnetically targeted nanocarrier system, Cu9S5@mSiO2@Fe3O4-PEG (labelled as CMF), which integrates NIR triggered photothermal therapy, pH/NIR-responsive chemotherapy and MR imaging into one nanoplatform to enhance the therapeutic efficacy. This new multifunctional paradigm has a uniform and monodisperse sesame ball-like structure by decorating tiny Fe3O4 nanoparticles on the surface of Cu9S5@mSiO2 before a further PEG modification to improve its hydrophilicity and biocompatibility. With doxorubicin (DOX) payload, the as-obtained CMF-DOX composites can simultaneously provide an intense heating effect and enhanced DOX release upon 980 nm NIR light exposure, achieving a combined chemo/photothermal therapy. Under the influence of an external magnetic field, the magnetically targeted synergistic therapeutic effect of CMF-DOX can lead to highly superior inhibition of animal H22 tumor in vivo when compared to any of the single approaches alone. The results revealed that this Cu9S5 based magnetically targeted chemo/photothermal synergistic nanocarrier system has great promise in future MR imaging assisted tumor targeted therapy of cancer.

  5. Construction of pH-responsive and up-conversion luminescent NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite for colon targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Tian, Boshi; Liu, Shaohua; Lu, Wei; Jin, Lin; Li, Qingfeng; Shi, Yurong; Li, Chunyang; Wang, Zhenling; Du, Yaping

    2016-02-01

    Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon.

  6. Theoretical and empirical studies of impurity incorporation into beta-SiC thin films during epitaxial growth

    NASA Astrophysics Data System (ADS)

    Kim, H. J.; Davis, R. F.

    1986-11-01

    A theoretical determination of the vapor species present, and their respective partial pressures, is made using the SOLGASMIX-PV program for the n-type and p-type dopants of N and P, and B, respectively, under conditions used to grow monocrystalline beta-SiC thin films via CVD. The model shows that Al and P behave ideally while B and N apparently interact with the C or Si in the SiC or fill normally unoccupied interstitial positions. The relationship between the carrier concentrations or the atomic concentrations and the partial pressure of the dopant source gases is linear and parallel. The more efficient n-type and p-type dopants of N and Al have been used to produce what is suggested to be the first p-n junction diode in a beta-SiC film.

  7. Re-examination of siRNA specificity questions role of PICH and Tao1 in the spindle checkpoint and identifies Mad2 as a sensitive target for small RNAs.

    PubMed

    Hübner, Nadja C; Wang, Lily Hui-Ching; Kaulich, Manuel; Descombes, Patrick; Poser, Ina; Nigg, Erich A

    2010-04-01

    The DNA-dependent adenosine triphosphatase (ATPase) Plk1-interacting checkpoint helicase (PICH) has recently been implicated in spindle checkpoint (SAC) signaling (Baumann et al., Cell 128(1):101-114, 2007). Depletion of PICH by siRNA abolished the SAC and resulted in an apparently selective loss of Mad2 from kinetochores, suggesting a role for PICH in the regulation of the Mad1-Mad2 interaction. An apparent rescue of SAC functionality by overexpression of PICH in PICH-depleted cells initially seemed to confirm a role for PICH in the SAC. However, we have subsequently discovered that all PICH-directed siRNA oligonucleotides that abolish the SAC also reduce Mad2 mRNA and protein expression. This reduction is functionally significant, as PICH siRNA does not abolish SAC activity in a cell line that harbors a bacterial artificial chromosome driving the expression of murine Mad2. Moreover, we identified several siRNA duplexes that effectively deplete PICH but do not significantly affect SAC functionality or Mad2 abundance or localization. Finally, we discovered that the ability of overexpressed PICH to restore SAC activity in PICH-depleted cells depends on sequestration of the mitotic kinase Plk1 rather than ATPase activity of PICH, pointing to an underlying mechanism of "bypass suppression." In support of this view, depletion or inhibition of Plk1 also rescued SAC activity in cells harboring low levels of Mad2. This observation suggests that a reduction of Plk1 activity partially compensates for reduced Mad2 levels and argues that Plk1 normally reduces the strength of SAC signaling. Collectively, our results question the role of PICH in the SAC and instead identify Mad2 as a sensitive off target for small RNA duplexes. In support of the latter conclusion, our evidence suggests that an off-target effect on Mad2 may also contribute to explain the apparent role of the Tao1 kinase in SAC signaling.

  8. Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro.

    PubMed

    Guo, H H; Yu, C C; Sun, S X; Ma, X J; Yang, X C; Sun, K N; Jin, Q H

    2013-10-01

    Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.

  9. Systemic siRNA Delivery with a Dual pH-Responsive and Tumor-targeted Nanovector for Inhibiting Tumor Growth and Spontaneous Metastasis in Orthotopic Murine Model of Breast Carcinoma

    PubMed Central

    Fan, Bo; Kang, Lin; Chen, Liqing; Sun, Ping; Jin, Mingji; Wang, Qiming; Bae, You Han; Huang, Wei; Gao, Zhonggao

    2017-01-01

    Phenylboronic acid (PBA)-mediated tumor targeting nanovector is an attractive strategy for enhancing siRNA delivery and treatment of metastatic cancers. However, its nonspecific binding with various biological membranes containing cis-diol moieties restricts its potential application by systematic administration. Herein, we constructed a novel pH-activated “sheddable” PEG-coated nanoparticle for effective treatment of primary tumors and metastases, which was based on the conjugation of catechol group modified poly(ethylene glycol) (PEG-Cat) and PBA-terminated polyethylenimine (PEI-PBA) via the borate ester formed between PBA and Cat. By virtue of the pH-dependent stability of borate ester in an aqueous medium, the PEG-shell could “shield” the PBA ligand in systemic circulation to reduce its “off-target effect”, while PEG was detached at tumor extracellular pH (~6.5) to expose intact PBA moiety. Simultaneously, the PBA ligand could bind with overexpressed sialic acid residues on cancer cells, giving rise to enhanced cellular internalization. In addition, the PBA moieties could also couple with each 3'-end ribose of double-stranded siRNA. siRNAs were used as both a payload and a pH-responsive intermolecular cross-linker, and thereby acquired sufficient stability during circulating in blood and a rapidly triggered release in response to acidic endosomal/lysosomal pH-stimuli. As a result, this dual pH-sensitive nanoparticle showed enhanced siRNA uptake, gene silencing efficacy and anti-metastatic effects in vitro. Furthermore, in vivo studies demonstrated that PBA-based nanoparticles effectively accumulated in tumor and inhibited tumor growth and metastasis in 4T1 orthotopic mammary tumor model after intravenous administration. PMID:28042340

  10. Performance Comparison of Stion CIGS Modules to Baseline Monocrystalline Modules at the New Mexico Florida and Vermont Regional Test Centers: January 2015-December 2016.

    SciTech Connect

    Lave, Matthew Samuel; Stein, Joshua; Burnham, Laurie

    2017-01-01

    This report provides performance data and analysis for two Stion copper indium gallium selenide (CIGS) module types, one framed, the other frameless, and installed at the New Mexico, Florida and Vermont RTCs. Sandia looked at data from both module types and compared the latter with data from an adjacent monocrystalline baseline array at each RTC. The results indicate that the Stion modules are slightly outperforming their rated power, with efficiency values above 100% of rated power, at 25degC cell temperatures. In addition, Sandia sees no significant performance differences between module types, which is expected because the modules differ only in their framing. In contrast to the baseline systems, the Stion strings showed increasing efficiency with increasing irradiance, with the greatest increase between zero and 400 Wm -2 but still noticeable increases at 1000 Wm -2 . Although baseline data availability in Vermont was spotty and therefore comparative trends are difficult to discern, the Stion modules there may offer snow- shedding advantages over monocrystalline-silicon modules but these findings are preliminary.

  11. Target rapidity baryon distributions in {sup 28}Si + {sup 197}Au and {sup 197}Au + {sup 197}Au collisions at 14.6 and 11.7 A{center_dot}GeV/c

    SciTech Connect

    Sangster, T.C.; Costales, J.B.; Namboodiri, M.N.; E802 Collaboration

    1993-02-25

    Proton and deuteron kinetic energy spectra have been measured at target rapidities for both minimum bias and central collisions of 14.6 A{center_dot}GeV/c {sup 28}Si and 11.7 A{center_dot}GeV/c {sup 197}Au beams with a {sup 197}Au target. The spectra were measured from a low energy threshold of approximately E{sub kin}=35 MeV to well over 200 MeV for laboratory angles of 50{degree} to 130{degree} ({vert_bar}{eta}{vert_bar} {le}0.76). The acceptance-corrected spectra have been fit over a limited range of kinetic energies using a Boltzmann distribution. The integrated yields and the inverse slope parameters are presented as a function of centrality for the {sup 28}Si + {sup 197}Au reaction and as a function of trigger for the {sup 197}Au + {sup 197}Au reaction. These quantities are also compared with the proton spectra generated using both the ARC and RQMD codes.

  12. Assembly of Multifunctional Phi29 pRNA Nanoparticles for Specific Delivery of SiRNA and other Therapeutics to Targeted Cells

    PubMed Central

    Shu, Yi; Cinier, Mathieu; Shu, Dan; Guo, Peixuan

    2011-01-01

    Recent advances in RNA nanotechnology have led to the emergence of a new field and brought vitality to the area of therapeutics (Guo P, The Emerging Field of RNA Nanotechnology, Nature Nanotechnology, 2010). Due to the complementary nature of the four nucleotides and its special catalytic activity, RNA can be manipulated with simplicity characteristic of DNA, while possessing versatile structure and diverse function similar to proteins. Loops and tertiary architecture serve as mounting dovetails or wedges to eliminate external linking dowels. Unique features in transcription, termination, self-assembly, self-processing, and acid-resistance enable in vivo production of nanoparticles harboring aptamer, siRNA, ribozyme, riboswitch, or other regulators for therapy, detection, regulation, and intracellular computation. The unique property of noncanonical base-pairing and stacking enables RNA to fold into well-defined structures for constructing nanoparticles with special functionalities. Bacteriophage phi29 DNA packaging motor is geared by a ring consisting of six packaging RNA (pRNA) molecules. pRNA is able to form a multimeric complex via the interaction of two reengineered interlocking loops. This unique feature makes it an ideal polyvalent vehicle for nanomachine fabrication, pathogen detection, and delivery of siRNA or other therapeutics. This review describes methods in using pRNA as a building block for the construction of RNA dimers, trimers and hexamers as nanoparticles in medical applications. Methods for industrial-scale production of large and stable RNA nanoparticles will be introduced. The unique favorable PK (pharmokinetics) profile with a half life (T1/2) of 5–10 hours comparing to 0.25 of conventional 2′-F siRNA, and advantageous in vivo features such as non-toxicity, non-induction of interferons or non-stimulating of cytokine response in animals will also be reviewed. PMID:21320601

  13. Assembly of multifunctional phi29 pRNA nanoparticles for specific delivery of siRNA and other therapeutics to targeted cells.

    PubMed

    Shu, Yi; Cinier, Mathieu; Shu, Dan; Guo, Peixuan

    2011-06-01

    Recent advances in RNA nanotechnology have led to the emergence of a new field and brought vitality to the area of therapeutics [P. Guo, The emerging field of RNA nanotechnology, Nat. Nanotechnol., 2010]. Due to the complementary nature of the four nucleotides and its special catalytic activity, RNA can be manipulated with simplicity characteristic of DNA, while possessing versatile structure and diverse function similar to proteins. Loops and tertiary architecture serve as mounting dovetails or wedges to eliminate external linking dowels. Unique features in transcription, termination, self-assembly, self-processing, and acid-resistance enable in vivo production of nanoparticles harboring aptamer, siRNA, ribozyme, riboswitch, or other regulators for therapy, detection, regulation, and intracellular computation. The unique property of noncanonical base-pairing and stacking enables RNA to fold into well-defined structures for constructing nanoparticles with special functionalities. Bacteriophage phi29 DNA packaging motor is geared by a ring consisting of six packaging RNA (pRNA) molecules. pRNA is able to form a multimeric complex via the interaction of two reengineered interlocking loops. This unique feature makes it an ideal polyvalent vehicle for nanomachine fabrication, pathogen detection, and delivery of siRNA or other therapeutics. This review describes methods in using pRNA as a building block for the construction of RNA dimers, trimers, and hexamers as nanoparticles in medical applications. Methods for industrial-scale production of large and stable RNA nanoparticles will be introduced. The unique favorable PK (pharmacokinetics) profile with a half life (T(1/2)) of 5-10h comparing to 0.25 of conventional 2'-F siRNA, and advantageous in vivo features such as non-toxicity, non-induction of interferons or non-stimulating of cytokine response in animals will also be reviewed.

  14. Targeted knockout of TNF-α by injection of lentivirus-mediated siRNA into the subacromial bursa for the treatment of subacromial bursitis in rats.

    PubMed

    Wang, Yi; Li, Quan; Wei, Xianzhao; Xu, Jie; Chen, Qi; Song, Shuang; Lu, Zhe; Wang, Zimin

    2015-09-01

    Subacromial bursitis (SAB) is the major source of pain in rotator cuff disease. Although multiple investigations have provided support for the role of inflammatory cytokines in SAB, few have focussed on the use these cytokines in the treatment of SAB. The aim of the present study was to observe the therapeutic efficacy of lentivirus‑mediated RNA interference (RNAi) on carrageenan‑induced SAB by injecting lentivirus‑tumor necrosis factor (TNF)‑α‑RNAi expressing TNF‑α small interfering (si)RNA. Using screened siRNA segments, an siRNA was designed. A lentivirus vector expressing siRNA was established and packed as lentivirus particles. A lentivirus that expressed the negative sequence was used as a lentivirus‑negative control (NC). The carrageenan‑induced SAB model was established in 32 male Sprague‑Dawley rats. The modeled rats were randomly assigned to four groups: Lentivirus‑RNAi treatment group, lentivirus‑NC group, SAB group and phosphate‑buffered saline (PBS) blank control group. The lentivirus was injected (1x10(7) transducing units) into the subacromial bursa of the rats in the lentivirus‑RNAi group and lentivirus‑NC group, whereas 100 µl PBS was injected at the same site in the SAB group and the PBS blank control group. At 5 weeks following injection, the animals were sacrificed and venous blood was obtained. The effect of TNF‑α interference and the expression of inflammatory cytokines were determined by reverse transcription‑quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining, Van Gieson's staining and immunofluorescence. The expression of TNF‑α was decreased in the lentivirus‑TNF‑α‑RNAi group compared with that in the SAB group. Morphological observations revealed that the number of inflammatory cells were reduced and damage to tendon fibers was attenuated in this group, suggesting that the downregulation of the protein expression levels of TNF‑α‑associated nuclear

  15. Transgenic tobacco plants expressing siRNA targeted against the Mungbean yellow mosaic virus transcriptional activator protein gene efficiently block the viral DNA accumulation.

    PubMed

    Shanmugapriya, Gnanasekaran; Das, Sudhanshu Sekhar; Veluthambi, Karuppannan

    2015-06-01

    Mungbean yellow mosaic virus (MYMV) is a bipartite begomovirus that infects many pulse crops such as blackgram, mungbean, mothbean, Frenchbean, and soybean. We tested the efficacy of the transgenically expressed intron-spliced hairpin RNA gene of the transcriptional activator protein (hpTrAP) in reducing MYMV DNA accumulation. Tobacco plants transformed with the MYMV hpTrAP gene accumulated 21-22 nt siRNA. Leaf discs of the transgenic plants, agroinoculated with the partial dimers of MYMV, displayed pronounced reduction in MYMV DNA accumulation. Thus, silencing of the TrAP gene, a suppressor of gene silencing, emerged as an effective strategy to control MYMV.

  16. Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity

    PubMed Central

    Hajdu, Péter; Chimote, Ameet A.; Thompson, Tyler; Koo, Youngmi; Yun, Yeoheung; Conforti, Laura

    2013-01-01

    Effector memory T cells (TM) play a key role in the pathology of certain autoimmune disorders. The activity of effector TM cells is under the control of Kv1.3 ion channels, which facilitate the Ca2+ influx necessary for T cell activation and function, i.e. cytokine release and proliferation. Consequently, the knock-down of Kv1.3 expression in effector TM’s may be utilized as a therapy for the treatment of autoimmune diseases. In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into TM cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of TM’s) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into TM’s. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of Kv1.3 channels decreased significantly in TM’s, which led to a remarkable decrease in Ca2+ influx. Our results can form the basis of an innovative therapeutic approach in autoimmunity. PMID:24075407

  17. Structural and photoluminescent properties of nanowires formed by the metal-assisted chemical etching of monocrystalline silicon with different doping level

    SciTech Connect

    Georgobiani, V. A. Gonchar, K. A.; Osminkina, L. A.; Timoshenko, V. Yu.

    2015-08-15

    Silicon-nanowire layers grown by the metal-assisted chemical etching of (100)-oriented p-type monocrystalline silicon substrates with a resistivity of 10 and 0.001 Ω · cm are studied by electron microscopy, Raman scattering, and photoluminescence measurements. It is established that nanowires grown on lightly doped substrates are structurally nonporous and formed as crystalline cores covered by nanocrystals 3–5 nm in dimensions. Nanowires grown on heavily doped substrates are structurally porous and contain both small nanocrystals and coarser crystallites with equilibrium charge carriers that influence interband radiative recombination. It is found that the photoluminescence intensity of nanowires in the spectral range 1.3–2.0 eV depends on the presence of molecular oxygen.

  18. Physical and Structural Characterization of a Monocrystalline Cu-13.7Al-4.2Ni Alloy Subjected to Thermal Cycling Treatments

    NASA Astrophysics Data System (ADS)

    Pereira, Elaine Cristina; Matlakhova, Lioudmila Aleksandrovna; Matlakhov, Anatoliy Nikolaevich; Shigue, Carlos Yujiro; Monteiro, Sérgio Neves

    2014-04-01

    A monocrystalline alloy with nominal 82wt pctCu-13.7wt pctAl-4.2wt pctNi composition and exhibiting reversible martensitic transformation (RMT) was subjected to multiple heating and cooling cycles within the RMT range of critical temperatures. Both untreated and cyclic treated alloy samples were characterized by X-ray diffraction, optical microscopy, differential scanning calorimetry, and Vickers microhardness. The results indicated that the alloy presents a complex RMT behavior disclosing a sequence of transformation steps: β 1 ↔ R and R ↔ β'1 + γ'1 as well as possible β 1 ↔ β'1 and β'1 ↔ γ'1 direct reactions. The thermal cycling treatment inhibits the development of γ'1 martensite without much change in both the physical and microstructure characteristics. This suggests a good resistance of the alloy to irreversible structural changes.

  19. Junction formation and current transport mechanisms in hybrid n-Si/PEDOT:PSS solar cells

    PubMed Central

    Jäckle, Sara; Mattiza, Matthias; Liebhaber, Martin; Brönstrup, Gerald; Rommel, Mathias; Lips, Klaus; Christiansen, Silke

    2015-01-01

    We investigated hybrid inorganic-organic solar cells combining monocrystalline n-type silicon (n-Si) and a highly conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). The build-in potential, photo- and dark saturation current at this hybrid interface are monitored for varying n-Si doping concentrations. We corroborate that a high build-in potential forms at the hybrid junction leading to strong inversion of the n-Si surface. By extracting work function and valence band edge of the polymer from ultraviolet photoelectron spectroscopy, a band diagram of the hybrid n-Si/PEDOT:PSS heterojunction is presented. The current-voltage characteristics were analyzed using Schottky and abrupt pn-junction models. The magnitude as well as the dependence of dark saturation current on n-Si doping concentration proves that the transport is governed by diffusion of minority charge carriers in the n-Si and not by thermionic emission of majorities over a Schottky barrier. This leads to a comprehensive explanation of the high observed open-circuit voltages of up to 634 mV connected to high conversion efficiency of almost 14%, even for simple planar device structures without antireflection coating or optimized contacts. The presented work clearly shows that PEDOT:PSS forms a hybrid heterojunction with n-Si behaving similar to a conventional pn-junction and not, like commonly assumed, a Schottky junction. PMID:26278010

  20. Junction formation and current transport mechanisms in hybrid n-Si/PEDOT:PSS solar cells

    NASA Astrophysics Data System (ADS)

    Jäckle, Sara; Mattiza, Matthias; Liebhaber, Martin; Brönstrup, Gerald; Rommel, Mathias; Lips, Klaus; Christiansen, Silke

    2015-08-01

    We investigated hybrid inorganic-organic solar cells combining monocrystalline n-type silicon (n-Si) and a highly conductive polymer poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS). The build-in potential, photo- and dark saturation current at this hybrid interface are monitored for varying n-Si doping concentrations. We corroborate that a high build-in potential forms at the hybrid junction leading to strong inversion of the n-Si surface. By extracting work function and valence band edge of the polymer from ultraviolet photoelectron spectroscopy, a band diagram of the hybrid n-Si/PEDOT:PSS heterojunction is presented. The current-voltage characteristics were analyzed using Schottky and abrupt pn-junction models. The magnitude as well as the dependence of dark saturation current on n-Si doping concentration proves that the transport is governed by diffusion of minority charge carriers in the n-Si and not by thermionic emission of majorities over a Schottky barrier. This leads to a comprehensive explanation of the high observed open-circuit voltages of up to 634 mV connected to high conversion efficiency of almost 14%, even for simple planar device structures without antireflection coating or optimized contacts. The presented work clearly shows that PEDOT:PSS forms a hybrid heterojunction with n-Si behaving similar to a conventional pn-junction and not, like commonly assumed, a Schottky junction.

  1. siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression

    PubMed Central

    Yang, Zi-Zhao; Li, Li; Wang, Lu; Xu, Ming-Cheng; An, Sai; Jiang, Chen; Gu, Jing-Kai; Wang, Zai-Jie Jim; Yu, Lu-Shan; Zeng, Su

    2016-01-01

    Regulating main brain-uptake transporter of morphine may restrict its tolerance generation, then modify its antinociception. In this study, more than 2 fold higher intracellular uptake concentrations for morphine and morphine-6-glucuronide (M6G) were observed in stable expression cells, HEK293-hOATP2B1 than HEK293-MOCK. Specifically, the Km value of morphine to OATP2B1 (57.58 ± 8.90 μM) is 1.4-time more than that of M6G (80.31 ± 21.75 μM); Cyclosporine A (CsA), an inhibitor of OATP2B1, can inhibit their intracellular accumulations with IC50 = 3.90 ± 0.50 μM for morphine and IC50 = 6.04 ± 0.86 μM for M6G, respectively. To further investigate the role of OATP2B1 in morphine brain transport and tolerance, the novel nanoparticles of DGL-PEG/dermorphin capsulated siRNA (OATP2B1) were applied to deliver siRNA into mouse brain. Along with OATP2B1 depressed, a main reduction was found for each of morphine or M6G in cerebrums or epencephalons of acute morphine tolerance mice. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) in mouse prefrontal cortex (mPFC) underwent dephosphorylation at Thr286. In conclusion, OATP2B1 downregulation in mouse brain can suppress tolerance via blocking morphine and M6G brain transport. These findings might help to improve the pharmacological effects of morphine. PMID:27629937

  2. Target-triggered signal turn-on detection of prostate specific antigen based on metal-enhanced fluorescence of Ag@SiO2@SiO2-RuBpy composite nanoparticles

    NASA Astrophysics Data System (ADS)

    Deng, Yun-Liang; Xu, Dang-Dang; Pang, Dai-Wen; Tang, Hong-Wu

    2017-02-01

    A three-layer core-shell nanostructure consisting of a silver core, a silica spacer, and a fluorescent dye RuBpy-doped outer silica layer was fabricated, and the optimal metal-enhanced fluorescence (MEF) distance was explored through adjusting the thickness of the silica spacer. The results show that the optimal distance is ˜10.4 nm with the maximum fluorescence enhancement factor 2.12. Then a new target-triggered MEF ‘turn-on’ strategy based on the optimized composite nanoparticles was successfully constructed for quantitative detection of prostate specific antigen (PSA), by using RuBpy as the energy donor and BHQ-2 as the acceptor. The hybridization of the complementary DNA of PSA-aptamer immobilized on the surface of the MEF nanoparticles with PSA-aptamer modified with BHQ-2, brought BHQ-2 in close proximity to RuBpy-doped silica shell and resulted in the decrease of fluorescence. In the presence of target PSA molecules, the BHQ-PSA aptamer is dissociated from the surface of the nanoparticles with the fluorescence switched on. Therefore, the assay of PSA was achieved by measuring the varying fluorescence intensity. The results show that PSA can be detected in the range of 1-100 ng ml-1 with a detection limit of 0.20 ng ml-1 (6.1 pM), which is 6.7-fold increase of that using hollow RuBpy-doped silica nanoparticles. Moreover, satisfactory results were obtained when PSA was detected in 1% serum.

  3. Assessment of Nanobiotechnology-Targeted siRNA Designed to Inhibit NF-kappaB Classical And Alternative Signaling in Breast Tumor Macrophages

    DTIC Science & Technology

    2012-07-01

    cancer. J Mammary Gland Biol Neoplasia, 2003. 8:215-23. 11. Eliopoulos, A.G., et al., Epstein - Barr virus -encoded latent infection membrane protein...Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J Leukoc Biol 80 (6), 1183-96. 2. M. Marsh & A. Helenius. (2006) Virus ...2012) Macrophage-Specific RNAi Targeting via ‘Click’, Mannosylated Polymeric Micelles. (Submitted).  Common viruses interact with endocytotic

  4. High-k gadolinium scandate on Si obtained by high pressure sputtering from metal targets and in-situ plasma oxidation

    NASA Astrophysics Data System (ADS)

    Pampillón, M. A.; San Andrés, E.; Feijoo, P. C.; Fierro, J. L. G.

    2017-03-01

    This article studies the physical and electrical behavior of Gd2‑x Sc x O3 layers grown by high pressure sputtering from metallic Gd and Sc targets. The aim is to obtain a high permittivity dielectric for microelectronic applications. The films were obtained by the deposition of a metallic nanolaminate of Gd and Sc alternating layers, which is afterwards in-situ oxidized by plasma. The oxide films obtained were close to stoichiometry, amorphous and with minimal interfacial regrowth. By fabricating metal–insulator–semiconductor capacitors we found that a moderate temperature annealing is needed to enhance permittivity, which reaches a high value of 32 while keeping moderate leakage. Finally, the feasibility of interface scavenging in this material with Ti gate electrodes is also demonstrated.

  5. SEMICONDUCTOR TECHNOLOGY Texturization of mono-crystalline silicon solar cells in TMAH without the addition of surfactant

    NASA Astrophysics Data System (ADS)

    Weiying, Ou; Yao, Zhang; Hailing, Li; Lei, Zhao; Chunlan, Zhou; Hongwei, Diao; Min, Liu; Weiming, Lu; Jun, Zhang; Wenjing, Wang

    2010-10-01

    Etching was performed on (100) silicon wafers using silicon-dissolved tetramethylammonium hydroxide (TMAH) solutions without the addition of surfactant. Experiments were carried out in different TMAH concentrations at different temperatures for different etching times. The surface phenomena, etching rates, surface morphology and surface reflectance were analyzed. Experimental results show that the resulting surface covered with uniform pyramids can be realized with a small change in etching rates during the etching process. The etching mechanism is explained based on the experimental results and the theoretical considerations. It is suggested that all the components in the TMAH solutions play important roles in the etching process. Moreover, TMA+ ions may increase the wettability of the textured surface. A good textured surface can be obtained in conditions where the absorption of OH-/H2O is in equilibrium with that of TMA+/SiO2 (OH)22-.

  6. Differential cross sections measurement of 28Si(p,p/γ)28Si and 29Si(p,p/γ)29Si reactions for PIGE applications

    NASA Astrophysics Data System (ADS)

    Jokar, A.; Kakuee, O.; Lamehi-Rachti, M.

    2016-03-01

    Differential cross sections for gamma-ray emission from the 28Si(p,p/γ)28Si (Eγ = 1779 keV) and the 29Si(p,p/γ)29Si (Eγ = 1273 keV) nuclear reactions were measured in the energy range of 2.0-3.2 MeV and 2.0-3.0 MeV, respectively. The thin Si targets were prepared by evaporating natural SiO onto self-supporting Ag films. The gamma-rays and backscattered protons were detected simultaneously. An HPGe detector placed at an angle of 90° with respect to beam direction was employed to collect gamma-rays while an ion implanted Si detector placed at a scattering angle of 165° was used to detect backscattered protons. The great advantage of this work is that differential cross sections were obtained with a procedure irrespective of absolute value of the collected beam charge.

  7. Sputtered Ta-Si-N diffusion barriers in Cu metallizations for Si

    NASA Technical Reports Server (NTRS)

    Kolawa, E.; Pokela, P. J.; Reid, J. S.; Chen, J. S.; Nicolet, Marc A.; Ruiz, R. P.

    1991-01-01

    Electrical measurements on shallow Si n+-p junction diodes with a 30-nm TiSi2 contacting layer demonstrate that an 80-nm-thick amorphous Ta36Si14N50 film prepared by reactive RF sputtering of a Ta5Si3 target in an Ar/N2 plasma very effectively prevents the interaction between the Si substrate with the TiSi2 contacting layer and a 500-nm Cu overlayer. The Ta36Si14N50 diffusion barrier maintains the integrity of the I-V characteristics up to 900 C for 30-min annealing in vacuum. It is concluded that the amorphous Ta36Si14N50 alloy is not only a material with a very low reactivity for copper, titanium, and silicon, but must have a small diffusivity for copper as well.

  8. Crystallization of amorphous Si nanoclusters in SiO(x) films using femtosecond laser pulse annealings.

    PubMed

    Korchagina, T T; Gutakovsky, A K; Fedina, L I; Neklyudova, M A; Volodin, V A

    2012-11-01

    The SiO(x) films of various stoichiometries deposited on Si substrates with the use of the co-sputtering from two separate Si and SiO2 targets were annealed by femtosecond laser pulses. Femtosecond laser treatments were applied for crystallization of amorphous silicon nanoclusters in the silicon-rich oxide films. The treatments were carried out with the use of Ti-Sapphire laser with wavelength 800 nm and pulse duration about 30 fs. Regimes of crystallization of amorphous Si nanoclusters in the initial films were found. Ablation thresholds for SiO(x) films of various stoichiometries were discovered. The effect of laser assisted formation of a-Si nanoclusters in the non-stoichiometric dielectric films with relatively low concentration of additional Si atoms was also observed. This approach is applicable for the creation of dielectric films with semiconductor nanoclusters on non-refractory substrates.

  9. Generation of siRNA Nanosheets for Efficient RNA Interference

    NASA Astrophysics Data System (ADS)

    Kim, Hyejin; Lee, Jae Sung; Lee, Jong Bum

    2016-04-01

    After the discovery of small interference RNA (siRNA), nanostructured siRNA delivery systems have been introduced to achieve an efficient regulation of the target gene expression. Here we report a new siRNA-generating two dimensional nanostructure in a formation of nanosized sheet. Inspired by tunable mechanical and functional properties of the previously reported RNA membrane, siRNA nanosized sheets (siRNA-NS) with multiple Dicer cleavage sites were prepared. The siRNA-NS has two dimensional structure, providing a large surface area for Dicer to cleave the siRNA-NS for the generation of functional siRNAs. Furthermore, downregulation of the cellular target gene expression was achieved by delivery of siRNA-NS without chemical modification of RNA strands or conjugation to other substances.

  10. Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy: siRNA knockdown of network targets in MDA-MB-231 cells as an in vitro model for inhibition of tumor development

    PubMed Central

    Tilli, Tatiana M.; Carels, Nicolas; Tuszynski, Jack A.; Pasdar, Manijeh

    2016-01-01

    Network-based strategies provided by systems biology are attractive tools for cancer therapy. Modulation of cancer networks by anticancer drugs may alter the response of malignant cells and/or drive network re-organization into the inhibition of cancer progression. Previously, using systems biology approach and cancer signaling networks, we identified top-5 highly expressed and connected proteins (HSP90AB1, CSNK2B, TK1, YWHAB and VIM) in the invasive MDA-MB-231 breast cancer cell line. Here, we have knocked down the expression of these proteins, individually or together using siRNAs. The transfected cell lines were assessed for in vitro cell growth, colony formation, migration and invasion relative to control transfected MDA-MB-231, the non-invasive MCF-7 breast carcinoma cell line and the non-tumoral mammary epithelial cell line MCF-10A. The knockdown of the top-5 upregulated connectivity hubs successfully inhibited the in vitro proliferation, colony formation, anchorage independence, migration and invasion in MDA-MB-231 cells; with minimal effects in the control transfected MDA-MB-231 cells or MCF-7 and MCF-10A cells. The in vitro validation of bioinformatics predictions regarding optimized multi-target selection for therapy suggests that protein expression levels together with protein-protein interaction network analysis may provide an optimized combinatorial target selection for a highly effective anti-metastatic precision therapy in triple-negative breast cancer. This approach increases the ability to identify not only druggable hubs as essential targets for cancer survival, but also interactions most susceptible to synergistic drug action. The data provided in this report constitute a preliminary step toward the personalized clinical application of our strategy to optimize the therapeutic use of anti-cancer drugs. PMID:27527857

  11. A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.

    PubMed

    Siebring-van Olst, Ellen; Blijlevens, Maxime; de Menezes, Renee X; van der Meulen-Muileman, Ida H; Smit, Egbert F; van Beusechem, Victor W

    2017-03-13

    Reinstating wild-type tumor suppressor p53 activity could be a valuable option for the treatment of cancer. To contribute to development of new treatment options for non-small cell lung cancer (NSCLC), we performed genome-wide siRNA screens for determinants of p53 activity in NSCLC cells. We identified many genes not previously known to be involved in regulating p53 activity. Silencing p53 pathway inhibitor genes was associated with loss of cell viability. The largest functional gene cluster influencing p53 activity was mRNA splicing. Prominent p53 activation was observed upon silencing of specific spliceosome components, rather than by general inhibition of the spliceosome. Ten genes were validated as inhibitors of p53 activity in multiple NSCLC cell lines: genes encoding the Ras-pathway activator SOS1, the zinc finger protein TSHZ3, the mitochondrial membrane protein COX16 and the spliceosome components SNRPD3, SF3A3, SF3B1, SF3B6, XAB2, CWC22 and HNRNPL. Silencing these genes generally increased p53 levels, with distinct effects on CDKN1A expression, induction of cell cycle arrest and cell death. Silencing spliceosome components was associated with alternative splicing of MDM4 mRNA, which could contribute to activation of p53. In addition, silencing splice factors was particularly effective in killing NSCLC cells, albeit in a p53-independent manner. Interestingly, silencing SNRPD3 and SF3A3 exerted much stronger cytotoxicity to NSCLC cells than to lung fibroblasts, suggesting that these genes could represent useful therapeutic targets. This article is protected by copyright. All rights reserved.

  12. Defect recognition by means of light and electron probe techniques for the characterization of mc-Si wafers and solar cells

    NASA Astrophysics Data System (ADS)

    Moralejo, B.; Tejero, A.; Hortelano, V.; Martínez, O.; González, M. A.; Jiménez, J.

    2016-11-01

    Multicristalline Silicon (mc-Si) is the preferred material for current terrestrial photovoltaic applications. However, the high density of defects present in mc-Si deteriorates the material properties, in particular the minority carrier diffusion length. For this reason, a large effort to characterize the mc-Si material is demanded, aiming to visualize the defective areas and to quantify the type of defects, density and its origin. In this work, several complementary light and electron probe techniques are used for the analysis of both mc-Si wafers and solar cells. These techniques comprise both fast and whole-area detection techniques such as Photoluminescence imaging, and highly spatially resolved time consuming techniques, such as light and electron beam induced current techniques and μRaman spectroscopy. These techniques were applied to the characterization of different mc-Si wafers for solar cells, e.g. ribbon wafers, cast mc-Si as well as quasi-monocrystalline material, upgraded metallurgical mc-Si wafers, and finished solar cells.

  13. Si/SiGe MMIC's

    NASA Astrophysics Data System (ADS)

    Luy, Johann-Friedrich; Strohm, Karl M.; Sasse, Hans-Eckard; Schueppen, Andreas; Buechler, Josef; Wollitzer, Michael; Gruhle, Andreas; Schaeffler, Friedrich; Guettich, Ulrich; Klaassen, Andreas

    1995-04-01

    Silicon-based millimeter-wave integrated circuits (SIMMWIC's) can provide new solutions for near range sensor and communication applications in the frequency range above 50 GHz. This paper gives a survey on the state-of-the-art performance of this technology and on first applications. The key devices are IMPATT diodes for mm-wave power generation and detection in the self-oscillating mixer mode, p-i-n diodes for use in switches and phase shifters, and Schottky diodes in detector and mixer circuits. The silicon/silicon germanium heterobipolar transistor (SiGe HBT) with f(sub max) values of more than 90 GHz is now used for low-noise oscillators at Ka-band frequencies. First system applications are discussed.

  14. Nucleation kinetics of SrTiO3 3D islands and nanorings on Si substrates.

    PubMed

    Tejedor, Paloma; Benedicto, Marcos; Vázquez, Luis; Galiana, Beatriz

    2014-11-07

    The nucleation of SrTiO3 three-dimensional (3D) islands and nanorings on Si substrates via a novel metalorganic decomposition (MOD) process has been investigated as a function of temperature and solution concentration of the SrTi(OC3H7)6 precursor. Quantitative analysis of island density and size distribution by atomic force microscopy (AFM) has revealed the existence of a nucleation regime at solution concentrations below 5 × 10(-3) M, in which the critical nucleus is a trimer and a coalescence regime at higher concentrations, dominated by growth of immobile clusters. Nanorings form preferentially under high supersaturation conditions and their size distribution is consistent with a dynamic coalescence. On the basis of recent theoretical models (Gill, 2012), we have proposed that the island-to-nanoring transition in the SrTiO3/Si system occurs above a critical size as a result of a competition between energetic and kinetic factors. The combination of high-resolution transmission electron microscopy (HRTEM) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) has shown that the monocrystalline SrTiO3 nanoclusters grow pseudomorphically on the Si substrate and exhibit a strain-induced tetragonal lattice distortion.

  15. Improvement of a Si solar cell efficiency using pure and Fe3+ doped PVA films

    NASA Astrophysics Data System (ADS)

    Khalifa, N.; Kaouach, H.; Chtourou, R.

    2015-07-01

    One of the most important key driving the economic viability of solar cells is the high efficiency. This research focuses on the enhancement of commercial Si solar cell performance by deposing a pure and Fe3+ doped polyvinyl alcohol (PVA) layer on the top of the Si wafer of the considered cells. The use of such polymer to improve solar cells efficiency is actually a first. The authors will rely on the optical characteristics of the pure and doped PVA films including absorption and emission properties to justify the effect on Si cells. Commercial monocrystalline silicon solar cells of 15 cm2 (0.49 V/460 mA) are used in this work. Films of almost 80 μm of the ferric polymer are deposed on the cells. Films with the same thickness are characterized by UV-Vis spectroscopy and photoluminescent emission of the films is then investigated. The electrical properties of the cells with and without the organometallic layer are evaluated. It will be deduced an important improvement of all electrical parameters, including short-circuit current, open-circuit voltage, fill factor and spatially the conversion efficiency by almost 3%.

  16. Microstructural Properties of NC-Si/SiO2 Films IN SITU Grown by Reactive Magnetron Co-Sputtering

    NASA Astrophysics Data System (ADS)

    Lu, Wanbing; Guo, Shaogang; Wang, Jiantao; Li, Yun; Wang, Xinzhan; Yu, Gengxi; Fan, Shanshan; Fu, Guangsheng

    2012-01-01

    Nanocrystalline silicon embedded in silicon oxide (nc-Si/SiO2) films have been in situ grown at a low substrate temperature of 300°C by reactive magnetron co-sputtering of Si and SiO2 targets in a mixed Ar/H2 discharge. The influences of H2 flow rate (FH) on the microstructural properties of the deposited nc-Si/SiO2 films were investigated. The results of XRD and the deposition rate of nc-Si/SiO2 films show that the introduction of H2 contributes to the growth of nc-Si grains in silicon oxide matrix. With further increasing FH, the average size of nc-Si grains increases and the deposition rate of nc-Si/SiO2 films decreases gradually. Fourier transform infrared spectra analyses reveal that introduction of hydrogen contributes to the phase separation of nc-Si and SiOx in the deposited films. Moreover, the Si-O4-nSin(n = 0, 1) concentration of the deposited nc-Si/SiO2 films reduces with the increase of FH, while that of Si-O4-nSin(n = 2, 3) concentration increases. These results can be explained by that active hydrogen atoms increase the probability of reducing oxygen from precursor in the plasma and prompting oxygen desorption from the growing surface. This low-temperature procedure for preparing nc-Si/SiO2 films opens up the possibility of fabricating the silicon-based thin-film solar cells onto low-cost glass substrates using nc-Si/SiO2 films.

  17. Purity of targets prepared on Cu substrates

    NASA Astrophysics Data System (ADS)

    Méens, A.; Rossini, I.; Sens, J. C.

    1993-09-01

    The purity of several elemental self-supporting targets usually prepared by evaporation onto soluble Cu substrates has been studied. The targets were analysed by Rutherford backscattering and instrumental neutron activation analysis. Because of the high percentage of Cu observed in some Si targets, further measurements, including transmission electron microscopy, have been performed on Si targets deposited by e-gun bombardment onto Cu and ion-beam sputtering onto betaine.

  18. The Basic SI Model

    ERIC Educational Resources Information Center

    Hurley, Maureen; Jacobs, Glen; Gilbert, Melinda

    2006-01-01

    A general overview of the SI model is provided, including the SI philosophy, essential components of the program, program structures, key roles, outcomes, and evaluation. A review of what we have learned about the importance of planning SI sessions, providing ongoing training for leaders, conducting regular SI program assessments, and implementing…

  19. Gettering effects in Si{sub x}Ge{sub 1-x} single crystalline wafers

    SciTech Connect

    Wollweber, J.; Schulz, D.; Schroeder, W.

    1995-08-01

    The new interest in single crystal growth of SiGe solid solutions is caused by the development of advanced electronics. The SiGe alloys are mostly used in the form of Si/Si{sub x}Ge{sub 1-x} epitaxial layers in heterostructures, the perfect bulk crystals are required to study fundamental properties. Furthermore, Si{sub x}Ge{sub 1-x} crystals can be used as a substrate material instead of Silicon in order to avoid the buffer layers between the Silicon substrate and strained Si{sub x}Ge{sub 1-x}. Monocrystalline SiGe alloys may be a potential candidate as a base material for infrared solar cells too because of an enhanced IR-sensitivity. In this paper we report a new approach to the growth of Si{sub x}Ge{sub 1-x} single crystals (up to 2{double_prime} in diameter) using the crucible free rf-heated float zone technique as well as the Czochralski-technique for solar cells. The goal is to produce solar cells with an increased photo current in comparison to Silicon cells. based on the lower bandgap of the alloyed crystal. In order to be able to use the Si cells technology (a matter still pending to be proven), low contents of Ge are intended, desirably in the range of about x=0.2. It is worth to mention, that in the conventional Silicon cell processes which give efficiencies up to 18-19%, this efficiency is not limited by the bulk base recombination in the lifetime is above 200 {mu}s there. We can conclude, that there is no basic limitation did prevents Si{sub x}Ge{sub 1-x} wafers to present high lifetimes, above 200{mu}s, at least if the Ge content is below 5%. We can also conclude that the phosphorous gettering from a POCl{sub 3} source, used in silicon, can be successfully used to enhance lifetimes in Si{sub x}Ge{sub 1-x}, at least for the Ge concentration used here.

  20. Bone site-specific delivery of siRNA

    PubMed Central

    Liu, Xinli

    2016-01-01

    Abstract Small interfering RNAs (siRNA) have enormous potential as therapeutics to target and treat various bone disorders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeutics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides (Asp)8 and (AspSerSer)6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast-specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models. PMID:26642236

  1. Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level

    NASA Astrophysics Data System (ADS)

    He, Fei; Han, Ye; Gong, Jianting; Song, Jiazhi; Wang, Han; Li, Yanwen

    2017-03-01

    Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms.

  2. Predicting siRNA efficacy based on multiple selective siRNA representations and their combination at score level

    PubMed Central

    He, Fei; Han, Ye; Gong, Jianting; Song, Jiazhi; Wang, Han; Li, Yanwen

    2017-01-01

    Small interfering RNAs (siRNAs) may induce to targeted gene knockdown, and the gene silencing effectiveness relies on the efficacy of the siRNA. Therefore, the task of this paper is to construct an effective siRNA prediction method. In our work, we try to describe siRNA from both quantitative and qualitative aspects. For quantitative analyses, we form four groups of effective features, including nucleotide frequencies, thermodynamic stability profile, thermodynamic of siRNA-mRNA interaction, and mRNA related features, as a new mixed representation, in which thermodynamic of siRNA-mRNA interaction is introduced to siRNA efficacy prediction for the first time to our best knowledge. And then an F-score based feature selection is employed to investigate the contribution of each feature and remove the weak relevant features. Meanwhile, we encode the siRNA sequence and existed empirical design rules as a qualitative siRNA representation. These two kinds of siRNA representations are combined to predict siRNA efficacy by supported Vector Regression (SVR) at score level. The experimental results indicate that our method may select the features with powerful discriminative ability and make the two kinds of siRNA representations work at full capacity. The prediction results also demonstrate that our method can outperform other popular siRNA efficacy prediction algorithms. PMID:28317874

  3. Electrical behavior of MIS devices based on Si nanoclusters embedded in SiOxNy and SiO2 films

    PubMed Central

    2011-01-01

    We examined and compared the electrical properties of silica (SiO2) and silicon oxynitride (SiOxNy) layers embedding silicon nanoclusters (Sinc) integrated in metal-insulator-semiconductor (MIS) devices. The technique used for the deposition of such layers is the reactive magnetron sputtering of a pure SiO2 target under a mixture of hydrogen/argon plasma in which nitrogen is incorporated in the case of SiOxNy layer. Al/SiOxNy-Sinc/p-Si and Al/SiO2-Sinc/p-Si devices were fabricated and electrically characterized. Results showed a high rectification ratio (>104) for the SiOxNy-based device and a resistive behavior when nitrogen was not incorporating (SiO2-based device). For rectifier devices, the ideality factor depends on the SiOxNy layer thickness. The conduction mechanisms of both MIS diode structures were studied by analyzing thermal and bias dependences of the carriers transport in relation with the nitrogen content. PMID:21711698

  4. Characterization of Si/CoSi2/Si(111) heterostructures using Auger plasmon losses

    NASA Technical Reports Server (NTRS)

    Schowengerdt, F. D.; Lin, T. L.; Fathauer, R. W.; Grunthaner, P. J.

    1989-01-01

    The Si/CoSi2/Si heterostructures prepared by codeposition and solid-phase epitaxy on Si(111) substrates were characterized using Auger plasmon data as a measure of Si overlayer thickness. The method of calibration is described, and the results of two studies, including a study of islanding in Si/CoSi2/Si and a study of diffusion in CoSi2/Si are presented, illustrating the utility of the Auger plasmon loss technique. It is shown that, most likely, the diffusion proceeds through residual defects in the CoSi2.

  5. Electromagnetic dissociation of relativistic [sup 28]Si by nucleon emission

    SciTech Connect

    Sonnadara, U.J.

    1992-12-01

    A detailed study of the electromagnetic dissociation of [sup 28]Si by nucleon emission at E[sub lab]/A = 14.6 (GeV/nucleon was carried out with [sup 28]Si beams interacting on [sup 208]Pb). [sup 120]Sn. [sup 64]C targets. The measurements apparatus consists of detectors in the target area which measure the energy and charged multiplicity, and a forward spectrometer which measures the position, momentum and energy of the reaction fragments. The exclusive electromagnetic dissociation cross sections for decay channels having multiple nucleons in the final state have been measured which enables the selection of events produced in pure electromagnetic interactions. The measured cross sections agree well with previous measurements obtained for the removal of a few nucleons as well as with measurements on total charge removal cross sections from other experiments. The dependence of the integrated cross sections on the target charge Z[sub T] and the target mass AT confirms that for higher Z targets the excitation is largely electromagnetic. Direct measurements of the excitation energy for the electromagnetic dissociation of [sup 28]Si [yields] p+[sup 27]Al and [sup 28]Si [yields] n+[sup 27]Si have been obtained through a calculation of the invariant mass in kinematically, reconstructed events. The excitation energy spectrum for all targets peak near the isovector giant dipole resonance in [sup 28]Si. These distributions are well reproduced by combining the photon spectrum calculated using the Weizsaecker-Williams approximation with the experimental data on the photonuclear [sup 28]Si([sub [gamma],p])[sup 27]Al and [sup 28]Si([sub [gamma],n])[sup 27]Si. The possibilities of observing double giant dipole resonance excitations in [sup 28]Si have been investigated with cross section measurements as well as with excitation energy reconstruction.

  6. Electromagnetic dissociation of relativistic {sup 28}Si by nucleon emission

    SciTech Connect

    Sonnadara, U.J.

    1992-12-01

    A detailed study of the electromagnetic dissociation of {sup 28}Si by nucleon emission at E{sub lab}/A = 14.6 (GeV/nucleon was carried out with {sup 28}Si beams interacting on {sup 208}Pb). {sup 120}Sn. {sup 64}C targets. The measurements apparatus consists of detectors in the target area which measure the energy and charged multiplicity, and a forward spectrometer which measures the position, momentum and energy of the reaction fragments. The exclusive electromagnetic dissociation cross sections for decay channels having multiple nucleons in the final state have been measured which enables the selection of events produced in pure electromagnetic interactions. The measured cross sections agree well with previous measurements obtained for the removal of a few nucleons as well as with measurements on total charge removal cross sections from other experiments. The dependence of the integrated cross sections on the target charge Z{sub T} and the target mass AT confirms that for higher Z targets the excitation is largely electromagnetic. Direct measurements of the excitation energy for the electromagnetic dissociation of {sup 28}Si {yields} p+{sup 27}Al and {sup 28}Si {yields} n+{sup 27}Si have been obtained through a calculation of the invariant mass in kinematically, reconstructed events. The excitation energy spectrum for all targets peak near the isovector giant dipole resonance in {sup 28}Si. These distributions are well reproduced by combining the photon spectrum calculated using the Weizsaecker-Williams approximation with the experimental data on the photonuclear {sup 28}Si({sub {gamma},p}){sup 27}Al and {sup 28}Si({sub {gamma},n}){sup 27}Si. The possibilities of observing double giant dipole resonance excitations in {sup 28}Si have been investigated with cross section measurements as well as with excitation energy reconstruction.

  7. (30)Si mole fraction of a silicon material highly enriched in (28)Si determined by instrumental neutron activation analysis.

    PubMed

    D'Agostino, Giancarlo; Di Luzio, Marco; Mana, Giovanni; Oddone, Massimo; Pramann, Axel; Prata, Michele

    2015-06-02

    The latest determination of the Avogadro constant, carried out by counting the atoms in a pure silicon crystal highly enriched in (28)Si, reached the target 2 × 10(-8) relative uncertainty required for the redefinition of the kilogram based on the Planck constant. The knowledge of the isotopic composition of the enriched silicon material is central; it is measured by isotope dilution mass spectrometry. In this work, an independent estimate of the (30)Si mole fraction was obtained by applying a relative measurement protocol based on Instrumental Neutron Activation Analysis. The amount of (30)Si isotope was determined by counting the 1266.1 keV γ-photons emitted during the radioactive decay of the radioisotope (31)Si produced via the neutron capture reaction (30)Si(n,γ)(31)Si. The x((30)Si) = 1.043(19) × 10(-6) mol mol(-1) is consistent with the value currently adopted by the International Avogadro Coordination.

  8. Aperiodic SiSn/Si multilayers for thermoelectric applications

    NASA Astrophysics Data System (ADS)

    Tonkikh, A. A.; Zakharov, N. D.; Eisenschmidt, C.; Leipner, H. S.; Werner, P.

    2014-04-01

    We report on novel defect-free SiSn/Si heterostructures grown pseudomorphically on Si(001) substrates using temperature-modulated molecular beam epitaxy. This approach results in a sustainable epitaxial growth for SiSn/Si multilayers. Transmission electron microscopy and electron diffraction manifest that SiSn layers possess a diamond lattice structure. X-ray diffraction reveals up to 9.5 at% Sn in the crystal lattice of SiSn layers.

  9. Scientific Teaching Targeting Faculty from Diverse Institutions

    ERIC Educational Resources Information Center

    Gregg, Christopher S.; Ales, Jo Dale; Pomarico, Steven M.; Wischusen, E. William; Siebenaller, Joseph F.

    2013-01-01

    We offered four annual professional development workshops called STAR (for Scientific Teaching, Assessment, and Resources) modeled after the National Academies Summer Institute (SI) on Undergraduate Education in Biology. In contrast to the SI focus on training faculty from research universities, STAR's target was faculty from community colleges,…

  10. Nuclear target development

    SciTech Connect

    Greene, J.P.; Thomas, G.E.

    1995-08-01

    The Physics Division operates a target development laboratory that produces thin foil targets needed for experiments performed at the ATLAS and Dynamitron accelerators. Targets are not only produced for the Physics Division but also for other divisions and occasionally for other laboratories and universities. In the past year, numerous targets were fabricated by vacuum evaporation either as self-supporting foils or on various substrates. Targets produced included Ag, Au, {sup 10,11}B, {sup 138}Ba, Be, {sup 12}C, {sup 40}Ca, {sup 116}Cd, {sup 155,160}Gd, {sup 76}Ge, In, LID, {sup 6}LiH, Melamine, Mg, {sup 142,150}Nd, {sup 58}Ni, {sup 206,208}Pb, {sup 194}Pt, {sup 28}Si, {sup 144,148}Sm, {sup 120,122,124}Sn, Ta, {sup 130}Te, ThF{sub 4}, {sup 46,50}Ti, TiH, U, UF{sub 4}, {sup 182}W and {sup 170}Yb. Polypropylene and aluminized polypropylene, along with metallized Mylar were produced for experiments at ATLAS. A number of targets of {sup 11}B of various thickness were made for the DEP 2-MeV Van de Graff accelerator. An increased output of foils fabricated using our small rolling mill included targets of Au, C, {sup 50}Cr, Cu, {sup 155,160}Gd, Mg, {sup 58}Ni, {sup 208}Pb, {sup 105,110}Pd. Sc, Ti, and {sup 64,66}Zn.

  11. Strategies for siRNA navigation to desired cells.

    PubMed

    Sioud, Mouldy

    2015-01-01

    Whilst small interfering (si) RNAs have emerged as a promising therapeutic modality for treating a diversity of human diseases, delivery constitutes the most serious obstacle to siRNA drug development. As the most used delivery agents can enter all cell types, specificity must be built into the delivery agents or directly attached to the siRNA molecules. The use of antibodies, peptides, Peptide-Fc fusions, aptamers, and other targeting ligands has now enabled efficient gene silencing in the desired cell populations/tissues in vitro and in vivo. The present review summarizes these current innovations, which are important for the design of safe therapeutic siRNAs.

  12. Utilizing Selected Di- and Trinucleotides of siRNA to Predict RNAi Activity

    PubMed Central

    Han, Ye; Liu, Yuanning; Zhang, Hao; He, Fei; Shu, Chonghe

    2017-01-01

    Small interfering RNAs (siRNAs) induce posttranscriptional gene silencing in various organisms. siRNAs targeted to different positions of the same gene show different effectiveness; hence, predicting siRNA activity is a crucial step. In this paper, we developed and evaluated a powerful tool named “siRNApred” with a new mixed feature set to predict siRNA activity. To improve the prediction accuracy, we proposed 2-3NTs as our new features. A Random Forest siRNA activity prediction model was constructed using the feature set selected by our proposed Binary Search Feature Selection (BSFS) algorithm. Experimental data demonstrated that the binding site of the Argonaute protein correlates with siRNA activity. “siRNApred” is effective for selecting active siRNAs, and the prediction results demonstrate that our method can outperform other current siRNA activity prediction methods in terms of prediction accuracy. PMID:28243313

  13. Ellipsometric study of Si(0.5)Ge(0.5)/Si strained-layer superlattices

    NASA Technical Reports Server (NTRS)

    Sieg, R. M.; Alterovitz, S. A.; Croke, E. T.; Harrell, M. J.

    1993-01-01

    An ellipsometric study of two Si(0.5)Ge(0.5)/Si strained-layer super lattices grown by MBE at low temperature (500 C) is presented, and results are compared with x ray diffraction (XRD) estimates. Excellent agreement is obtained between target values, XRD, and ellipsometry when one of two available Si(x)Ge(1-x) databases is used. It is shown that ellipsometry can be used to nondestructively determine the number of superlattice periods, layer thicknesses, Si(x)Ge(1-x) composition, and oxide thickness without resorting to additional sources of information. It was also noted that we do not observe any strain effect on the E(sub 1) critical point.

  14. Ellipsometric study of Si(0.5)Ge(0.5)/Si strained-layer superlattices

    NASA Technical Reports Server (NTRS)

    Sieg, R. M.; Alterovitz, S. A.; Croke, E. T.; Harrell, M. J.

    1993-01-01

    We present an ellipsometric study of two Si(0.5)Ge(0.5)/Si strained-layer superlattices grown by MBE at low temperature (500 C), and compare our results with X-ray diffraction (XRD) estimates. Excellent agreement is obtained between target values, XRD, and ellipsometry when one of two available Si(x)Ge(1-x) databases is used. We show that ellipsometry can be used to nondestructively determine the number of superlattice periods, layer thicknesses, Si(x)Ge(1-x) composition, and oxide thickness without resorting to additional sources of information. We also note that we do not observe any strain effect on the E1 critical point.

  15. Photocurrent saturation and negative differential photoconductivity in Mn4Si7-Si-Mn4Si7 and Mn4Si7-Si- M heterojunctions

    NASA Astrophysics Data System (ADS)

    Kamilov, T. S.; Klechkovskaya, V. V.; Sharipov, B. Z.; Ivakin, G. I.

    2013-06-01

    A mechanism behind the saturation of the photocurrent and occurrence of negative differential photoconductivity in Mn4Si7-Si-Mn4Si7 and Mn4Si7-Si- M heterojunctions is found. Mn4Si7-Si-Mn4Si7 and Mn4Si7-Si- M structures are studied with a model of back-to-back diodes. Photocurrent-voltage characteristics are taken at high constant and pulsed applied biases. It is found that the nonlinearity of the photocurrent-voltage characteristics and photoconductivity kinetics are due to the quenching of photoconductivity by Joule self-heating.

  16. Molecular-dynamics study of amorphous SiO{sub 2} relaxation

    SciTech Connect

    Fadhilah, Irfan Muhammad; Rosandi, Yudi

    2015-09-30

    Using Molecular-Dynamics simulation we observed the generation of amorphous SiO{sub 2} target from a randomly distributed Si and O atoms. We applied a sequence of annealing of the target with various temperature and quenching to room temperature. The relaxation time required by the system to form SiO{sub 4} tetrahedral mesh after a relatively long simulation time, is studied. The final amorphous target was analyzed using the radial distribution function method, which can be compared with the available theoretical and experimental data. We found that up to 70% of the target atoms form the tetrahedral SiO{sub 4} molecules. The number of formed tetrahedral increases following the growth function and the rate of SiO{sub 4} formation follows Arrhenius law, depends on the annealing temperature. The local structure of amorphous SiO{sub 2} after this treatment agrees well with those reported in some literatures.

  17. DNA repair investigations using siRNA.

    PubMed

    Miller, Holly; Grollman, Arthur P

    2003-06-11

    Small interfering RNA (siRNA) is a revolutionary tool for the experimental modulation of gene expression, in many cases making redundant the need for specific gene mutations and allowing examination of the effect of modulating essential genes. It has now been shown that siRNA phenotypes resulting from stable transfection with short hairpin RNA (shRNA) can be transmitted through the mouse germ line and Rosenquist and his colleagues have used shRNA, which is processed in vivo to siRNA, to create germline transgenic mice in which a target DNA repair gene has been silenced. Here, Holly Miller and Arthur P. Grollman give the background of these discoveries, provide an overview of current uses, and look at future applications of this research.

  18. Endotaxial Si nanolines in Si(001):H

    NASA Astrophysics Data System (ADS)

    Owen, James; Bianco, François; Köster, Sigrun A.; Mazur, Daniel; Renner, Christoph; Bowler, David

    2011-03-01

    The study of one dimensional wires is of great interest in the area of low-dimensional physics, and these structures also have potential applications in future nanodevices. A perfectly straight nanoline embedded in a H-terminated silicon surface has been fabricated by a process of hydrogenation of a Bi nanoline surface using an atomic H beam source, and comprises a triangular core of Si embedded in the top five layers of the Si substrate. The defect density of this nanoline is extremely low, and being H- terminated, it is stable in air for limited periods of time. Scanning Tunnelling Microscopy experimental data and Density Functional Theory calculations have been used to determine the atomic structure of this nanoline, so-called the Haiku Stripe, and have revealed that there exists a 1D state localised to the nanoline core, lying just above the conduction band minimum. This work is supported by the Swiss National Science Fundation.

  19. Primary and Secondary siRNAs in Geminivirus-induced Gene Silencing

    PubMed Central

    Rajeswaran, Rajendran; Gubaeva, Ekaterina G.; Zvereva, Anna S.; Windels, David; Vazquez, Franck; Blevins, Todd; Farinelli, Laurent; Pooggin, Mikhail M.

    2012-01-01

    In plants, RNA silencing-based antiviral defense is mediated by Dicer-like (DCL) proteins producing short interfering (si)RNAs. In Arabidopsis infected with the bipartite circular DNA geminivirus Cabbage leaf curl virus (CaLCuV), four distinct DCLs produce 21, 22 and 24 nt viral siRNAs. Using deep sequencing and blot hybridization, we found that viral siRNAs of each size-class densely cover the entire viral genome sequences in both polarities, but highly abundant siRNAs correspond primarily to the leftward and rightward transcription units. Double-stranded RNA precursors of viral siRNAs can potentially be generated by host RDR-dependent RNA polymerase (RDR). However, genetic evidence revealed that CaLCuV siRNA biogenesis does not require RDR1, RDR2, or RDR6. By contrast, CaLCuV derivatives engineered to target 30 nt sequences of a GFP transgene by primary viral siRNAs trigger RDR6-dependent production of secondary siRNAs. Viral siRNAs targeting upstream of the GFP stop codon induce secondary siRNAs almost exclusively from sequences downstream of the target site. Conversely, viral siRNAs targeting the GFP 3′-untranslated region (UTR) induce secondary siRNAs mostly upstream of the target site. RDR6-dependent siRNA production is not necessary for robust GFP silencing, except when viral siRNAs targeted GFP 5′-UTR. Furthermore, viral siRNAs targeting the transgene enhancer region cause GFP silencing without secondary siRNA production. We conclude that the majority of viral siRNAs accumulating during geminiviral infection are RDR1/2/6-independent primary siRNAs. Double-stranded RNA precursors of these siRNAs are likely generated by bidirectional readthrough transcription of circular viral DNA by RNA polymerase II. Unlike transgenic mRNA, geminiviral mRNAs appear to be poor templates for RDR-dependent production of secondary siRNAs. PMID:23028332

  20. Sputter target

    DOEpatents

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  1. Guide Strand 3'-End Modifications Regulate siRNA Specificity.

    PubMed

    Valenzuela, Rachel A P; Onizuka, Kazumitsu; Ball-Jones, Alexi A; Hu, Tiannan; Suter, Scott R; Beal, Peter A

    2016-12-14

    Short interfering RNA (siRNA)-triggered gene knockdown through the RNA interference (RNAi) pathway is widely used to study gene function, and siRNA-based therapeutics are in development. However, as the guide strand of an siRNA can function like a natural microRNA (miRNA), siRNAs often repress hundreds of off-target transcripts with complementarity only to the seed region (nucleotides 2-8) of the guide strand. Here, we describe novel guide strand 3'-end modifications derived from 1-ethynylribose (1-ER) and copper-catalyzed azide-alkyne cycloaddition reactions and evaluate their impact on target versus miRNA-like off-target knockdown. Surprisingly, when positioned at the guide strand 3'-end, the parent 1-ER modification substantially reduced off-target knockdown while having no measurable effect on on-target knockdown potency. In addition, these modifications were shown to modulate siRNA affinity for the hAgo2 PAZ domain. However, the change in PAZ domain binding affinity was not sufficient to predict the modification's effect on miRNA-like off targeting.

  2. Surface etching, chemical modification and characterization of silicon nitride and silicon oxide--selective functionalization of Si3N4 and SiO2.

    PubMed

    Liu, Li-Hong; Michalak, David J; Chopra, Tatiana P; Pujari, Sidharam P; Cabrera, Wilfredo; Dick, Don; Veyan, Jean-François; Hourani, Rami; Halls, Mathew D; Zuilhof, Han; Chabal, Yves J

    2016-03-09

    The ability to selectively chemically functionalize silicon nitride (Si3N4) or silicon dioxide (SiO2) surfaces after cleaning would open interesting technological applications. In order to achieve this goal, the chemical composition of surfaces needs to be carefully characterized so that target chemical reactions can proceed on only one surface at a time. While wet-chemically cleaned silicon dioxide surfaces have been shown to be terminated with surficial Si-OH sites, chemical composition of the HF-etched silicon nitride surfaces is more controversial. In this work, we removed the native oxide under various aqueous HF-etching conditions and studied the chemical nature of the resulting Si3N4 surfaces using infrared absorption spectroscopy (IRAS), x-ray photoelectron spectroscopy (XPS), low energy ion scattering (LEIS), and contact angle measurements. We find that HF-etched silicon nitride surfaces are terminated by surficial Si-F and Si-OH bonds, with slightly subsurface Si-OH, Si-O-Si, and Si-NH2 groups. The concentration of surficial Si-F sites is not dependent on HF concentration, but the distribution of oxygen and Si-NH2 displays a weak dependence. The Si-OH groups of the etched nitride surface are shown to react in a similar manner to the Si-OH sites on SiO2, and therefore no selectivity was found. Chemical selectivity was, however, demonstrated by first reacting the -NH2 groups on the etched nitride surface with aldehyde molecules, which do not react with the Si-OH sites on a SiO2 surface, and then using trichloro-organosilanes for selective reaction only on the SiO2 surface (no reactivity on the aldehyde-terminated Si3N4 surface).

  3. Surface etching, chemical modification and characterization of silicon nitride and silicon oxide—selective functionalization of Si3N4 and SiO2

    NASA Astrophysics Data System (ADS)

    Liu, Li-Hong; Michalak, David J.; Chopra, Tatiana P.; Pujari, Sidharam P.; Cabrera, Wilfredo; Dick, Don; Veyan, Jean-François; Hourani, Rami; Halls, Mathew D.; Zuilhof, Han; Chabal, Yves J.

    2016-03-01

    The ability to selectively chemically functionalize silicon nitride (Si3N4) or silicon dioxide (SiO2) surfaces after cleaning would open interesting technological applications. In order to achieve this goal, the chemical composition of surfaces needs to be carefully characterized so that target chemical reactions can proceed on only one surface at a time. While wet-chemically cleaned silicon dioxide surfaces have been shown to be terminated with surficial Si-OH sites, chemical composition of the HF-etched silicon nitride surfaces is more controversial. In this work, we removed the native oxide under various aqueous HF-etching conditions and studied the chemical nature of the resulting Si3N4 surfaces using infrared absorption spectroscopy (IRAS), x-ray photoelectron spectroscopy (XPS), low energy ion scattering (LEIS), and contact angle measurements. We find that HF-etched silicon nitride surfaces are terminated by surficial Si-F and Si-OH bonds, with slightly subsurface Si-OH, Si-O-Si, and Si-NH2 groups. The concentration of surficial Si-F sites is not dependent on HF concentration, but the distribution of oxygen and Si-NH2 displays a weak dependence. The Si-OH groups of the etched nitride surface are shown to react in a similar manner to the Si-OH sites on SiO2, and therefore no selectivity was found. Chemical selectivity was, however, demonstrated by first reacting the -NH2 groups on the etched nitride surface with aldehyde molecules, which do not react with the Si-OH sites on a SiO2 surface, and then using trichloro-organosilanes for selective reaction only on the SiO2 surface (no reactivity on the aldehyde-terminated Si3N4 surface).

  4. SiC Technology

    NASA Technical Reports Server (NTRS)

    Neudeck, Philip G.

    1998-01-01

    Silicon carbide (SiC)-based semiconductor electronic devices and circuits are presently being developed for use in high-temperature, high-power, and/or high-radiation conditions under which conventional semiconductors cannot adequately perform. Silicon carbide's ability to function under such extreme conditions is expected to enable significant improvements to a far-ranging variety of applications and systems. These range from greatly improved high-voltage switching [1- 4] for energy savings in public electric power distribution and electric motor drives to more powerful microwave electronics for radar and communications [5-7] to sensors and controls for cleaner-burning more fuel-efficient jet aircraft and automobile engines. In the particular area of power devices, theoretical appraisals have indicated that SiC power MOSFET's and diode rectifiers would operate over higher voltage and temperature ranges, have superior switching characteristics, and yet have die sizes nearly 20 times smaller than correspondingly rated silicon-based devices [8]. However, these tremendous theoretical advantages have yet to be realized in experimental SiC devices, primarily due to the fact that SiC's relatively immature crystal growth and device fabrication technologies are not yet sufficiently developed to the degree required for reliable incorporation into most electronic systems [9]. This chapter briefly surveys the SiC semiconductor electronics technology. In particular, the differences (both good and bad) between SiC electronics technology and well-known silicon VLSI technology are highlighted. Projected performance benefits of SiC electronics are highlighted for several large-scale applications. Key crystal growth and device-fabrication issues that presently limit the performance and capability of high temperature and/or high power SiC electronics are identified.

  5. Kinetics study of the evolution of oxygen-related defects in mono-crystalline silicon subjected to electron-irradiation and thermal treatment

    NASA Astrophysics Data System (ADS)

    Quemener, V.; Raeissi, B.; Herklotz, F.; Murin, L. I.; Monakhov, E. V.; Svensson, B. G.

    2015-10-01

    The diffusion and dissociation mechanisms governing the evolution of oxygen and vacancy-oxygen defects in Czochralski-grown Si samples have been studied. The samples were irradiated at (i) room temperature or (ii) elevated temperature (350 °C) by MeV electrons and then isothermally annealed at 8 different temperatures in the range of 300 °C to 500 °C. The evolution of the concentrations of oxygen complexes (On, n ≤ 3) and mono-vacancy-oxygen defects (VOn, n ≤ 4) have been followed by infrared absorption measurements of local vibrational modes originating from the individual defects. The experimental kinetics data have been compared with simulation results based on the theory for diffusion limited reactions, assuming a model where sequential build-up of the VOn defects is a key ingredient. A close quantitative agreement is obtained for both sets of samples despite quite different initial conditions prior to the annealing, which adds evidence to the validity of the model. Values for the diffusivity and dissociation rates of VOn (n ≤ 4) and On (n ≤ 3) have been deduced and in general, the mobility and stability of VOn decrease and increase with n, respectively. For all the defects, partial dissociation appears as a prevailing process during diffusion, while full dissociation of VOn is limited by an energy barrier identical to that of interstitial oxygen (Oi) diffusion (˜2.55 eV). The oxygen dimer and trimer are fast diffusers but slower than substitutional oxygen, i.e., VO; VO is found to be the most mobile species, whilst Oi is the slowest one with a difference in diffusivity of up to 7 orders of magnitude in the studied temperature range.

  6. Kinetics study of the evolution of oxygen-related defects in mono-crystalline silicon subjected to electron-irradiation and thermal treatment

    SciTech Connect

    Quemener, V. Raeissi, B.; Herklotz, F.; Monakhov, E. V.; Svensson, B. G.

    2015-10-07

    The diffusion and dissociation mechanisms governing the evolution of oxygen and vacancy-oxygen defects in Czochralski-grown Si samples have been studied. The samples were irradiated at (i) room temperature or (ii) elevated temperature (350 °C) by MeV electrons and then isothermally annealed at 8 different temperatures in the range of 300 °C to 500 °C. The evolution of the concentrations of oxygen complexes (O{sub n}, n ≤ 3) and mono-vacancy-oxygen defects (VO{sub n}, n ≤ 4) have been followed by infrared absorption measurements of local vibrational modes originating from the individual defects. The experimental kinetics data have been compared with simulation results based on the theory for diffusion limited reactions, assuming a model where sequential build-up of the VO{sub n} defects is a key ingredient. A close quantitative agreement is obtained for both sets of samples despite quite different initial conditions prior to the annealing, which adds evidence to the validity of the model. Values for the diffusivity and dissociation rates of VO{sub n} (n ≤ 4) and O{sub n} (n ≤ 3) have been deduced and in general, the mobility and stability of VO{sub n} decrease and increase with n, respectively. For all the defects, partial dissociation appears as a prevailing process during diffusion, while full dissociation of VO{sub n} is limited by an energy barrier identical to that of interstitial oxygen (O{sub i}) diffusion (∼2.55 eV). The oxygen dimer and trimer are fast diffusers but slower than substitutional oxygen, i.e., VO; VO is found to be the most mobile species, whilst O{sub i} is the slowest one with a difference in diffusivity of up to 7 orders of magnitude in the studied temperature range.

  7. Low surface energy and corrosion resistant ultrathin TiSiC disk overcoat

    NASA Astrophysics Data System (ADS)

    Rose, F.; Pocker, D.; Xiao, Q.-F.; Rawat, V.; Brinkman, E.; Marchon, B.

    2013-06-01

    Ultra-thin films of titanium silicon carbide (TiSiC) were deposited by magnetron sputtering (using Ti2SiC3 targets) to form protection overcoats (OCs) onto magnetic recording media of hard disk drives. The chemico-physical properties (composition, optical constants, electrical resistivity, mass density, and surface energy) of titanium silicon nitride (TiSiN) films were measured and correlated to their OC performances in terms of protection against Si oxidation, Co corrosion, and Co diffusion. Performances of TiSiC OCs were compared to those of silicon carbide (SiC), silicon nitride (SiN), and TiSiN OCs. It was found that Ti incorporation into SiC and SiN considerably densifies the films, reduces their surface energy, and renders them more metallic. 25 Å thick TiSiC OC forms stable protecting barriers than can sustain hydrolysis conditions without growth of surface silicon oxide or cobalt diffusion or oxidation in the underlying recording magnetic medium. Overall, TiSiC OCs outperformed TiSiN, SiC, and SiN OCs as disk protection layers. We could directly correlate good protection against surface silicon oxide formation with film's lower surface energy, and good protection against Co diffusion with film's higher mass density.

  8. Synthesis and characterization of Si-SiO 2 nanocomposites

    NASA Astrophysics Data System (ADS)

    Zhou, W. M.; Liu, X.; Zhang, Y. F.; Lai, Y. J.; Guo, X. Q.

    2007-01-01

    The bulk SiC/SiO 2 nanocomposites were synthesized without the presence of catalyst by high-frequency induction heating of SiO and activated carbon fibers in the temperature of 1400 °C for 20 min. The as-synthesized materials exhibit the morphologies of self-assembly nanograss, nanocolumn and Pine-tree-branch-like nanostructure. The Si-SiO 2 nanocomposites would open up new opportunities for fundamental nanodevice studies and applications.

  9. Ultralow Resistivity Ge:Sb heterostructures on Si Using Hydride Epitaxy of Deuterated Stibine and Trigermane.

    PubMed

    Xu, Chi; Senaratne, Charutha L; Sims, Patrick; Kouvetakis, John; Menéndez, José

    2016-09-14

    The nonconventional deuterated stibine (SbD3) compound has been used for the first time in combination with trigermane (Ge3H8) to produce hyper-doped Ge-on-Si films with carrier concentrations n > 10(20) cm(-3) and record-low resistivities ρ = 1.8 × 10(-4) Ω cm. The growth takes place on Ge and Ge1-xSix buffered Si(100) wafers at ultralow temperatures (∼330 °C) at which Sb diffusion is negligible, leading to extremely flat atomic profiles of the constituents. The Sb substitution in the Ge lattice is determined by RBS channeling and corroborated by high-resolution XRD, which also reveal a systematic increase in lattice constant vs concentration, as expected due to the incorporation of the larger Sb. High-resolution TEM illustrates defect-free monocrystalline structures with device-quality morphologies. The electrical characteristics of the samples are measured using Hall effect and resistivity measurements combined with contactless infrared ellipsometry and are found to be consistent with an extrapolation of the bulk Ge:Sb properties to the high carrier concentrations achieved in our films. The Sb/Ge ratio in the doped layers is approximately the same as that in the precursor reaction mixture, indicating a highly efficient Sb incorporation afforded by the compatible reactivity of the molecules employed in this study. The resultant films are attractive for next generation germanium technologies that require low-resistance n+ junctions or a Fermi level that approaches the direct gap minimum in the conduction band, which drastically enhances the optical emission efficiency of n-type Ge.

  10. Interfacial reaction of eutectic AuSi solder with Si (100) and Si (111) surfaces

    NASA Astrophysics Data System (ADS)

    Jang, Jin-Wook; Hayes, Scott; Lin, Jong-Kai; Frear, Darrel R.

    2004-06-01

    The dissolution behavior of Si (100) and (111) dies by eutectic AuSi solder was investigated. On the Si (100) surface, the dissolution primarily occurred by the formation of craters resulting in a rough surface. The dissolution of the Si (111) resulted in a relatively smooth surface. The morphology of the Si (100) surface during a AuSi soldering reaction exhibited more time-dependent behavior and the etching craters on a Si (100) surface grew larger with time whereas Si (111) did not significantly change. This difference was ascribed to the surface energy differences between Si (111) and (100) surfaces that resulted in the two- and three-dimensional dissolution behaviors, respectively. This difference plays an important role in the formation of voids during the AuSi die bonding. The etching craters on Si (100) act as a AuSi solder sink and the regions surrounded by etch pits tend to become voids. For Si (111), flat surfaces were observed in the voided regions. Cross section analysis showed that no solder reaction occurred in the voided region of the Si (111) surface. This suggests the possibility of the formation of a thin inert layer in a potentially voided region prior to assembly. To achieve void-free die bonding, different parameters must be adjusted to the Si (100) and Si (111) surfaces with the AuSi alloy.

  11. Kapitza resistance of Si/SiO2 interface

    SciTech Connect

    Bowen Deng; Aleksandr Chenatynskiy; Marat Khafizov; David Hurley; Simon Phillpot

    2014-02-01

    A phonon wave packet dynamics method is used to characterize the Kapitza resistance of a Si/SiO2 interface in a Si/SiO2/Si heterostructure. By varying the thickness of SiO2 layer sandwiched between two Si layers, we determine the Kapitza resistance for the Si/SiO2 interface from both wave packet dynamics and a direct, non-equilibrium molecular dynamics approach. The good agreement between the two methods indicates that they have each captured the anharmonic phonon scatterings at the interface. Moreover, detailed analysis provides insights as to how individual phonon mode scatters at the interface and their contribution to the Kapitza resistance.

  12. Non-viral Methods for siRNA Delivery

    PubMed Central

    Gao, Kun; Huang, Leaf

    2009-01-01

    RNA interference (RNAi) as a mechanism to selectively degrade messenger RNA (mRNA) expression has emerged as a potential novel approach for drug target validation and the study of functional genomics. Small interfering RNAs (siRNA) therapeutics has developed rapidly and already there are clinical trials ongoing or planned. Although other challenges remain, delivery strategies for siRNA become the main hurdle that must be resolved prior to the full-scale clinical development of siRNA therapeutics. This article provides an overview of the current delivery strategies for synthetic siRNA, focusing on the targeted, self-assembled nanoparticles which show potential to become a useful and efficient tool in cancer therapy. PMID:19115957

  13. SI (Metric) handbook

    NASA Astrophysics Data System (ADS)

    Artusa, Elisa A.

    1994-03-01

    This guide provides information for an understanding of SI units, symbols, and prefixes; style and usage in documentation in both the US and in the international business community; conversion techniques; limits, fits, and tolerance data; and drawing and technical writing guidelines. Also provided is information of SI usage for specialized applications like data processing and computer programming, science, engineering, and construction. Related information in the appendixes include legislative documents, historical and biographical data, a list of metric documentation, rules for determining significant digits and rounding, conversion factors, shorthand notation, and a unit index.

  14. SI (Metric) handbook

    NASA Technical Reports Server (NTRS)

    Artusa, Elisa A.

    1994-01-01

    This guide provides information for an understanding of SI units, symbols, and prefixes; style and usage in documentation in both the US and in the international business community; conversion techniques; limits, fits, and tolerance data; and drawing and technical writing guidelines. Also provided is information of SI usage for specialized applications like data processing and computer programming, science, engineering, and construction. Related information in the appendixes include legislative documents, historical and biographical data, a list of metric documentation, rules for determining significant digits and rounding, conversion factors, shorthand notation, and a unit index.

  15. HIVsirDB: A Database of HIV Inhibiting siRNAs

    PubMed Central

    Thakur, Nishant; Sharma, Arun; Raghava, Gajendra P. S.; Kumar, Manoj

    2011-01-01

    Background Human immunodeficiency virus (HIV) is responsible for millions of deaths every year. The current treatment involves the use of multiple antiretroviral agents that may harm patients due to their toxic nature. RNA interference (RNAi) is a potent candidate for the future treatment of HIV, uses short interfering RNA (siRNA/shRNA) for silencing HIV genes. In this study, attempts have been made to create a database HIVsirDB of siRNAs responsible for silencing HIV genes. Descriptions HIVsirDB is a manually curated database of HIV inhibiting siRNAs that provides comprehensive information about each siRNA or shRNA. Information was collected and compiled from literature and public resources. This database contains around 750 siRNAs that includes 75 partially complementary siRNAs differing by one or more bases with the target sites and over 100 escape mutant sequences. HIVsirDB structure contains sixteen fields including siRNA sequence, HIV strain, targeted genome region, efficacy and conservation of target sequences. In order to facilitate user, many tools have been integrated in this database that includes; i) siRNAmap for mapping siRNAs on target sequence, ii) HIVsirblast for BLAST search against database, iii) siRNAalign for aligning siRNAs. Conclusion HIVsirDB is a freely accessible database of siRNAs which can silence or degrade HIV genes. It covers 26 types of HIV strains and 28 cell types. This database will be very useful for developing models for predicting efficacy of HIV inhibiting siRNAs. In summary this is a useful resource for researchers working in the field of siRNA based HIV therapy. HIVsirDB database is accessible at http://crdd.osdd.net/raghava/hivsir/. PMID:22022467

  16. LIQUID TARGET

    DOEpatents

    Martin, M.D.; Salsig, W.W. Jr.

    1959-01-13

    A liquid handling apparatus is presented for a liquid material which is to be irradiated. The apparatus consists essentially of a reservoir for the liquid, a target element, a drain tank and a drain lock chamber. The target is in the form of a looped tube, the upper end of which is adapted to be disposed in a beam of atomic particles. The lower end of the target tube is in communication with the liquid in the reservoir and a means is provided to continuously circulate the liquid material to be irradiated through the target tube. Means to heat the reservoir tank is provided in the event that a metal is to be used as the target material. The apparatus is provided with suitable valves and shielding to provide maximum safety in operation.

  17. Enhancing endosomal escape for nanoparticle mediated siRNA delivery

    NASA Astrophysics Data System (ADS)

    Ma, Da

    2014-05-01

    Gene therapy with siRNA is a promising biotechnology to treat cancer and other diseases. To realize siRNA-based gene therapy, a safe and efficient delivery method is essential. Nanoparticle mediated siRNA delivery is of great importance to overcome biological barriers for systemic delivery in vivo. Based on recent discoveries, endosomal escape is a critical biological barrier to be overcome for siRNA delivery. This feature article focuses on endosomal escape strategies used for nanoparticle mediated siRNA delivery, including cationic polymers, pH sensitive polymers, calcium phosphate, and cell penetrating peptides. Work has been done to develop different endosomal escape strategies based on nanoparticle types, administration routes, and target organ/cell types. Also, enhancement of endosomal escape has been considered along with other aspects of siRNA delivery to ensure target specific accumulation, high cell uptake, and low toxicity. By enhancing endosomal escape and overcoming other biological barriers, great progress has been achieved in nanoparticle mediated siRNA delivery.

  18. Fabrication of core-shell nanostructures via silicon on insulator dewetting and germanium condensation: towards a strain tuning method for SiGe-based heterostructures in a three-dimensional geometry.

    PubMed

    Naffouti, Meher; David, Thomas; Benkouider, Abdelmalek; Favre, Luc; Cabie, Martiane; Ronda, Antoine; Berbezier, Isabelle; Abbarchi, Marco

    2016-07-29

    We report on a novel method for the implementation of core-shell SiGe-based nanocrystals combining silicon on insulator dewetting in a molecular beam epitaxy reactor with an ex situ Ge condensation process. With an in situ two-step process (annealing and Ge deposition) we produce two families of islands on the same sample: Si-rich, formed during the first step and, all around them, Ge-rich formed after Ge deposition. By increasing the amount of Ge deposited on the annealed samples from 0 to 18 monolayers, the islands' shape in the Si-rich zones can be tuned from elongated and flat to more symmetric and with a larger vertical aspect ratio. At the same time, the spatial extension of the Ge-rich zones is progressively increased as well as the Ge content in the islands. Further processing by ex situ rapid thermal oxidation results in the formation of a core-shell composition profile in both Si and Ge-rich zones with atomically sharp heterointerfaces. The Ge condensation induces a Ge enrichment of the islands' shell of up to 50% while keeping a pure Si core in the Si-rich zones and a ∼25% SiGe alloy in the Ge-rich ones. The large lattice mismatch between core and shell, the absence of dislocations and the islands' monocrystalline nature render this novel class of nanostructures a promising device platform for strain-based band-gap engineering. Finally, this method can be used for the implementation of ultralarge scale meta-surfaces with dielectric Mie resonators for light manipulation at the nanoscale.

  19. Fabrication of core-shell nanostructures via silicon on insulator dewetting and germanium condensation: towards a strain tuning method for SiGe-based heterostructures in a three-dimensional geometry

    NASA Astrophysics Data System (ADS)

    Naffouti, Meher; David, Thomas; Benkouider, Abdelmalek; Favre, Luc; Cabie, Martiane; Ronda, Antoine; Berbezier, Isabelle; Abbarchi, Marco

    2016-07-01

    We report on a novel method for the implementation of core-shell SiGe-based nanocrystals combining silicon on insulator dewetting in a molecular beam epitaxy reactor with an ex situ Ge condensation process. With an in situ two-step process (annealing and Ge deposition) we produce two families of islands on the same sample: Si-rich, formed during the first step and, all around them, Ge-rich formed after Ge deposition. By increasing the amount of Ge deposited on the annealed samples from 0 to 18 monolayers, the islands’ shape in the Si-rich zones can be tuned from elongated and flat to more symmetric and with a larger vertical aspect ratio. At the same time, the spatial extension of the Ge-rich zones is progressively increased as well as the Ge content in the islands. Further processing by ex situ rapid thermal oxidation results in the formation of a core-shell composition profile in both Si and Ge-rich zones with atomically sharp heterointerfaces. The Ge condensation induces a Ge enrichment of the islands’ shell of up to 50% while keeping a pure Si core in the Si-rich zones and a ˜25% SiGe alloy in the Ge-rich ones. The large lattice mismatch between core and shell, the absence of dislocations and the islands’ monocrystalline nature render this novel class of nanostructures a promising device platform for strain-based band-gap engineering. Finally, this method can be used for the implementation of ultralarge scale meta-surfaces with dielectric Mie resonators for light manipulation at the nanoscale.

  20. Endotaxial Si nanolines in Si(001):H

    NASA Astrophysics Data System (ADS)

    Bianco, F.; Owen, J. H. G.; Köster, S. A.; Mazur, D.; Renner, Ch.; Bowler, D. R.

    2011-07-01

    We present a detailed study of the structural and electronic properties of a self-assembled silicon nanoline embedded in the H-terminated silicon (001) surface, known as the Haiku stripe. The nanoline is a perfectly straight and defect-free endotaxial structure of huge aspect ratio; it can grow micrometer long at a constant width of exactly four Si dimers (1.54 nm). Another remarkable property is its capacity to be exposed to air without suffering any degradation. The nanoline grows independently of any step edges at tunable densities from isolated nanolines to a dense array of nanolines. In addition to these unique structural characteristics, scanning tunneling microscopy and density functional theory reveal a one-dimensional state confined along the Haiku core. This nanoline is a promising candidate for the long-sought-after electronic solid-state one-dimensional model system to explore the fascinating quantum properties emerging in such reduced dimensionality.

  1. SI: The Stellar Imager

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth G.; Schrijver, Carolus J.; Karovska, Margarita

    2006-01-01

    The ultra-sharp images of the Stellar Imager (SI) will revolutionize our view of many dynamic astrophysical processes: The 0.1 milliarcsec resolution of this deep-space telescope will transform point sources into extended sources, and simple snapshots into spellbinding evolving views. SI s science focuses on the role of magnetism in the Universe, particularly on magnetic activity on the surfaces of stars like the Sun. SI s prime goal is to enable long-term forecasting of solar activity and the space weather that it drives in support of the Living With a Star program in the Exploration Era by imaging a sample of magnetically active stars with enough resolution to map their evolving dynamo patterns and their internal flows. By exploring the Universe at ultra-high resolution, SI will also revolutionize our understanding of the formation of planetary systems, of the habitability and climatology of distant planets, and of many magnetohydrodynamically controlled structures and processes in the Universe.

  2. U-Mo/Al-Si interaction: Influence of Si concentration

    NASA Astrophysics Data System (ADS)

    Allenou, J.; Palancher, H.; Iltis, X.; Cornen, M.; Tougait, O.; Tucoulou, R.; Welcomme, E.; Martin, Ph.; Valot, C.; Charollais, F.; Anselmet, M. C.; Lemoine, P.

    2010-04-01

    Within the framework of the development of low enriched nuclear fuels for research reactors, U-Mo/Al is the most promising option that has however to be optimised. Indeed at the U-Mo/Al interfaces between U-Mo particles and the Al matrix, an interaction layer grows under irradiation inducing an unacceptable fuel swelling. Adding silicon in limited content into the Al matrix has clearly improved the in-pile fuel behaviour. This breakthrough is attributed to an U-Mo/Al-Si protective layer around U-Mo particles appeared during fuel manufacturing. In this work, the evolution of the microstructure and composition of this protective layer with increasing Si concentrations in the Al matrix has been investigated. Conclusions are based on the characterization at the micrometer scale (X-ray diffraction and energy dispersive spectroscopy) of U-Mo7/Al-Si diffusion couples obtained by thermal annealing at 450 °C. Two types of interaction layers have been evidenced depending on the Si content in the Al-Si alloy: the threshold value is found at about 5 wt.% but obviously evolves with temperature. It has been shown that for Si concentrations ranging from 2 to 10 wt.%, the U-Mo7/Al-Si interaction is bi-layered and the Si-rich part is located close to the Al-Si for low Si concentrations (below 5 wt.%) and close to the U-Mo for higher Si concentrations. For Si weight fraction in the Al alloy lower than 5 wt.%, the Si-rich sub-layer (close to Al-Si) consists of U(Al, Si) 3 + UMo 2Al 20, when the other sub-layer (close to U-Mo) is silicon free and made of UAl 3 and U 6Mo 4Al 43. For Si weight concentrations above 5 wt.%, the Si-rich part becomes U 3(Si, Al) 5 + U(Al, Si) 3 (close to U-Mo) and the other sub-layer (close to Al-Si) consists of U(Al, Si) 3 + UMo 2Al 20. On the basis of these results and of a literature survey, a scheme is proposed to explain the formation of different types of ILs between U-Mo and Al-Si alloys (i.e. different protective layers).

  3. Reconsideration of in silico siRNA design from a perspective of heterogeneous data integration: problems and solutions.

    PubMed

    Liu, Qi; Zhou, Han; Zhu, Ruixin; Xu, Ying; Cao, Zhiwei

    2014-03-01

    The success of RNA interference (RNAi) depends on the interaction between short interference RNAs (siRNAs) and mRNAs. Design of highly efficient and specific siRNAs has become a challenging issue in applications of RNAi. Here, we present a detailed survey on the state-of-the-art siRNAs design, focusing on several key issues with the current in silico RNAi studies, including: (i) inconsistencies among the proposed guidelines for siRNAs design and the incomplete list of siRNAs features, (ii) improper integration of the heterogeneous cross-platform siRNAs data, (iii) inadequate consideration of the binding specificity of the target mRNAs and (iv) reduction in the 'off-target' effect in siRNAs design. With these considerations, the popular in silico siRNAs design rules are reexamined and several inconsistent viewpoints toward siRNAs feature identifications are clarified. In addition, novel computational models for siRNAs design using state-of-art machine learning techniques are discussed, which focus on heterogeneous data integration, joint feature selection and customized siRNAs screening toward highly specific targets. We believe that addressing such issues in siRNA study will provide new clues for further improved design of more efficient and specific siRNAs in RNAi.

  4. Gene silencing by chemically modified siRNAs.

    PubMed

    Engels, Joachim W

    2013-03-25

    RNA interference (RNAi) has not only already risen as a gold standard for validating gene function in basic science studies, but also holds great promise as a new therapeutic paradigm. Advantages of RNAi-based therapeutics include relatively fast initial screening and the ability to target proteins not yet addressable by traditional drug design strategies. In this review we describe the development of chemically modified small inhibiting siRNAs and their application as potential therapeutics during the past decade. Focus is on proper siRNA design, choice of chemical modification and how to circumvent immunogenicity as well as off-target effects.

  5. Helimagnetic order in bulk MnSi and CoSi/MnSi superlattices

    NASA Astrophysics Data System (ADS)

    Loh, G. C.; Khoo, K. H.; Gan, C. K.

    2017-01-01

    Skyrmions are nanoscopic whirls of spins that reside in chiral magnets. It is only fairly recent that a plethora of applications for these quasiparticles emerges, especially in data storage. On the other hand, spin spirals are the periodic analogs of skyrmions, and are equally imperative in the course of exploration to enhance our understanding of helimagnetism. In this study, a new infrastructure based on the B20 compound, MnSi is propounded as a hosting material for spin spirals; alternating thin layers of CoSi and MnSi in the superlattice form provides a facile way of varying the properties of the spin spirals across a continuum. Using first-principles calculations based on full-potential linearized augmented plane-wave (FLAPW)-based density functional theory (DFT), the spin order of bulk MnSi, MnSi film, and the CoSi/MnSi superlattice is investigated. Spin dispersion plots as a function of propagation vectors show that the spiral size changes in the presence of CoSi - we find that the size of the spiral is reduced in the superlattice with thin CoSi layers (CoSi:MnSi=1:1 thickness ratio), whilst at a larger CoSi:MnSi=2:1 thickness ratio, the material behaves as a ferromagnet. In a similar fashion, the spin moment and orbital occupancy depend significantly on the thickness of the CoSi layers. However, the exchange interaction between Mn atoms appears to be generally impervious to the presence of CoSi. Succinctly, the CoSi/MnSi superlattice could be an excellent functional material in data storage applications.

  6. Thermoelectric properties of BaSi2, SrSi2, and LaSi

    NASA Astrophysics Data System (ADS)

    Hashimoto, Kohsuke; Kurosaki, Ken; Imamura, Yasushi; Muta, Hiroaki; Yamanaka, Shinsuke

    2007-09-01

    We studied the thermoelectric properties of BaSi2, SrSi2, and LaSi. The polycrystalline samples were prepared by spark plasma sintering (SPS). The electrical resistivity (ρ), Seebeck coefficient (S), and thermal conductivity (κ) were measured above room temperature. The power factor (S2/ρ) is quite low (below 10-5 Wm-1 K-2 over the whole temperature range) for BaSi2 and LaSi, while relatively high (1.19×10-3 Wm-1 K-2 at 331 K) for SrSi2. BaSi2 exhibits quite low κ. The κ values at room temperature are 1.56, 5.25, and 6.71 Wm-1 K-1 for BaSi2, SrSi2, and LaSi, respectively. The maximum values of the dimensionless figure of merit, ZT =S2T/ρ/κ, are 0.01 at 954 K for BaSi2, 0.09 at 417 K for SrSi2, and 0.002 at 957 K for LaSi.

  7. Foreign Object Damage Resistance of Uncoated SiC/SiC Composites

    NASA Technical Reports Server (NTRS)

    Bhatt, R. T.; Choi, S. R.; Cosgriff, L. M.; Fox, D. S.; Lee, K. N.

    2005-01-01

    2-D woven SiC/SiC composites fabricated by melt infiltration method were impact tested at room temperature and at 1316 C in air using 1.59 mm steel-ball projectiles at projectile velocities ranging from 110 m/s to 400 m/s. The extent of substrate damage with increasing projectile velocity was imaged and analyzed using optical microscopy and nondestructive evaluation (NDE) methods. The impacted specimens were flexure and tensile tested at room temperature to determine their residual mechanical properties. Results indicate that as the projectile velocity increases, internal damage in the target material also increases and the mechanical properties degrade. At velocities > 300 m/s, the projectile penetrates through the target material, but it still retains approx. 50% ultimate strength of the as-fabricated composites and exhibits non-brittle failure.

  8. Long-Wavelength Stacked SiGe/Si Heterojunction Internal Photoemission Infrared Detectors Using Multiple SiGe/Si Layers

    NASA Technical Reports Server (NTRS)

    Park, J. S.; Lin, T. L.; Jones, E. W.; Castillo, H. M. Del; Gunapala, S. D.

    1994-01-01

    Utilizing low temperature silicon molecular beam epitaxy (MBE) growth, long-wavelength stacked SiGe/Si heterojunction internal photoemission (HIP) infrared detectors with multiple SiGe/Si layers have been fabricated and demonstrated. Using an elemental boron source, high doping concentrations (approximately equal to 4 x 10(sup 20) cm(sup -3)) has been achieved and high crystalline quality multiple Si(sub 0.7)Ge(sub 0.3)/Si layers have been obtained. The detector structure consists of several periods of degenerately boron doped (approximately equal to 4 x 10(sup 20) cm(sup -3)) thin (less than or equal to 50 u Si(sub 0.7)Ge(sub 0.3) layers and undoped thick (approximately equal to 300u Si layers. The multiple p(sup +) - Si(sub 0.7)Ge(sub 0.3)/undoped-Si layers show strong infrared absorption in the long-wavelength regime mainly through free carrier absorption. The stacked Si(sub 0.7)Ge(sub 0.3)/Si HIP detectors with p = 4 x 10(sup 20) cm(sup -3) exhibit strong photoresponse at wavelengths ranging from 2 to 20 (micro)m with quantum efficiencies of about 4% and 1.5% at 10 and 15 (micro)m wavelengths, respectively. The detectors show near ideal thermionic-emission limited dark current characteristics.

  9. FeSi diffusion barriers in Fe/FeSi/Si/FeSi/Fe multilayers and oscillatory antiferromagnetic exchange coupling

    NASA Astrophysics Data System (ADS)

    Stromberg, F.; Bedanta, S.; Antoniak, C.; Keune, W.; Wende, H.

    2008-10-01

    We study the diffusion of 57Fe probe atoms in Fe/FeSi/Si/FeSi/Fe multilayers on Si(111) prepared by molecular beam epitaxy by means of 57Fe conversion electron Mössbauer spectroscopy (CEMS). We demonstrate that the application of FeSi boundary layers successfully inhibits the diffusion of 57Fe into the Si layer. The critical thickness for the complete prevention of Fe diffusion takes place at a nominal FeSi thickness of tFeSi = 10-12 Å, which was confirmed by the evolution of the isomer shift δ of the crucial CEM subspectrum. The formation of the slightly defective c-FeSi phase for thicker FeSi boundary layers (~20 Å) was confirmed by CEMS and reflection high-energy electron diffraction (RHEED). Ferromagnetic resonance (FMR) shows that, for tFeSi = 0-14 Å, the Fe layers in all samples are antiferromagnetically coupled and we observe an oscillatory antiferromagnetic coupling strength with FMR and superconducting quantum interference device (SQUID) magnetometry for varying FeSi thickness with a period of ~6 Å.

  10. Processing and Properties of SiC/MoSi2-SiC Composites Fabricated by Melt Infiltration

    NASA Technical Reports Server (NTRS)

    Bhatt, Ramakrishna T.; Hebsur, Mohan G.

    2000-01-01

    Hi-Nicalon SiC fiber reinforced MoSi2-SiC matrix composites (SiC/MoSi2-SiC) have been fabricated by the melt infiltration approach. The composite consists of approximately 60 vol%, 2-D woven BN/SiC coated Hi-Nicalon SiC fibers and approximately 40 vol% MoSi2-SiC matrix. The room temperature tensile properties and thermal conductivity of the SiC/MoSi2-SiC composites were measured and compared with those of the melt infiltrated SiC/SiC composites. The influence oi fiber architecture on tensile properties was also evaluated. Results indicate that the primary modulus, stress corresponding to deviation from linearity, and transverse thermal conductivity values for the SiC/MoSi2-SiC composites are significantly lower than those for the SiC/SiC composites. Microcracking of the matrix due to the large difference in thermal expansion between MoSi2 and SiC appears to be the reason for the lower matrix dominated properties of SiC/MoSi2-SiC composites.

  11. Near interface oxide degradation in high temperature annealed Si/SiO{sub 2}/Si structures

    SciTech Connect

    Devine, R.A.B.; Mathiot, D.; Warren, W.L.; Fleetwood, D.M.

    1993-12-31

    Degradation of 430 nm thick SiO{sub 2} layers in Si/SiO{sub 2}/Si structures which results from high temperature annealing (1320 C) has been studied using electron spin resonance, infra-red and refractive index measurements. Large numbers of oxygen vacancies are found in a region {le}100 nm from each Si/SiO{sub 2} interface. Two types of paramagnetic defects are observed following {gamma} or x-irradiation or hole injection. The 1106 cm{sup {minus}1} infra-red absorption associated with O interstitials in the Si substrate is found to increase with annealing time. The infra-red and spin resonance observations can be explained qualitatively and quantitatively in terms of a model in which oxygen atoms are gettered from the oxide into the under or overlying Si, the driving force being the increased O solubility limit associated with the anneal temperature.

  12. SiC formation for a solar cell passivation layer using an RF magnetron co-sputtering system

    PubMed Central

    2012-01-01

    In this paper, we describe a method of amorphous silicon carbide film formation for a solar cell passivation layer. The film was deposited on p-type silicon (100) and glass substrates by an RF magnetron co-sputtering system using a Si target and a C target at a room-temperature condition. Several different SiC [Si1-xCx] film compositions were achieved by controlling the Si target power with a fixed C target power at 150 W. Then, structural, optical, and electrical properties of the Si1-xCx films were studied. The structural properties were investigated by transmission electron microscopy and secondary ion mass spectrometry. The optical properties were achieved by UV-visible spectroscopy and ellipsometry. The performance of Si1-xCx passivation was explored by carrier lifetime measurement. PMID:22221730

  13. Positron diffusion in Si

    SciTech Connect

    Nielsen, B.; Lynn, K.G.; Vehanen, A.; Schultz, P.J.

    1985-06-01

    Positron diffusion in Si(100) and Si(111) has been studied using a variable energy positron beam. The positron diffusion coefficient is found to be D/sub +/ = 2.7 +- 0.3 cm/sup 2//sec using a Makhov-type positron implantation profile, which is demonstrated to fit the data more reliably than the more commonly applied exponential profile. The diffusion related parameter, E/sub 0/, which results from the exponential profile, is found to be 4.2 +- 0.2 keV, significantly longer than previously reported values. A drastic reduction in E/sub 0/ is found after annealing the sample at 1300 K, showing that previously reported low values of E/sub 0/ are probably associated with the thermal history of the sample.

  14. Large Area and Depth-Profiling Dislocation Imaging and Strain Analysis in Si/SiGe/Si Heterostructures

    DTIC Science & Technology

    2014-01-01

    by high-resolution X-ray 387 diffraction. In Characterization of Semiconductor Heterostructures 388and Nanostructures , Lamberti C. (Ed.), pp. 93–132...combined advantage of Si semiconductor 29 technology and band gap engineering (Kittler et al., 1995). 30 Inside the Si/SiGe/Si heterostructure , SiGe is...and Depth-Profiling Dislocation Imaging and Strain Analysis in Si/SiGe/Si Heterostructures Report Title We demonstrate the combined use of large area

  15. Brazing SiC/SiC Composites to Metals

    NASA Technical Reports Server (NTRS)

    Steffier, Wayne S.

    2004-01-01

    Experiments have shown that active brazing alloys (ABAs) can be used to join SiC/SiC composite materials to metals, with bond strengths sufficient for some structural applications. The SiC/SiC composite coupons used in the experiments were made from polymerbased SiC fiber preforms that were chemical-vapor-infiltrated with SiC to form SiC matrices. Some of the metal coupons used in the experiments were made from 304 stainless steel; others were made from oxygen-free, high-conductivity copper. Three ABAs were chosen for the experiments: two were chosen randomly from among a number of ABAs that were on hand at the time; the third ABA was chosen because its titanium content (1.25 percent) is less than those of the other two ABAs (1.75 and 4.5 percent, respectively) and it was desired to evaluate the effect of reducing the titanium content, as described below. The characteristics of ABAs that are considered to be beneficial for the purpose of joining SiC/SiC to metal include wettability, reactivity, and adhesion to SiC-based ceramics. Prior to further development, it was verified that the three chosen ABAs have these characteristics. For each ABA, suitable vacuum brazing process conditions were established empirically by producing a series of (SiC/SiC)/ABA wetting samples. These samples were then sectioned and subjected to scanning electron microscopy (SEM) and energy-dispersive x-ray spectrometry (EDS) for analysis of their microstructures and compositions. Specimens for destructive mechanical tests were fabricated by brazing of lap joints between SiC/SiC coupons 1/8-in. (.3.2- mm) thick and, variously, stainless steel or copper tabs. The results of destructive mechanical tests and the SEM/EDS analysis were used to guide the development of a viable method of brazing the affected materials.

  16. Highly sensitive NIR PtSi/Si-nanostructure detectors

    NASA Astrophysics Data System (ADS)

    Li, Hua-gao; Guo, Pei; Yuan, An-bo; Long, Fei; Li, Rui-zhi; Li, Ping; Li, Yi

    2016-10-01

    We report a high external quantum efficiency (EQE) photodiode detector with PtSi/Si-nanostructures. Black silicon nanostructures were fabricated by metal-assist chemical etching (MCE), a 2 nm Pt layer was subsequently deposited on black silicon surface by DC magnetron sputtering system, and PtSi/Si-nanostructures were formed in vacuum annealing at 450 oC for 5 min. As the PtSi/Si-nanostructures presented a spiky shape, the absorption of incident light was remarkably enhanced for the repeat reflection and absorption. The breakdown voltage, dark current, threshold voltage and responsivity of the device were investigated to evaluate the performance of the PtSi/Si-nanostructures detector. The threshold voltage and dark currents of the PtSi/Si-nanostructure photodiode tends to be slightly higher than those of the standard diodes. The breakdown voltage remarkably was reduced because of existing avalanche breakdown in PtSi/Si-nanostructures. However, the photodiodes had high response at room temperature in near infrared region. At -5 V reverse bias voltage, the responsivity was 0.72 A/W in 1064 nm wavelength, and the EQE was 83.9%. By increasing the reverse bias voltage, the responsivity increased. At -60 V reverse bias voltage, the responsivity was 3.5 A/W, and the EQE was 407.5%, which means the quantum efficiency of PtSi/Si-nanostructure photodiodes was about 10 times higher than that of a standard diode. Future research includes how to apply this technology to enhance the NIR sensitivity of image sensors, such as Charge Coupled Devices (CCD).

  17. SiC-Si interfacial thermal and mechanical properties of reaction bonded SiC/Si ceramic composites

    NASA Astrophysics Data System (ADS)

    Hsu, Chun-Yen; Deng, Fei; Karandikar, Prashant; Ni, Chaoying

    Reaction bonded SiC/Si (RBSC) ceramic composites are broadly utilized in military, semiconductor and aerospace industries. RBSC affords advanced specific stiffness, hardness and thermal. Interface is a key region that has to be considered when working with any composites. Both thermal and mechanical behaviors of the RBSC are highly dependent on the SiC-Si interface. The SiC-Si interface had been found to act as a thermal barrier in restricting heat transferring at room temperature and to govern the energy absorption ability of the RBSC. However, up to present, the role of the SiC-Si interface to transport heat at higher temperatures and the interfacial properties in the nanoscale have not been established. This study focuses on these critically important subjects to explore scientific phenomena and underlying mechanisms. The RBSC thermal conductivity with volume percentages of SiC at 80 and 90 vol% was measured up to 1,200 °C, and was found to decrease for both samples with increasing environmental temperature. The RBSC with 90 vol% SiC has a higher thermal conductivity than that of the 80 vol%; however, is still significantly lower than that of the SiC. The interfacial thermal barrier effect was found to decrease at higher temperatures close 1200 °C. A custom-made in-situ tensile testing device which can be accommodated inside a ZEISS Auriga 60 FIB/SEM has been setup successfully. The SiC-Si interfacial bonding strength was measured at 98 MPa. The observation and analysis of crack propagation along the SiC-Si interface was achieved with in-situ TEM.

  18. Nanoscale η-NiSi formation via ion irradiation of Si/Ni/Si

    NASA Astrophysics Data System (ADS)

    Banu, Nasrin; Satpati, Biswarup; Bhukta, Anjan; Dev, B. N.

    2017-01-01

    Nickel monosilicide (NiSi) has emerged as an excellent material of choice for source-drain contact applications below 45 nm node complementary metal-oxide-semiconductor technology. We have investigated the formation of nanoscale NiSi by ion irradiation of Si (˜5 nm)/Ni(˜15 nm)/Si, grown in an ultrahigh vacuum environment. Irradiation was carried out at room temperature with 1 MeV Si+ ions. X-ray diffraction (XRD) and transmission electron microscopy (TEM) were employed for analysis. With increasing ion fluence, ion beam mixing occurs and more and more Si is incorporated into the Ni layer, and this layer gets amorphized. At an even higher fluence, a recrystallized uniform nickel monosilicide (η-NiSi) layer is formed. Several planar spacings of different Miller indices of η-NiSi have been observed in XRD and TEM. Additionally, an interesting amorphization and recrystallization behavior has been observed in the substrate Si with increasing ion fluence. To our knowledge, this has never been observed in ion irradiation of bare Si in decades of work in this area. This kind of amorphization/recrystallization in Si is apparently Ni-induced. Irradiation displaces Ni and produces a distribution of Ni in amorphized Si. Irradiation at a higher fluence produces two recrystallized Si bands in amorphous Si with concomitant accumulation of Ni at the amorphous/crystalline interfaces. On a further increase in irradiation fluence, the recrystallized Si bands again pass through amorphization and recrystallization. The total thickness of recrystallized, as well as amorphous Si, shows an oscillatory behavior as a function of ion fluence.

  19. Nanofabricated SiO{sub 2}-Si-SiO{sub 2} Resonant Tunneling Diodes

    SciTech Connect

    FLEMING,JAMES G.; CHOW,KAI-CHEUNG; LIN,SHAWN-YU

    2000-04-06

    Resonance Tunneling Diodes (RTDs) are devices that can demonstrate very high-speed operation. Typically they have been fabricated using epitaxial techniques and materials not consistent with standard commercial integrated circuits. The authors report here the first demonstration of SiO{sub 2}-Si-SiO{sub 2} RTDs. These new structures were fabricated using novel combinations of silicon integrated circuit processes.

  20. Non-Catalytic RISCs and Kinetics Determine Mammalian siRNA Sub-Cellular Localization.

    PubMed

    Ji, Fengmin; Liu, Lianyun; Tien, Ya-Hsin; Peng, Yi-Hsien; Lee, Hoong-Chien

    2015-01-01

    Small interfering RNAs (siRNAs) are fundamental to the regulation of cell function. Much is known about its gene interfering mechanism, but a kinetic description of it is still lacking. Here, we derived a set of reaction-diffusion equations for multiple RNA-induced silencing complex (RISC) pathways that give quantitative temporal and spatial descriptions of the siRNA process in mammalian cell, and are able to correctly describe all salient experimentally observed patterns of sub-cellular siRNA localization, including those that, at first glance, appear irreconcilable. These results suggest siRNA sub-cellular localization mainly concerns the non-catalytic RISC-target complex, and is caused by the selectiveness of RISC-target interaction and the permeability of the nuclear membrane to siRNA strands but not to RISC-target complexes. Our method is expected to be useful in devising RNAi based cell regulation strategies.

  1. Technologies for Controlled, Local Delivery of siRNA

    PubMed Central

    Sarett, Samantha M.; Nelson, Christopher E.; Duvall, Craig L.

    2015-01-01

    The discovery of RNAi in the late 1990s unlocked a new realm of therapeutic possibilities by enabling potent and specific silencing of theoretically any desired genetic target. Better elucidation of the mechanism of action, the impact of chemical modifications that stabilize and reduce nonspecific effects of siRNA molecules, and the key design considerations for effective delivery systems has spurred progress toward developing clinically-successful siRNA therapies. A logical aim for initial siRNA translation is local therapies, as delivering siRNA directly to its site of action helps to ensure that a sufficient dose reaches the target tissue, lessens the potential for off-target side effects, and circumvents the substantial systemic delivery barriers. While topical siRNA delivery has progressed into numerous clinical trials, an enormous opportunity also exists to develop sustained-release, local delivery systems that enable both spatial and temporal control of gene silencing. This review focuses on material platforms that establish both localized and controlled gene silencing, with emphasis on the systems that show most promise for clinical translation. PMID:26476177

  2. siRNA and cancer immunotherapy.

    PubMed

    Ghafouri-Fard, Soudeh; Ghafouri-Fard, Somayyeh

    2012-09-01

    Immunotherapeutic approaches have been gaining attention in the field of cancer treatment because of their possible ability to eradicate cancer cells as well as metastases by recruiting the host immune system. On the other hand, RNA-based therapeutics with the ability to silence expression of specific targets are currently under clinical investigation for various disorders including cancer. As the mechanisms of tumor evasion from the host immune system are versatile, different molecules have the capacity to be targeted by RNAi technology in order to enhance the immune response against tumors. This technology has been used to silence specific targets in tumor cells, as well as immune cells in cancer cell lines, animal models and clinical trials. siRNAs can also stimulate innate immune responses through activation of Toll-like receptors. Although currently clinical trials of the application of siRNA in cancer immunotherapy are few, it is predicted that in future this technology will be used broadly in cancer treatment.

  3. .Si≡Si3 defect at thermally grown (111)Si/Si3N4 interfaces

    NASA Astrophysics Data System (ADS)

    Stesmans, A.; van Gorp, G.

    1995-09-01

    Electron-spin resonance on various dehydrogenated (111)Si/(oxy)nitride structures, thermally grown at 1000-1150 °C in NH3, reveals the presence of two defects. The major one, called PbN, is identified as a Si dangling bond (.Si≡Si3) at the (111)Si/nitride interface aligned perpendicular to the interface; x-ray photoelectron spectroscopy actually shows that the in situ removal of the native Si oxide prior to nitridation is a prerequisite to obtaining stoichiometric Si3N4 films. The identification is based on strong similarities with the Pb defect at the (111)Si/SiO2 interface, such as the g matrix, the location at the interface, and linewidth anisotropy. This observation of the .Si≡Si3 defect at a natural Si/solid interface other than the Si/SiO2 one confirms Pb as a prototype dangling-bond center, its salient properties being set by the underside Si matrix-not by the overlaying insulator. Yet, secondary ESR signatures do differ as the large interface strain, resulting from the greater rigidity of the (oxy)nitrides as compared to SiO2 films, causes a slight perturbation of the Pb(N) symmetry, thereby lifting its C3v symmetry. This is born out at 4.3 K by specific distortions of the PbN line shape. Upon increasing temperature, the perturbation of the defect's symmetry is smoothed due to thermally activated averaging over the various defect distortions. The properties of the Pb and PbN defects at higher temperatures become largely identical. Comparison of the extracted unresolved 14N PbN and 17O Pb hf broadenings shows that their relative strengths comply with the known isotopic properties. A second defect, the intrinsic K center (.Si≡N3), with isotropic g=2.0028+/-0.0001, is observed only in stoichiometric Si3N4 films.

  4. Research needs of c-Si technology required to meet roadmap milestones

    SciTech Connect

    RUBY,DOUGLAS S.; CISZEK,T.F.; SOPORI,B.L.

    2000-04-22

    In this paper, the authors examined the areas in c-Si growth, materials, and processing that require improvement through research to overcome barriers to the implementation of the photovoltaic road maps's Si goals. To obtain PV module throughput to the roadmap target of 200 MW/factory/year, the typical Si PV factory must produce >4,000 m{sup 2}/day of silicon.

  5. Mechanical properties, stress evolution and high-temperature thermal stability of nanolayered Mo{endash}Si{endash}N/SiC thin films

    SciTech Connect

    Torri, P.; Hirvonen, J.; Kung, H.; Lu, Y.; Nastasi, M.; Gibson, P.N.

    1999-07-01

    A study of the microstructure, thermal stability, nanoindentation mechanical properties, and residual stress evolution of nanolayered Mo{endash}Si{endash}N/SiC thin films as a function of vacuum annealing time and temperature is reported. Multilayers of Mo{endash}Si{endash}N (MoSi{sub 2.2}N{sub 2.5}) and SiC were deposited by magnetron sputtering from planar MoSi{sub 2} and SiC targets onto single crystal silicon wafers. The relative amount of both components was varied (12.5{endash}50 vol.thinsp{percent} of SiC) while keeping the bilayer thickness constant (12 nm), or the bilayer thickness was varied (6{endash}24 nm) with constant Mo{endash}Si{endash}N to SiC ratio (25 vol.thinsp{percent} of SiC). Mechanical properties were measured by nanoindentation on as-deposited films and films annealed in vacuum at 500 and 900thinsp{degree}C. Microstructure and thermal stability were examined by cross-sectional transmission electron microscopy, glancing angle x-ray diffraction and nuclear resonance broadening. Stress evolution induced by thermal annealing was determined by measuring optically the change in curvature of coated silicon beams. In the as-deposited state, all films exhibited an amorphous microstructure. At 900thinsp{degree}C SiC still remained amorphous, but Mo{endash}Si{endash}N had developed a microstructure where nanocrystals of Mo{sub 5}Si{sub 3} were embedded in an amorphous matrix. The interface between Mo{endash}Si{endash}N and SiC was indirectly shown to be stable at least up to 41 h annealing at 1075thinsp{degree}C in vacuum. The potential of Mo{endash}Si{endash}N as a barrier layer against intermixing between nanolayered MoSi{sub 2} and SiC at 900thinsp{degree}C has been demonstrated. Hardness, modulus and residual stress followed the volume fraction rule of mixture of both constituents of the nanolayered Mo{endash}Si{endash}N/SiC structure. Consequently, by optimizing the volume fraction of the constituents, zero residual stress on a silicon substrate

  6. Tackling Targets.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    This document is designed to help British training and enterprise councils (TECs) and further education (FE) colleges develop and implement strategies for achieving the National Targets for Education and Training (NTET), which were developed by the Confederation of British Industry in 1992 and endorsed by the British government. The findings from…

  7. On Target.

    ERIC Educational Resources Information Center

    Barbalich, Andrea

    1991-01-01

    Campus public relations professionals offer advice for improving the effectiveness of public relations efforts by (1) setting behavioral goals; (2) targeting audiences carefully; (3) focusing appeals by making messages explicit; (4) connecting the public relations message with larger societal issues; and (5) reaching internal as well as external…

  8. Observations on Si-based micro-clusters embedded in TaN thin film deposited by co-sputtering with oxygen contamination

    SciTech Connect

    Lee, Young Mi; Jung, Min-Sang; Choi, Duck-Kyun E-mail: mcjung@oist.jp; Jung, Min-Cherl E-mail: mcjung@oist.jp

    2015-08-15

    Using scanning electron microscopy (SEM) and high-resolution x-ray photoelectron spectroscopy with the synchrotron radiation we investigated Si-based micro-clusters embedded in TaSiN thin films having oxygen contamination. TaSiN thin films were deposited by co-sputtering on fixed or rotated substrates and with various power conditions of TaN and Si targets. Three types of embedded micro-clusters with the chemical states of pure Si, SiO{sub x}-capped Si, and SiO{sub 2}-capped Si were observed and analyzed using SEM and Si 2p and Ta 4f core-level spectra were derived. Their different resistivities are presumably due to the different chemical states and densities of Si-based micro-clusters.

  9. Resistance behavior of Cr-Si-O thin films

    SciTech Connect

    Jankowski, A.F.; Hayes, J.P.; Musket, R.; Cosandey, F.; Gorla, C.E.; Besser, R.S.; Westerlind, V.; Cobai, G.

    1996-10-23

    Thin coatings of Cr-Si-O are assessed for use as a resistor. The submicron thick films are sputter deposited using a (l-x)Ar-(x)O{sub 2} working gas. Several compacts of metal and oxide powders are commercially prepared for use as the sputter targets. The deposition process yields film compositions which range from 2 to 30 at.% Cr and 20 to 45 at.% Si as measured using Rutherford backscattering. A broad range of resistivities from 10{sup 1} to 10{sup 14}{Omega} cm are found as measured through the film thickness between metal pads deposited onto the Cr-Si-O surface. The film structure and morphology are characterized using transmission electron microscopy from which the resistance behavior can be correlated to the distribution of metallic particles. Thermal aging reveals the metastability of the Cr- Si-O film morphology and resistance behavior.

  10. Development of SiC Large Tapered Crystal Growth

    NASA Technical Reports Server (NTRS)

    Neudeck, Phil

    2011-01-01

    Research Focus Area: Power Electronics, Temperature Tolerant Devices. Demonstrate initial feasibility of totally new "Large Tapered Crystal" (LTC) process for growing vastly improved large-diameter wide-band gap wafers. Addresses Targets: The goal of this research is to experimentally investigate and demonstrate feasibility of the key unproven LTC growth processes in SiC. Laser-assisted growth of long SiC fiber seeds. Radial epitaxial growth enlargement of seeds into large SiC boules. Uniqueness and Impacts open a new technology path to large-diameter SiC and GaN wafers with 1000-fold defect density improvement at 2-4 fold lower cost. Leapfrog improvement in wide band gap power device capability and cost.

  11. Constructing monocrystalline covalent organic networks by polymerization

    NASA Astrophysics Data System (ADS)

    Beaudoin, Daniel; Maris, Thierry; Wuest, James D.

    2013-10-01

    An emerging strategy for making ordered materials is modular construction, which connects preformed molecular subunits to neighbours through interactions of properly selected reactive sites. This strategy has yielded remarkable materials, including metal-organic frameworks joined by coordinative bonds, supramolecular networks linked by strong non-covalent interactions, and covalent organic frameworks in which atoms of carbon and other light elements are bonded covalently. However, the strategy has not yet produced covalently bonded organic materials in the form of large single crystals. Here we show that such materials can result from reversible self-addition polymerizations of suitably designed monomers. In particular, monomers with four tetrahedrally oriented nitroso groups polymerize to form diamondoid azodioxy networks that can be fully characterized by single-crystal X-ray diffraction. This work forges a strong new link between polymer science and supramolecular chemistry by showing how predictably ordered covalent or non-covalent structures can both be built using a single modular strategy.

  12. Dicetyl phosphate-tetraethylenepentamine-based liposomes for systemic siRNA delivery.

    PubMed

    Asai, Tomohiro; Matsushita, Saori; Kenjo, Eriya; Tsuzuku, Takuma; Yonenaga, Norihito; Koide, Hiroyuki; Hatanaka, Kentaro; Dewa, Takehisa; Nango, Mamoru; Maeda, Noriyuki; Kikuchi, Hiroshi; Oku, Naoto

    2011-03-16

    Dicetyl phosphate-tetraethylenepentamine (DCP-TEPA) conjugate was newly synthesized and formed into liposomes for efficient siRNA delivery. Formulation of DCP-TEPA-based polycation liposomes (TEPA-PCL) complexed with siRNA was examined by performing knockdown experiments using stable EGFP-transfected HT1080 human fibrosarcoma cells and siRNA for GFP. An adequate amount of DCP-TEPA in TEPA-PCL and N/P ratio of TEPA-PCL/siRNA complexes were determined based on the knockdown efficiency. Then, the biodistribution of TEPA-PCL modified with poly(ethylene glycol) (PEG) was examined in BALB/c mice. As a result, TEPA-PCL modified with PEG6000 avoided reticuloendothelial system uptake and showed long circulation in the bloodstream. On the other hand, PEGylation of TEPA-PCL/siRNA complexes caused dissociation of a portion of the siRNA from the liposomes. However, we found that the use of cholesterol-conjugated siRNA improved the interaction between TEPA-PCL and siRNA, which allowed PEGylation of TEPA-PCL/siRNA complexes without siRNA dissociation. In addition, TEPA-PCL complexed with cholesterol-conjugated siRNA showed potent knockdown efficiency in stable luciferase-transfected B16-F10 murine melanoma cells. Finally, the biodistribution of cholesterol-conjugated siRNA formulated in PEGylated TEPA-PCL was examined by performing near-infrared fluorescence imaging in Colon26 NL-17 murine carcinoma-bearing mice. Our results showed that tumor targeting with siRNA via systemic administration was achieved by using PEGylated TEPA-PCL combined with active targeting with Ala-Pro-Arg-Pro-Gly, a peptide used for targeting angiogenic endothelium.

  13. Chemical and structural diversity of siRNA molecules.

    PubMed

    Nawrot, Barbara; Sipa, Katarzyna

    2006-01-01

    Short interfering RNAs (siRNAs) are 21-23 nt long double-stranded oligoribonucleotides which in mammalian cells exhibit a potency for sequence-specific gene silencing via an RNA interference (RNAi) pathway. It has been already proven that exogenous, chemically synthesized siRNA molecules are effective inhibitors of gene expression and are widely applied for analysis of protein function and proteomics-based target identification. Moreover, since their discovery siRNA molecules have been implemented as potential candidates for therapeutic applications. Variously modified siRNA molecules containing sugar modifications (2'-OMe, -F, -O-allyl, -amino, orthoesters and LNA analogues), internucleotide phospodiester bond modifications (phosphorothioates, boranophosphates), base modifications (s(2)U) as well as 3'-terminal cholesterol-conjugated constructs were investigated as potential candidates for effective inhibition of gene expression. This chapter reviews an impact of chemical and structural modifications of siRNA molecules on their serum and thermal stability, cellular and in vivo activity, cellular uptake, biodistribution and cytotoxicity. Functional analysis of chemically modified siRNA molecules allows for better understanding of the mechanism of the RNA interference process as well as demonstrates immense efforts in optimizing in vivo potency of siRNA molecules for RNAi-based drug design.

  14. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    PubMed Central

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-01-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects. PMID:27457182

  15. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity

    NASA Astrophysics Data System (ADS)

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-07-01

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

  16. Local administration of siRNA through Microneedle: Optimization, Bio-distribution, Tumor Suppression and Toxicity.

    PubMed

    Tang, Tao; Deng, Yan; Chen, Jiao; Zhao, Yi; Yue, Ruifeng; Choy, Kwong Wai; Wang, Chi Chiu; Du, Quan; Xu, Yan; Han, Linxiao; Chung, Tony Kwok Hung

    2016-07-26

    Although RNA interference may become a novel therapeutic approach for cancer treatment, target-site accumulation of siRNA to achieve therapeutic dosage will be a major problem. Microneedle represents a better way to deliver siRNAs and we have evaluated for the first time the capability of a silicon microneedle array for delivery of Gapdh siRNA to the skin in vivo and the results showed that the microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. For the further study in this field, we evaluated the efficacy of the injectable microneedle device for local delivery of siRNA to the mouse xenograft. The results presented here indicate that local administration of siRNA through injectable microneedle could effectively deliver siRNA into the tumor region, and inhibit tumor progression without major adverse effects.

  17. Therapeutic siRNA: Principles, Challenges, and Strategies

    PubMed Central

    Gavrilov, Kseniya; Saltzman, W. Mark

    2012-01-01

    RNA interference (RNAi) is a remarkable endogenous regulatory pathway that can bring about sequence-specific gene silencing. If harnessed effectively, RNAi could result in a potent targeted therapeutic modality with applications ranging from viral diseases to cancer. The major barrier to realizing the full medicinal potential of RNAi is the difficulty of delivering effector molecules, such as small interfering RNAs (siRNAs), in vivo. An effective delivery strategy for siRNAs must address limitations that include poor stability and non-targeted biodistribution, while protecting against the stimulation of an undesirable innate immune response. The design of such a system requires rigorous understanding of all mechanisms involved. This article reviews the mechanistic principles of RNA interference, its potential, the greatest challenges for use in biomedical applications, and some of the work that has been done toward engineering delivery systems that overcome some of the hurdles facing siRNA-based therapeutics. PMID:22737048

  18. RNase non-sensitive and endocytosis independent siRNA delivery system: delivery of siRNA into tumor cells and high efficiency induction of apoptosis

    NASA Astrophysics Data System (ADS)

    Jiang, Xinglu; Wang, Guobao; Liu, Ru; Wang, Yaling; Wang, Yongkui; Qiu, Xiaozhong; Gao, Xueyun

    2013-07-01

    To date, RNase degradation and endosome/lysosome trapping are still serious problems for siRNA-based molecular therapy, although different kinds of delivery formulations have been tried. In this report, a cell penetrating peptide (CPP, including a positively charged segment, a linear segment, and a hydrophobic segment) and a single wall carbon nanotube (SWCNT) are applied together by a simple method to act as a siRNA delivery system. The siRNAs first form a complex with the positively charged segment of CPP via electrostatic forces, and the siRNA-CPP further coats the surface of the SWCNT via hydrophobic interactions. This siRNA delivery system is non-sensitive to RNase and can avoid endosome/lysosome trapping in vitro. When this siRNA delivery system is studied in Hela cells, siRNA uptake was observed in 98% Hela cells, and over 70% mRNA of mammalian target of rapamycin (mTOR) is knocked down, triggering cell apoptosis on a significant scale. Our siRNA delivery system is easy to handle and benign to cultured cells, providing a very efficient approach for the delivery of siRNA into the cell cytosol and cleaving the target mRNA therein.

  19. Absorption in a-Si/SiO2 Superlattices

    NASA Astrophysics Data System (ADS)

    Kilpelä, O.; Karppinen, M.; Novikov, S.; Sokolov, V.; Yliniemi, S.

    a-Si/SiO2 superlattices were grown on quartz by MBD (Molecular Beam Deposition) using in situ oxidation by an RF-plasma source. The a-Si layer thicknesses were varied from 0.5-2.5nm while the SiO2 layer thicknesses (1.0nm) were kept constant. Optical transmission and reflection measurements were performed on these samples at room temperature. The recorded spectra were then analyzed with a commercial optical thin film analysis program. The band gaps were derived from constant-n and non-constant-n forms of Tauc and Cody laws. The observed blueshift of the band gap, with decreasing a-Si layer thickness, is attributed to quantum confinement in the a-Si sublayers.

  20. Synthesis and characterization of laminated Si/SiC composites

    PubMed Central

    Naga, Salma M.; Kenawy, Sayed H.; Awaad, Mohamed; Abd El-Wahab, Hamada S.; Greil, Peter; Abadir, Magdi F.

    2012-01-01

    Laminated Si/SiC ceramics were synthesized from porous preforms of biogenous carbon impregnated with Si slurry at a temperature of 1500 °C for 2 h. Due to the capillarity infiltration with Si, both intrinsic micro- and macrostructure in the carbon preform were retained within the final ceramics. The SEM micrographs indicate that the final material exhibits a distinguished laminar structure with successive Si/SiC layers. The produced composites show weight gain of ≈5% after heat treatment in air at 1300 °C for 50 h. The produced bodies could be used as high temperature gas filters as indicated from the permeability results. PMID:25685404

  1. Study of Si/Si, Si/SiO sub 2 , and metal-oxide-semiconductor (MOS) using positrons

    SciTech Connect

    Leung, To Chi.

    1991-01-01

    A variable-energy positron beam is used to study Si/Si, Si/SiO{sub 2}, and metal-oxide-semiconductor (MOS) structures. The capability of depth resolution and the remarkable sensitivity to defects have made the positron annihilation technique a unique tool in detecting open-volume defects in the newly innovated low temperature (300C) molecular-beam-epitaxy (MBE) Si/Si. These two features of the positron beam have further shown its potential role in the study of the Si/SiO{sub 2}. Distinct annihilation characteristics has been observed at the interface and has been studied as a function of the sample growth conditions, annealing (in vacuum), and hydrogen exposure. The MOS structure provides an effective way to study the electrical properties of the Si/SiO{sub 2} interface as a function of applied bias voltage. The annihilation characteristics show a large change as the device condition is changed from accumulation to inversion. The effect of forming gas (FG) anneal is studied using positron annihilation and the result is compared with capacitance-voltage (C-V) measurements. The reduction in the number of interface states is found correlated with the changes in the positron spectra. The present study shows the importance of the positron annihilation technique as a non-contact, non-destructive, and depth-sensitive characterization tool to study the Si-related systems, in particular, the Si/SiO{sub 2} interface which is of crucial importance in semiconductor technology, and fundamental understanding of the defects responsible for degradation of the electrical properties.

  2. siMacro: A Fast and Easy Data Processing Tool for Cell-Based Genomewide siRNA Screens.

    PubMed

    Singh, Nitin Kumar; Seo, Bo Yeun; Vidyasagar, Mathukumalli; White, Michael A; Kim, Hyun Seok

    2013-03-01

    Growing numbers of studies employ cell line-based systematic short interfering RNA (siRNA) screens to study gene functions and to identify drug targets. As multiple sources of variations that are unique to siRNA screens exist, there is a growing demand for a computational tool that generates normalized values and standardized scores. However, only a few tools have been available so far with limited usability. Here, we present siMacro, a fast and easy-to-use Microsoft Office Excel-based tool with a graphic user interface, designed to process single-condition or two-condition synthetic screen datasets. siMacro normalizes position and batch effects, censors outlier samples, and calculates Z-scores and robust Z-scores, with a spreadsheet output of >120,000 samples in under 1 minute.

  3. Fabrication of lightweight Si/SiC LIDAR mirrors

    NASA Technical Reports Server (NTRS)

    Goela, Jitendra S.; Taylor, Raymond L.

    1991-01-01

    A new, chemical vapor deposition (CVD) process was developed for fabricating lightweight, polycrystalline silicon/silicon-carbide (Si/SiC) mirrors. The process involves three CVD steps: (1) to produce the mirror faceplate; (2) to form the lightweight backstructure, which is deposited integral to the faceplate; and (3) to deposit a layer of optical-grade material, e.g., Si, onto the front surface of the faceplate. The mirror figure and finish are fabricated into the faceplate.

  4. Bright photoluminescence from ordered arrays of SiGe nanowires grown on Si(111)

    PubMed Central

    Rowell, N L; Benkouider, A; Ronda, A; Favre, L; Berbezier, I

    2014-01-01

    Summary We report on the optical properties of SiGe nanowires (NWs) grown by molecular beam epitaxy (MBE) in ordered arrays on SiO2/Si(111) substrates. The production method employs Au catalysts with self-limited sizes deposited in SiO2-free sites opened-up in the substrate by focused ion beam patterning for the preferential nucleation and growth of these well-organized NWs. The NWs thus produced have a diameter of 200 nm, a length of 200 nm, and a Ge concentration x = 0.15. Their photoluminescence (PL) spectra were measured at low temperatures (from 6 to 25 K) with excitation at 405 and 458 nm. There are four major features in the energy range of interest (980–1120 meV) at energies of 1040.7, 1082.8, 1092.5, and 1098.5 meV, which are assigned to the NW-transverse optic (TO) Si–Si mode, NW-transverse acoustic (TA), Si–substrate–TO and NW-no-phonon (NP) lines, respectively. From these results the NW TA and TO phonon energies are found to be 15.7 and 57.8 meV, respectively, which agree very well with the values expected for bulk Si1− xGex with x = 0.15, while the measured NW NP energy of 1099 meV would indicate a bulk-like Ge concentration of x = 0.14. Both of these concentrations values, as determined from PL, are in agreement with the target value. The NWs are too large in diameter for a quantum confinement induced energy shift in the band gap. Nevertheless, NW PL is readily observed, indicating that efficient carrier recombination is occurring within the NWs. PMID:25671145

  5. Interface-structure of the Si/SiC heterojunction grown on 6H-SiC

    SciTech Connect

    Li, L. B.; Chen, Z. M.; Zang, Y.

    2015-01-07

    The Si/SiC heterojunctions were prepared on 6H-SiC (0001) C-face by low-pressure chemical vapour deposition at 850 ∼ 1050 °C. Transmission electron microscopy and selected area electron diffraction were employed to investigate the interface-structure of Si/SiC heterojunctions. The Si/6H-SiC heterostructure of large lattice-mismatch follows domain matching epitaxy mode, which releases most of the lattice-mismatch strain, and the coherent Si epilayers can be grown on 6H-SiC. Si(1-11)/6H-SiC(0001) heterostructure is obtained at 900 °C, and the in-plane orientation relationship of Si/6H-SiC heterostructure is (1–11)[1-1-2]{sub Si}//(0001)[-2110]{sub 6H-SiC}. The Si(1-11)/6H-SiC(0001) interface has the same 4:5 Si-to-SiC matching mode with a residual lattice-mismatch of 0.26% along both the Si[1-1-2] and Si[110] orientations. When the growth temperature increases up to 1000 °C, the 〈220〉 preferential orientation of the Si film appears. SAED patterns at the Si/6H-SiC interface show that the in-plane orientation relationship is (-220)[001]{sub Si}//(0001)[2-1-10]{sub 6H-SiC}. Along Si[110] orientation, the Si-to-SiC matching mode is still 4:5; along the vertical orientation Si[001], the Si-to-SiC mode change to approximate 1:2 and the residual mismatch is 1.84% correspondingly. The number of the atoms in one matching-period decreases with increasing residual lattice-mismatch in domain matching epitaxy and vice versa. The Si film grows epitaxially but with misfit dislocations at the interface between the Si film and the 6H-SiC substrate. And the misfit dislocation density of the Si(1-11)/6H-SiC(0001) and Si(-220)/6H-SiC(0001) obtained by experimental observations is as low as 0.487 × 10{sup 14 }cm{sup −2} and 1.217 × 10{sup 14 }cm{sup −2}, respectively, which is much smaller than the theoretical calculation results.

  6. SiGe/Si Monolithically Integrated Amplifier Circuits

    NASA Technical Reports Server (NTRS)

    Katehi, Linda P. B.; Bhattacharya, Pallab

    1998-01-01

    With recent advance in the epitaxial growth of silicon-germanium heterojunction, Si/SiGe HBTs with high f(sub max) and f(sub T) have received great attention in MMIC applications. In the past year, technologies for mesa-type Si/SiGe HBTs and other lumped passive components with high resonant frequencies have been developed and well characterized for circuit applications. By integrating the micromachined lumped passive elements into HBT fabrication, multi-stage amplifiers operating at 20 GHz have been designed and fabricated.

  7. Characterization of near-infrared n-type {beta}-FeSi{sub 2}/p-type Si heterojunction photodiodes at room temperature

    SciTech Connect

    Shaban, Mahmoud; Nomoto, Keita; Izumi, Shota; Yoshitake, Tsuyoshi

    2009-06-01

    n-type {beta}-FeSi{sub 2}/p-type Si heterojunctions were fabricated from {beta}-FeSi{sub 2} films epitaxially grown on Si(111) by facing-target direct-current sputtering. Sharp film-substrate interfaces were confirmed by scanning electron microscopy. The current-voltage and photoresponse characteristics were measured at room temperature. They exhibited good rectifying properties and a change of approximately one order of magnitude in the current at a bias voltage of -1 V under illumination by a 6 mW, 1.31 {mu}m laser. The estimated detectivity was 1.5x10{sup 9} cm {radical}Hz W at 1.31 {mu}m. The results suggest that the {beta}-FeSi{sub 2}/Si heterojunctions can be used as near-infrared photodetectors that are compatible with silicon integrated circuits.

  8. Target assembly

    DOEpatents

    Lewis, Richard A.

    1980-01-01

    A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

  9. Ultrasound targeted microbubble destruction for novel dual targeting of HSP72 and HSC70 in prostate cancer.

    PubMed

    Wang, Hang-Hui; Song, Yi-Xin; Bai, Min; Jin, Li-Fang; Gu, Ji-Ying; Su, Yi-Jin; Liu, Long; Jia, Chao; Du, Lian-Fang

    2014-01-01

    The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

  10. Microcrystalline silicon oxides for silicon-based solar cells: impact of the O/Si ratio on the electronic structure

    NASA Astrophysics Data System (ADS)

    Bär, M.; Starr, D. E.; Lambertz, A.; Holländer, B.; Alsmeier, J.-H.; Weinhardt, L.; Blum, M.; Gorgoi, M.; Yang, W.; Wilks, R. G.; Heske, C.

    2014-10-01

    of Si 3p - O 2p hybridization in the upper valence band. This coincides with a significant increase of the material's resistivity, possibly indicating the breakdown of the conducting crystalline Si network. Silicon oxide layers with a thickness of several hundred nanometres were deposited in a PECVD (plasma-enhanced chemical vapor deposition) multi chamber system using an excitation frequency of 13.56 MHz with a plasma power density of 0.3 W/cm2. Glass (Corning type Eagle) and mono-crystalline silicon wafer substrates were coated in the same run at a substrate temperature of 185°C. The deposition pressure was 4 mbar and the substrate-electrode distance 20 mm. Mixtures of silane (SiH4), 1% TMB (B(CH3)3) diluted in helium, hydrogen (H2), and carbon dioxide (CO2) gases were used at flow rates of 1.25 - 0.18/0.32/500/0 - 1.07) sccm (standard cubic centimeters per minute) for the deposition of μc-SiOx:H(B) layers. By changing the CO2/SiH4 gas flow rate ratio from 0 to 6, μc-SiOx:H(B) layers with a composition of 0 <= x = O/Si <= 1 were prepared using a constant sum of SiH4 and CO2. The TMB flow and the H2 flow were kept constant within the series. For more details see Ref. [1]. The oxygen content in the films was determined using Rutherford Backscattering Spectroscopy (RBS). With RBS, the area-related atomic density of oxygen and silicon can be determined (+/- 2% [2]), and thus x can be calculated. This quantity considers only the number of silicon / oxygen atoms and not the number of atoms of other elements, such as hydrogen, which is also incorporated to a considerable extent: up to 20% in μc-SiOx:H (measured using the hydrogen effusion method). To avoid charging effects, the measurements were performed on films deposited on a substrate of mono-crystalline silicon wafers. The electrical conductivity was measured in the planar direction of the film in a vacuum cryostat, using voltages from - 100 V to + 100 V. For that two co-planar Ag contacts were evaporated

  11. Current progress on aptamer-targeted oligonucleotide therapeutics

    PubMed Central

    Dassie, Justin P; Giangrande, Paloma H

    2014-01-01

    Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted. PMID:24304250

  12. Inherent paramagnetic defects in layered Si/SiO{sub 2} superstructures with Si nanocrystals

    SciTech Connect

    Jivanescu, M.; Stesmans, A.; Zacharias, M.

    2008-11-15

    An extensive electron spin resonance (ESR) analysis has been carried out on structures comprised of Si nanoparticles ({approx}2 nm across) embedded in a regular pattern in an amorphous SiO{sub 2} matrix, fabricated by the SiO/SiO{sub 2} superlattice approach, with the intent to reveal and quantify occurring paramagnetic defects. The as-grown state is found to exhibit only a Si dangling bond (DB) signal, which through combination of first and second harmonic X-, K-, and Q-band observations in combination with computer spectra simulation, could be conclusively disentangled as solely comprised of overlapping powder pattern spectra of P{sub b(0)} and P{sub b1} defects, the archetypal intrinsic defects of the Si/SiO{sub 2} interface, with no evidence for a D line (Si DBs in disordered Si). This indicates a full crystalline system of randomly oriented Si nanocrystals (NCs). The P{sub b(0)}/P{sub b1} defect system, pertaining to the NC-Si/SiO{sub 2} interfaces, is found to be both qualitatively and quantitatively much alike that of standard (high-quality) thermal Si/SiO{sub 2}. The system is inherent, remaining unaffected by subsequent UV/vacuum UV irradiations. Relying on the known properties of P{sub b}-type defects in standard microscopic Si/SiO{sub 2}, the data would comply with Si nanocrystallites, in average, predominantly bordered by (111) and (100) facets, perhaps with morphology, schematically, of [100] truncated (111) octahedrons. Based on independent NC particles counting, there appears a P{sub b}-type center at {approx}71% of the Si NCs indicating the latter to be comprised of two subsystems-with or without an incorporated strain relaxing interface defect-which in that case will exhibit drastically different defect-sensitive properties, such as, e.g., photoluminescence (PL). Upon additional optical irradiation, two more defects appear, i.e., the SiO{sub 2}-associated E{sub {gamma}}{sup '} and EX centers, where the observed density of the former, taken as

  13. Simple gene silencing using the trans-acting siRNA pathway.

    PubMed

    Jacobs, Thomas B; Lawler, Noah J; LaFayette, Peter R; Vodkin, Lila O; Parrott, Wayne A

    2016-01-01

    In plants, particular micro-RNAs (miRNAs) induce the production of a class of small interfering RNAs (siRNA) called trans-acting siRNA (ta-siRNA) that lead to gene silencing. A single miRNA target is sufficient for the production of ta-siRNAs, which target can be incorporated into a vector to induce the production of siRNAs, and ultimately gene silencing. The term miRNA-induced gene silencing (MIGS) has been used to describe such vector systems in Arabidopsis. Several ta-siRNA loci have been identified in soybean, but, prior to this work, few of the inducing miRNAs have been experimentally validated, much less used to silence genes. Nine ta-siRNA loci and their respective miRNA targets were identified, and the abundance of the inducing miRNAs varies dramatically in different tissues. The miRNA targets were experimentally verified by silencing a transgenic GFP gene and two endogenous genes in hairy roots and transgenic plants. Small RNAs were produced in patterns consistent with the utilization of the ta-siRNA pathway. A side-by-side experiment demonstrated that MIGS is as effective at inducing gene silencing as traditional hairpin vectors in soybean hairy roots. Soybean plants transformed with MIGS vectors produced siRNAs and silencing was observed in the T1 generation. These results complement previous reports in Arabidopsis by demonstrating that MIGS is an efficient way to produce siRNAs and induce gene silencing in other species, as shown with soybean. The miRNA targets identified here are simple to incorporate into silencing vectors and offer an effective and efficient alternative to other gene silencing strategies.

  14. Strategies for in vivo delivery of siRNAs: recent progress.

    PubMed

    Higuchi, Yuriko; Kawakami, Shigeru; Hashida, Mitsuru

    2010-06-01

    RNA interference (RNAi) is a post-transcriptional gene-silencing mechanism that involves the degradation of messenger RNA in a highly sequence-specific manner. Double-stranded small interfering RNA (siRNA), consisting of 21-25 nucleotides, can induce RNAi and inhibit the expression of target proteins. Therefore, siRNA is considered a promising therapeutic for treatment of a variety of diseases, including genetic and viral diseases, and cancer. Clinical trials of siRNA are ongoing or have been planned, although some issues need to be addressed. For example, cellular uptake of naked siRNA is extremely low due to its polyanionic nature. Furthermore, siRNA is easily degraded by enzymes in blood, tissues, and cells. Several types of chemically modified siRNA have been produced and investigated to improve stability; these have involved modification of the siRNA backbone, the sugar moiety, and the nucleotide bases of antisense and/or sense strands. Because the accumulation at the target site after administration is extremely low, even if stability is improved, an effective delivery system is required to induce RNAi at the site of action. Delivery strategies can be categorized into physical methods, conjugation methods, and drug delivery system carrier-mediated methods. Physical techniques can enhance siRNA uptake at a specific tissue site using electroporation, pressure, mechanical massage, etc. Terminal modification of siRNAs can enhance their resistance to degradation by exonucleases in serum and tissue. Moreover, modification with a suitable ligand can achieve targeted delivery. Several types of carrier for drug delivery have been developed for siRNA in addition to traditional cationic liposome and cationic polymer systems. Ultrasound and microbubbles or liposomal bubbles have also been used in combination with a carrier for siRNA delivery. New materials with unique characteristics such as carbon nanotubes, gold nanoparticles, and gold nanorods have attracted attention

  15. Accelerator target

    DOEpatents

    Schlyer, D.J.; Ferrieri, R.A.; Koehler, C.

    1999-06-29

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression. 5 figs.

  16. Accelerator target

    DOEpatents

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  17. Joining of SiC ceramics and SiC/SiC composites

    SciTech Connect

    Rabin, B.H.

    1996-08-01

    This project has successfully developed a practical and reliable method for fabricating SiC ceramic-ceramic joints. This joining method will permit the use of SiC-based ceramics in a variety of elevated temperature fossil energy applications. The technique is based on a reaction bonding approach that provides joint interlayers compatible with SiC, and excellent joint mechanical properties at temperatures exceeding 1000{degrees}C. Recent emphasis has been given to technology transfer activities, and several collaborative research efforts are in progress. Investigations are focusing on applying the joining method to sintered {alpha}-SiC and fiber-reinforced SiC/SiC composites for use in applications such as heat exchangers, radiant burners and gas turbine components.

  18. Joining of SiC ceramics and SiC/SiC composites

    SciTech Connect

    Rabin, B.H.

    1995-08-01

    This project has successfully developed a practical and reliable method for fabricating SiC ceramic-ceramic joints. This joining method has the potential to facilitate the use of SiC-based ceramics in a variety of elevated temperature fossil energy applications. The technique is based on a reaction bonding approach that provides joint interlayers compatible with SiC, and excellent joint mechanical properties at temperatures exceeding 1000{degrees}C. Recent efforts have focused on transferring the joining technology to industry. Several industrial partners have been identified and collaborative research projects are in progress. Investigations are focusing on applying the joining method to sintered a-SiC and fiber-reinforced SiC/SiC composites for use in applications such as heat exchangers, radiant burners and gas turbine components.

  19. Fabrication of SiO2/c-Si/SiO2 Double Barrier Structure Using Lateral Solid Phase Epitaxy

    NASA Astrophysics Data System (ADS)

    Novikov, S. V.; Sinkkonen, J.

    Formation of an ultra-thin-film silicon-on-insulator structure by lateral solid state epitaxy (LSPE) of amorphous Si on SiO2 has been investigated. The LSPE growth length was found. The SiO2/Si/SiO2 double barrier structure with single crystalline silicon well has been grown.

  20. Methods of radiation effects evaluation of SiC/SiC composite and SiC fibers

    SciTech Connect

    Youngblood, G.E.; Jones, R.H.

    1998-03-01

    This report covers material presented at the IEA/Jupiter Joint International Workshop on SiC/SiC Composites for Fusion structural Applications held in conjunction with ICFRM-8, Sendai, Japan, Oct. 23--24, 1997. Several methods for radiation effects evaluation of SiC fibers and fiber-reinforced SiC/SiC composite are presented.

  1. SiC-SiC composites for optical applications

    NASA Astrophysics Data System (ADS)

    Kowbel, Witold; Woida, Rigel; Withers, J. C.

    2005-08-01

    SiC optics has been considered for a very long time. Today, there are a few military and commercial applications. Future imaging and energy transfer applications require robustness on a par with metallic systems. Intrinsic, low fracture toughness of several classes of monolithic SiC is the key impediment in these applications. A new form of SiC-SiC composite for optical applications has been developed. It features high modulus combined with high fracture toughness. This new, highly innovative technology offers the potential in demanding government applications, as well as large surveillance optics (increased toughness can translate into lower aerial density) and high energy commercial lasers. SiC-SIC is a novel technology for optical structures consisting of integrated composite materials and structures which exhibits excellent fracture toughness and homogeneous CTE.

  2. Microstructure and mechanical properties of Ti–B–C–N–Si nanocomposite films deposited by unbalanced magnetron sputtering

    SciTech Connect

    Jang, Jaeho; An, Eunsol; Park, In-Wook; Nam, Dae-Geun; Jo, Ilguk; Lin, Jianliang; Moore, John J.; Ho Kim, Kwang; Park, Ikmin

    2013-11-15

    Quinary Ti–B–C–N–Si nanocomposite thin films were deposited on AISI 304 stainless steel substrates by d.c. unbalanced magnetron sputtering from a TiB{sub 2}–TiC compound target and a pure Si target. The relationship between microstructure and mechanical properties of the films was investigated in terms of the nanosized crystallites/amorphous system. The synthesized Ti–B–C–N–Si films were characterized using x-ray diffraction, x-ray photoelectron spectroscopy, atomic force microscopy, and high resolution transmission electron microscopy. The results showed that the Ti–B–C–N–Si films were nanocomposites composed of nanosized TiB{sub 2}, TiC, and TiSi{sub 2} crystallites (2-3 nm in size) embedded in an amorphous matrix. The addition of Si to the Ti–B–C–N film led to precipitation of nanosized crystalline TiSi{sub 2} and percolation of amorphous SiC phases. The Ti–B–C–N–Si films with up to 7 at. % Si content presented high hardness (≥35 GPa), H/E (≥0.0095), and W{sub e} (>50%) with compressive residual stress (∼0.5 GPa). A systematic investigation on the microstructure and mechanical properties of Ti–B–C–N–Si films containing different Si contents is reported.

  3. Targeting circuits

    PubMed Central

    Rajasethupathy, Priyamvada; Ferenczi, Emily; Deisseroth, Karl

    2017-01-01

    Current optogenetic methodology enables precise inhibition or excitation of neural circuits, spanning timescales as needed from the acute (milliseconds) to the chronic (many days or more), for experimental modulation of network activity and animal behavior. Such broad temporal versatility, unique to optogenetic control, is particularly powerful when combined with brain activity measurements that span both acute and chronic timescales as well. This enables, for instance, the study of adaptive circuit dynamics across the intact brain, and tuning interventions to match activity patterns naturally observed during behavior in the same individual. Although the impact of this approach has been greater on basic research than on clinical translation, it is natural to ask if specific neural circuit activity patterns discovered to be involved in controlling adaptive or maladaptive behaviors could become targets for treatment of neuropsychiatric diseases. Here we consider the landscape of such ideas related to therapeutic targeting of circuit dynamics, taking note of developments not only in optical but also in ultrasonic, magnetic, and thermal methods. We note the recent emergence of first-in-kind optogenetically-guided clinical outcomes, as well as opportunities related to the integration of interventions and readouts spanning diverse circuit-physiology, molecular, and behavioral modalities. PMID:27104976

  4. [In vivo imaging of liposomal small interfering RNA (siRNA) trafficking by positron emission tomography].

    PubMed

    Ando, Hidenori; Yonenaga, Norihito; Asai, Tomohiro; Hatanaka, Kentaro; Koide, Hiroyuki; Tsuzuku, Takuma; Harada, Norihiro; Tsukada, Hideo; Oku, Naoto

    2012-01-01

    In the development of nucleic acid medicines such as small interfering RNA (siRNA) drugs, one problem is how to study the pharmacokinetics and pharmacodynamics, since the precise in vivo behavior of siRNA is hard to detect. In this research, to establish a highly sensitive detection system of siRNA biodistribution in the whole body, the technology of positron imaging was applied. First, a one-step synthetic method in which double-stranded siRNA was directly labeled by a positron emitter, (18)F, was developed. By using [(18)F]-labeled siRNA ([(18)F]-siRNA), the complex of siRNA and polycation liposomes (PCL) containing dicetylphosphate tetraethylenepentamine (TEPA-PCL) was prepared. Then, the biodistribution of the siRNA after intravenous administration to mice was analyzed by planar positron imaging system (PPIS). As a result, whereas naked [(18)F]-siRNA was immediately excreted in mouse bladder after administration, the complex with cationic liposome (CL) was trapped in the lungs. Furthermore, [(18)F]-siRNA carried with PEGylated CL (PL) was distributed throughout the body, suggesting that it circulated in the bloodstream for an extended period of time. Additionally, PET imaging revealed more detailed biodistribution of the siRNA than in vivo imaging system (IVIS) because PET imaging is not affected by the depth variation of target tissues. On the other hand, to induce high accumulation of siRNAs against c-myc, MDM2, and VEGF in tumor tissue, a tumor-targeting probe, RGD peptide, was grafted at the top of PEG chain in PEGylated TEPA-PCL and the effect of the complex on experimental lung metastasis of B16 melanoma was examined. The complex suppressed the progression of tumor. We believe that the positron imaging data would support the development of siRNA agent for clinical use.

  5. MoSi2-Base Composites

    NASA Technical Reports Server (NTRS)

    Hebsur, Mohan G.

    2003-01-01

    Addition of 30 to 50 vol% of Si3N4 particulate to MoSi2 eliminated its low temperature catastrophic failure, improved room temperature fracture toughness and the creep resistance. The hybrid composite SCS-6/MoSi2-Si3N4 did not show any matrix cracking and exhibited excellent mechanical and environmental properties. Hi-Nicalon continuous fiber reinforced MoSi2-Si3N4 also showed good strength and toughness. A new MoSi2-base composite containing in-situ whisker-type (Beta)Si3N4 grains in a MoSi2 matrix is also described.

  6. Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using nanoparticle-stabilized nanocapsules

    NASA Astrophysics Data System (ADS)

    Hardie, Joseph; Jiang, Ying; Tetrault, Emily R.; Ghazi, Phaedra C.; Yesilbag Tonga, Gulen; Farkas, Michelle E.; Rotello, Vincent M.

    2016-09-01

    We report on nanoparticle-stabilized capsules (NPSCs) as a platform for the co-delivery of survivin-targeted siRNA and tamoxifen. These capsules feature an inner oil core that provides a carrier for tamoxifen, and is coated on the surface with positively charged nanoparticles self-assembled with siRNA. The multifaceted chemical nature of the NPSC system enables the simultaneous delivery of both payloads directly into the cytosol in vitro. The NPSC co-delivery of tamoxifen and survivin-targeted siRNA into breast cancer cells disables the pathways that inhibit apoptosis, resulting in enhanced breast cell death.

  7. Nanotechnology As Potential Tool for siRNA Delivery in Parkinson's Disease.

    PubMed

    Cortés, Hernán; Alcalá-Alcalá, Sergio; Ávalos-Fuentes, Arturo; Mendoza-Muñoz, Nestor; Quintanar-Guerrero, David; Leyva-Gómez, Gerardo; Florán, Benjamín

    2017-03-21

    The lack of an outright treatment for Parkinson's disease (PD) is a pivotal concern in medicine and has driven the search for novel alternatives for treating the disease. Among the proposed approaches, small interfering RNA (siRNA)-based therapy is attracting significant attention as a potential method for the treatment of PD; however, siRNAs delivery possesses potential drawbacks, such as reduced stability in blood circulation and low capacity for reaching the target site. Therefore, siRNA delivery to the brain is a key issue that remains unsolved to date. In this regard, nanoparticles are being developed as carriers for siRNAs and represent an alternative to common vectors; the formulation of siRNAs in nanoparticles would possess several advantages over other vectors, such as controlled delivery and low toxicity profiles. Therefore, in this article we focus on siRNA-based approaches to PD and the latest advances for designing nanoparticles that effectively target siRNAs to the action site and that protect these against degradation in blood circulation. Additionally, we discuss the technological aspects for tackling the challenge that siRNAs targeting to the brain represents.

  8. Kinesin spindle protein SiRNA slows tumor progression.

    PubMed

    Marra, Emanuele; Palombo, Fabio; Ciliberto, Gennaro; Aurisicchio, Luigi

    2013-01-01

    The kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently being studied in clinical trials and provide new opportunities for the development of novel anticancer therapeutics. RNA interference (RNAi) may represent a powerful strategy to interfere with key molecular pathways involved in cancer. In this study, we have established an efficient method for intratumoral delivery of siRNA. We evaluated short interfering RNA (siRNA) duplexes targeting luciferase as surrogate marker or KSP sequence. To examine the potential feasibility of RNAi therapy, the siRNA was transfected into pre-established lesions by means of intratumor electro-transfer of RNA therapeutics (IERT). This technology allowed cell permeation of the nucleic acids and to efficiently knock down gene expression, albeit transiently. The KSP-specific siRNA drastically reduced outgrowth of subcutaneous melanoma and ovarian cancer lesions. Our results show that intratumoral electro-transfer of siRNA is feasible and KSP-specific siRNA may provide a novel strategy for therapeutic intervention.

  9. Measurements, Standards, and the SI.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1983

    1983-01-01

    Highlights six papers presented at the Seventh Biennial Conference on Chemical Education (Stillwater, Oklahoma 1982). Topics addressed included history, status, and future of SI units, algebra of SI units, periodic table, new standard-state pressure unit, and suggested new names for mole concept ("numerity" and "chemical amount"). (JN)

  10. SI: Prognosis for the Future.

    ERIC Educational Resources Information Center

    Goldman, David T.

    1981-01-01

    Presents a survey of the International System of Units, usually denoted by its French abbreviation, SI (Systeme International), how it came about, and how it is likely to develop in the future. Describes SI units (base, derived, and supplementary) and new definitions for base units. (Author/SK)

  11. Using SI Units in Mechanics.

    ERIC Educational Resources Information Center

    Meriam, J. L.

    This paper provides an historical account of the development of the International System of Units (SI), a complete listing of these units, and rules concerning their use and proper abbreviation. Ambiguities concerning the use of the system are explained. Appendices contain conversion factors for U.S. - British to SI units along with several…

  12. A comparative structural and magnetic study of Fe100-xPdx(x=15, 20 and 36) thin films deposited on Si (100) and glass substrates

    NASA Astrophysics Data System (ADS)

    Bahamida, S.; Fnidiki, A.; Laggoun, A.; Guittoum, A.

    2015-10-01

    Various structural and magnetic characterization techniques have been used to investigate Fe100-xPdx (x=15, 20 and 36) thin films deposited onto silicon and glass substrates, by thermal evaporation technique. X-ray diffraction analysis shows the presence of supersaturated solid solution with bcc structure for Pd concentrations of 15% and 20%. However, for 36% of Pd, in addition to the supersaturated α-FePd (bcc) phase, another disordered FePd3 phase with fcc structure is present. At 20 at% Pd, the magnetic characterization shows a saturation of the bcc (α-FePd) phase and the appearance of the fcc phase. The correlation between the structure and magnetic properties allows us to compare the two substrates effects on deposited thin films. As results, the measurements indicate that the grain size D, the thin film thickness and the d(110) spacing significantly affect the magnetic coercivity HC. The Fe-Pd alloys deposited on a monocrystalline Si (100) and glass substrate show that the coercivity HC is given by the random anisotropy model.

  13. Preclinical and clinical development of siRNA-based therapeutics

    PubMed Central

    Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L.; Sood, Anil K.; Lopez-Berestein, Gabriel

    2015-01-01

    Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. PMID:25666164

  14. The localization and crystallographic dependence of Si suboxide species at the SiO2/Si interface

    NASA Technical Reports Server (NTRS)

    Grunthaner, P. J.; Hecht, M. H.; Grunthaner, F. J.; Johnson, N. M.

    1987-01-01

    X-ray photoemission spectroscopy has been used to examine the localization and crystallographic dependence of Si(+), Si(2+), and Si(3+) suboxide states at the SiO2/Si interface for (100)and (111)-oriented substrates with gate oxide quality thermal oxides. The Si(+) and Si(2+) states are localized within 6-10 A of the interface while the Si(3+) state extends about 30 A into the bulk SiO2. The distribution of Si(+) and Si(2+) states shows a strong crystallographic dependence with Si(2+) dominating on (100) substrates and Si(+) dominating on (111) substrates. This crystallographic dependence is anticipated from consideration of ideal unreconstructed (100) and (111) Si surfaces, suggesting that (1) the Si(+) and Si(2+) states are localized immediately within the first monolayer at the interface and (2) the first few monolayers of substrate Si atoms are not significantly displaced from the bulk. The total number of suboxide states observed at the SiO2/Si interface corresponds to 94 and 83 percent of a monolayer for these (100) and (111) substrates, respectively.

  15. SiRNA Crosslinked Nanoparticles for the Treatment of Inflammation‐induced Liver Injury

    PubMed Central

    Tang, Yaqin; Zeng, Ziying; He, Xiao; Wang, Tingting

    2016-01-01

    RNA interference mediated by small interfering RNA (siRNA) provides a powerful tool for gene regulation, and has a broad potential as a promising therapeutic strategy. However, therapeutics based on siRNA have had limited clinical success due to their undesirable pharmacokinetic properties. This study presents pH‐sensitive nanoparticles‐based siRNA delivery systems (PNSDS), which are positive‐charge‐free nanocarriers, composed of siRNA chemically crosslinked with multi‐armed poly(ethylene glycol) carriers via acid‐labile acetal linkers. The unique siRNA crosslinked structure of PNSDS allows it to have minimal cytotoxicity, high siRNA loading efficiency, and a stimulus‐responsive property that enables the selective intracellular release of siRNA in response to pH conditions. This study demonstrates that PNSDS can deliver tumor necrosis factor alpha (TNF‐α) siRNA into macrophages and induce the efficient down regulation of the targeted gene in complete cell culture media. Moreover, PNSDS with mannose targeting moieties can selectively accumulate in mice liver, induce specific inhibition of macrophage TNF‐α expression in vivo, and consequently protect mice from inflammation‐induced liver damages. Therefore, this novel siRNA delivering platform would greatly improve the therapeutic potential of RNAi based therapies. PMID:28251047

  16. Properties of SiC-SiC composites produced using CVR converted graphite cloth to SiC cloth

    SciTech Connect

    Kowbel, W.; Kyriacou, C.; Gao, F.; Bruce, C.A.; Withers, J.C.

    1995-10-01

    Nicalon fiber is the primary reinforcement in SiC-SiC composites currently produced by a variety of techniques including CVI and polymer infiltration. Low strength retention at high temperatures of the Nicalon fibers limits the choice of manufacturing processes which can be employed to produce low cost SiC-SiC composites. MER has developed a new SiC reinforcement based upon a conversion of low cost carbon fabric to SiC via a Chemical Vapor Reaction (CVR) process. This new SiC filaments exhibit an excellent creep resistance at temperatures up to 1,600 C. Several SiC-SiC composites were fabricated using graphite fabric converted to SiC fabric utilizing the CVR process combined with a slurry infiltration and CVI densification. A correlation between processing conditions, microstructure and properties of the SiC-SiC composites are discussed in detail.

  17. Heteroepitaxial Ge-on-Si by DC magnetron sputtering

    SciTech Connect

    Steglich, Martin; Schrempel, Frank; Füchsel, Kevin; Kley, Ernst-Bernhard; Patzig, Christian; Berthold, Lutz; Höche, Thomas; Tünnermann, Andreas

    2013-07-15

    The growth of Ge on Si(100) by DC Magnetron Sputtering at various temperatures is studied by Spectroscopic Ellipsometry and Transmission Electron Microscopy. Smooth heteroepitaxial Ge films are prepared at relatively low temperatures of 380°C. Typical Stransky-Krastanov growth is observed at 410°C. At lower temperatures (320°C), films are essentially amorphous with isolated nanocrystallites at the Si-Ge interface. A minor oxygen contamination at the interface, developing after ex-situ oxide removal, is not seen to hinder epitaxy. Compensation of dislocation-induced acceptors in Ge by sputtering from n-doped targets is proposed.

  18. Systemic Administration of siRNA via cRGD-containing Peptide

    PubMed Central

    Huang, Yuanyu; Wang, Xiaoxia; Huang, Weiyan; Cheng, Qiang; Zheng, Shuquan; Guo, Shutao; Cao, Huiqing; Liang, Xing-Jie; Du, Quan; Liang, Zicai

    2015-01-01

    Although small interfering RNAs (siRNAs) have been demonstrated to specifically silence their target genes in disease models and clinical trials, in vivo siRNA delivery is still the technical bottleneck that limits their use in therapeutic applications. In this study, a bifunctional peptide named RGD10-10R was designed and tested for its ability to deliver siRNA in vitro and in vivo. Because of their electrostatic interactions with polyarginine (10R), negatively charged siRNAs were readily complexed with RGD10-10R peptides, forming spherical RGD10-10R/siRNA nanoparticles. In addition to enhancing their serum stability by preventing RNase from attacking siRNA through steric hindrance, peptide binding facilitated siRNA transfection into MDA-MB-231 cells, as demonstrated by FACS and confocal microscopy assays and by the repressed expression of target genes. When RGD10 peptide, a receptor competitor of RGD10-10R, was added to the transfection system, the cellular internalization of RGD10-10R/siRNA was significantly compromised, suggesting a mechanism of ligand/receptor interaction. Tissue distribution assays indicated that the peptide/siRNA complex preferentially accumulated in the liver and in several exocrine/endocrine glands. Furthermore, tumor-targeted delivery of siRNA was also demonstrated by in vivo imaging and cryosection assays. In summary, RGD10-10R might constitute a novel siRNA delivery tool that could potentially be applied in tumor treatment. PMID:26300278

  19. Fabrication of multilayered Ge nanocrystals embedded in SiO xGeN y films

    NASA Astrophysics Data System (ADS)

    Gao, Fei; Green, Martin A.; Conibeer, Gavin; Cho, Eun-Chel; Huang, Yidan; Perez-Wurfl, Ivan; Flynn, Chris

    2008-09-01

    Multilayered Ge nanocrystals embedded in SiO xGeN y films have been fabricated on Si substrate by a (Ge + SiO 2)/SiO xGeN y superlattice approach, using a rf magnetron sputtering technique with a Ge + SiO 2 composite target and subsequent thermal annealing in N 2 ambient at 750 °C for 30 min. X-ray diffraction (XRD) measurement indicated the formation of Ge nanocrystals with an average size estimated to be 5.4 nm. Raman scattering spectra showed a peak of the Ge-Ge vibrational mode downward shifted to 299.4 cm -1, which was caused by quantum confinement of phonons in the Ge nanocrystals. Transmission electron microscopy (TEM) revealed that Ge nanocrystals were confined in (Ge + SiO 2) layers. This superlattice approach significantly improved both the size uniformity of Ge nanocrystals and their uniformity of spacing on the 'Z' growth direction.

  20. ELECTRONIC TRANSITIONS OF JET-COOLED SiC{sub 2}, Si{sub 2}C{sub n} (n=1−3), Si{sub 3}C{sub n} (n = 1,2), AND SiC{sub 6}H{sub 4} BETWEEN 250 AND 710 nm

    SciTech Connect

    Steglich, M.; Maier, J. P. E-mail: j.p.maier@unibas.ch

    2015-03-10

    Electronic transitions of the title molecules were measured between 250 and 710 nm using a mass-resolved 1 + 1’ resonant two-photon ionization technique at a resolution of 0.1 nm. Calculations at the B3LYP/aug-cc-pVQZ level of theory support the analyses. Because of their spectral properties, SiC{sub 2}, linear Si{sub 2}C{sub 2}, Si{sub 3}C, and SiC{sub 6}H{sub 4} are interesting target species for astronomical searches in the visible spectral region. Of special relevance is the Si–C{sub 2}–Si chain, which features a prominent band at 516.4 nm of a strong transition (f = 0.25). This band and one from SiC{sub 6}H{sub 4} at 445.3 nm were also investigated at higher resolution (0.002 nm)

  1. Improvement of parameters in a-Si(p)/c-Si(n)/a-Si(n) solar cells

    NASA Astrophysics Data System (ADS)

    Moustafa Bouzaki, Mohammed; Aillerie, Michel; Ould Saad Hamady, Sidi; Chadel, Meriem; Benyoucef, Boumediene

    2016-10-01

    We analyzed and discussed the influence of thickness and doping concentration of the different layers in a-Si(p)/c-Si(n)/a-Si(n) photovoltaic (PV) cells with the aim of increasing its efficiency while decreasing its global cost. Compared to the efficiency of a standard marketed PV cell, elaborated with a ZnO transparent conductive oxide (TCO) layer but without Back Surface Field (BSF) layer, an optimization of the thickness and dopant concentration of both the emitter a-Si(p) and absorber c-Si(n) layers will gain about 3% in the global efficiency of the cell. The results also reveal that with introduction of the third layer, i.e. the BSF layer, the efficiency always achieves values above 20% and all other parameters of the cell, such as the open-circuit voltage, the short-circuit current and the fill-factor, are strongly affected by the thickness and dopant concentration of the layers. The values of all parameters are given and discussed in the paper. Thereby, the simulation results give for an optimized a-Si(p)/c-Si(n)/a-Si(n) PV cells the possibility to decrease the thickness of the absorber layer down to 50 μm which is lower than in the state-of-the-art. This structure of the cell achieves suitable properties for high efficiency, cost-effectiveness and reliable heterojunction (HJ) solar cell applications.

  2. A Universal Protein Tag for Delivery of SiRNA-Aptamer Chimeras

    PubMed Central

    Liu, Hong Yan; Gao, Xiaohu

    2013-01-01

    siRNA-aptamer chimeras have emerged as one of the most promising approaches for targeted delivery of siRNA due to the modularity of their diblock RNA structure, relatively lower cost over other targeted delivery approaches, and, most importantly, the outstanding potential for clinical translation. However, additional challenges must be addressed for efficient RNA interference (RNAi), in particular, endosomal escape. Currently, vast majority of siRNA delivery vehicles are based on cationic materials, which form complexes with negatively charged siRNA. Unfortunately, these approaches complicate the formulations again by forming large complexes with heterogeneous sizes, unfavorable surface charges, colloidal instability, and poor targeting ligand orientation. Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. The protein selectively tags along the siRNA block of individual chimera, rendering the overall size of the complex small, desirable for deep tissue penetration, and the aptamer block accessible for target recognition. More interestingly, we found that extending the c-terminal polyhistidine segment in the protein tag to 18 amino acids completely abolishes the RNA binding function of dsRBD. PMID:24196104

  3. Molecular targeting in childhood malignancies using nanoparticles

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Barisone, Gustavo; Diaz, Elva; Nitin, Nitin; Nolta, Jan; Lam, Kit

    2012-06-01

    The goal of our project is to develop a new therapy for childhood malignancies using nanoformulated siRNA targeting Mxd3, a molecule in the Sonic Hedgehog signaling pathway, which we believe is important for cell survival. We plan to use cancer-specific ligands and superparamagnetic iron oxide nanoparticles (SPIO NPs) to carry siRNA. This delivery system will be tested in mouse xenograft models that we developed with primary cancer tissues. Our current focus is acute lymphoblastic leukemia (ALL), the most common cancer in children. We report our progress to date.

  4. Cationic Poly-L-Lysine-Fe2O3/SiO2 nanoparticles loaded with small interference RNA: Application to silencing gene expression in primary rat neurons.

    PubMed

    Cui, Xuewen; Liu, Ruijiang; Liu, Ziwen; Shen, Xiangqian; Wang, Qiuju; Tan, Xiaoli

    2014-04-01

    The cationic PLL-Fe2o3/SiO2-siRNA nanoparticles with an average crystallite size of about 20 nm were prepared and delivered into primary rat neurons for knockdown of gene expression. Primary rat fetal neurons were scratched to simulate the injury of central nervous system and then were transfected with PLL-Fe2O3/SiO2-siRNA nanoparticles. Optical microscopy, fluorescence microscopy, Western blotting, immunofluorescence, and MTT assays were employed to test the cytotoxicity, the efficiency of encapsulation and targeted gene silencing. The results indicated that the PLL-Fe2O3/SiO2-siRNA nanoparticles have a remarkable efficiency of encapsulation and targeted gene silencing with negligible cytotoxicity. It could be concluded that the PLL-Fe2O3/SiO2 nanoparticles are a promising delivery carrier of siRNA.

  5. Targeted fibrillar nanocarbon RNAi treatment of acute kidney injury

    PubMed Central

    Alidori, Simone; Akhavein, Nima; Thorek, Daniel L. J.; Behling, Katja; Romin, Yevgeniy; Queen, Dawn; Beattie, Bradley J.; Manova-Todorova, Katia; Bergkvist, Magnus; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    RNA interference has tremendous yet unrealized potential to treat a wide range of illnesses. Innovative solutions are needed to protect and selectively deliver small interfering RNA (siRNA) cargo to and within a target cell to fully exploit siRNA as a therapeutic tool in vivo. Herein, we describe ammonium-functionalized carbon nanotube (fCNT)–mediated transport of siRNA selectively and with high efficiency to renal proximal tubule cells in animal models of acute kidney injury (AKI). fCNT enhanced siRNA delivery to tubule cells compared to siRNA alone and effectively knocked down the expression of several target genes, including Trp53, Mep1b, Ctr1, and EGFP. A clinically relevant cisplatin-induced murine model of AKI was used to evaluate the therapeutic potential of fCNT-targeted siRNA to effectively halt the pathogenesis of renal injury. Prophylactic treatment with a combination of fCNT/siMep1b and fCNT/siTrp53 significantly improved progression-free survival compared to controls via a mechanism that required concurrent reduction of meprin-1β and p53 expression. The fCNT/siRNA was well tolerated, and no toxicological consequences were observed in murine models. Toward clinical application of this platform, fCNTs were evaluated for the first time in nonhuman primates. The rapid and kidney-specific pharmacokinetic profile of fCNT in primates was comparable to what was observed in mice and suggests that this approach is amenable for use in humans. The nanocarbon-mediated delivery of siRNA provides a therapeutic means for the prevention of AKI to safely overcome the persistent barrier of nephrotoxicity during medical intervention. PMID:27009268

  6. Si Isotopes of Brownleeite

    NASA Technical Reports Server (NTRS)

    Nakamura-Messenger, K.; Messenger, Scott R.; Ito, M.; Keller, L. P.; Clemett, S. J.; Jones, J. H.; Tatsuoka, H.; Zolensky, M. E.; Tatsuoka, H.

    2010-01-01

    Brownleeite is a manganese silicide, ideally stoichiometric MnSi, not previously observed in nature until its discovery within an interplanetary dust particle (IDP) that likely originated from a comet [1]. Three discrete brownleeite grains in the IDP L2055 I3 (4 microns in size, hereafter IDP I3) were identified with maximum dimensions of 100, 250 and 600 nm and fully analyzed using scanning-transmission electron microscopy (STEM) [1]. One of the grains (100 nm in size) was poikilitically enclosed by low-Fe, Mn-enriched (LIME) olivine. LIME olivine is epitaxial to the brownleeite with the brownleeite (200) parallel to the olivine c* [1]. LIME olivine is an enigmatic phase first reported from chondritic porous IDPs and some unequilibrated ordinary chondrites [ 2], that is commonly observed in chondritic-porous IDPs. Recently, LIME olivine has been also found in comet Wild-2 (Stardust) samples [3], indicating that LIME olivine is a common mineral component of comets. LIME olivine has been proposed to form as a high temperature condensate in the protosolar nebula [2]. Brownleeite grains also likely formed as high-temperature condensates either in the early Solar System or in the outflow of an evolved star or supernova explosion [1]. The isotopic composition of the brownleeite grains may strongly constrain their ultimate source. To test this hypothesis, we performed isotopic analyses of the brownleeite and the associated LIME olivine, using the NASA/JSC NanoSIMS 50L ion microprobe.

  7. Epitaxial growth of Si deposited on (100) Si

    NASA Astrophysics Data System (ADS)

    Hung, L. S.; Lau, S. S.; von Allmen, M.; Mayer, J. W.; Ullrich, B. M.; Baker, J. E.; Williams, P.; Tseng, W. F.

    1980-11-01

    Epitaxial growth of deposited amorphous Si on chemically cleaned (100) Si has been found and layer-by-layer growth occurred at rates comparable to those in self-ion-implanted-amorphous Si. There is no evidence for appreciable oxygen penetration into the deposited layer during storage in air. The critical factors in achieving epitaxial growth are fast (˜50 Å/sec) deposition of Si onto a surface cleaned with a HF dip as a last rinse before loading into the vacuum system. Channeling and transmission electron microscopy measurements indicated that the epitaxial layers are essentially defect free. Secondary-ion mass spectroscopic analysis showed about 1014 oxygen/cm2 at the amorphous/crystal interface. With either higher interfacial oxygen coverage or slow (˜2 Å/sec) deposition, epitaxial growth rates are significantly slower.

  8. siRNA-loaded PEGylated porous silicon nanoparticles for lung cancer therapy

    NASA Astrophysics Data System (ADS)

    Chen, Shaomu; Ni, Bin; Huang, Haitao; Chen, Xiaochun; Ma, Haitao

    2014-10-01

    Biocompatible and biodegradable porous silicon nanoparticles (pSiNPs) with tunable pore size have been used as vehicles for drug delivery. Our pSiNPs have a mean size of 110 nm with an average pore size of 26 nm. Approximately 16.3 µg of siRNA can be loaded per mg of pSiNPs followed by polyethylene glycol (PEG) surface coating. siRNA-loaded PEGylated pSiNPs (P-pSiNPs) can be uptaken by A549 cells, and target pyruvate kinase isozyme type M2 (PKM2) mRNA and protein expression were effectively downregulated to 6.3 and 26.8 %, respectively. Cell viability decreased to 37.6 %; meanwhile, cell apoptosis upregulated to 17.3 %. The results prove that the siRNA-loaded pSiNPs coated with PEG can effectively deliver siRNA into cancer cells, and the efficiency is comparable to that of lipofectamine.

  9. siRNA vs. shRNA: similarities and differences.

    PubMed

    Rao, Donald D; Vorhies, John S; Senzer, Neil; Nemunaitis, John

    2009-07-25

    RNA interference (RNAi) is a natural process through which expression of a targeted gene can be knocked down with high specificity and selectivity. Using available technology and bioinformatics investigators will soon be able to identify relevant bio molecular tumor network hubs as potential key targets for knockdown approaches. Methods of mediating the RNAi effect involve small interfering RNA (siRNA), short hairpin RNA (shRNA) and bi-functional shRNA. The simplicity of siRNA manufacturing and transient nature of the effect per dose are optimally suited for certain medical disorders (i.e. viral injections). However, using the endogenous processing machinery, optimized shRNA constructs allow for high potency and sustainable effects using low copy numbers resulting in less off-target effects, particularly if embedded in a miRNA scaffold. Bi-functional design may further enhance potency and safety of RNAi-based therapeutics. Remaining challenges include tumor selective delivery vehicles and more complete evaluation of the scope and scale of off-target effects. This review will compare siRNA, shRNA and bi-functional shRNA.

  10. Synthesis and structural property of Si nanosheets connected to Si nanowires using MnCl2/Si powder source

    NASA Astrophysics Data System (ADS)

    Meng, Erchao; Ueki, Akiko; Meng, Xiang; Suzuki, Hiroaki; Itahara, Hiroshi; Tatsuoka, Hirokazu

    2016-08-01

    Si nanosheets connected to Si nanowires were synthesized using a MnCl2/Si powder source with an Au catalyst. The synthesis method has benefits in terms of avoiding conventionally used air-sensitive SiH4 or SiCl4. The existence of the Si nanosheets connected to the Si<111> nanowires, like sprouts or leaves with petioles, was observed, and the surface of the nanosheets was Si{111}. The nanosheets were grown in the growth direction of <211> perpendicular to that of the Si nanowires. It was evident from these structural features of the nanosheets that the nanosheets were formed by the twin-plane reentrant-edge mechanism. The feature of the observed lattice fringes, which do not appear for Si bulk crystals, of the Si(111) nanosheets obtained by high resolution transmission electron microscopy was clearly explained due to the extra diffraction spots that arose by the reciprocal lattice streaking effect.

  11. Luminescence of Degraded Si-SiO2 Structures

    NASA Astrophysics Data System (ADS)

    Baraban, A. P.; Dmitriev, V. A.; Gadzhala, A. A.

    2014-09-01

    Possibilities of using electroluminescence (EL) and cathodoluminescence (CL) in the spectral range 250-800 nm to investigate physical-chemical processes taking place in Si-SiO2 structures as a result of extreme external actions (strong electric fields or γ-radiation) are considered. It is found that degradation processes along with changes in the electrophysical characteristics of Si-SiO2 structures are revealed in changes in the luminescence spectra, especially in the red region. The similarity of the changes in the CL and EL spectra of Si-SiO2 structures exposed to field and radiation points to a similarity in the processes taking place during degradation, which is confirmed by the qualitative similarity of the changes in the charge characteristics. The near-invariance of the spectral composition of the luminescence is an indication that the processes taking place during degradation do not lead to the formation of new luminescence centers, but modify the concentration of already existing biographical defects. This is evidence of the existence of a direct link between resistance to degradation and the technology of formation of the oxide layer on the silicon surface.

  12. Formation of microtubes from strained SiGe/Si heterostructures

    NASA Astrophysics Data System (ADS)

    Qin, H.; Shaji, N.; Merrill, N. E.; Kim, H. S.; Toonen, R. C.; Blick, R. H.; Roberts, M. M.; Savage, D. E.; Lagally, M. G.; Celler, G.

    2005-11-01

    We report the formation of micrometre-sized SiGe/Si tubes by releasing strained SiGe/Si bilayers from substrates in a wet chemical-etching process. In order to explore statistical studies of dynamic formation of microtubes, we fabricated arrays of square bilayers. Due to the dynamic change in curvature of the bilayers, and hence the underlying etch channels, the etching process deviates from a transport-controlled regime to one of kinetic controlled. We identified two distinct modes of etching. A slow etching mode is associated with symmetric surface deformation in which the bilayers mostly retain their initial pattern. In the fast mode, bilayers are asymmetrically deformed while large etch channels are induced and etching becomes kinetically controlled. Etch rate dispersion is directly related to the degree of asymmetry in surface deformation. When the dimensions of the bilayers become significantly larger than the curvature radius, kinetic etching dominates. During the formation of tubes, SiGe/Si bilayers strongly interact with the liquid environment of etchant and solvent. Assisted by the surface tension of evaporating liquids, the tubes are drawn near the substrate and eventually fixed to it because of van der Waals forces. Our study illuminates the dynamic etching and curling processes involved with and provides insight on how a uniform etch rate and consistent curling directions can be maintained.

  13. Characterization of gadolinium and lanthanum oxide films on Si (100)

    NASA Astrophysics Data System (ADS)

    Wu, X.; Landheer, D.; Sproule, G. I.; Quance, T.; Graham, M. J.; Botton, G. A.

    2002-05-01

    High-resolution transmission electron microscopy, electron energy loss spectroscopy, and Auger electron spectroscopy, were used to study gadolinium and lanthanum oxide films deposited on Si (100) substrates using electron-beam evaporation from pressed-powder targets. As-deposited films consist of a crystalline oxide layer and an amorphous interfacial layer. A complicated distinct multilayer structure consisting of oxide layers, silicate layers, and SiO2-rich layers in thick (~30 nm) annealed films has been observed for both gadolinium and lanthanum films. For thinner annealed films (~8 nm), there is no longer a crystalline oxide layer but an amorphous gadolinium or lanthanum silicate layer and an interfacial SiO2-rich layer. The formation of the lanthanum silicate by annealing lanthanum oxide is found to be thermodynamically more favorable than the formation of gadolinium silicate.

  14. Evaluation of resonances above the proton threshold in 26Si

    NASA Astrophysics Data System (ADS)

    Chipps, K. A.

    2016-09-01

    26Al remains an intriguing target for observational gamma-ray astronomy, thanks to its characteristic decay. The 25Al(p, γ)26Si reaction is the crucial link in a sequence that bypasses the production of the observable 26Alg . s . in favor of the isomeric state, and as such has been the focus of many studies. Considerable confusion in this regard has arisen from the use of outdated excitation energies and masses in reaction studies and rate evaluations. Recalibration of existing data from the literature has resulted in updated excitation and resonance energies, but open questions remain, particularly with regard to spin assignments and partial widths/resonance strengths. A discussion of the levels just above the proton threshold in 26Si relevant to the astrophysical 25Al(p, γ)26Si reaction rate will be presented. This work is funded by the US Department of Energy, Office of Science, Office of Nuclear Physics.

  15. Students' Target

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03648 Ascraeus Mons

    After examining numerous THEMIS images and using the JMars targeting software, eighth grade students from Charleston Middle School in Charleston, IL, selected the location of -8.37N and 276.66E for capture by the THEMIS visible camera during Mars Odyssey's sixth orbit of Mars on Nov. 22, 2005. The students are investigating relationships between channels, craters, and basins on Mars. The Charleston Middle School students participated in the Mars Student Imaging Project (MSIP) and submitted a proposal to use the THEMIS visible camera.

    Image information: VIS instrument. Latitude 8.8S, Longitude 279.6E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  16. Fabrication and characterization of CuxSi1-x films on Si (111) and Si (100) by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Zhang, Song; Wu, Jun; He, Zhiqiang; Xie, Jun; Lu, Jingqi; Tu, Rong; Zhang, Lianmeng; Shi, Ji

    2016-05-01

    The CuxSi1-x thin films have been successfully fabricated by pulsed laser deposition (PLD). The influences of laser energy fluency (I0) and deposition temperature (Td) on the phase structure were investigated. The results show that Cu deposited on Si (001) at I0 = 0.5-2.0 J/cm2, and η"-Cu3Si formed on Si (111) at I0 = 1.0-2.0 J/cm2. The films were consisted of Cu, η'-Cu3Si, ɛ-Cu15Si4 and δ-Cu0.83Si0.17 at Td = 100-500 °C on Si (001). The films were the single phase of η-Cu3Si at Td = 700 °C. In the case of Si (111), the phase structures transformed from Cu to Cu + η'-Cu3Si to η'-Cu3Si to η'-Cu3Si + η-Cu3Si with the increasing of Td. Rectangular grains were formed on Si (001), whereas triangular grains on Si (111). Cu (001) film was epitaxially grown on Si (001) at I0 = 1.5 J/cm2 and Td = 20 °C. η-Cu3Si (001) epitaxial layer was formed on Si (111) at I0 = 1.5 J/cm2 and Td = 700 °C. The epitaxial relationships of Cu (001)[100]//Si (001)[110] and η-Cu3Si (001)[-110]//Si (111)[11-2] were identified.

  17. Characterization of β-FeSi II films as a novel solar cell semiconductor

    NASA Astrophysics Data System (ADS)

    Fukuzawa, Yasuhiro; Ootsuka, Teruhisa; Otogawa, Naotaka; Abe, Hironori; Nakayama, Yasuhiko; Makita, Yunosuke

    2006-04-01

    β-FeSi II is an attractive semiconductor owing to its extremely high optical absorption coefficient (α>10 5 cm -1), and is expected to be an ideal semiconductor as a thin film solar cell. For solar cell use, to prepare high quality β-FeSi II films holding a desired Fe/Si ratio, we chose two methods; one is a molecular beam epitaxy (MBE) method in which Fe and Si were evaporated by using normal Knudsen cells, and occasionally by e-gun for Si. Another one is the facing-target sputtering (FTS) method in which deposition of β-FeSi II films is made on Si substrate that is placed out of gas plasma cloud. In both methods to obtain β-FeSi II films with a tuned Fe/Si ratio, Fe/Si super lattice was fabricated by varying Fe and Si deposition thickness. Results showed significant in- and out-diffusion of host Fe and Si atoms at the interface of Si substrates into β-FeSi II layers. It was experimentally demonstrated that this diffusion can be suppressed by the formation of template layer between the epitaxial β-FeSi II layer and the substrate. The template layer was prepared by reactive deposition epitaxy (RDE) method. By fixing the Fe/Si ratio as precisely as possible at 1/2, systematic doping experiments of acceptor (Ga and B) and donor (As) impurities into β-FeSi II were carried out. Systematical changes of electron and hole carrier concentration in these samples along variation of incorporated impurities were observed through Hall effect measurements. Residual carrier concentrations can be ascribed to not only the remaining undesired impurities contained in source materials but also to a variety of point defects mainly produced by the uncontrolled stoichiometry. A preliminary structure of n-β-FeSi II/p-Si used as a solar cell indicated a conversion efficiency of 3.7%.

  18. Development of Nanosphere Lithography Technique with Enhanced Lithographical Accuracy on Periodic Si Nanostructure for Thin Si Solar Cell Application

    NASA Astrophysics Data System (ADS)

    Choi, Jeayoung

    for the target spectral range (600 ˜ 1100nm), which is attributed to (1) the effective confinement of resonant scattering within the Si NP and (2) increased high order diffraction of transmitted light providing an extended absorption length. From the research, therefore, it is successfully demonstrated that the nano-fabrication process with SNS lithography can offer enhanced lithographical accuracy to fabricate desired Si nanostructures which can realize enhanced light absorption for thin Si solar cell.

  19. Effect of the working gas of the ion-assisted source on the optical and mechanical properties of SiO2 films deposited by dual ion beam sputtering with Si and SiO2 as the starting materials.

    PubMed

    Wu, Jean-Yee; Lee, Cheng-Chung

    2006-05-20

    Silicon and fused-silica targets are used as the starting materials for depositing silicon oxide (SiO2) films. The SiO2 films are prepared by a dual ion beam sputtering deposition system with a main ion source and an ion-assisted source with different working gases. The films deposited are then examined and compared by using a visible spectrophotometer, a Fourier-transform IR spectrophotometer, an atomic force microscope, and contact angle instruments. A Twyman-Green interferometer is employed to study the film stress by phase-shift interferometry. All the SiO2 films show excellent optical properties with extra-low extinction coefficients (below 2x10(-5)) and have no water absorption. When the working gas is O2 for the ion-assisted source, the deposited SiO2 films show good properties in terms of stress and roughness and with a good molecular bonding structure order for both targets. However, SiO2 films deposited from the fused-silica target had a larger contact angle, while those deposited from the silicon target had 2.5 times the deposition rate.

  20. Gene targeting in primary human trophoblasts

    PubMed Central

    Rosario, Fredrick J; Sadovsky, Yoel; Jansson, Thomas

    2012-01-01

    Studies in primary human trophoblasts provide critical insights into placental function in normal and complicated pregnancies. Mechanistic studies in these cells require experimental tools to modulate gene expression. Lipid-based methods to transfect primary trophoblasts are fairly simple to use and allow for the efficient delivery of nucleic acids, but potential toxic effects limit these methods. Viral vectors are versatile transfection tools of native trophoblastic or foreign cDNAs, providing high transfection efficiency, low toxicity and stable DNA integration into the trophoblast genome. RNA interference (RNAi), using small interfering RNA (siRNA) or microRNA, constitutes a powerful approach to silence trophoblast genes. However, off-target effects, such as regulation of unintended complementary transcripts, inflammatory responses and saturation of the endogenous RNAi machinery, are significant concerns. Strategies to minimize off-target effects include using multiple individual siRNAs, elimination of pro-inflammatory sequences in the siRNA construct and chemical modification of a nucleotide in the guide strand or of the ribose moiety. Tools for efficient gene targeting in primary human trophoblasts are currently available, albeit not yet extensively validated. These methods are critical for exploring the function of human trophoblast genes and may provide a foundation for the future application of gene therapy that targets placental trophoblasts. PMID:22831880

  1. Nitriding kinetics of Si-SiC powder mixtures as simulations of reaction bonded Si3N4-SiC composites

    NASA Technical Reports Server (NTRS)

    Lightfoot, A.; Sheldon, B. W.; Flint, J. H.; Haggerty, J. S.

    1989-01-01

    The nitriding kinetics of Si and Si plus SiC powder mixtures were studied to simulate the fabrication of RBSN-SiC ceramic matrix composites. Very clean, assynthesized, and solvent-exposed powders were studied; C-rich and Si-rich SiC 0.04-0.05 micron diameter powders were mixed in varying concentrations with SiH4-derived 0.2-0.3 micron diameter Si powder. Complete nitridation is achieved with C-rich SiC powders in 140 min at 1250 C, and in the centers of Si-rich SiC powders in 15 min. The effects on the incubation periods, fast reaction periods, and slow reaction periods that characterize these nitriding processes were studied to explain unusual reverse reaction gradients and other effects of contamination.

  2. Design of a platform technology for systemic delivery of siRNA to tumours using rolling circle transcription

    NASA Astrophysics Data System (ADS)

    Jang, Mihue; Kim, Jong Hwan; Nam, Hae Yun; Kwon, Ick Chan; Ahn, Hyung Jun

    2015-08-01

    For therapeutic applications of siRNA, there are technical challenges with respect to targeted and systemic delivery. We here report a new siRNA carrier, RNAtr NPs, in a way that multiple tandem copies of RNA hairpins as a result of rolling circle transcription (RCT) can be readily adapted in tumour-targeted and systemic siRNA delivery. RNAtr NPs provide a means of condensing large amounts of multimeric RNA transcripts into the compact nanoparticles, especially without the aid of polycationic agents, and thus reduce the risk of immunogenicity and cytotoxicity by avoiding the use of synthetic polycationic reagents. This strategy allows the design of a platform technology for systemic delivery of siRNA to tumour sites, because RCT reaction, which enzymatically generates RNA polymers in multiple copy numbers at low cost, can lead to directly accessible routes to targeted and systemic delivery. Therefore, RNAtr NPs suggest great potentials as the siRNA therapeutics for cancer treatment.

  3. Ag-Pd-Si (009)

    NASA Astrophysics Data System (ADS)

    Carow-Watamura, U.; Louzguine, D. V.; Takeuchi, A.

    This document is part of Part 1 http://dx.doi.org/10.1007/97.etType="URL"/> 'Systems from Ag-Al-Ca to Au-Pd-Si' of Subvolume B 'Physical Properties of Ternary Amorphous Alloys' of Volume 37 'Phase Diagrams and Physical Properties of Nonequilibrium Alloys' of Landolt-Börnstein - Group III 'Condensed Matter'. It contains the Chapter 'Ag-Pd-Si (009)' with the content:

  4. Electronic stopping powers for heavy ions in SiC and SiO{sub 2}

    SciTech Connect

    Jin, K.; Xue, H.; Zhang, Y. Weber, W. J.; Zhu, Z.; Grove, D. A.; Xue, J.

    2014-01-28

    Accurate information on electronic stopping power is fundamental for broad advances in materials science, electronic industry, space exploration, and sustainable energy technologies. In the case of slow heavy ions in light targets, current codes and models provide significantly inconsistent predictions, among which the Stopping and Range of Ions in Matter (SRIM) code is the most commonly used one. Experimental evidence, however, has demonstrated considerable errors in the predicted ion and damage profiles based on SRIM stopping powers. In this work, electronic stopping powers for Cl, Br, I, and Au ions are experimentally determined in two important functional materials, SiC and SiO{sub 2}, based on a single ion technique, and new electronic stopping power values are derived over the energy regime from 0 to 15 MeV, where large deviations from the SRIM predictions are observed. As an experimental validation, Rutherford backscattering spectrometry (RBS) and secondary ion mass spectrometry (SIMS) are utilized to measure the depth profiles of implanted Au ions in SiC for energies from 700 keV to 15 MeV. The measured ion distributions by both RBS and SIMS are considerably deeper than the SRIM predictions, but agree well with predictions based on our derived stopping powers.

  5. Enhanced Gene Silencing through Human Serum Albumin-Mediated Delivery of Polyethylenimine-siRNA Polyplexes

    PubMed Central

    Nicolì, Elena; Syga, Marie Isabel; Bosetti, Michela; Shastri, V. Prasad

    2015-01-01

    Small interfering RNA (siRNA) targeted therapeutics (STT) offers a compelling alternative to tradition medications for treatment of genetic diseases by providing a means to silence the expression of specific aberrant proteins, through interference at the expression level. The perceived advantage of siRNA therapy is its ability to target, through synthetic antisense oligonucleotides, any part of the genome. Although STT provides a high level of specificity, it is also hindered by poor intracellular uptake, limited blood stability, high degradability and non-specific immune stimulation. Since serum proteins has been considered as useful vehicles for targeting tumors, in this study we investigated the effect of incorporation of human serum albumin (HSA) in branched polyethylenimine (bPEI)-siRNA polyplexes in their internalization in epithelial and endothelial cells. We observed that introduction of HSA preserves the capacity of bPEI to complex with siRNA and protect it against extracellular endonucleases, while affording significantly improved internalization and silencing efficiency, compared to bPEI-siRNA polyplexes in endothelial and metastatic breast cancer epithelial cells. Furthermore, the uptake of the HSA-bPEI-siRNA ternary polyplexes occurred primarily through a caveolae-mediated endocytosis, thus providing evidence for a clear role for HSA in polyplex internalization. These results provide further impetus to explore the role of serum proteins in delivery of siRNA. PMID:25856158

  6. Cationic derivatives of biocompatible hyaluronic acids for delivery of siRNA and antisense oligonucleotides.

    PubMed

    Han, Su-Eun; Kang, Hyungu; Shim, Ga Yong; Kim, Sun Jae; Choi, Han-Gon; Kim, Jiseok; Hahn, Sei Kwang; Oh, Yu-Kyoung

    2009-02-01

    In this study, we tested the use of cationic polymer derivatives of biocompatible hyaluronic acid (HA) as a delivery system of siRNA and antisense oligonucleotides. HA was modified with cationic polymer polyethylenimine (PEI). When compared with PEI alone, cationic PEI derivatives of HA (HA-PEI) provided increased cellular delivery of Small interfering RNA (siRNA) in B16F1, A549, HeLa, and Hep3B tumor cells. Indeed, more than 95% of the cells were positive for siRNA following its delivery with HA-PEI. A survivin-specific siRNA that was delivered using HA-PEI potently reduced the mRNA expression levels of the target gene in all of the cell lines. By contrast, survivin-specific siRNA delivered by PEI alone did not induce a significant reduction in mRNA levels. In green fluorescent protein (GFP)-expressing 293 T cells, a loss of GFP expression was evident in the cells that had been treated with GFP-specific siRNA and HA-PEI complex. The inhibition of target gene expression by antisense oligonucleotide G3139 was also enhanced after delivery with HA-PEI. Moreover, HA-PEI displayed lower cytotoxicity than PEI alone. These results suggest that HA-PEI could be further developed as biocompatible delivery systems of siRNA and antisense oligonucleotides for enhanced cellular uptake and inhibition of target gene expression.

  7. FGFR3 silencing by siRNA inhibits invasion of A549 cells

    PubMed Central

    Li, Yuhua; Liu, Xiguang; Zhang, Hongjun; Jiang, Tao; Xiao, Wenjing; Zhao, Shufen; Yu, Xiaoyun; Han, Fanjie

    2016-01-01

    The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated. Human lung adenocarcinoma A549 cells were transfected with synthetic specific siRNAs targeting a fragment of the FGFR3 gene (namely, siRNA-855, siRNA-1447 and siRNA-2076) or with negative control (NC) siRNA. Cells were divided into five groups (A, siRNA-855 group; B, siRNA-1447 group; C, siRNA-2076 group; D, NC-siRNA group; and E, blank control group). The effect of the above siRNAs targeting FGFR3 on the invasion capacity of A549 cells was detected by Transwell assay. siRNAs against FGFR3 were transfected into A549 cells with by Lipofectamine® 2000, and the expression levels of FGFR3, E-cadherin and MMP9 were measured by reverse transcription-quantitative polymerase chain reaction and western blot assay. The experimental findings indicated that the expression levels of FGFR3 and MMP9 were significantly reduced in the siRNA-FGFR3-transfected groups (A-C groups), compared with those in the D and E groups (P<0.01). In addition, the expression levels of E-cadherin were markedly elevated in the A-C groups, compared with those in the D and E groups (P<0.01). There was no significant difference in E-cadherin expression between the A-C groups, or between the D and E groups (P>0.05). These results indicated that siRNA-FGFR3 was able to decrease the invasiveness of A549 cells, inhibit the expression of MMP9 and increase the expression of E-cadherin by downregulating the expression of FGFR3. Taken

  8. Integrated siRNA design based on surveying of features associated with high RNAi effectiveness

    PubMed Central

    Gong, Wuming; Ren, Yongliang; Xu, Qiqi; Wang, Yejun; Lin, Dong; Zhou, Haiyan; Li, Tongbin

    2006-01-01

    Background Short interfering RNAs have allowed the development of clean and easily regulated methods for disruption of gene expression. However, while these methods continue to grow in popularity, designing effective siRNA experiments can be challenging. The various existing siRNA design guidelines suffer from two problems: they differ considerably from each other, and they produce high levels of false-positive predictions when tested on data of independent origins. Results Using a distinctly large set of siRNA efficacy data assembled from a vast diversity of origins (the siRecords data, containing records of 3,277 siRNA experiments targeting 1,518 genes, derived from 1,417 independent studies), we conducted extensive analyses of all known features that have been implicated in increasing RNAi effectiveness. A number of features having positive impacts on siRNA efficacy were identified. By performing quantitative analyses on cooperative effects among these features, then applying a disjunctive rule merging (DRM) algorithm, we developed a bundle of siRNA design rule sets with the false positive problem well curbed. A comparison with 15 online siRNA design tools indicated that some of the rule sets we developed surpassed all of these design tools commonly used in siRNA design practice in positive predictive values (PPVs). Conclusion The availability of the large and diverse siRNA dataset from siRecords and the approach we describe in this report have allowed the development of highly effective and generally applicable siRNA design rule sets. Together with ever improving RNAi lab techniques, these design rule sets are expected to make siRNAs a more useful tool for molecular genetics, functional genomics, and drug discovery studies. PMID:17129386

  9. Kinetics of a-Si:H bulk defect and a-Si:H/c-Si interface-state reduction

    NASA Astrophysics Data System (ADS)

    de Wolf, Stefaan; Ballif, Christophe; Kondo, Michio

    2012-03-01

    Low-temperature annealing of hydrogenated amorphous silicon (a-Si:H) is investigated. An identical energy barrier is found for the reduction of deep defects in the bulk of a-Si:H films and at the interface such layers form with crystalline Si (c-Si) surfaces. This finding gives direct physical evidence that the defects determining a-Si:H/c-Si interface recombination are silicon dangling bonds and that also kinetically this interface has no unique features compared to the a-Si:H bulk.

  10. Delivery of Therapeutic RNAs Into Target Cells IN VIVO

    NASA Astrophysics Data System (ADS)

    Ng, Mei Ying; Hagen, Thilo

    2014-02-01

    RNA-based therapy is one of the most promising approaches to treat human diseases. Specifically, the use of short interfering RNA (siRNA) siRNA and microRNA (miRNA) mimics for in vivo RNA interference has immense potential as it directly lowers the expression of the therapeutic target protein. However, there are a number of major roadblocks to the successful implementation of siRNA and other RNA based therapies in the clinic. These include the instability of RNAs in vivo and the difficulty to efficiently deliver the RNA into the target cells. Hence, various innovative approaches have been taken over the years to develop effective RNA delivery methods. These methods include liposome-, polymeric nanoparticle- and peptide-mediated cellular delivery. In a recent innovative study, bioengineered bacterial outer membrane vesicles were used as vehicles for effective delivery of siRNA into cells in vivo.

  11. CNx/Si thin heterostructures for miniaturized temperature sensors

    NASA Astrophysics Data System (ADS)

    Simeonov, S.; Szekeres, A.; György, E.; Mihailescu, I. N.; Perrone, A.

    2004-05-01

    CNx/Si thin heterostructures were synthesized on Si <111> substrates by XeCl* excimer laser (λ=308 nm, τFWHM≅30 ns) ablation of nuclear grade graphite targets in 5 Pa nitrogen at room temperature. We investigated the current-voltage and capacitance-voltage characteristics of heterostructures obtained at 77 and 300 K. We monitored their conductance and capacitance as a function of the bias voltage applied, in the 100 Hz-1 MHz frequency range. Our results revealed the formation of deep localized electron states both inside the thin CNx films and at the CNx/Si substrate interface. The investigations evidenced that conduction through the CNx/Si thin heterostructure is of trap-assisted tunneling type. The experimental studies show quite a large decrease in capacitance and increase in conductance with the increase of applied frequency. The capacitance of the CNx/Si thin heterostructures increases with a decrease of the temperature. All the results support the potential development of new types of high sensitivity temperature sensors.

  12. Preparation of crystallographically aligned layers of silicon carbide by pulsed laser deposition of carbon onto Si wafers

    NASA Astrophysics Data System (ADS)

    Rimai, L.; Ager, R.; Weber, W. H.; Hangas, J.; Poindexter, B. D.

    1994-10-01

    It is demonstrated that SiC films can be deposited epitaxially on [001] and [111] Si wafers by excimer laser ablation of just a carbon target, in vacuum, at deposition temperatures as low as 1100 °C. Diffraction studies show that the SiC films have the same crystalline orientation as the substrates. The film growth on the Si substrate to thicknesses as large as 4000 Å with no significant excess carbon indicates that in addition to reaction of the carbon in the plume with Si of the substrate, there is transport of Si within the SiC film. For continued deposition beyond this thickness a carbon layer will form.

  13. Improving Thermomechanical Properties of SiC/SiC Composites

    NASA Technical Reports Server (NTRS)

    DiCarlo, James A.; Bhatt, Ramakrishna T.

    2006-01-01

    Today, a major thrust toward improving the thermomechanical properties of engine components lies in the development of fiber-reinforced silicon carbide matrix composite materials, including SiC-fiber/SiC-matrix composites. These materials are lighter in weight and capable of withstanding higher temperatures, relative to state-of-the-art metallic alloys and oxide-matrix composites for which maximum use temperatures are in the vicinity of 1,100 C. In addition, the toughness or damage tolerance of the SiC-matrix composites is significantly greater than that of unreinforced silicon-based monolithic ceramics. For successful application in advanced engine systems, the SiC-matrix composites should be able to withstand component service stresses and temperatures for the desired component lifetimes. Inasmuch as the high-temperature structural lives of ceramic materials are typically limited by creep-induced growth of flaws, a key property required of such composite materials is high resistance to creep under conditions of use. Also, the thermal conductivity of the materials should be as high as possible so as to minimize component thermal gradients and thermal stresses. A state-of-the-art SiC-matrix composite is typically fabricated in a three-step process: (1) fabrication of a component-shaped architectural preform reinforced by thermally stable high-performance fibers, (2) chemical-vapor infiltration (CVI) of a fiber-coating material such as boron nitride (BN) into the preform, and (3) infiltration of an SiC-based matrix into the remaining porosity in the preform. Generally, the matrices of the highest-performing composites are fabricated by initial use of a CVI SiC matrix component that is typically more thermally stable and denser than matrix components formed by processes other than CVI. As such, the initial SiC matrix component made by CVI provides better environmental protection to the coated fibers embedded within it. Also, the denser CVI SiC imparts to the

  14. An Introduction to the New SI

    ERIC Educational Resources Information Center

    Knotts, Sandra; Mohr, Peter J.; Phillips, William D.

    2017-01-01

    Plans are under way to redefine the International System of Units (SI) around 2018. The new SI specifies the values of certain physical constants to define units. This article explains the new SI in order to provide a resource for high school teachers as well as for advanced students already familiar with the pre-2018 SI.

  15. Bio-inspired materials in drug delivery: Exploring the role of pulmonary surfactant in siRNA inhalation therapy.

    PubMed

    De Backer, Lynn; Cerrada, Alejandro; Pérez-Gil, Jesús; De Smedt, Stefaan C; Raemdonck, Koen

    2015-12-28

    Many pathologies of the respiratory tract are inadequately treated with existing small molecule-based therapies. The emergence of RNA interference (RNAi) enables the post-transcriptional silencing of key molecular disease factors that cannot readily be targeted with conventional small molecule drugs. Pulmonary administration of RNAi effectors, such as small interfering RNA (siRNA), allows direct delivery into the lung tissue, hence reducing systemic exposure. Unfortunately, the clinical translation of RNAi is severely hampered by inefficient delivery of siRNA therapeutics towards the cytoplasm of the target cells. In order to have a better control of the siRNA delivery process, both extra- and intracellular, siRNAs are typically formulated in nanosized delivery vehicles (nanoparticles, NPs). In the lower airways, which are the targeted sites of action for multiple pulmonary disorders, these siRNA-loaded NPs will encounter the pulmonary surfactant (PS) layer, covering the entire alveolar surface. The interaction between the instilled siRNA-loaded NPs and the PS at this nano-bio interface results in the adsorption of PS components onto the surface of the NPs. The formation of this so-called biomolecular corona conceals the original NP surface and will therefore profoundly determine the biological efficacy of the NP. Though this interplay has initially been regarded as a barrier towards efficient siRNA delivery to the respiratory target cell, recent reports have illustrated that the interaction with PS might also be beneficial for local pulmonary siRNA delivery.

  16. Crystallinity control of SiC grown on Si by sputtering method

    NASA Astrophysics Data System (ADS)

    Watanabe, Ryosuke; Tsukamoto, Takahiro; Kamisako, Koichi; Suda, Yoshiyuki

    2017-04-01

    We investigated a method of controlling the crystallinity of an n-type SiC (n-SiC) layer grown on a p-type 4°-off-axis Si(1 1 1) (p-Si) substrate by our sputtering method for use as SiC/Si devices. An n-SiC layer grown on p-Si at 810 °C exhibits columnar 3C-SiC(1 1 1) crystal growth. However, it contains many defects near the n-SiC/p-Si interface. We then propose a method in which a 10-nm-thick nondoped SiC (i-SiC) interlayer is grown at a low temperature of 640 °C prior to the growth of the n-SiC layer at 810 °C, which results in a decrease in the number of defects at the SiC/p-Si interface and an intensive increase in the crystallinity of the n-SiC, compared with that of n-SiC grown at 810 °C without the interlayer, probably via effective interlayer reconstruction and an enhancement in the crystallinity of the i-SiC interlayer itself during the n-SiC growth. Furthermore, the n-SiC/i-SiC-interlayer/p-Si structure was applied as a Si-based solar cell and the energy conversion efficiency of the n-SiC/p-Si solar cell effectively increased with the insertion of the i-SiC interlayer.

  17. Revealing heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys

    PubMed Central

    Li, Jiehua; Hage, Fredrik S.; Liu, Xiangfa; Ramasse, Quentin; Schumacher, Peter

    2016-01-01

    The heterogeneous nucleation of primary Si and eutectic Si can be attributed to the presence of AlP. Although P, in the form of AlP particles, is usually observed in the centre of primary Si, there is still a lack of detailed investigations on the distribution of P within primary Si and eutectic Si in hypereutectic Al-Si alloys at the atomic scale. Here, we report an atomic-scale experimental investigation on the distribution of P in hypereutectic Al-Si alloys. P, in the form of AlP particles, was observed in the centre of primary Si. However, no significant amount of P was detected within primary Si, eutectic Si and the Al matrix. Instead, P was observed at the interface between the Al matrix and eutectic Si, strongly indicating that P, in the form of AlP particles (or AlP ‘patch’ dependent on the P concentration), may have nucleated on the surface of the Al matrix and thereby enhanced the heterogeneous nucleation of eutectic Si. The present investigation reveals some novel insights into heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys and can be used to further develop heterogeneous nucleation mechanisms based on adsorption. PMID:27120994

  18. Revealing heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys

    NASA Astrophysics Data System (ADS)

    Li, Jiehua; Hage, Fredrik S.; Liu, Xiangfa; Ramasse, Quentin; Schumacher, Peter

    2016-04-01

    The heterogeneous nucleation of primary Si and eutectic Si can be attributed to the presence of AlP. Although P, in the form of AlP particles, is usually observed in the centre of primary Si, there is still a lack of detailed investigations on the distribution of P within primary Si and eutectic Si in hypereutectic Al-Si alloys at the atomic scale. Here, we report an atomic-scale experimental investigation on the distribution of P in hypereutectic Al-Si alloys. P, in the form of AlP particles, was observed in the centre of primary Si. However, no significant amount of P was detected within primary Si, eutectic Si and the Al matrix. Instead, P was observed at the interface between the Al matrix and eutectic Si, strongly indicating that P, in the form of AlP particles (or AlP ‘patch’ dependent on the P concentration), may have nucleated on the surface of the Al matrix and thereby enhanced the heterogeneous nucleation of eutectic Si. The present investigation reveals some novel insights into heterogeneous nucleation of primary Si and eutectic Si by AlP in hypereutectic Al-Si alloys and can be used to further develop heterogeneous nucleation mechanisms based on adsorption.

  19. Thermodynamics of Si-C-O system

    NASA Technical Reports Server (NTRS)

    Jacobson, N. S.; Opila, E. J.

    1993-01-01

    The Si-C-O predominance diagram, in conjunction with a free-energy minimum of the gas phase, has been used to explain several observations in the reactions of SiC and/or carbon with SiO2. In the predominance diagram, the axes are chosen as the primary activity units for carbon and oxygen. The predominance diagram shows only the stable condensed phases SiO2, SiC, carbon, and silicon. It also shows the isobars for SiO(g) and CO(g), which are the primary gas-phase species. Only the thermodynamics of the system is considered. The observations explained include the general adjustment of carbon-rich SiC to a free-energy minimum on the SiC/SiO2 coexistence line and the inability to form free silicon from SiO2 and carbon, except at very high temperatures.

  20. Detector production for the R3B Si-tracker

    NASA Astrophysics Data System (ADS)

    Borri, M.; Lemmon, R.; Thornhill, J.; Bate, R.; Chartier, M.; Clague, N.; Herzberg, R.-D.; Labiche, M.; Lindsay, S.; Nolan, P.; Pearce, F.; Powell, W.; Wells, D.

    2016-11-01

    R3B is a fixed target experiment which will study reactions with relativistic radioactive beams at FAIR. Its Si-tracker will surround the target volume and it will detect light charged-particles like protons. The detector technology in use consists of double-sided silicon strip sensors wire bonded to the custom made R3B-ASIC. The tracker allows for a maximum of two outer layers and one inner layer. This paper reports on the production of detectors necessary to build the minimum tracking configuration: one inner layer and one outer layer.

  1. Construction and characterization of spherical Si solar cells combined with SiC electric power inverter

    NASA Astrophysics Data System (ADS)

    Oku, Takeo; Matsumoto, Taisuke; Hiramatsu, Kouichi; Yasuda, Masashi; Shimono, Akio; Takeda, Yoshikazu; Murozono, Mikio

    2015-02-01

    Spherical silicon (Si) photovoltaic solar cell systems combined with an electric power inverter using silicon carbide (SiC) field-effect transistor (FET) were constructed and characterized, which were compared with an ordinary Si-based converter. The SiC-FET devices were introduced in the direct current-alternating current (DC-AC) converter, which was connected with the solar panels. The spherical Si solar cells were used as the power sources, and the spherical Si panels are lighter and more flexible compared with the ordinary flat Si solar panels. Conversion efficiencies of the spherical Si solar cells were improved by using the SiC-FET.

  2. Inhibition of hepatitis C virus replication by intracellular delivery of multiple siRNAs by nanosomes.

    PubMed

    Chandra, Partha K; Kundu, Anup K; Hazari, Sidhartha; Chandra, Sruti; Bao, Lili; Ooms, Tara; Morris, Gilbert F; Wu, Tong; Mandal, Tarun K; Dash, Srikanta

    2012-09-01

    Sustained antiviral responses of chronic hepatitis C virus (HCV) infection have improved recently by the use of direct-acting antiviral agents along with interferon (IFN)-α and ribavirin. However, the emergence of drug-resistant variants is expected to be a major problem. We describe here a novel combinatorial small interfering RNA (siRNA) nanosome-based antiviral approach to clear HCV infection. Multiple siRNAs targeted to the highly conserved 5'-untranslated region (UTR) of the HCV genome were synthesized and encapsulated into lipid nanoparticles called nanosomes. We show that siRNA can be repeatedly delivered to 100% of cells in culture using nanosomes without toxicity. Six siRNAs dramatically reduced HCV replication in both the replicon and infectious cell culture model. Repeated treatments with two siRNAs were better than a single siRNA treatment in minimizing the development of an escape mutant, resulting in rapid inhibition of viral replication. Systemic administration of combinatorial siRNA-nanosomes is well tolerated in BALB/c mice without liver injury or histological toxicity. As a proof-of-principle, we showed that systemic injections of siRNA nanosomes significantly reduced HCV replication in a liver tumor-xenotransplant mouse model of HCV. Our results indicate that systemic delivery of combinatorial siRNA nanosomes can be used to minimize the development of escape mutants and inhibition of HCV infection.

  3. siRNAs induce efficient RNAi response in Bombyx mori embryos.

    PubMed

    Yamaguchi, Junichi; Mizoguchi, Takayuki; Fujiwara, Haruhiko

    2011-01-01

    Short interference RNA (siRNA) is widely used in mammalian cells. In insects, however, reports concerning the suitablility of siRNA in vivo is very limited compared with that of long dsRNA, which is thought to be more effective. There is insufficient information on the essential rules of siRNA design in insects, as very few siRNAs have been tested in this context. To establish an effective method of gene silencing using siRNA in vivo in insects, we determined the effects of siRNA on seven target genes. We designed siRNAs according to a new guideline and injected them into eggs of Bombyx mori. At the mRNA level, the expression of most of these genes was successfully silenced, down to less than half the constitutive level, which in some cases led to the development of distinctive phenotypes. In addition, we observed stronger effect of siRNA both on the mRNA level and the phenotype than that of long dsRNA under comparable conditions. These results indicate that direct injection of siRNA is an effective reverse-genetics tool for the analysis of embryogenesis in vivo in insects.

  4. Pourous Si(x)Ge(1-x) Layers Within Single Crystals Of Si

    NASA Technical Reports Server (NTRS)

    Fathauer, Robert W.; George, Thomas

    1994-01-01

    Layers of porous Si(x)Ge(1-x) buried within single crystals of Si formed by epitaxial growth of Si/Si(x)Ge(1-x)/Si structures followed by etching in solutions of HF:HNO3:H2O. Electroluminescence from these layers utilized in novel optoelectronic devices.

  5. Long-Wavelength Stacked Si(sub 1-x)/Si Heterojunction Internal Photoemission Infrared Detectors

    NASA Technical Reports Server (NTRS)

    Park, J. S.; Lin, T. L.; Jones, E. W.; Castillo, H. M. Del; George, T.; Gunapala, S. D.

    1993-01-01

    Utilizing the low temperature silicon molecular beam epitaxy (MBE) growth of degenerately doped SiGe layers on Si, long wavelength stacked SiGe/Si heterojunction internal photoemission (HIP) infrared detectors with multiple SiGe/Se layers have been fabricated and demonstrated.

  6. Selective Growth of Nanocrystalline 3C-SiC Thin Films on Si

    NASA Astrophysics Data System (ADS)

    Beke, D.; Pongrácz, A.; Battistig, G.; Josepovits, K.; Pécz, B.

    2010-11-01

    Epitaxial formation of SiC nanocrystals has been investigated on single crystal silicon surfaces. A simple and cheap method using reactive annealing in CO has been developed and patented by our group (BME AFT and MTA MFA). By this technique epitaxial 3C-SiC nanocrystals can be grown at the Si side of a SiO2/Si interface without void formation at the SiC/Si interface. CO diffusion and SiC nanocrystal formation on different silicon based systems (SiO2/Si, Si3N4/3Si and SiO2/LPCVD poly-Si) after CO treatment at 105 Pa at elevated temperatures (T>1000° C) will be presented. By optimizing the annealing time a thin continuous nanocrystalline SiC layer has been formed. Applying a patterned Si3N4 capping layer as a barrier layer against CO diffusion, SiC nanocrystal formation at the Si3N4/Si interface is inhibited. We will present the selective growth of SiC nanocrystals using the before mentioned technique.

  7. Flexible Solar Cells Using Doped Crystalline Si Film Prepared by Self-Biased Sputtering Solid Doping Source in SiCl4/H2 Microwave Plasma.

    PubMed

    Hsieh, Ping-Yen; Lee, Chi-Young; Tai, Nyan-Hwa

    2016-02-01

    We developed an innovative approach of self-biased sputtering solid doping source process to synthesize doped crystalline Si film on flexible polyimide (PI) substrate via microwave-plasma-enhanced chemical vapor deposition (MWPECVD) using SiCl4/H2 mixture. In this process, P dopants or B dopants were introduced by sputtering the solid doping target through charged-ion bombardment in situ during high-density microwave plasma deposition. A strong correlation between the number of solid doping targets and the characteristics of doped Si films was investigated in detail. The results show that both P- and B-doped crystalline Si films possessed a dense columnar structure, and the crystallinity of these structures decreased with increasing the number of solid doping targets. The films also exhibited a high growth rate (>4.0 nm/s). Under optimal conditions, the maximum conductivity and corresponding carrier concentration were, respectively, 9.48 S/cm and 1.2 × 10(20) cm(-3) for P-doped Si film and 7.83 S/cm and 1.5 × 10(20) cm(-3) for B-doped Si film. Such high values indicate that the incorporation of dopant with high doping efficiency (around 40%) into the Si films was achieved regardless of solid doping sources used. Furthermore, a flexible crystalline Si film solar cell with substrate configuration was fabricated by using the structure of PI/Mo film/n-type Si film/i-type Si film/p-type Si film/ITO film/Al grid film. The best solar cell performance was obtained with an open-circuit voltage of 0.54 V, short-circuit current density of 19.18 mA/cm(2), fill factor of 0.65, and high energy conversion of 6.75%. According to the results of bending tests, the critical radius of curvature (RC) was 12.4 mm, and the loss of efficiency was less than 1% after the cyclic bending test for 100 cycles at RC, indicating superior flexibility and bending durability. These results represent important steps toward a low-cost approach to high-performance flexible crystalline Si film

  8. Flex Fuel Optimized SI and HCCI Engine

    SciTech Connect

    Zhu, Guoming; Schock, Harold; Yang, Xiaojian; Huisjen, Andrew; Stuecken, Tom; Moran, Kevin; Zhen, Ron; Zhang, Shupeng

    2013-09-30

    the electrical variable valve timing (VVT) actuating system and satisfactory electrical VVT responses were obtained. Target engine control system was designed and fabricated at MSU for both single-cylinder optical and multi-cylinder metal engines. Finally, the developed control-oriented engine model was successfully implemented into the HIL simulation environment. The Chrysler 2.0L I4 DI engine was modified to fit the two-step vale with electrical variable valve timing actuating system. A used prototype engine was used as the base engine and the cylinder head was modified for the two-step valve with electrical VVT actuating system. Engine validation tests indicated that cylinder #3 has very high blow-by and it cannot be reduced with new pistons and rings. Due to the time constraint, it was decided to convert the four-cylinder engine into a single cylinder engine by blocking both intake and exhaust ports of the unused cylinders. The model-based combustion mode transition control algorithm was developed in the MSU HIL simulation environment and the Simulink based control strategy was implemented into the target engine controller. With both single-cylinder metal engine and control strategy ready, stable HCCI combustion was achived with COV of 2.1% Motoring tests were conducted to validate the actuator transient operations including valve lift, electrical variable valve timing, electronic throttle, multiple spark and injection controls. After the actuator operations were confirmed, 15-cycle smooth combustion mode transition from SI to HCCI combustion was achieved; and fast 8-cycle smooth combustion mode transition followed. With a fast electrical variable valve timing actuator, the number of engine cycles required for mode transition can be reduced down to five. It was also found that the combustion mode transition is sensitive to the charge air and engine coolant temperatures and regulating the corresponding temperatures to the target levels during the combustion mode

  9. Optimum condition to fabricate 5-10 nm SiO2/Si structure using advanced nitric acid oxidation of Si method with Si source

    NASA Astrophysics Data System (ADS)

    Imamura, Kentaro; Matsumoto, Taketoshi; Kobayashi, Hikaru

    2012-12-01

    A low temperature (≦120 °C) fabrication method to form relatively thick SiO2/Si structure with a Si source has been developed using the advanced nitric acid oxidation of Si (NAOS) method, and the formation mechanism has been investigated. The reaction mechanism consists of direct oxidation of Si, dissolution of Si sources, and surface reaction of the dissolved Si species. The dissolved Si species is present in HNO3 solutions as mono-silicic acid and reacts with oxidizing species formed by decomposition of HNO3 on an ultrathin SiO2 layer (i.e., 1.4 nm) produced by the direct oxidation of Si substrates with HNO3 solutions. To achieve a uniform thickness of SiO2 layer with a smooth surface, HNO3 solutions with concentrations higher than 60 wt. % are needed because the dissolved Si species polymerizes in HNO3 solutions when the concentration is below 60 wt. %, resulting in the formation of SiO2 particles in HNO3, which are deposited afterwards on the SiO2 layer. In spite of the low temperature formation at 120 °C, the electrical characteristics of the advanced NAOS SiO2 layer formed with 68 wt. % HNO3 and subsequent post-metallization anneal at 250 °C are nearly identical to those of thermal oxide formed at 900 °C.

  10. Rescue of Mtp siRNA-induced hepatic steatosis by DGAT2 siRNA silencing.

    PubMed

    Tep, Samnang; Mihaila, Radu; Freeman, Alexander; Pickering, Victoria; Huynh, Felicia; Huyhn, Felicia; Tadin-Strapps, Marija; Stracks, Allison; Hubbard, Brian; Caldwell, Jeremy; Flanagan, W Michael; Kuklin, Nelly A; Ason, Brandon

    2012-05-01

    Microsomal triglyceride transfer protein (Mtp) inhibitors represent a novel therapeutic approach to lower circulating LDL cholesterol, although therapeutic development has been hindered by the observed increase in hepatic triglycerides and liver steatosis following treatment. Here, we used small interfering RNAs (siRNA) targeting Mtp to achieve target-specific silencing to study this phenomenon and to determine to what extent liver steatosis is induced by changes in Mtp expression. We observed that Mtp silencing led to a decrease in many genes involved in hepatic triglyceride synthesis. Given the role of diacylglycerol O-acyltransferase 2 (Dgat2) in regulating hepatic triglyceride synthesis, we then evaluated whether target-specific silencing of both Dgat2 and Mtp were sufficient to attenuate Mtp silencing-induced liver steatosis. We showed that the simultaneous inhibition of Dgat2 and Mtp led to a decrease in plasma cholesterol and a reduction in the accumulation of hepatic triglycerides caused by the inhibition of Mtp. Collectively, these findings provide a proof-of-principle for a triglyceride synthesis/Mtp inhibitor combination and represent a potentially novel approach for therapeutic development in which targeting multiple pathways can achieve the desired response.

  11. Epigenome Editing of Potato by Grafting Using Transgenic Tobacco as siRNA Donor

    PubMed Central

    Hojo, Hatsune; Harada, Takeo

    2016-01-01

    In plants, it is possible to induce heritable transcriptional gene silencing (TGS) via RNA-directed DNA methylation (RdDM) using artificially synthesized small RNA (siRNA) homologous to the 5'-flanking region of the target gene. As the siRNA signal with a specific RNA determinant moves through plasmodesmata and sieve elements, we attempted to induce TGS of a transgene and an endogenous gene of potato (Solanum tuberosum) rootstock by grafting using siRNA produced in a tobacco (Nicotiana benthamiana) scion. Our results provide evidence that this system can induce TGS of target genes in tubers formed on potato rootstock. The TGS is maintained in the progeny tubers lacking the transported siRNAs. Our findings reveal that epigenome editing using mobile RNA has the potential to allow breeding of artificial sport cultivars in vegetative propagation crops. PMID:27564864

  12. Development of streptavidin-based nanocomplex for siRNA delivery.

    PubMed

    Shukla, Ravi S; Tai, Wanyi; Mahato, Rubi; Jin, Wei; Cheng, Kun

    2013-12-02

    In our previous study, we have identified a PCBP2 siRNA that exhibits antifibrotic activity in rat hepatic stellate cells (HSCs) by inhibition of αCP2, a protein responsible for stabilization of the collagen α1 (I) mRNA in alcoholic liver fibrosis. This study aims to develop a streptavidin-based nanocomplex that can efficiently deliver the PCBP2 siRNA to HSCs. Biotin-siRNA and biotin-cholesterol were mixed with streptavidin to form the streptavidin-biotin complex, which was further condensed electrostatically with positively charged protamine to form the final multicomponent siRNA nanocomplex in the size range of 150-250 nm. The siRNA nanocomplex does not induce cytotoxicity in rat HSCs as compared to commercially available transfection agents. The cellular uptake efficiency of the siRNA nanocomplex is higher in rat HSCs than other cell lines, such as Caco-2 and PC-3, indicating that receptor-mediated endocytosis mainly contributes to the cellular uptake of the siRNA nanocomplex. The siRNA nanocomplex exhibits more than 85% silencing effect on the PCBP2 mRNA in HSCs. Stability study indicates that the nanocomplex can efficiently protect siRNA from degradation in the serum. The streptavidin-based multicomponent siRNA nanocomplex provides a promising strategy to deliver the PCBP2 siRNA to HSCs. Moreover, the nanocomplex can be used as a platform for other diseases by changing the siRNA sequence and targeting ligand.

  13. Dynamics of SiO2 Buried Layer Removal from Si-SiO2-Si and Si-SiO2-SiC Bonded Substrates by Annealing in Ar

    NASA Astrophysics Data System (ADS)

    Li, L.-G.; Rubino, S.; Vallin, Ö.; Olsson, J.

    2014-02-01

    Silicon-on-silicon-carbide substrates could be ideal for high-power and radiofrequency silicon devices. Such hybrid wafers, when made by wafer bonding, contain an intermediate silicon dioxide layer with poor thermal characteristics, which can be removed by high-temperature annealing in an inert atmosphere. To understand the dynamics of this process, removal of 2.4-nm-thick SiO2 layers from Si-SiO2-Si and Si-SiO2-SiC substrates has been studied at temperatures ranging from 1100°C to 1200°C. The substrates were analyzed by transmission electron microscopy, electron energy-loss spectroscopy, secondary-ion mass spectroscopy, and ellipsometry, before and after annealing. For oxide thickness less than 2.4 nm, the activation energy for oxide removal was estimated to be 6.4 eV, being larger than the activation energy reported for removal of thicker oxides (4.1 eV). Under the same conditions, the SiO2 layer became discontinuous. In the time domain, three steps could be distinguished: bulk diffusion, bulk diffusion with void formation, and bulk diffusion with disintegration. The void formation, predominant here, has an energetic cost that could explain the larger activation energy. The oxide remaining after prolonged annealing corresponds to one layer of oxygen atoms.

  14. Efficient Gene Silencing in Metastatic Tumor by siRNA Formulated in Surface-modified Nanoparticles

    PubMed Central

    Li, Shyh-Dar; Chono, Sumio; Huang, Leaf

    2009-01-01

    We have developed a nanoparticle (NP) formulation for systemically delivering siRNA into metastatic tumors. The NP, composed of nucleic acids, a polycationic peptide and cationic liposome, was prepared in a self-assembling process. The NP was then modified by PEG-lipid containing a targeting ligand, anisamide, and thus was decorated for targeting sigma receptor expressing B16F10 tumor. The activity of the targeted NP was compared with the naked NP (no PEGylation) and non-targeted NP (no ligand). The delivery efficiency of the targeted NP was 4-fold higher than the non-targeted NP and could be competed by excess free ligand. Luciferase siRNA was used to evaluate the gene silencing activity in the B16F10 cells, which were stably transduced with a luciferase gene, in a lung metastasis model. The gene silencing activity of the targeted NP was significantly higher than the other formulations and lasted for 4 days. While confocal microscopy showed the naked NP provided no tissue selectivity and non-targeted NP was ineffective for tumor uptake, the targeted NP effectively penetrated the lung metastasis, but not the liver. It resulted in 70-80% gene silencing in the metastasis model after a single i.v. injection (150 μg siRNA/kg). This effective formulation also showed very little immunotoxicity. PMID:18083264

  15. siRNA and miRNA processing: new functions for Cajal bodies.

    PubMed

    Pontes, Olga; Pikaard, Craig S

    2008-04-01

    In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) regulate important processes that include mRNA inactivation, viral defense, chromatin modification, and transposon silencing. Recently, nucleolus-associated Cajal bodies in plants have been implicated as sites of siRNA and miRNA biogenesis, whereas in animals siRNA and miRNA dicing occurs in the cytoplasm. The plant nucleolus also contains proteins of the nonsense-mediated mRNA decay pathway that in animals are found associated with cytoplasmic processing bodies (P-bodies). P-bodies also function in the degradation of mRNAs subjected to miRNA and siRNA targeting. Collectively, these observations suggest interesting variations in the way siRNAs and miRNAs can accomplish their similar functions in plants and animals.

  16. Technologies for Investigating the Physiological Barriers to Efficient Lipid Nanoparticle–siRNA Delivery

    PubMed Central

    Abrams, Marc

    2013-01-01

    Small interfering RNA (siRNA) therapeutics have advanced from bench to clinical trials in recent years, along with new tools developed to enable detection of siRNA delivered at the organ, cell, and subcellular levels. Preclinical models of siRNA delivery have benefitted from methodologies such as stem-loop quantitative polymerase chain reaction, histological in situ immunofluorescent staining, endosomal escape assay, and RNA-induced silencing complex loading assay. These technologies have accelerated the detection and optimization of siRNA platforms to overcome the challenges associated with delivering therapeutic oligonucleotides to the cytosol of specific target cells. This review focuses on the methodologies and their application in the biodistribution of siRNA delivered by lipid nanoparticles. PMID:23504369

  17. Co-sputtering NbTiN thin films on PSG/Si substrates

    NASA Astrophysics Data System (ADS)

    Wang, Chen; Zhang, Jingjiao; Zhang, Lu; You, Lixing; Su, Xiaodong

    2016-02-01

    Single-crystalline silicon is one of a few promising substrate materials on which to grow NbTiN ultrathin films for applications in superconducting single photon detection devices. In this work, a buffer layer of phosphorus silicate glass (PSG) ∼250 nm is formed rapidly on the silicon substrate under a relatively low temperature to ease the mismatching between NbTiN and substrate, and simultaneously act as an antireflection layer at the working wavelength. (111)-oriented NbTiN films were deposited on both SiO2/Si and PSG/Si substrates by using a dc reactive magnetron co-sputtering system of independent Nb and Ti targets. The superconducting critical temperature T c of the 5 nm-NbTiN/PSG/Si sample reaches ∼8.8 K due to effectively relieving the mismatch between NbTiN and Si by PSG buffer layer.

  18. Abasic pivot substitution harnesses target specificity of RNA interference

    PubMed Central

    Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

    2015-01-01

    Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA–target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼80–100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications. PMID:26679372

  19. Abasic pivot substitution harnesses target specificity of RNA interference.

    PubMed

    Lee, Hye-Sook; Seok, Heeyoung; Lee, Dong Ha; Ham, Juyoung; Lee, Wooje; Youm, Emilia Moonkyung; Yoo, Jin Seon; Lee, Yong-Seung; Jang, Eun-Sook; Chi, Sung Wook

    2015-12-18

    Gene silencing via RNA interference inadvertently represses hundreds of off-target transcripts. Because small interfering RNAs (siRNAs) can function as microRNAs, avoiding miRNA-like off-target repression is a major challenge. Functional miRNA-target interactions are known to pre-require transitional nucleation, base pairs from position 2 to the pivot (position 6). Here, by substituting nucleotide in pivot with abasic spacers, which prevent base pairing and alleviate steric hindrance, we eliminate miRNA-like off-target repression while preserving on-target activity at ∼ 80-100%. Specifically, miR-124 containing dSpacer pivot substitution (6pi) loses seed-mediated transcriptome-wide target interactions, repression activity and biological function, whereas other conventional modifications are ineffective. Application of 6pi allows PCSK9 siRNA to efficiently lower plasma cholesterol concentration in vivo, and abolish potentially deleterious off-target phenotypes. The smallest spacer, C3, also shows the same improvement in target specificity. Abasic pivot substitution serves as a general means to harness the specificity of siRNA experiments and therapeutic applications.

  20. Mo-Si alloy development

    SciTech Connect

    Liu, C.T.; Heatherly, L.; Wright, J.L.

    1996-06-01

    The objective of this task is to develop new-generation corrosion-resistant Mo-Si intermetallic alloys as hot components in advanced fossil energy conversion and combustion systems. The initial effort is devoted to Mo{sub 5}-Si{sub 3}-base (MSB) alloys containing boron additions. Three MSB alloys based on Mo-10.5Si-1.1B (wt %), weighing 1500 g were prepared by hot pressing of elemental and alloy powders at temperatures to 1600{degrees}C in vacuum. Microporosities and glassy-phase (probably silicate phases) formations are identified as the major concerns for preparation of MSB alloys by powder metallurgy. Suggestions are made to alleviate the problems of material processing.

  1. SiRNA-based therapies for pulmonary diseases.

    PubMed

    Koli, Uday; Krishnan, R Akhil; Pofali, Prasad; Jain, Ratnesh; Dandekar, Prajakta

    2014-09-01

    Various delivery strategies, involving siRNA as a therapeutic tool for gene silencing, have been highlighted through several investigations all over the world. One such medical target, where the siRNA-based therapies have been immensely explored and have met with considerable success, is the area of pulmonary disorders. Lung dis