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

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

Absorption properties of type-II InAs/InAsSb superlattices measured by spectroscopic ellipsometry

Strain-balanced InAs/InAsSb superlattices offer access to the mid- to long-wavelength infrared region with what is essentially a ternary material system at the GaSb lattice constant. The absorption coefficients of InAs/InAsSb superlattices grown by molecular beam epitaxy on (100)-oriented GaSb substrates are measured at room temperature over the 30 to 800 meV photon energy range using spectroscopic ellipsometry, and the miniband structure of each superlattice is calculated using a Kronig-Penney model. The InAs/InAsSb conduction band offset is used as a fitting parameter to align the calculated superlattice ground state transition energy to the measured absorption onset at room temperature and to the photoluminescence peak energy at low temperature. It is observed that the ground state absorption coefficient and transition strength are proportional to the square of the wavefunction overlap and the ground state absorption coefficient approaches a maximum value of around 5780 cm-1as the wavefunction overlap approaches 100%. The absorption analysis of these samples indicates that the optical joint density of states is weakly dependent on the period thickness and Sb content of the superlattice, and that wavefunction overlap is the principal design parameter in terms of obtaining strong absorption in these structures

Distribution and abundance of fish and crayfish in a Waikato stream in relation to basin area

The aim of this study was to relate the longitudinal distribution of fish and crayfish to increasing basin area and physical site characteristics in the Mangaotama Stream, Waikato region, North Island, New Zealand. Fish and crayfish were captured with two-pass removal electroshocking at 11 sites located in hill-country with pasture, native forest, and mixed land uses within the 21.6 km2 basin. Number of fish species and lineal biomass of fish increased with increasing basin area, but barriers to upstream fish migration also influenced fish distribution; only climbing and non-migratory species were present above a series of small waterfalls. Fish biomass increased in direct proportion to stream width, suggesting that fish used much of the available channel, and stream width was closely related to basin area. Conversely, the abundance of crayfish was related to the amount of edge habitat, and therefore crayfish did not increase in abundance as basin area increased. Densities of all fish species combined ranged from 17 to 459 fish 100 m-2, and biomass ranged from 14 to 206 g m-2. Eels dominated the fish assemblages, comprising 85-100% of the total biomass; longfinned eels the majority of the biomass at most sites. Despite the open access of the lower sites to introduced brown trout, native species dominated all the fish communities sampled

Feasibility investigation of allogeneic endometrial regenerative cells

Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type

Phase Transitions and Spatio-Temporal Fluctuations in Stochastic Lattice Lotka-Volterra Models

We study the general properties of stochastic two-species models for predator-prey competition and coexistence with Lotka-Volterra type interactions defined on a $d$-dimensional lattice. Introducing spatial degrees of freedom and allowing for stochastic fluctuations generically invalidates the classical, deterministic mean-field picture. Already within mean-field theory, however, spatial constraints, modeling locally limited resources, lead to the emergence of a continuous active-to-absorbing state phase transition. Field-theoretic arguments, supported by Monte Carlo simulation results, indicate that this transition, which represents an extinction threshold for the predator population, is governed by the directed percolation universality class. In the active state, where predators and prey coexist, the classical center singularities with associated population cycles are replaced by either nodes or foci. In the vicinity of the stable nodes, the system is characterized by essentially stationary localized clusters of predators in a sea of prey. Near the stable foci, however, the stochastic lattice Lotka-Volterra system displays complex, correlated spatio-temporal patterns of competing activity fronts. Correspondingly, the population densities in our numerical simulations turn out to oscillate irregularly in time, with amplitudes that tend to zero in the thermodynamic limit. Yet in finite systems these oscillatory fluctuations are quite persistent, and their features are determined by the intrinsic interaction rates rather than the initial conditions. We emphasize the robustness of this scenario with respect to various model perturbations.Comment: 19 pages, 11 figures, 2-column revtex4 format. Minor modifications. Accepted in the Journal of Statistical Physics. Movies corresponding to Figures 2 and 3 are available at http://www.phys.vt.edu/~tauber/PredatorPrey/movies

Preliminary archaeoentomological analyses of permafrost-preserved cultural layers from the pre-contact Yup’ik Eskimo site of Nunalleq, Alaska : implications, potential and methodological considerations

Acknowledgements Site excavation and samples collection were conducted by archaeologists from the University of Aberdeen, with the help of archaeologists and student excavators from the University of Aberdeen University of Alaska Fairbanks and Bryn Mawr College, Kuskokwim Campus, College of Rural Alaska and residents of Quinhagak and Mekoryuk. This study is funded through AHRC grant to the project ‘Understanding Cultural Resilience and Climate Change on the Bering Sea through Yup’ik Ecological Knowledge, Lifeways, Learning and Archaeology’ to Rick Knecht, Kate Britton and Charlotta Hillderal (University of Aberdeen; AH/K006029/1). Thanks are due to Qanirtuuq Inc. and Quinhagak, Alaska for sampling permissions and to entomologists working at the CNC in Ottawa for allowing access to reference collections of beetles, lice and fleas. Yves Bousquet, Ales Smetana and Anthony E. Davies are specially acknowledged for their help with the identification of coleopteran specimens. Finally, we would also like to thank Scott Elias for useful comments on the original manuscript.Peer reviewedPublisher PD

Umbral Calculus, Discretization, and Quantum Mechanics on a Lattice

`Umbral calculus' deals with representations of the canonical commutation relations. We present a short exposition of it and discuss how this calculus can be used to discretize continuum models and to construct representations of Lie algebras on a lattice. Related ideas appeared in recent publications and we show that the examples treated there are special cases of umbral calculus. This observation then suggests various generalizations of these examples. A special umbral representation of the canonical commutation relations given in terms of the position and momentum operator on a lattice is investigated in detail.Comment: 19 pages, Late