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

Regions of beta 2 and beta 4 responsible for differences between the steady state dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 neuronal nicotinic receptors

We constructed chimeras of the rat beta 2 and beta 4 neuronal nicotinic subunits to locate the regions that contribute to differences between the acetylcholine (ACh) dose-response relationships of the alpha 3 beta 2 and alpha 3 beta 4 receptors. Expressed in Xenopus oocytes, the alpha 3 beta 2 receptor displays an EC50 for ACh approximately 20-fold less than the EC50 of the alpha 3 beta 4 receptor. The apparent Hill slope (n(app)) of alpha 3 beta 2 is near one whereas the alpha 3 beta 4 receptor displays an n(app) near two. Substitutions within the first 120 residues convert the EC50 for ACh from one wild-type value to the other. Exchanging just beta 2:104-120 for the corresponding region of beta 4 shifts the EC50 of ACh dose-response relationship in the expected direction but does not completely convert the EC50 of the dose- response relationship from one wild-type value to the other. However, substitutions in the beta 2:104-120 region do account for the relative sensitivity of the alpha 3 beta 2 receptor to cytisine, tetramethylammonium, and ACh. The expression of beta 4-like (strong) cooperativity requires an extensive region of beta 4 (beta 4:1-301). Relatively short beta 2 substitutions (beta 2:104-120) can reduce cooperativity to beta 2-like values. The results suggest that amino acids within the first 120 residues of beta 2 and the corresponding region of beta 4 contribute to an agonist binding site that bridges the alpha and beta subunits in neuronal nicotinic receptors

Collisional decay of a strongly driven Bose-Einstein condensate

We study the collisional decay of a strongly driven Bose-Einstein condensate oscillating between two momentum modes. The resulting products of the decay are found to strongly deviate from the usual s-wave halo. Using a stochastically seeded classical field method we simulate the collisional manifold. These results are also explained by a model of colliding Bloch states.Comment: 4 pages, 4 figure

Damping of bulk excitations over an elongated BEC - the role of radial modes

We report the measurement of Beliaev damping of bulk excitations in cigar shaped Bose Einstein condensates of atomic vapor. By using post selection, excitation line shapes of the total population are compared with those of the undamped excitations. We find that the damping depends on the initial excitation energy of the decaying quasi particle, as well as on the excitation momentum. We model the condensate as an infinite cylinder and calculate the damping rates of the different radial modes. The derived damping rates are in good agreement with the experimentally measured ones. The damping rates strongly depend on the destructive interference between pathways for damping, due to the quantum many-body nature of both excitation and damping products.Comment: 5 pages, 4 figure

Precision measurement of the branching ratio in the 6P3/2 decay of BaII with a single trapped ion

We present a measurement of the branching ratios from the 6P3/2 state of BaII into all dipoleallowed decay channels (6S1/2, 5D3/2 and 5D5/2). Measurements were performed on single 138Ba+ ions in a linear Paul trap with a frequency-doubled mode-locked Ti:Sapphire laser resonant with the 6S1/2->6P3/2 transition at 455 nm by detection of electron shelving into the dark 5D5/2 state. By driving a pi Rabi rotation with a single femtosecond pulse, a absolute measurement of the branching ratio to 5D5/2 state was performed. Combined with a measurement of the relative decay rates into 5D3/2 and 5D5/2 states performed with long trains of highly attenuated 455 nm pulses, it allowed the extraction of the absolute ratios of the other two decays. Relative strengths normalized to unity are found to be 0.756+/-0.046, 0.0290+/-0.0015 and 0.215+/-0.0064 for 6S1/2, 5D3/2 and 5D5/2 respectively. This approximately constitutes a threefold improvement over the best previous measurements and is a sufficient level of precision to compare to calculated values for dipole matrix elements.Comment: 6 pages, 5 figures, 1 tabl

Reification and Truthmaking Patterns

Reification is a standard technique in conceptual modeling, which consists of including in the domain of discourse entities that may otherwise be hidden or implicit. However, deciding what should be rei- fied is not always easy. Recent work on formal ontology offers us a simple answer: put in the domain of discourse those entities that are responsible for the (alleged) truth of our propositions. These are called truthmakers. Re-visiting previous work, we propose in this paper a systematic analysis of truthmaking patterns for properties and relations based on the ontolog- ical nature of their truthmakers. Truthmaking patterns will be presented as generalization of reification patterns, accounting for the fact that, in some cases, we do not reify a property or a relationship directly, but we rather reify its truthmakers

On rigidly rotating perfect fluid cylinders

The gravitational field of a rigidly rotating perfect fluid cylinder with gamma- law equation of state is found analytically. The solution has two parameters and is physically realistic for gamma in the interval (1.41,2]. Closed timelike curves always appear at large distances.Comment: 10 pages, Revtex (galley

Magnetic Field Structure around Low-Mass Class 0 Protostars: B335, L1527 and IC348-SMM2

We report new 350 micron polarization observations of the thermal dust emission from the cores surrounding the low-mass, Class 0 YSOs L1527, IC348-SMM2 and B335. We have inferred magnetic field directions from these observations, and have used them together with results in the literature to determine whether magnetically regulated core-collapse and star-formation models are consistent with the observations. These models predict a pseudo-disk with its symmetry axis aligned with the core magnetic field. The models also predict a magnetic field pinch structure on a scale less than or comparable to the infall radii for these sources. In addition, if the core magnetic field aligns (or nearly aligns) the core rotation axis with the magnetic field before core collapse, then the models predict the alignment (or near alignment) of the overall pinch field structure with the bipolar outflows in these sources. We show that if one includes the distorting effects of bipolar outflows on magnetic fields, then in general the observational results for L1527 and IC348-SMM2 are consistent with these magnetically regulated models. We can say the same for B335 only if we assume the distorting effects of the bipolar outflow on the magnetic fields within the B335 core are much greater than for L1527 and IC348-SMM2. We show that the energy densities of the outflows in all three sources are large enough to distort the magnetic fields predicted by magnetically regulated models.Comment: Accepted for publication in The Astrophysical Journa

Dimensionless Measures of Turbulent Magnetohydrodynamic Dissipation Rates

The magnetic Reynolds number R_M, is defined as the product of a characteristic scale and associated flow speed divided by the microphysical magnetic diffusivity. For laminar flows, R_M also approximates the ratio of advective to dissipative terms in the total magnetic energy equation, but for turbulent flows this latter ratio depends on the energy spectra and approaches unity in a steady state. To generalize for flows of arbitrary spectra we define an effective magnetic dissipation number, R_{M,e}, as the ratio of the advection to microphysical dissipation terms in the total magnetic energy equation, incorporating the full spectrum of scales, arbitrary magnetic Prandtl numbers, and distinct pairs of inner and outer scales for magnetic and kinetic spectra. As expected, for a substantial parameter range R_{M,e}\sim {O}(1) << R_M. We also distinguish R_{M,e} from {\tilde R}_{M,e} where the latter is an effective magnetic Reynolds number for the mean magnetic field equation when a turbulent diffusivity is explicitly imposed as a closure. That R_{M,e} and {\tilde R}_{M,e} approach unity even if R_M>>1 highlights that, just as in hydrodynamic turbulence,energy dissipation of large scale structures in turbulent flows via a cascade can be much faster than the dissipation of large scale structures in laminar flows. This illustrates that the rate of energy dissipation by magnetic reconnection is much faster in turbulent flows, and much less sensitive to microphysical reconnection rates compared to laminar flows.Comment: 14 pages (including 2 figs), accepted by MNRA