Different vimentin expression in two clones derived from a human colocarcinoma cell line (LoVo) showing different sensitivity to doxorubicin.

We selected two clones, isolated from the human colocarcinoma cell line LoVo, showing a sensitivity to doxorubicin similar to (LoVo clone 5) or three times lower than (LoVo clone 7) the parental cell line. Since vimentin was atypically expressed in a human breast carcinoma cell line made resistant to doxorubicin, we looked at vimentin expression in these two clones with spontaneously different sensitivity to the drug. For comparison we used the parental cell line LoVo WT and LoVo/DX made resistant pharmacologically. mRNA for vimentin was undetectable by Northern blot analysis in LoVo WT and in LoVo clone 5, while expression of this gene was high in LoVo clone 7 and in LoVo/DX. This increase in mRNA levels was not related to an amplification of DNA, as suggested by Southern blot analysis. Immunofluorescence and immunocytochemistry findings confirmed, at protein level, the mRNA data. In LoVo clones 5 and 7, there were respectively 8.6% and 71% vimentin-positive cells, although the two clones showed similar expression of multidrug resistance gene 1 (mdr-1) and accumulated intracellular doxorubicin at similar levels. Similarly, drug efflux was the same for both clones. Our results show for the first time that cells resistant to doxorubicin express vimentin independently of the mdr glycoprotein. However when cells from clone 5 were transfected with human vimentin cDNA, they did not become resistant, indicating that vimentin can be considered as a marker of resistance in these cells but does not give rise to a resistant phenotype by itself

Characterization of a clonal human colon adenocarcinoma line intrinsically resistant to doxorubicin.

Intrinsic low-level resistance to anti-cancer drugs is a major problem in the treatment of gastrointestinal malignancies. To address the problem presented by intrinsically resistant tumours, we have isolated two monoclonal lines from LoVo human colon adenocarcinoma cells: LoVo/C7, which is intrinsically resistant to doxorubicin (DOX); and LoVo/C5, which shows the same resistance index for DOX as the mixed parental cell population. For comparison, we have included in the study a LoVo-resistant line selected by continuous exposure to DOX and expressing a typical multidrug resistant (MDR) phenotype. In these cell lines we have studied the expression and/or activity of a number of proteins, including P-glycoprotein 170 (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione (GSH)-dependent enzymes and protein kinase C (PKC) isoforms, which have been implicated in anti-cancer drug resistance. Intracellular DOX distribution has been assessed by confocal microscopy. The results of the present study indicate that resistance in LoVo/C7 cells cannot be attributed to alterations in P-gp, LRP or GSH/GSH-dependent enzyme levels. Increased expression of MRP, accompanied by alterations in the subcellular distribution of DOX, has been observed in LoVo/C7 cells; changes in PKC isoform pattern have been detected in both intrinsically and pharmacologically resistant cells

Relativistic effects and two-body currents in 2H(e⃗,e′p)n^{2}H(\vec{e},e^{\prime}p)n using out-of-plane detection

Measurements of the ${^2}H(\vec{e},e^{\prime}p)n$ reaction were performed using an 800-MeV polarized electron beam at the MIT-Bates Linear Accelerator and with the out-of-plane magnetic spectrometers (OOPS). The longitudinal-transverse, $f_{LT}$ and $f_{LT}^{\prime}$, and the transverse-transverse, $f_{TT}$, interference responses at a missing momentum of 210 MeV/c were simultaneously extracted in the dip region at Q$^2$=0.15 (GeV/c)$^2$. On comparison to models of deuteron electrodisintegration, the data clearly reveal strong effects of relativity and final-state interactions, and the importance of the two-body meson-exchange currents and isobar configurations. We demonstrate that these effects can be disentangled and studied by extracting the interference response functions using the novel out-of-plane technique.Comment: 4 pages, 4 figures, and submitted to PRL for publicatio

Relativistically invariant analysis of polarization effects in exclusive deuteron electrodisintegration process

A general formalism for the calculation of the differential cross section and polarization observables, for the process of deuteron electrodisintegration, is developed in the framework of relativistic impulse approximation. A detailed analysis of the general structure of the differential cross section and polarization observables for the $e^-+d\to e^-+n+p$ reaction is derived, using the formalism of the structure functions. The obtained expressions have a general nature and they hold in the one--photon--exchange mechanism, assuming P--invariance of the hadron electromagnetic interaction. The model of relativistic impulse approximation is introduced and the final state interaction is taken into account by means of the unitarization of the helicity amplitudes. A detailed description of the unitarization procedure is also presented. Using different parametrizations of the deuteron wave functions, the following polarization observables are calculated in the kinematical region of quasi--elastic deuteron electrodisintegration: the asymmetry for the scattering of longitudinally polarized electrons on a polarized deuteron target, the proton and neutron polarizations (for longitudinally polarized electron beam or vector--polarized deuteron target). The sensitivity to the neutron electric form factor is also thorougly investigated. The predictions of the model are compared with the results of recent polarization measurements and a good agreement with the existing experimental data has been obtained.Comment: 90 pages, 17 figure

Speech listening entails neural encoding of invisible articulatory features

Speech processing entails a complex interplay between bottom-up and top-down computations. The former is reflected in the neural entrainment to the quasi-rhythmic properties of speech acoustics while the latter is supposed to guide the selection of the most relevant input subspace. Top-down signals are believed to originate mainly from motor regions, yet similar activities have been shown to tune attentional cycles also for simpler, non-speech stimuli. Here we examined whether, during speech listening, the brain reconstructs articulatory patterns associated to speech production. We measured electroencephalographic (EEG) data while participants listened to sentences during the production of which articulatory kinematics of lips, jaws and tongue were also recorded (via Electro-Magnetic Articulography, EMA). We captured the patterns of articulatory coordination through Principal Component Analysis (PCA) and used Partial Information Decomposition (PID) to identify whether the speech envelope and each of the kinematic components provided unique, synergistic and/or redundant information regarding the EEG signals. Interestingly, tongue movements contain both unique as well as synergistic information with the envelope that are encoded in the listener's brain activity. This demonstrates that during speech listening the brain retrieves highly specific and unique motor information that is never accessible through vision, thus leveraging audio-motor maps that arise most likely from the acquisition of speech production during development

WARP: a WIMP double phase Argon detector

The WARP programme for dark matter search with a double phase argon detector is presented. In such a detector both excitation and ionization produced by an impinging particle are evaluated by the contemporary measurement of primary scintillation and secondary (proportional) light signal, this latter being produced by extracting and accelerating ionization electrons in the gas phase. The proposed technique, verified on a 2.3 liters prototype, could be used to efficiently discriminate nuclear recoils, induced by WIMP's interactions, and measure their energy spectrum. An overview of the 2.3 liters results and of the proposed 100 liters detector is shown.Comment: Proceeding for IDM200

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

General Survey of Polarization Observables in Deuteron Electrodisintegration

Polarization observables in inclusive and exclusive electrodisintegration of the deuteron using a polarized beam and an oriented target are systematically surveyed using the standard nonrelativistic framework of nuclear theory but with leading order relativistic contributions included. The structure functions and the asymmetries corresponding to the various nucleon polarization components are studied in a variety of kinematic regions with respect to their sensitivity to realistic $NN$-potential models, to subnuclear degrees of freedom in terms of meson exchange currents, isobar configurations and to relativistic effects in different kinematical regions, serving as a benchmark for a test of present standard nuclear theory with effective degrees of freedom.Comment: 56 pages, 32 figures, revtex