Gold Nanoparticle Delivery of Modified CpG Stimulates Macrophages and Inhibits Tumor Growth for Enhanced Immunotherapy

Gold nanoparticle accumulation in immune cells has commonly been viewed as a side effect for cancer therapeutic delivery; however, this phenomenon can be utilized for developing gold nanoparticle mediated immunotherapy. Here, we conjugated a modified CpG oligodeoxynucleotide immune stimulant to gold nanoparticles using a simple and scalable selfassembled monolayer scheme that enhanced the functionality of CpG in vitro and in vivo. Nanoparticles can attenuate systemic side effects by enhancing CpG delivery passively to innate effector cells. The use of a triethylene glycol (TEG) spacer on top of the traditional poly-thymidine spacer increased CpG macrophage stimulatory effects without sacrificing DNA content on the nanoparticle, which directly correlates to particle uptake. In addition, the immune effects of modified CpGAuNPs were altered by the core particle size, with smaller 15 nm AuNPs generating maximum immune response. These TEG modified CpG-AuNP complexes induced macrophage and dendritic cell tumor infiltration, significantly inhibited tumor growth, and promoted survival in mice when compared to treatments with free CpG

The Energetic Trans-Iron Composition Experiment (ENTICE) on the Heavy Nuclei Explorer (HNX) Mission

The HNX mission is composed of the ENTICE and ECCO experiments. The experimental goal of ENTICE is to measure with high precision the elemental abundances of all nuclei with 10≤Z≤82. This will enable us to determine if the injection mechanism for the cosmic ray accelerator is controlled by FIP or Volatility and to study the mix of nucleosynthetic processes that contribute to the galactic cosmic ray source. The ENTICE experiment utilizes the dE/dx-C method of charge determination and consists of silicon dE/dx detectors, Cherenkov detectors with two different refractive indices, and a fiber hodoscope. We will describe the instrument and its performance based on beam tests of a prototype instrument

Construction and selection of bead-bound combinatorial oligonucleoside phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing

Chemically synthesized combinatorial libraries of unmodified or modified nucleic acids have not previously been used in methods to rapidly select oligonucleotides binding to target biomolecules such as proteins. Phosphorothioate oligonucleotides (S-ODNs) or phosphorodithioate oligonucleotides (S(2)-ODNs) with sulfurs replacing one or both of the non-bridging phosphate oxygens bind to proteins more tightly than unmodified oligonucleotides and have the potential to be used as diagnostic reagents and therapeutics. We have applied a split synthesis methodology to create one-bead one-S-ODN and one-bead one-S(2)-ODN libraries. Binding and selection of specific beads to the transcription factor NF-κB p50/p50 protein were demonstrated. Sequencing both the nucleic acid bases and the positions of any 3′-O-thioate/dithioate linkages was carried out by using a novel PCR-based identification tag of the selected beads. This approach allows us to rapidly and conveniently identify S-ODNs or S(2)-ODNs that bind to proteins

Measurements of atmospheric muon neutrino oscillations, global analysis of the data collected with MACRO detector

The final analysis of atmospheric neutrino events collected with the MACRO detector is presented. Three different classes of events, generated by neutrinos in different energy ranges, are studied looking at rates, angular distributions and estimated energies. The results are consistent for all the subsamples and indicate a flux deficit that depends on energy and path - length of neutrinos. The no - oscillation hypothesis is excluded at similar to 5sigma, while the hypothesis of nu(mu) --> nu(tau) oscillation gives a satisfactory description of all data. The parameters with highest probability in a two flavor scenario are sin(2) 2theta(m) = 1 and Deltam(2) = 0.0023 eV(2). This result is independent of the absolute normalization of the atmospheric neutrino fluxes. The data can also be used to put experimental constrain on this normalization

Measurements of atmospheric muon neutrino oscillations,global analysis of the data collected with MACRO detector

The final analysis of atmospheric neutrino events collected with the MACRO detector is presented. Three different classes of events, generated by neutrinos in different energy ranges, are studied looking at rates, angular distributions and estimated energies. The results are consistent for all the subsamples and indicate a flux deficit that depends on energy and path-length of neutrinos. The no-oscillation hypothesis is excluded at ∼ 5σ, while the hypothesis of νμ → ντ oscillation gives a satisfactory description of all data. The parameters with highest probability in a two flavor scenario are sin2 2θm= 1 and Δm2 = 0.0023 eV2. This result is independent of the absolute normalization of the atmospheric neutrino fluxes. The data can also be used to put experimental constrain on this normalization