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M. Hussein, M. Karam, Catherine Brand, G. Pearce, J. Reed, K. Bruening, P. Sartori, G. Srkalović et al.

DVd in combination with Thalidomide (T) and the appropriate supportive care measures resulted in a high response rate (88%) as well as an improved quality response (50% CR & NCR) similar to what is achieved with high dose therapy. Immunomodulatory drugs (IMiDs) are potent T derivatives. R is 50 to 2000 times more potent than T in stimulating T-cell proliferation triggered via the T-cell receptor, and 50 to 100 times more potent than T in augmenting IL-2 and IFN-a production. A recent phase I trial showed responses of at least 25% reduction in paraprotein in 17 (71%) of 24. We therefore initiated a phase I/II trial to define MTD of R in combination with DVd, then we proceeded to expand the MTD dose level to evaluate the efficacy and safety of the combination in patients with Rmm. SWOG criteria were used to assess response, and NCR was defined as a decrease of the M-Protein by >90%. Refractory patients were defined as those patients progressing on active therapy. R was started a week prior to DVd in cycle 1 to evaluate different coagulation parameters, from there on R was started on day 1 of therapy. The regimen was given as follows: on day 1 D was given at 40 mg/m 2 IVPB; V at 2 mg IVP; d at 40 mg PO daily X 4 days; R was started at 5 mg a day for 21 days with one week off. A standard phase 1 dose escalation of R was performed to identify the MTD. 3 pts were enrolled at each dose level, with up to 6 pts assigned to each dose level, depending on DLT. DVd was repeated q 4W, for a minimum of 4 cycles & 2 cycles after best response. Pts were maintained on R +/− prednisone 50 mg QOD. All patients received amoxicillin, acyclovir and aspirin 81mg prophylactically. 25 pts Rmm pts are enrolled with 21 evaluable for toxicity and mature data available for response on 21 pts (refractory: 15 (71%); relapsed: 6 (29%). 17/21 patients were stage 3, median age of 62 ± 9 years, baseline b 2 microglobulin level (mean 5.04 ± 2) and serum albumin (mean 3.4 ± 0.7). 14/21 patients failed T containing regimens. The DLT was sepsis/septic shock that occurred at dose level 3 (R 15mg) with two of the patients developing non neutropenic sepsis. The MTD for R was defined at 10mg. Three patients started therapy with a neutrophil count 25% reduction of the m-protein after one cycle of therapy and 3/4 after 2 cycles. R at 10mg is the MTD in combination with the DVd in RMM. DVd-R is an extremely effective regimen with a SWOG response rate >66%, CR+NCR of 33% in refractory stage 3 patients with minimal toxicity.

D. Milošević, A. Čerkić

Electron-atom scattering in a strong laser field is analyzed using the strong-field approximation and modeling elastic scattering of electrons by atoms with a realistic analytical potential derived from an independent-particle model. The results that include both direct scattering and scattering with a repeated scattering (rescattering) are presented. In the latter case, in the intermediate step of the process, the electron can absorb the energy from the laser field and additional plateau structures appear. The features of these plateaus and their cutoffs are analyzed for various incident electron energies and scattering angles, for different laser intensities, and for various atomic gases. The boundaries of these plateaus are compared with classical estimates.

D. Hodžić, R. Navratil, L. Marković-Puač, R. Rališ, M. Grce

I. Barišić, R. Gjergja, V. Tokić, J. Knežević, J. Sertić

I. Barišić, R. Gjergja, V. Tokić, J. Knežević, J. Sertić

O. Cvijanović, D. Bobinac, S. Zoričić, Z. Ostojić, I. Marić, Ž. Crnčević-Orlić, Ines Krištofić, L. Ostojić

Q. Zhou, J. G. Park, Z. Jiang, J. Holik, P Mitra, S. Semiz, A. Guilherme, A. Powelka et al.

Using siRNA-mediated gene silencing in cultured adipocytes, we have dissected the insulin-signalling pathway leading to translocation of GLUT4 glucose transporters to the plasma membrane. RNAi (RNA interference)-based depletion of components in the putative TC10 pathway (CAP, CrkII and c-Cbl plus Cbl-b) or the phospholipase Cgamma pathway failed to diminish insulin signalling to GLUT4. Within the phosphoinositide 3-kinase pathway, loss of the 5'-phosphatidylinositol 3,4,5-trisphosphate phosphatase SHIP2 was also without effect, whereas depletion of the 3'-phosphatase PTEN significantly enhanced insulin action. Downstream of phosphatidylinositol 3,4,5-trisphosphate and PDK1, silencing the genes encoding the protein kinases Akt1/PKBalpha, or CISK(SGK3) or protein kinases Clambda/zeta had little or no effect, but loss of Akt2/PKBbeta significantly attenuated GLUT4 regulation by insulin. These results show that Akt2/PKBbeta is the key downstream intermediate within the phosphoinositide 3-kinase pathway linked to insulin action on GLUT4 in cultured adipocytes, whereas PTEN is a potent negative regulator of this pathway.

Djenan Ganic, X. Gan, M. Gu

A physical model is presented to understand and calculate trapping force exerted on a dielectric micro-particle under focused evanescent wave illumination. This model is based on our recent vectorial diffraction model by a high numerical aperture objective operating under the total internal condition. As a result, trapping force in a focused evanescent spot generated by both plane wave (TEM00) and doughnut beam (TEM*01) illumination is calculated, showing an agreement with the measured results. It is also revealed by this model that unlike optical trapping in the far-field region, optical axial trapping force in an evanescent focal spot increases linearly with the size of a trapped particle. This prediction shows that it is possible to overcome the force of gravity to lift a polystyrene particle of up to 800 nm in radius with a laser beam of power 10 microW.

Djenan Ganic, X. Gan, M. Gu

In this letter we present a physical model, both theoretically and experimentally, which describes the mechanism for the conversion of evanescent photons into propagating photons detectable by an imaging system. The conversion mechanism consists of two physical processes, near-field Mie scattering enhanced by morphology dependant resonance and vectorial diffraction. For dielectric probe particles, these two processes lead to the formation of an interference-like pattern in the far-field of a collecting objective. The detailed knowledge of the far-field structure of converted evanescent photons is extremely important for designing novel detection systems. This model should find broad applications in near-field imaging, optical nanometry and near-field metrology.

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