Dendritic cell maturation and activation via RNA/DNA danger signals : co-delivery of protein antigen with siRNA or CpG DNA

Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2005."June 2005."Includes bibliographical references (p. 40-43).Traditional vaccines consisting of live attenuated pathogens or inactivated toxins cannot be readily applied to the more challenging diseases of the present e.g. hepatitis C and the human immunodeficiency virus. As such, there is a need to develop new methods of priming the immune system against such foreign invaders. Recombinant protein subunits and peptides are relatively safe alternatives to live attenuated pathogens. However, these antigens are poorly immunogenic when administered alone in solution form and thus require the use of an adjuvant. To this end, we have developed a hydrogel-based nanoparticulate system to encapsulate protein antigen and to co-deliver it with DNA/RNA-based adjuvants to dendritic cells, the key antigen presenting cells in primary immune responses. Using CpG oligonucleotides or siRNA as adjuvants, we observed via enzyme-linked immunosorbent assays for interleukin 12 and interferon-[alpha], respectively, that DCs were activated by CpG oligonucleotide- and siRNA-functionalized nanoparticles [approx.]10-fold more potently than by soluble CpG or siRNA ligands.by Jonathan Woon Teck Yap.M.Eng

Mass spectrometry-directed synthesis of early–late sulfide-bridged heterobimetallic complexes from the metalloligand [Pt₂(PPh₃)₄(μ-S)₂] and oxo compounds of vanadium(V), molybdenum(VI) and uranium(VI)

The metalloligand [Pt₂(PPh₃)₄(μ-S)₂] has been found to react with the transition metal oxo compounds, ammonium metavanadate, sodium molybdate, and the actinide complex uranyl nitrate to give sulfide-bridged heterobimetallic complexes [Pt₂(PPh₃)₄(μ₃-S)₂VO(OMe)₂]⁺, [Pt₂(PPh₃)₄(μ₃-S)₂MoO₂(OMe)]⁺, and [Pt₂(PPh₃)₄(μ₃-S)₂UO₂( ₂-NO₃)₂], respectively. Electrospray mass spectrometry (ESMS) was used to probe the reactivity of [Pt₂(PPh₃)₄(μ-S)₂] and thus identify likely targets for isolation and characterization. ESMS has also been used to investigate fragmentation pathways of the new species. No bimetallic species were detected with hydrated La(NO₃)₃or Th(NO₃)₄, or with the lanthanide shift reagent Eu(fod)₃ (fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate). X-Ray crystal structure determinations have been carried out on [Pt₂(PPh₃)₄(μ₃-S)₂VO(OMe)₂]⁺, 2, (as its hexafluorophosphate salt) and [Pt₂(PPh₃)₄(μ₃-S)₂UO₂( ₂-NO₃)₂], 4. The vanadium atom of 2 has a distorted square pyramidal geometry, while the uranium in 4 has the expected linear dioxo coordination geometry, with two bidentate nitrates and a bidentate {Pt₂S₂} moiety

A combinatorial-like probe on the reactivity of the {Pt2S2} core of Pt2(PPh3)4(μ-S)2 by electrospray mass spectrometry. Synthesis and structures of novel heterometallic sulfide aggregates of gold(III), mercury(II), and tin(IV) with platinum(II)

Journal of the Chemical Society, Dalton Transactions131986-200

Achieving high data compression of self-similar satellite imagesusing fractal

The authors examine and describe an implementation of a fractal compression method on optical satellite images. The basic principle is that an image can be reconstructed by using the self similarities in the image itself. The satellite image is first partitioned into a set of non-overlapping ranges. For each range, a “best matching” domain block would be found and a set of affine transformation would be performed. The compression would be obtained by storing only the descriptions of this transformation. The fractal compression method is implemented on two images, a complicated city image and a simple coastal area image. Using a fractal algorithm, the data integrity of the coastal area image was maintained with a peak signal-to-noise ratio (PSNR) of approximately 34.9 dB while achieving a compression ratio of 172:1. A novel approach of using a combination of fractal and wavelet algorithms for data compression is also described.</p

Achieving high data compression of self-similar satellite imagesusing fractal

The authors examine and describe an implementation of a fractal compression method on optical satellite images. The basic principle is that an image can be reconstructed by using the self similarities in the image itself. The satellite image is first partitioned into a set of non-overlapping ranges. For each range, a “best matching” domain block would be found and a set of affine transformation would be performed. The compression would be obtained by storing only the descriptions of this transformation. The fractal compression method is implemented on two images, a complicated city image and a simple coastal area image. Using a fractal algorithm, the data integrity of the coastal area image was maintained with a peak signal-to-noise ratio (PSNR) of approximately 34.9 dB while achieving a compression ratio of 172:1. A novel approach of using a combination of fractal and wavelet algorithms for data compression is also described.</p

A Biodegradable Nanoparticle Platform for the Induction of Antigen-Specific Immune Tolerance for Treatment of Autoimmune Disease

Targeted immune tolerance is a coveted therapy for the treatment of a variety of autoimmune diseases, as current treatment options often involve nonspecific immunosuppression. Intravenous (iv) infusion of apoptotic syngeneic splenocytes linked with peptide or protein autoantigens using ethylene carbodiimide (ECDI) has been demonstrated to be an effective method for inducing peripheral, antigen-specific tolerance for treatment of autoimmune disease. Here, we show the ability of biodegradable poly(lactic-<i>co</i>-glycolic acid) (PLG) nanoparticles to function as a safe, cost-effective, and highly efficient alternative to cellular carriers for the induction of antigen-specific T cell tolerance. We describe the formulation of tolerogenic PLG particles and demonstrate that administration of myelin antigen-coupled particles both prevented and treated relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE), a CD4 T cell-mediated mouse model of multiple sclerosis (MS). PLG particles made on-site with surfactant modifications surpass the efficacy of commercially available particles in their ability to couple peptide and to prevent disease induction. Most importantly, myelin antigen-coupled PLG nanoparticles are able to significantly ameliorate ongoing disease and subsequent relapses when administered at onset or at peak of acute disease, and minimize epitope spreading when administered during disease remission. Therapeutic treatment results in significantly reduced CNS infiltration of encephalitogenic Th1 (IFN-γ) and Th17 (IL-17a) cells as well as inflammatory monocytes/macrophages. Together, these data describe a platform for antigen display that is safe, low-cost, and highly effective at inducing antigen-specific T cell tolerance. The development of such a platform carries broad implications for the treatment of a variety of immune-mediated diseases