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C Goldenberg

Publications and source records attributed to C Goldenberg.

3 recordsLinked to original sources

Force chains, microelasticity, and macroelasticity.

It has been claimed that quasistatic granular materials, as well as nanoscale materials, exhibit departures from elasticity even at small loadings. It is demonstrated, using 2D and 3D models with interparticle harmonic interactions, that such departures are expected at small scales [below O(100) particle diameters], at which continuum elasticity is invalid, and vanish at large scales. The models exhibit force chains on small scales, and force and stress distributions which agree with experimental findings. Effects of anisotropy, disorder, and boundary conditions are discussed as well.

Journal Article↗

Achievement of high cell density and high antibody productivity by a controlled-fed perfusion bioreactor process.

Controlled feeding of nutrient supplements to a cell culture to enhance monoclonal antibody productivity has been practiced widely in high-yield, fed-batch processes. In this study, a similar feeding concept has been applied to a perfused culture and evaluated for the effects on bioreactor productivity and product quality. Our experimental results show that, by using such a "controlled-fed perfusion" approach, the volumetric antibody productivity (antibody per liter per day) was significantly increased by nearly twofold over the perfusion process, and surpassed fed-batch and batch processes by almost tenfold. The substantial boost in the overall productivity is attributable primarily to the combined effects of increased cell density as well as reduced product dilution. Both were achieved through careful nutrient supplementation in conjunction with metabolite minimization. As the manufacturing process evolved from roller bottles to the controlled-fed perfusion bioreactor system, the immunoreactivity and the cDNA sequences of the antibody were well preserved. However, the product glycosylation distribution patterns did alter. The controlled-feed perfusion process demonstrated a unique encompassment of the advantages of fed-batch and perfusion methods; that is, high product concentration with high volume throughput. Therefore, it may be very suitable for large-scale production of monoclonal antibodies.

Animals↗

Idiotype-specific T cell suppression of light chain mRNA expression in MOPC-315 cells is accompanied by a posttranscriptional inhibition of heavy chain expression.

Earlier studies have shown that idiotype-specific T suppressor cells can directly inhibit the biosynthesis and subsequent secretion of immunoglobulin from the BALB/c myeloma, MOPC-315. This suppression is highly specific and does not affect nonimmunoglobulin protein synthesis in these cells. The selective character of this suppression suggested a transcriptional or translational mechanism of control. Therefore, we analyzed suppressed MOPC-315 cells for the expression of light and heavy chain mRNAs. Since the events that occur in a B cell subsequent to reception of suppressive signals from T cells are presently unknown, these experiments address a fundamental aspect of B cell regulation. Another important aspect of these studies is that they deal with a suppressor T cell that clearly operates directly upon the antibody-secreting cell. This system involves regulation of a B cell differentiative function without influencing the B cell clonal size. We have employed the trinitrophenyl (TNP)-specific myeloma, MOPC-315, because it provides a source of monoclonal B cells which in earlier studies have been shown to be responsive to idiotype-specific and TNP-antigen-specific immunoregulatory signals. The idiotype-specific T cells were generated by hyperimmunizing BALB/c mice with the myeloma protein bearing the 315 idiotype, in complete Freund's adjuvant. Poly A+ mRNA was isolated from MOPC-315 cells following coculture with either normal or idiotype-immune T cells. The mRNA was analyzed using hybridization techniques and cDNA probes specific for alpha or lambda 2 light chain constant regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗