Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene

Although apoptosis can be induced by the enforced expression of exogenously introduced c-myc genes, it is not clear whether overexpression resulting from the amplification of the resident c-myc gene in tumor cells is sufficient to induce apoptosis. We have investigated the relationship between c-myc gene amplification and the propensity of tumor cells to undergo apoptosis, using the SW613-12A1 and SW613-B3 cell lines, which are representatives, respectively, of tumorigenic and non-tumorigenic clones isolated from the SW613-S human colon carcinoma cell line. Tumorigenic clones are characterized by a high level of amplification and expression of the c-myc gene, whereas cells of non-tumorigenic clones have a small number of copies and a lower level of expression of this gene. Analysis of c-myc mRNA level in cells cultured under low serum conditions indicated that the expression of the gene is tightly regulated by serum growth factors in non-tumorigenic B3 cells, whereas it is poorly regulated in tumorigenic 12A1 cells, the level of mRNAs remaining relatively high in serum-starved 12A1 cells. Under these conditions, 12A1 cells showed clear evidence of apoptosis, whereas B3 cells were completely refractory to the induction of apoptosis. Moreover, the study of cell lines derived from non-tumorigenic apoptosis-resistant clones following the introduction by transfection of exogenous c-myc gene copies showed that they have acquired an apoptosisprone phenotype. Altogether, our results strongly suggest that deregulated c-myc expression due to high-level amplification confers an apoptosis-prone phenotype to tumor cells. The possible consequences of these observations for cancer therapy are discussed.     

Development of “kink” in the output I–V characteristics of pseudomorphic hemt's after hot-electron accelerated testing

Large decreases in the drain current in the linear and low V_ds region followed by a “kink” in the output I_d-V_ds characteristics have been found after hot electron stress test in AlGaAs/InGaAs/GaAs power pseudomorphic HEMT's. Decrease in the transconductance measured in linear region, increase in the drain parasitic resistance and trasconductance frequency dispersion have also been observed and attributed to the generation of electron traps in the gate-to-drain access region.     

Fracture toughness characterization of light alloys for aeronautical use

The fracture resistence properties of a rod and a plate, both made of 2024 aluminium alloy, are evaluated according to standard and non-standard methods. The materials are tested after heat treatments involving material microstructures different especially as to size and dispersion of the hardening precipitates.The sensitivity of various fracture-toughness parameters to microstructure conditions, specimen geometry, as well as their interactions is analyzed. Correlations established between standard and non-standard parameters confirm that alternative testing procedures are adequate to evaluate the fracture toughness of this alloy.

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Résumé On évalue les propriétés de résistance à la rupture d'un barreau et d'une plaque, en alliage d'aluminium 2024, selon des méthodes standard et non standard. Les matériaux sont essayés après divers traitements thermiques conférant des microstructures différentes en ce qui regarde la taille et la dispersion des précipités de durcissement.On analyse la sensibilité de divers paramètres de ténacité à la rupture vis-à-vis de la microstructure, de la géométrie des éprouvettes et de leur intégration.Des corrélations établies entre paramètres standard et non standard confirment que des procédures d'essai alternatives peuvent être utilisées pour evaluer la ténacité à la rupture de cette famille d'alliage.

     

Correlation between thermal resistance, channel temperature, infrared thermal maps and failure mechanisms in low power MESFET devices

Channel temperature T_ch of GaAs MESFETs, determined by means of electrical measurements (ΔV_gs), has been compared and correlated with thermal maps obtained by high resolution infrared microscopy. Results show that in low power devices with a small number of gates, the value of T_ch derived from ΔV_gs measurements is close to the maximum values of temperature measured on the hottest junctions on the chip. Local thermal inhomogeneities, in particular those observed in devices characterized by high values of R_th, can explain and confirm results of failure analyses of MESFETs submitted to accelerated life tests in operating conditions where degradation phenomena occur in localized areas of the device.     

Efficient development of mass producible MMIC circuits

The state-of-the-art criteria and tools for an efficient development of mass producible MMICs are discussed with reference to a specific development philosophy. The available yield evaluation systems are then critically analyzed and the results of a systematic functional yield evaluation performed on a large number of monolithic circuit components are reported. A statistically meaningful database (including both FET equivalent circuit and S parameters) developed for parametric yield evaluation and yield-driven design centering is described. Through a significant example, the possibility is demonstrated of drastically improving the accuracy of the parametric circuit yield forecasts by using a small set of mutually uncorrelated process dependent parameters and by making reference to a physically based semiempirical FET model     

Multiparametric staining to identify apoptotic human cells

To analyze relevant features of HeLa and HL60 cells driven into apoptosis by etoposide, we have developed a new "tricolor" assay, based on the simultaneous analysis in the single cell of chromatin condensation, DNA degradation, and cellular poly(ADP-ribose) synthesis. The latter reaction is catalyzed by poly(ADP-ribose)-polymerase (E.C. 2.4.2.30), an enzyme which is activated by the presence of DNA free ends. The protocol consists in the visualization of apoptotic cells by Hoechst staining, TUNEL assay, and immunoreaction with anti-poly(ADP-ribose) antibody. We thus provide the first evidence that endogenous poly(ADP-ribose) production is indeed stimulated in cells undergoing apoptosis after treatment with antitumoral drugs, and that the monitoring of this endogenous enzymatic reaction, combined with morphological and other biochemical parameters, should facilitate the detection of apoptotic cells.     

Evaluating COTS component dependability in context

The software industry has increasingly expanded its adoption of COTS components for complex, mission-critical applications. Using COTS products can shorten development and deployment time because they let system developers focus on creating domain-specific services. Selecting the right COTS component, however, is no easy task. We present a practical process that developers can use to empirically evaluate component dependability in their context. Our approach uses the unified model of dependability, a requirements engineering approach specially devised to capture dependability in context. This model clearly specifies the measurable characteristics the component must have to be dependable in a specific context. The model then serves as a reference, providing guidance on effectively designing experiments to compare similar components and interpret collected data. The process can be applied to any specific context and COTS component. Here, we describe our comparison of the dependability of real-time Java virtual machines (RT JVM) in the spacecraft software context.     

High-yield self-alignment method for submicrometre GaAs m.e.s.f.e.t.s

A high-yield self-alignment technique for submicrometer GaAs m.e.s.f.e.t.s is described. This method allows the production of submicrometre gate lengths and source-drain spacings by means of standard contact photolithography without requiring a particularly fine geometry on the masks. A 0.5 ?m long gate and a source-drain spacing of 2 ?m were obtained.