Modulating cell surface immunoreactivity by metabolic induction of unnatural carbohydrate antigens

BACKGROUND: Sialic acid is a component of many tumor-associated oligosaccharide antigens. The repertoire of sialic acids presented by cells can be expanded to include unnatural variants by intercepting the sialic acid biosynthetic pathway with unnatural precursors. We explored whether unnatural cell surface sialosides produced by metabolism can act as neo-antigens and modulate the immunogenicity of cells. RESULTS: Immunization of rabbits with synthetic conjugates of an unnatural sialic acid bound to keyhole limpet hemocyanin produced significant titers of antibodies that were specific for the structurally altered sialic acid. The antibodies recognized cells that were fed the unnatural biosynthetic precursor, and were capable of directing complement-mediated lysis. CONCLUSIONS: Structural alteration of sialic acids replaces a tolerized self-antigen with an antigenic determinant. Incorporation of unnatural sialosides into cell surface glycoconjugates through biosynthetic means can alter the immunoreactivity of cells, providing new possibilities for tumor immunotherapy.     

Self-propelled particles with soft-core interactions: patterns, stability, and collapse

Understanding collective properties of driven particle systems is significant for naturally occurring aggregates and because the knowledge gained can be used as building blocks for the design of artificial ones. We model self-propelling biological or artificial individuals interacting through pairwise attractive and repulsive forces. For the first time, we are able to predict stability and morphology of organization starting from the shape of the two-body interaction. We present a coherent theory, based on fundamental statistical mechanics, for all possible phases of collective motion.     

3He spin-dependent cross sections and sum rules

We present a measurement of the spin-dependent cross sections for the 3He over -->(e over -->,e')X reaction in the quasielastic and resonance regions at a four-momentum transfer 0.1< or =Q2< or =0.9 GeV2. The spin-structure functions have been extracted and used to evaluate the nuclear Burkhardt-Cottingham and extended Gerasimov-Drell-Hearn sum rules for the first time. The data are also compared to an impulse approximation calculation and an exact three-body Faddeev calculation in the quasielastic region.     

Comparative analysis of different computer handling systems for gamma-spectrometric data developed at C.C.R. Ispra

Three different computer systems for gamma-spectrometric data-handling have been developed at the Joint Nuclear Research Center of Ispra. The systems are: (1) batchwise treatment of the data with a large computer, (2) time-shared teleprocessing by means of a centralised computer, (3) use of a small computer at the laboratory site. The paper describes both hardware and software of the three systems with emphasis on their practical use and on advantages and disadvantages in routine application. A partial analysis of the running costs of the systems is also presented.     

Synthetic glycopeptides and glycoproteins as tools for biology

Investigations into the roles of protein glycosylation have revealed functions such as modulating protein structure and localization, cell-cell recognition, and signaling in multicellular systems. However, detailed studies of these events are hampered by the heterogeneous nature of biosynthetic glycoproteins that typically exist in numerous glycoforms. Research into protein glycosylation, therefore, has benefited from homogeneous, structurally-defined glycoproteins obtained by chemical synthesis. This tutorial review focuses on recent applications of homogeneous synthetic glycopeptides and glycoproteins for studies of structure and function. In addition, the future of synthetic glycopeptides and glycoproteins as therapeutics is discussed.     

Chemoselective elaboration of O-linked glycopeptide mimetics by alkylation of 3-thioGalNAc.

A critical branch point in mucin-type oligosaccharides is the beta 1-->3 glycosidic linkage to the core alpha-N-acetylgalactosamine (GalNAc) residue. We report here a strategy for the synthesis of O-linked glycopeptide analogues that replaces this linkage with a thioether amenable to construction by chemoselective ligation. The key building block was a 2-azido-3-thiogalactose-Thr analogue that was incorporated into a peptide by fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. Higher order oligosaccharides were readily generated by alkylation of the corresponding 3-thioGalNAc with N-bromoacetamido sugars. The rapid assembly of "core 1"and "core 3" O-linked glycopeptide mimetics was accomplished in this fashion.     

Restricted rotation of the olefin and amine ligands in cis-dichloro(p-toluidine)(ethyl vinyl ether)platinum(II)

cis-Dichloro(p-toluidine)(olefin)platinum(II) complexes, in which the olefin is either ethyl vinyl ether or ethylene, have been investigated by ¹H NMR spectroscopy over a range of temperatures (+50 to ?60° C) in order to study the rotation of the olefin ligand.The results give no evidence of rotation of the amine or vinyl ether ligands even at the highest temperature investigated, +50°C; only one of the two possible rotational isomers is present, and this is attributed to the presence of intramolecular hydrogen bonding between the oxygen atom of the vinyl ether and the -NH- group of the amine.In contrast, the amine and vinyl ligands in the ethylene complex rotate freely at room temperature, coalescence being observed above ?25° C for the ethylene protons.     

A study of EWOD-driven droplets by PIV investigation

Despite the recent interest in droplet-based microfluidics using electrowetting-on-dielectric (EWOD), fundamental understanding of the fluid dynamics remains limited to two-dimensional (2D) reduction of the Navier-Stokes equation. Experimental data are in dire need to verify the predictions and advance the field. We report an investigation of the flow inside droplets actuated by EWOD in air using micro particle image velocimetry (micro-PIV). Using the continuity equation, we reconstruct the 3D velocity field from the 2D PIV experimental data. We present some fundamental findings and build valuable insights that will help design sophisticated EWOD microfluidic devices. For example, the results confirm that efficient mixing in a droplet may be achieved by moving the droplet along an irreversible pattern that breaks the symmetry of the two circulating inner flows.