Susceptibility of cloned K+ channels to reactive oxygen species

Free radical-induced oxidant stress has been implicated in a number of physiological and pathophysiological states including ischemia and reperfusion-induced dysrhythmia in the heart, apoptosis of T lymphocytes, phagocytosis, and neurodegeneration. We have studied the effects of oxidant stress on the native K+ channel from T lymphocytes and on K+ channels cloned from cardiac, brain, and T-lymphocyte cells and expressed in Xenopus oocytes. The activity of three Shaker K+ channels (Kv1.3, Kv1.4, and Kv1.5), one Shaw channel (Kv3.4), and one inward rectifier K+ channel (IRK3) was drastically inhibited by photoactivation of rose bengal, a classical generator of reactive oxygen species. Other channel types (such as Shaker K+ channel Kv1.2, Shab channels Kv2.1 and Kv2.2, Shal channel Kv4.1, inward rectifiers IRK1 and ROMK1, and hIsK) were completely resistant to this treatment. On the other hand tert-butyl hydroperoxide, another generator of reactive oxygen species, removed the fast inactivation processes of Kv1.4 and Kv3.4 but did not alter other channels. Xanthine/xanthine oxidase system had no effect on all channels studied. Thus, we show that different types of K+ channels are differently modified by reactive oxygen species, an observation that might be of importance in disease states.     

THEORY AND COMPUTATION OF THE CHARACTERISTICS OF THE THERMAL ELECTRIC PLASMA ARC FOR CHEMICAL ENGINEERING APPLICATIONS

A generalized mathematical model has been developed for calculation of the characteristics of a thermal plasma arc under convective conditions. The geometry of the system analyzed is based on a novel technique which has demonstrated the capability of having a stream of gas injected into the core of the arc column around a cathode electrode with a high degree of penetration without affecting the arc stability allowing high throughputs of material. The general problem of the simultaneous solution of the conservation equations of mass, momentum, energy, and charge for a continuous plasma had been shown using incremental iterative techniques. High throughput convective arcs will now make practical many chemical and physical transformation processes. The inclusion of a more comprehensive current density makes the thermal arc more characterized than heretofore.     

Ether lipid derivatives: Antineoplastic activity in vitro and the structure-activity relationship

The antineoplastic activity of two ether lipid derivatives, the alkyl-lysophospholipid derivative (ALP) ET-18-OCH₃ and the ether-linked lipoidal amine CP-46,665 was tested in a human tumor clonogenic assay (HTCA) in vitro. CP-46,665 suppresed the colony formation of various human tumors with a slight dose response relation after 1 hr incubation and with a clear optimum (85% response rate) after continuous exposure in the higher dose range tested (10 μg/ml). ET-18-0CH₃ did not have substantial activity after 1 hr of incubation. However, when continuous exposure to the compound was used, ET-18-OCH₃ seemed to have a modest dose response effect and yielded a response in about 60% of the tumor cell samples tested in the higher dose range (10 μg/ml). Thus, both compounds have in vitro antitumor activity in the HTCA within a dose range of 1–10 μg/ml, especially during continuous exposure. The tumor specific type activity was found in breast cancer, ovarian cancer, lung cancer and mesothelioma. Both compounds caused decreases in colony formation down to the 0%, 2% and 4% levels. In a comparison of specimens in which both compounds were used, only one of five times showed a discordance in sensitivity or resistance; therefore the compounds appear similar in their in vitro activity. In a second set of experiments we tested the structure-activity relationship among a variety of ALP in the [³H]thymidine incorporation assay after incubation with HL-60 leukemic blasts and other neoplastic cells from human origin. From these studies it can be concluded that in the ALP the alkyl linkage in the sn-1 position is a necessary prerequisite for cytotoxicity; furthermore, in the majority of tumors tested the substitution of the sn-2 position to prevent reacylation of the molecule is necessary for cytotoxicity.     

Enhanced analysis of poly(ethylene glycols) and peptides using thermospray mass spectrometry

The effects of a needle-tip repeller electrode on thermospray mass spectra of poly(ethylene glycols) and peptide samples have been studied. A significant increase in ion current was observed for increased repeller potentials in the low-mass region (m/z 300 to m/z 1100) and the high-mass region (m/z 1100 to m/z 1900). The change in ion current is due to a change in ion extraction efficiency because of increased ion diffusion rates. The amount of peptide sample needed for direct injection studies was decreased 1 to 2 orders of magnitude by using an ion source with both a needle-tip repeller electrode and a restricted vaporizer probe tip.     

Thermalhydraulics studies examining the feasibility for introducing slightly enriched uranium fuel into the Embalse CANDU reactor

A joint study on the technical feasibility of using 0.9% slightly enriched uranium (SEU) fuel in the Embalse CANDU reactor was performed by Atomic Energy of Canada Limited (AECL) and Nucleoeléctrica Argentina S.A. (NASA). The feasibility study focused on the following technical areas: reactor physics and fuel management, fuel performance, and safety. Part of the safety assessment involved detailed thermalhydraulics analyses of three accident scenarios for a full core of SEU fuel bundles: (i) slow loss-of-reactivity control (LORC) event, (ii) large-break loss-of-coolant accident (LBLOCA) with emergency core cooling system (ECCS) available, and (iii) end-fitting failure. Other accident scenarios possibly encountered during the demonstration irradiation exercise or transition core have also been examined. It is concluded that introducing SEU fuel into the Embalse CANDU reactor is feasible. Clear advantages (e.g., fuel cost saving, increase in fuel exit burnup, and reduction in spent fuel volume) have been identified. The reduction in maximum bundle powers and the shift of the maximum bundle-power location to the inlet of the channel for the SEU fuel improve operating and safety margins. These margins are higher with the CANFLEX SEU fuel than the 37-element SEU fuel, due to lower linear powers and improved thermalhydraulic design.     

Electrochemical deposition of Ni and Cu onto monocrystalline n-Si(100) wafers and into nanopores in Si/SiO2 template

Nickel and copper were potentiostatically deposited onto monocrystalline n-Si (100) wafers and in nanoporous SiO₂/Si template from 0.5 M NiSO₄ + 0.5 M H₃BO₃ and 0.005 M CuSO₄ + 0.5 M H₃BO₃ solutions. Nanoporous SiO₂/Si template was formed by etching in dilute HF solution of ion tracks. The latter were produced by high-energy (380 MeV) Au⁺ ions bombardment of silicon oxide thermally grown on silicon (100) substrate. The deposition of metals was studied using cyclic voltammetry (CV), chronoamperometry; the structure and morphology of products were ex-situ investigated by SEM and XRD. The level of pores filling was controlled by deposition time. Electrodeposition occurred selectively into nanopores and the deposition on SiO₂ layer was excluded. It was found out that Ni and Cu electrodeposited into nanopores of SiO₂/Si system formed the same structures as at electrodeposition on the surface of monocrystalline n-Si—granules for Ni and scale-shaped particles for Cu deposits.     

ARID1A Mutations and PI3K/AKT Pathway Alterations in Endometriosis and Endometriosis-Associated Ovarian Carcinomas

Endometriosis is a common gynecological disease affecting 6%–10% of women of reproductive age and is characterized by the presence of endometrial-like tissue in localizations outside of the uterine cavity as, e.g., endometriotic ovarian cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been molecularly and epidemiologically linked to endometriosis. Mutations in the gene encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been found to occur in high frequency in OCCC and EnOC. The majority of these mutations lead to a loss of expression of the ARID1A protein, which is a subunit of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor suppressor. ARID1A mutations frequently co-occur with mutations, leading to an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as mutations in PIK3CA encoding the catalytic subunit, p110α, of PI3K. In combination with recent functional observations, these findings strongly suggest cooperating mechanisms between the two pathways. The occurrence of ARID1A mutations and alterations in the PI3K/AKT pathway in endometriosis and endometriosis-associated ovarian carcinomas, as well as the possible functional and clinical implications are discussed in this review.     

Acoustic impact localization in plates: properties and stability to temperature variation

Localizing an impact generated by a simple finger knock on plate-shaped solid objects is made possible in an acoustic time reversal experiment. It is shown that the technique works with a single accelerometer. To better understand the phenomenon and to know exactly the nature of the created waves, a two-dimensional (2-D) elastic simulation is used, showing that in a very good approximation the A0 Lamb mode is the only propagating one. However, it is shown that, within one wavelength distance from the edges, evanescent waves must be taken into account. As a first consequence, the ability to distinguish two neighboring impacts improves when the plate thickness decreases and the frequency increases. As a second consequence, it is expected theoretically that temperature variations lead to a stretching or a contraction of acoustic signatures. The experimental demonstration used a heterodyne interferometer to measure the impulse responses created by a knock on a plate during the cooling. A simple algorithm is shown to perfectly compensate for temperature impacts, which demonstrates the feasibility of the technique for outdoor time reversal interactive experiments.     

Combined passive detection and ultrafast active imaging of cavitation events induced by short pulses of high-intensity ultrasound

The activation of natural gas nuclei to induce larger bubbles is possible using short ultrasonic excitations of high amplitude, and is required for ultrasound cavitation therapies. However, little is known about the distribution of nuclei in tissues. Therefore, the acoustic pressure level necessary to generate bubbles in a targeted zone and their exact location are currently difficult to predict. To monitor the initiation of cavitation activity, a novel all-ultrasound technique sensitive to single nucleation events is presented here. It is based on combined passive detection and ultrafast active imaging over a large volume using the same multi-element probe. Bubble nucleation was induced using a focused transducer (660 kHz, f-number = 1) driven by a high-power electric burst (up to 300 W) of one to two cycles. Detection was performed with a linear array (4 to 7 MHz) aligned with the single-element focal point. In vitro experiments in gelatin gel and muscular tissue are presented. The synchronized passive detection enabled radio-frequency data to be recorded, comprising high-frequency coherent wave fronts as signatures of the acoustic emissions linked to the activation of the nuclei. Active change detection images were obtained by subtracting echoes collected in the unnucleated medium. These indicated the appearance of stable cavitating regions. Because of the ultrafast frame rate, active detection occurred as quickly as 330 μs after the high-amplitude excitation and the dynamics of the induced regions were studied individually.