Voltage-dependent Block of the Cystic Fibrosis Transmembrane Conductance Regulator Cl- Channel by Two Closely Related Arylaminobenzoates

The gene defective in cystic fibrosis encodes a Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is blocked by diphenylamine-2-carboxylate (DPC) when applied extracellularly at millimolar concentrations. We studied the block of CFTR expressed in Xenopus oocytes by DPC or by a closely related molecule, flufenamic acid (FFA). Block of whole-cell CFTR currents by bath-applied DPC or by FFA, both at 200 µM, requires several minutes to reach full effect. Blockade is voltage dependent, suggesting open-channel block: currents at positive potentials are not affected but currents at negative potentials are reduced. The binding site for both drugs senses ~40% of the electric field across the membrane, measured from the inside. In single-channel recordings from excised patches without blockers, the conductance was 8.0 ± 0.4 pS in symmetric 150 mM Cl^-. A subconductance state, measuring ~60% of the main conductance, was often observed. Bursts to the full open state lasting up to tens of seconds were uninterrupted at depolarizing membrane voltages. At hyperpolarizing voltages, bursts were interrupted by brief closures. Either DPC or FFA (50 µM) applied to the cytoplasmic or extracellular face of the channel led to an increase in flicker at V_m =-100 mV and not at V_m = +100 mV, in agreement with whole-cell experiments. DPC induced a higher frequency of flickers from the cytoplasmic side than the extracellular side. FFA produced longer closures than DPC; the FFA closed time was roughly equal (~ 1.2 ms) at -100 mV with application from either side. In cell-attached patch recordings with DPC or FFA applied to the bath, there was flickery block at V_m = -100 mV, confirming that the drugs permeate through the membrane to reach the binding site. The data are consistent with the presence of a single binding site for both drugs, reached from either end of the channel. Open-channel block by DPC or FFA may offer tools for use with site-directed mutagenesis to describe the permeation pathway

Sensitivity of an image plate system in the XUV (60 eV < E < 900 eV)

Phosphor imaging plates (IPs) have been calibrated and proven useful for quantitative x-ray imaging in the 1 to over 1000 keV energy range. In this paper we report on calibration measurements made at XUV energies in the 60 to 900 eV energy range using beamline 6.3.2 at the Advanced Light Source at Lawrence Berkeley National Laboratory. We measured a sensitivity of ~25 plus or minus 15 counts/pJ over the stated energy range which is compatible with the sensitivity of Si photodiodes that are used for time-resolved measurements. Our measurements at 900 eV are consistent with the measurements made by Meadowcroft et al. at ~1 keV.Comment: 7 pages, 2 figure

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K 3, phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC 50 in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and non-proliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K 3. The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing. © 2001 Cancer Research Campaign http://www.bjcancer.co

Proof of two conjectures of Z.-W. Sun on congruences for Franel numbers

For all nonnegative integers n, the Franel numbers are defined as $$f_n=\sum_{k=0}^n {n\choose k}^3.$$ We confirm two conjectures of Z.-W. Sun on congruences for Franel numbers: \sum_{k=0}^{n-1}(3k+2)(-1)^k f_k &\equiv 0 \pmod{2n^2}, \sum_{k=0}^{p-1}(3k+2)(-1)^k f_k &\equiv 2p^2 (2^p-1)^2 \pmod{p^5}, where n is a positive integer and p>3 is a prime.Comment: 8 pages, minor changes, to appear in Integral Transforms Spec. Func

Statistical Properties of the Final State in One-dimensional Ballistic Aggregation

We investigate the long time behaviour of the one-dimensional ballistic aggregation model that represents a sticky gas of N particles with random initial positions and velocities, moving deterministically, and forming aggregates when they collide. We obtain a closed formula for the stationary measure of the system which allows us to analyze some remarkable features of the final `fan' state. In particular, we identify universal properties which are independent of the initial position and velocity distributions of the particles. We study cluster distributions and derive exact results for extreme value statistics (because of correlations these distributions do not belong to the Gumbel-Frechet-Weibull universality classes). We also derive the energy distribution in the final state. This model generates dynamically many different scales and can be viewed as one of the simplest exactly solvable model of N-body dissipative dynamics.Comment: 19 pages, 5 figures include

Book Reviews

Reviews of the following books: Was Baseball Really Invented in Maine? by Will Anderson; Acadian Hard Times: The Farm Security Administration in Maine\u27s St. John Valley, 1940-1943 by C. Stewart Doty; The Latchstring Was Always Out: A History of Lodging Hospitality and Tourism in Bartlett, New Hampshire by Aileen M. Carroll; A Fair Field and No Favor: A Concise History of the Maine State Grange by Stanley Russell Howe; Dell Turner: The Stories of His Life by John T. Meader; Hail Britannia: Maine Pewter and Silverplate: An Exhibition of Maine Britannia Ware and Silverplate, 1829-1941, in the Collections of the Maine State Museum, May 15, 1992-May 15, 1993 by Edwin A. Churchil

Breakdown of Lindstedt Expansion for Chaotic Maps

In a previous paper of one of us [Europhys. Lett. 59 (2002), 330--336] the validity of Greene's method for determining the critical constant of the standard map (SM) was questioned on the basis of some numerical findings. Here we come back to that analysis and we provide an interpretation of the numerical results by showing that no contradiction is found with respect to Greene's method. We show that the previous results based on the expansion in Lindstedt series do correspond to the transition value but for a different map: the semi-standard map (SSM). Moreover, we study the expansion obtained from the SM and SSM by suppressing the small divisors. The first case turns out to be related to Kepler's equation after a proper transformation of variables. In both cases we give an analytical solution for the radius of convergence, that represents the singularity in the complex plane closest to the origin. Also here, the radius of convergence of the SM's analogue turns out to be lower than the one of the SSM. However, despite the absence of small denominators these two radii are lower than the ones of the true maps for golden mean winding numbers. Finally, the analyticity domain and, in particular, the critical constant for the two maps without small divisors are studied analytically and numerically. The analyticity domain appears to be an perfect circle for the SSM analogue, while it is stretched along the real axis for the SM analogue yielding a critical constant that is larger than its radius of convergence.Comment: 12 pages, 3 figure

Powers of Hamilton cycles in pseudorandom graphs

We study the appearance of powers of Hamilton cycles in pseudorandom graphs, using the following comparatively weak pseudorandomness notion. A graph $G$ is $(\varepsilon,p,k,\ell)$-pseudorandom if for all disjoint $X$ and $Y\subset V(G)$ with $|X|\ge\varepsilon p^kn$ and $|Y|\ge\varepsilon p^\ell n$ we have $e(X,Y)=(1\pm\varepsilon)p|X||Y|$. We prove that for all $\beta>0$ there is an $\varepsilon>0$ such that an $(\varepsilon,p,1,2)$-pseudorandom graph on $n$ vertices with minimum degree at least $\beta pn$ contains the square of a Hamilton cycle. In particular, this implies that $(n,d,\lambda)$-graphs with $\lambda\ll d^{5/2 }n^{-3/2}$ contain the square of a Hamilton cycle, and thus a triangle factor if $n$ is a multiple of $3$. This improves on a result of Krivelevich, Sudakov and Szab\'o [Triangle factors in sparse pseudo-random graphs, Combinatorica 24 (2004), no. 3, 403--426]. We also extend our result to higher powers of Hamilton cycles and establish corresponding counting versions.Comment: 30 pages, 1 figur