Potentiation of anti-cancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors NU1025 and NU1064.

The ability of the potent poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025 (8-hydroxy-2-methyl-quinazolin-4-[3H]one) to potentiate the cytotoxicity of a panel of mechanistically diverse anti-cancer agents was evaluated in L1210 cells. NU1025 enhanced the cytotoxicity of the DNA-methylating agent MTIC, gamma-irradiation and bleomycin 3.5-, 1.4- and 2-fold respectively. The cytotoxicities of the thymidylate synthase inhibitor, nolatrexed, and the cytotoxic nucleoside, gemcitabine, were not increased. Potentiation of MTIC cytotoxicity by a delayed exposure to NU1025 was equally effective as by a simultaneous exposure to NU1025, indicating that the effects of NU1025 were mediated by an inhibition of the cellular recovery. The recovery from potentially lethal gamma-irradiation damage cytotoxicity in plateau-phase cells was also inhibited by NU1025. Investigation of DNA strand breakage and repair in gamma-irradiated cells by alkaline elution demonstrated that NU1025 caused a marked retardation of DNA repair. A structurally different PARP inhibitor, NU1064 (2-methylbenzimidazole-4-carboxamide), also potentiated the cytotoxicity of MTIC, to a similar extent to NU1025. NU1064 potentiated a sublethal concentration of a DNA methylating agent in a concentration-dependent manner. Collectively, these data suggest that the most suitable cytotoxic agents for use in combination with PARP inhibitors are methylating agents, bleomycin and ionizing radiation, but not anti-metabolites

Scaling and universality in the anisotropic Kondo model and the dissipative two-state system

Scaling and universality in the Ohmic two-state system is investigated by exploiting the equivalence of this model to the anisotropic Kondo model. For the Ohmic two-state system, we find universal scaling functions for the specific heat, $C_{\alpha}(T)$, static susceptibility, $\chi_{\alpha}(T)$, and spin relaxation function $S_{\alpha}(\omega)$ depending on the reduced temperature $T/\Delta_{r}$ (frequency $\omega/\Delta_{r}$), with $\Delta_{r}$ the renormalized tunneling frequency, and uniquely specified by the dissipation strength $\alpha$ ($0<\alpha<1$). The scaling functions can be used to extract $\alpha$ and $\Delta_{r}$ in experimental realizations.Comment: 5 pages (LaTeX), 4 EPS figures. Minor changes, typos corrected, journal reference adde

Short-wave infrared barriode detectors using InGaAsSb absorption material lattice matched to GaSb

Short-wave infrared barriode detectors were grown by molecular beam epitaxy. An absorption layer composition of In0.28Ga0.72As0.25Sb0.75 allowed for lattice matching to GaSb and cut-off wavelengths of 2.9 μm at 250 K and 3.0 μm at room temperature. Arrhenius plots of the dark current density showed diffusion limited dark currents approaching those expected for optimized HgCdTe-based detectors. Specific detectivity figures of around 7×1010 Jones and 1×1010 Jones were calculated, for 240 K and room temperature, respectively. Significantly, these devices could support focal plane arrays working at higher operating temperatures

Glycinergic Axonal Inhibition Subserves Acute Spatial Sensitivity To Sudden Increases In Sound Intensity

Locomotion generates adventitious sounds which enable detection and localization of predators and prey. Such sounds contain brisk changes or transients in amplitude. We investigated the hypothesis that ill-understood temporal specializations in binaural circuits subserve lateralization of such sound transients, based on different time of arrival at the ears (interaural time differences, ITDs). We find that Lateral Superior Olive (LSO) neurons show exquisite ITD-sensitivity, reflecting extreme precision and reliability of excitatory and inhibitory postsynaptic potentials, in contrast to Medial Superior Olive neurons, traditionally viewed as the ultimate ITD-detectors. In vivo, inhibition blocks LSO excitation over an extremely short window, which, in vitro, required synaptically evoked inhibition. Light and electron microscopy revealed inhibitory synapses on the axon initial segment as the structural basis of this observation. These results reveal a neural vetoing mechanism with extreme temporal and spatial precision and establish the LSO as the primary nucleus for binaural processing of sound transients

Sequence randomness and polymer collapse transitions

Contrary to expectations based on Harris' criterion, chain disorder with frustration can modify the universality class of scaling at the theta transition of heteropolymers. This is shown for a model with random two-body potentials in 2D on the basis of exact enumeration and accurate Monte Carlo results. When frustration grows beyond a certain finite threshold, the temperature below which disorder becomes relevant coincides with the theta one and scaling exponents definitely start deviating from those valid for homopolymers.Comment: 4 pages, 4 eps figure

Dynamics of Tunneling Centers in Metallic Systems

Dynamics of tunneling centers (TC) in metallic systems is studied, using the technique of bosonization. The interaction of the TC with the conduction electrons of the metal involves two processes, namely, the screening of the TC by electrons, and the so-called electron assisted tunneling. The presence of the latter process leads to a different form of the renormalized tunneling frequency of the TC, and the tunneling motion is damped with a temperature dependent relaxation rate. As the temperature is lowered, the relaxation rate per temperature shows a steep rise as opposed to that in the absence of electron assisted process. It is expected that this behavior should be observed at very low temperatures in a careful experiment. The present work thus tries to go beyond the existing work on the {\it dynamics} of a two-level system in metals, by treating the electron assisted process.Comment: REVTeX twocolumn format, 5 pages, two PostScript figures available on request. Preprint # : imsc 94/3

Luminous Infrared Galaxies with the Submillimeter Array: I. Survey Overview and the Central Gas to Dust Ratio

We present new data obtained with the Submillimeter Array for a sample of fourteen nearby luminous and ultraluminous infrared galaxies. The galaxies were selected to have luminosity distances D < 200 Mpc and far-infrared luminosities log(L_FIR) > 11.4. The galaxies were observed with spatial resolutions of order 1 kpc in the CO J=3-2, CO J=2-1, 13CO J=2-1, and HCO+ J=4-3 lines as well as the continuum at 880 microns and 1.3 mm. We have combined our CO and continuum data to measure an average gas-to-dust mass ratio of 120 +/- 28 (rms deviation 109) in the central regions of these galaxies, very similar to the value of 150 determined for the Milky Way. This similarity is interesting given the more intense heating from the starburst and possibly accretion activity in the luminous infrared galaxies compared to the Milky Way. We find that the peak H_2 surface density correlates with the far-infrared luminosity, which suggests that galaxies with higher gas surface densities inside the central kiloparsec have a higher star formation rate. The lack of a significant correlation between total H_2 mass and far-infrared luminosity in our sample suggests that the increased star formation rate is due to the increased availability of molecular gas as fuel for star formation in the central regions. In contrast to previous analyses by other authors, we do not find a significant correlation between central gas surface density and the star formation efficiency, as trace by the ratio of far-infrared luminosity to nuclear gas mass. Our data show that it is the star formation rate, not the star formation efficiency, that increases with increasing central gas surface density in these galaxies.Comment: 66 pages, 39 figures, aastex preprint format; to be published in ApJ Supplements. Version of paper with full resolution figures available at http://www.physics.mcmaster.ca/~wilson/www_xfer/ULIRGS_publi

Frequency Characteristics of Visually Induced Motion Sickness

This article was published in the journal, Human Factors [Sage Publications / © Human Factors and Ergonomics Society.]. The definitive version is available at: http://dx.doi.org/10.1177/0018720812469046Objective: The aim of this study was to explore the frequency response of visually induced motion sickness (VIMS) for oscillating linear motion in the foreand- aft axis. Background: Simulators, virtual environments, and commercially available video games that create an illusion of self-motion are often reported to induce the symptoms seen in response to true motion. Often this human response can be the limiting factor in the acceptability and usability of such systems. Whereas motion sickness in physically moving environments is known to peak at an oscillation frequency around 0.2 Hz, it has recently been suggested that VIMS peaks at around 0.06 Hz following the proposal that the summed response of the visual and vestibular selfmotion systems is maximized at this frequency. Methods: We exposed 24 participants to random dot optical flow patterns simulating oscillating foreand- aft motion within the frequency range of 0.025 to 1.6 Hz. Before and after each 20-min exposure, VIMS was assessed with the Simulator Sickness Questionnaire. Also, a standard motion sickness scale was used to rate symptoms at 1-min intervals during each trial. Results: VIMS peaked between 0.2 and 0.4 Hz with a reducing effect at lower and higher frequencies. Conclusion: The numerical prediction of the “crossover frequency” hypothesis, and the design guidance curve previously proposed, cannot be accepted when the symptoms are purely visually induced. Application: In conditions in which stationary observers are exposed to optical flow that simulates oscillating fore-and-aft motion, frequencies around 0.2 to 0.4 Hz should be avoided