Purpose: Lenalidomide has significant activity in myelodysplastic syndromes, multiple myeloma, and non-Hodgkin's lymphoma (NHL). In previous studies, natural killer (NK) cell expansion by lenalidomide was shown to enhance the cytotoxic effect of rituximab. This study assessed the ability of lenalidomide to enhance antibody-dependent cellular cytotoxicity (ADCC) in rituximab-treated NHL cell lines and primary tumor cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) in vitro. Experimental Design: An in vitro ADCC system was used to assess the ability of lenalidomide to enhance human NK cell and monocyte function in response to rituximab. Results: Lenalidomide directly enhanced IFN-g production via Fc-g receptor-mediated signaling in response to IgG. It was also a potent enhancer of NK cell-mediated and monocyte-mediated tumor cell ADCC for a variety of rituximab-treated NHL cell lines in vitro, an effect that was dependent on the presence of antibody and either interleukin-2 or interleukin-12. Lenalidomide also enhanced the ability of NK cells to kill primary tumor cells derived from three patients with B-CLL who have been treated previously with fludarabine plus cyclophosphamide. Enhanced NK cell ADCC was associated with enhanced granzyme B and Fas ligand expression and could be inhibited by a granzyme B inhibitor and partially inhibited by antibody to FasL. Enhanced NK cell Fc-g receptor signaling is associated with enhanced phosphorylated extracellular signal-related kinase levels leading to enhanced effector function. Conclusions: These findings suggest that lenalidomide has the potential to enhance the rituximab-induced killing of NHL cell lines and primary B-cell chronic lymphocytic leukemia cells via a NK cell-mediated and monocyte-mediated ADCC mechanism in vitro, providing a strong rationale for the combination of lenalidomide with IgG1 antibodies to target tumor-specific antigens in patients with cancer.

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Strongly intermittent turbulence is observed in the shadow of a limiter in the Large Plasma Device (LAPD) at UCLA [W. Gekelman, H. Pfister, Z. Lucky, J. Bamber, D. Leneman, and J. Maggs, Rev. Sci. Inst. 62, 2875(1991]. The amplitude probability distribution function (PDF) of the turbulence is strongly skewed, with density depletion events (or "holes") dominant in the high density region and density enhancement events (or "blobs") dominant in the low density region. Two-dimensional cross-conditional averaging shows that the blobs are detached, outwardpropagating filamentary structures with a clear dipolar potential while the holes appear to be part of a more extended turbulent structure. A statistical study of the blobs reveals a typical size of ten times the ion sound gyroradius and a typical velocity of one tenth the sound speed.

For the first time, profiles (0.3<ρ<0.9) of electron temperature and density fluctuations in a tokamak have been measured simultaneously and the results compared to nonlinear gyrokinetic simulations. Electron temperature and density fluctuations measured in neutral beam-heated, sawtooth-free low confinement mode (L-mode) plasmas in DIII-D [J. L. Luxon, Nucl. Fusion 42, 614 (2002)] are found to be similar in frequency and normalized amplitude, with amplitude increasing with radius. The measured radial profile of two fluctuation fields allows for a new and rigorous comparison with gyrokinetic results. Nonlinear gyrokinetic flux-tube simulations predict that electron temperature and density fluctuations have similar normalized amplitudes in L-mode. At ρ=0.5, simulation results match experimental heat diffusivities and density fluctuation amplitude, but overestimate electron temperature fluctuation amplitude and particle diffusivity. In contrast, simulations at ρ=0.75 do not match either the experimentally derived transport properties or the measured fluctuation levels.