Critical Involvement of the ATM-Dependent DNA Damage Response in the Apoptotic Demise of HIV-1-Elicited Syncytia

DNA damage can activate the oncosuppressor protein ataxia telangiectasia mutated (ATM), which phosphorylates the histone H2AX within characteristic DNA damage foci. Here, we show that ATM undergoes an activating phosphorylation in syncytia elicited by the envelope glycoprotein complex (Env) of human immunodeficiency virus-1 (HIV-1) in vitro. This was accompanied by aggregation of ATM in discrete nuclear foci that also contained phospho-histone H2AX. DNA damage foci containing phosphorylated ATM and H2AX were detectable in syncytia present in the brain or lymph nodes from patients with HIV-1 infection, as well as in a fraction of blood leukocytes, correlating with viral status. Knockdown of ATM or of its obligate activating factor NBS1 (Nijmegen breakage syndrome 1 protein), as well as pharmacological inhibition of ATM with KU-55933, inhibited H2AX phosphorylation and prevented Env-elicited syncytia from undergoing apoptosis. ATM was found indispensable for the activation of MAP kinase p38, which catalyzes the activating phosphorylation of p53 on serine 46, thereby causing p53 dependent apoptosis. Both wild type HIV-1 and an HIV-1 mutant lacking integrase activity induced syncytial apoptosis, which could be suppressed by inhibiting ATM. HIV-1-infected T lymphoblasts from patients with inactivating ATM or NBS1 mutations also exhibited reduced syncytial apoptosis. Altogether these results indicate that apoptosis induced by a fusogenic HIV-1 Env follows a pro-apoptotic pathway involving the sequential activation of ATM, p38MAPK and p53

Dielectric behavior of ternary composites of epoxy/BaTiO

The work we present in this article is an investigation of the optimal dielectric behaviour of a ternary composite based on a mixture of epoxy resin, titanates and oxides. Titanates are known by their capacity to provide high dielectric constant values that make their use very important in system of telecommunication, transmission microwaves, and in integrated circuit technology. A comparative study is established on two types of oxides added to titanates of either calcium, barium, or magnesium following different proportions. The protocol used to characterise different mixtures is the Time Domain Reflectometry (TDR). The acquired results show a good concordance between the experimental values of the ternary mixture dielectric constant and the theoretical models deduced from the Lichtenecker modified law. The copper oxide (CuO) is revealed to be more influential than the magnesium oxide (MgO) on the added titanate because of an insignificant dielectric behaviour that the latter presents. On the other hand, the linear behaviour of $\varepsilon_{s}$ appeared with a CuO concentration round about 15% in a RE.BT.CuO mixture. For a fixed barium titanate fraction (27%) this linear evolution is located between the upper and the lower limits derivative from direct and inverse Wiener laws

Modelling and dielectric behavior of ternary composites of epoxy (BaTiO

The aim of this article is to explore materials made of polymer-titanate composites for application towards the size reduction of high frequency electronic components. A study has therefore been done on the dielectric effect of composites made of an epoxy matrix loaded with a mixture of barium titanate and calcium titanate. The effects have been quantified according to volume fraction of load. Results obtained from time domain reflectometry have been compared to modelling predictions from the generalized Lichtenecker law. Low frequency analysis (in the range DC — 500 MHz) has also been performed throughout this work, and it has primarily concentrated on conductivity behaviour which may be attributed to the effects of a percolation process. The study has confirmed the validity of the ternary mixture law being applied in order to predict the electromagnetic behaviour of the composite material. This material family may therefore find use in microelectronic applications and in the miniaturization of circuit components (substrates, components, cavities, antennas, etc.)

Investigation of degradation of electrical properties after thermal oxidation of p-type Cz-silicon wafers

In this study we conducted thermal oxidation of Czochralski p-type silicon wafers. The oxidation was carried out at temperatures in the range of 850-1000°C, in a gas mixture of N₂:O₂, in order to deposit a thin layer (10 nm) of thermal silicon dioxide (SiO₂), generally used in the surface passivation of solar cells. The measurements of effective minority carriers lifetime τ_{eff} using the quasi-steady-state photoconductance have shown degradation of different samples after oxidation process. The calculation of surface recombination velocity after the oxidation process at different temperatures, gave the same value of 40 cm s¯¹, showing a low surface recombination velocity and, therefore, a good surface passivation. Finally, a study based on sample illumination technique, allowed us to conclude that our samples are dominated by bulk Shockley-Read-Hall recombination, caused by Fe-related centers, thereby causing the degradation of the lifetime of minority carriers