Magnetic characterization of superparamagnetic nanoparticles pulled through model membranes

BACKGROUND: To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM. METHODS: Three-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing was used to pull SPION through a three-layer cell culture RWM model. Similar maps were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other parameters needed to compute magnetic force were nanoparticle and polymer properties, including average radius, density, magnetic susceptibility, and volume fraction of magnetite. RESULTS: A minimum force of 5.04 × 10(-16 )N was determined to adequately pull nanoparticles through the in-vitro model. For the guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 × 10(-20 )N. Electron microscopy confirmed the movement of the particles through both RWM models. CONCLUSION: As prospective carriers of therapeutic substances, polymers containing superparamagnetic iron oxide nanoparticles were succesfully pulled through the live RWM. The force required to achieve in vivo transport was significantly lower than that required to pull nanoparticles through the in-vitro RWM model. Indeed very little force was required to accomplish measurable delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting that therapeutic delivery to the inner ear by SPION is feasible

The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field

BACKGROUND: Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear. The RWM model is a 3 cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter were pulled through the RWM model using permanent magnets with flux density 0.410 Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed in 4% paraformaldehyde. Transmission electron microscopy and fluorescence spectrophotometry were used to verify transepithelial transport of the SPION across the cell-culture model. Histological sections were examined for evidence of SPION toxicity, as well to generate a timeline of the position of the SPION at different times. SPION also were added to cells in culture to assess in vitro toxicity. RESULTS: Transepithelial electrical resistance measurements confirmed epithelial confluence, as SPION crossed a membrane consisting of three co-cultured layers of cells, under the influence of a magnetic field. Micrographs showed SPION distributed throughout the membrane model, in between cell layers, and sometimes on the surface of cells. TEM verified that the SPION were pulled through the membrane into the culture well below. Fluorescence spectrophotometry quantified the number of SPION that went through the SIS membrane. SPION showed no toxicity to cells in culture. CONCLUSION: A three-cell layer model of the human round window membrane has been constructed. SPION have been magnetically transported through this model, allowing quantitative evaluation of prospective targeted drug or gene delivery through the RWM. Putative in vivo carrier superparamagnetic nanoparticles may be evaluated using this model

Study of the reaction pbar p -> phi phi from 1.1 to 2.0 GeV/c

A study has been performed of the reaction pbar p -> 4K using in-flight antiprotons from 1.1 to 2.0 GeV/c incident momentum interacting with a hydrogen jet target. The reaction is dominated by the production of a pair of phi mesons. The pbar p -> phi phi cross section rises sharply above threshold and then falls continuously as a function of increasing antiproton momentum. The overall magnitude of the cross section exceeds expectations from a simple application of the OZI rule by two orders of magnitude. In a fine scan around the xi/f_J(2230) resonance, no structure is observed. A limit is set for the double branching ratio B(xi -> pbar p) * B(xi -> phi phi) < 6e-5 for a spin 2 resonance of M = 2.235 GeV and Width = 15 MeV.Comment: 13 pages, 13 figures, 2 tables, Latex. To be published in Phys. Rev.

A partial wave analysis of the centrally produced K+K- and K0K0 systems in pp interactions at 450 GeV/c and new information on the spin of the fJ(1710)

A partial wave analysis of the centrally produced K+K- and K0K0 channels has been performed in pp collisions using an incident beam momentum of 450 GeV/c. An unambiguous physical solution has been found in each channel. The striking feature is the observation of peaks in the S-wave corresponding to the f0(1500) and fJ(1710) with J = 0. The D-wave shows evidence for the f2(1270)/a2(1320), the f2(1525) and the f2(2150) but there is no evidence for a statistically significant contribution in the D-wave in the 1.7 GeV mass region.Comment: 15 pages, Latex, 5 Figure

Limits on diffuse fluxes of high energy extraterrestrial neutrinos with the AMANDA-B10 detector

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon-neutrinos, as predicted from, e.g., the sum of all active galaxies in the universe. This search yielded no excess events above those expected from the background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux. For an assumed E^-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E^2 Phi(E) = 8.4 x 10^-7 GeV cm^-2 s^-1 sr^-1 (for a predominant neutrino energy range 6-1000 TeV) which is the most restrictive bound placed by any neutrino detector. When specific predicted spectral forms are considered, it is found that some are excluded.Comment: Submitted to Physical Review Letter

Search for Point Sources of High Energy Neutrinos with AMANDA

This paper describes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector, an array of 302 photomultiplier tubes, used for the detection of Cherenkov light from upward traveling neutrino-induced muons, buried deep in ice at the South Pole. The absolute pointing accuracy and angular resolution were studied by using coincident events between the AMANDA detector and two independent telescopes on the surface, the GASP air Cherenkov telescope and the SPASE extensive air shower array. Using data collected from April to October of 1997 (130.1 days of livetime), a general survey of the northern hemisphere revealed no statistically significant excess of events from any direction. The sensitivity for a flux of muon neutrinos is based on the effective detection area for through-going muons. Averaged over the Northern sky, the effective detection area exceeds 10,000 m^2 for E_{mu} ~ 10 TeV. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the predicted performance of the detector. For a source with a differential energy spectrum proportional to E_{nu}^{-2} and declination larger than +40 degrees, we obtain E^2(dN_{nu}/dE) <= 10^{-6}GeVcm^{-2}s^{-1} for an energy threshold of 10 GeV.Comment: 46 pages, 22 figures, 4 tables, submitted to Ap.

Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of December 27th, 2004 with the AMANDA-II detector

On December 27th 2004, a giant gamma flare from the Soft Gamma-ray Repeater 1806-20 saturated many satellite gamma-ray detectors. This event was by more than two orders of magnitude the brightest cosmic transient ever observed. If the gamma emission extends up to TeV energies with a hard power law energy spectrum, photo-produced muons could be observed in surface and underground arrays. Moreover, high-energy neutrinos could have been produced during the SGR giant flare if there were substantial baryonic outflow from the magnetar. These high-energy neutrinos would have also produced muons in an underground array. AMANDA-II was used to search for downgoing muons indicative of high-energy gammas and/or neutrinos. The data revealed no significant signal. The upper limit on the gamma flux at 90% CL is dN/dE < 0.05 (0.5) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2). Similarly, we set limits on the normalization constant of the high-energy neutrino emission of 0.4 (6.1) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2).Comment: 14 pages, 3 figure

Sheep Updates 2005 - Part 4

This session covers twelve papers from different authors: REPRODUCTION 1. Is it worth increasing investment to increase lambing percentages? Lucy Anderton Department of Agriculture Western Australia. 2. What value is a lamb? John Young, Farming Systems Analysis Service, Kojonup, WA 3. Providing twin-bearing ewes with extra energy at lambing produces heavier lambs at marking. Rob Davidson WAMMCO International,, formerly University of Western Australia; Keith Croker, Ken Hart, Department of Agriculture Western Australia, Tim Wiese, Chuckem , Highbury, Western Australia. GENETICS 4. Underlying biological cause of trade-off between meat and wool. Part 1. Wool and muscle glycogen, BM Thomson, I Williams, University of WA, Crawley, JRBriegel, CSIRO Livestock Industries, Floreat Park WA &CRC for the Australian Sheep Industry, JC Greeff, Department of Agriculture Western Australia &CRC for the Australian Sheep Industry. 5. Underlying biological cause of trade-off between meat and wool. Part 2. Wool and fatness, NR Adams1,3, EN Bermingham1,3, JR Briegel1,3, JC Greeff2,3 1CSIRO Livestock Industries, Floreat Park WA 2Department of Agriculture Western Australia, 3CRC for the Australian Sheep Industry 6. Genetic trade-offs between lamb and wool production in Merino breeding programs, Johan Greeff, Department of Agriculture, Western Australia. 7. Clean fleece weight is no phenotypically independent of other traits. Sue Hatcherac and Gordon Refshaugebc aNSWDPI Orange Agricultural Institute, Orange NSW 2800 bUNE c/- NSWDPI Cowra AR&AS Cowra NSW 2794 cAustralian Sheep Industry CRC. 8. When you\u27re on a good thing, do it better: An economic analysis of sheep breed profitability. Emma Kopke, Ross Kingwell, Department of Agriculture, Western Australia, John Young, Farming Systems Analysis Service, Kojonup, WA. 9. Selection Demonstration Flocks: Demonstrating improvementsin productivity of merinos, K.E. Kemper, M.L. Hebart, F.D. Brien, K.S. Jaensch, R.J. Grimson, D.H. Smith South Australian Research and Development Institute 10. You are compromising yield by using Dust Penetration and GFW in breeding programs, Melanie Dowling, Department of Agriculture, Western Australia, A. (Tony) Schlink, CSIRO Livestock Industries, Wembley, Johan Greeff, Department of Agriculture Western Australia. 11. Merino Sheep can be bred for resistance to breech strike. Johan Greeff , John Karlsson, Department of Agriculture Western Australia 12. Parasite resistant sheep and hypersensitivity diarrhoea, L.J.E. Karlsson & J.C. Greeff, Department of Agriculture Western Australi