Use of ultraviolet-light irradiated multiple myeloma cells as immunogens to generate tumor-specific cytolytic T lymphocytes

Background

As the eradication of tumor cells in vivo is most efficiently performed by cytolytic T lymphocytes (CTL), various methods for priming tumor-reactive lymphocytes have been developed. In this study, a method of priming CTLs with ultraviolet (UV)-irradiated tumor cells, which results in termination of tumor cell proliferation, apoptosis, as well as upregulation of heat shock proteins (HSP) expression is described.

Methods

Peripheral blood mononuclear cells (PBMC) were primed weekly with UV-irradiated or mitomycin-treated RPMI 8226 multiple myeloma cells. Following three rounds of stimulation over 21 days, the lymphocytes from the mixed culture conditions were analyzed for anti-MM cell reactivity.

Results

By day 10 of cultures, PBMCs primed using UV-irradiated tumor cells demonstrated a higher percentage of activated CD8+/CD4- T lymphocytes than non-primed PBMCs or PBMCs primed using mitomycin-treated MM cells. Cytotoxicity assays revealed that primed PBMCs were markedly more effective (p < 0.01) than non-primed PBMCs in killing RPMI 8226 MM cells. Surface expression of glucose regulated protein 94 (Grp94/Gp96) and Grp78 were both found to be induced in UV-treated MM cells.

Conclusion

Since, HSP-associated peptides are known to mediate tumor rejection; these data suggest that immune-mediated eradication of MM cells could be elicited via a UV-induced HSP process. The finding that the addition of 17-allylamide-17-demethoxygeldanamycin (17AAG, an inhibitor of HSP 90-peptide interactions) resulted in decreased CTL-induced cytotoxicity supported this hypothesis. Our study, therefore, provides the framework for the development of anti-tumor CTL cellular vaccines for treating MM using UV-irradiated tumor cells as immunogens.     

Towards equitable distribution via proportional equity constraints

We propose a new approach to the formulation of models for solving problems of equitable distribution. Equity is achieved by the use of proportional equity constraints which require that each recipient must receive ashare of the total distribution which falls within a prespecified range. The algorithmic implications of this new approach are illustrated using two mathematical models. We consider the problem of maximizing total flow in a multiterminal network with proportional equity constraints. An efficient algorithm for solving this problem is provided. As a further application, we show that the introduction of such constraints still permits easy solutions for the linear knapsack problem.     

Phase Separation of Triblock Polymers and Tritons in the Presence of Biomolecules

Surfactant?Cbiomolecule interactions have been investigated by studying the additive effect of various kinds of biomolecules such as amino acids, dipeptides, amino alcohols, sugars, hydroxy acids and dicarboxylic acids on the cloud point behavior of nonionic surfactants including triblock polymers (L64, P84) and tritons (TX100, TX114). In most cases, addition of biomolecules has been found to cause a depression in the cloud point of the triblock polymers and tritons. The presence of biomolecules in the solution of a nonionic surfactant causes drastic changes to the clouding behavior of the surfactant, especially at high biomolecule concentrations. The results reveal that both hydrophobicity and structural aspects play important roles in the observed cloud point variation of the nonionic surfactants.     

Measurement and analysis of complex modulated motions in a weakly nonlinear system

The two-timing dynamics of a forced, weakly nonlinear system are considered. Experimental results on a roll-forced spherical pendulum verify the occurrence of slow-time, subharmonically and chaotically modulated oscillations in a frequency band near resonance; the modulatory behavior follows the occurrence of a Hopf bifurcation in the slow-time coordinates. A phase-sensitive detection method for experimentally isolating the slow-time behavior is described. A Lagrangian model for the pendulum is developed, and slow-time equations are presented. A two-thirds power scalling law relating roll angle to the appearance of the modulations is derived from the slow-time equations and tested with experimental results.     

Correlated equilibrium payoffs and public signalling in absorbing games

An absorbing game is a repeated game where some action combinations are absorbing, in the sense that whenever they are played, there is a positive probability that the game terminates, and the players receive some terminal payoff at every future stage.  We prove that every multi-player absorbing game admits a correlated equilibrium payoff. In other words, for every ε>0 there exists a probability distribution p _ε over the space of pure strategy profiles that satisfies the following. With probability at least 1−ε, if a pure strategy profile is chosen according to p _ε and each player is informed of his pure strategy, no player can profit more than ε in any sufficiently long game by deviating from the recommended strategy. Received: April 2001/Revised: June 4, 2002     

Pressure-induced superconductivity and structural transitions in Ba(Fe<Subscript>0.9</Subscript>Ru<Subscript>0.1</Subscript>)<Subscript>2</Subscript>As<Subscript>2</Subscript>

Electrical transport and structural characterizations of isoelectronically substituted Ba(Fe_0.9Ru_0.1)₂As₂ have been performed as a function of pressure up to ～ 30 GPa and temperature down to ～ 10 K using designer diamond anvil cell. Similar to undoped members of the AFe₂As₂ (A = Ca, Sr, Ba) family, Ba(Fe_0.9Ru_0.1)₂As₂ shows anomalous a-lattice parameter expansion with increasing pressure and a concurrent ThCr₂Si₂ type isostructural (I4/mmm) phase transition from tetragonal (T) phase to a collapsed tetragonal (cT) phase occurring between 12 and 17 GPa where the a is maximum. Above 17 GPa, the material remains in the cT phase up to 30 GPa at 200 K. The resistance measurements show evidence of pressure-induced zero resistance that may be indicative of high-temperature superconductivity for pressures above 3.9 GPa. The onset of the resistive transition temperature decreases gradually with increasing pressure before completely disappearing for pressures above ～ 10.6 GPa near the T-cT transition. We have determined the crystal structure of the high-T _c phase of Ru-doped BaFe₂As₂ to remain as tetragonal (I4/mmm) by analyzing the X-ray diffraction pattern obtained at 10 K and 9.7 ± 0.7 GPa, as opposed to inferring the structural transition from electrical resistance measurement, as in a previous report [S.K. Kim, M.S. Torikachvili, E. Colombier, A. Thaler, S.L. Bud’ko, P.C. Canfield, Phys. Rev. B 84, 134525 (2011)].     

Production of vibrationally excited OH in chemiluminescent reactions of ozone with monoterpenes

Emission from vibrationally excited OH molecules (Meinel bands) has been observed in chemiluminescent gas-phase reactions of ozone with myrcene, α-phellandrene, α-pinene, limonene and linallol. In addition emission from HCHO(¹A₂) and methylglyoxal(³A_u) has also been identified in reactions with myrcene, α-pinene and α-phellandrene.