2,287 research outputs found
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
Teleology and Realism in Leibniz's Philosophy of Science
This paper argues for an interpretation of Leibniz’s claim that physics requires both mechanical and teleological principles as a view regarding the interpretation of physical theories. Granting that Leibniz’s fundamental ontology remains non-physical, or mentalistic, it argues that teleological principles nevertheless ground a realist commitment about mechanical descriptions of phenomena. The empirical results of the new sciences, according to Leibniz, have genuine truth conditions: there is a fact of the matter about the regularities observed in experience. Taking this stance, however, requires bringing non-empirical reasons to bear upon mechanical causal claims. This paper first evaluates extant interpretations of Leibniz’s thesis that there are two realms in physics as describing parallel, self-sufficient sets of laws. It then examines Leibniz’s use of teleological principles to interpret scientific results in the context of his interventions in debates in seventeenth-century kinematic theory, and in the teaching of Copernicanism. Leibniz’s use of the principle of continuity and the principle of simplicity, for instance, reveal an underlying commitment to the truth-aptness, or approximate truth-aptness, of the new natural sciences. The paper concludes with a brief remark on the relation between metaphysics, theology, and physics in Leibniz
Random template placement and prior information
In signal detection problems, one is usually faced with the task of searching
a parameter space for peaks in the likelihood function which indicate the
presence of a signal. Random searches have proven to be very efficient as well
as easy to implement, compared e.g. to searches along regular grids in
parameter space. Knowledge of the parameterised shape of the signal searched
for adds structure to the parameter space, i.e., there are usually regions
requiring to be densely searched while in other regions a coarser search is
sufficient. On the other hand, prior information identifies the regions in
which a search will actually be promising or may likely be in vain. Defining
specific figures of merit allows one to combine both template metric and prior
distribution and devise optimal sampling schemes over the parameter space. We
show an example related to the gravitational wave signal from a binary inspiral
event. Here the template metric and prior information are particularly
contradictory, since signals from low-mass systems tolerate the least mismatch
in parameter space while high-mass systems are far more likely, as they imply a
greater signal-to-noise ratio (SNR) and hence are detectable to greater
distances. The derived sampling strategy is implemented in a Markov chain Monte
Carlo (MCMC) algorithm where it improves convergence.Comment: Proceedings of the 8th Edoardo Amaldi Conference on Gravitational
Waves. 7 pages, 4 figure
Studies of MCP-PMTs in the miniTimeCube neutrino detector
This report highlights two different types of cross-talk in the
photodetectors of the miniTimeCube neutrino experiment. The miniTimeCube
detector has 24 -anode Photonis MCP-PMTs Planacon XP85012,
totalling 1536 individual pixels viewing the 2-liter cube of plastic
scintillator
Imaging the Earth's Interior: the Angular Distribution of Terrestrial Neutrinos
Decays of radionuclides throughout the Earth's interior produce geothermal
heat, but also are a source of antineutrinos. The (angle-integrated)
geoneutrino flux places an integral constraint on the terrestrial radionuclide
distribution. In this paper, we calculate the angular distribution of
geoneutrinos, which opens a window on the differential radionuclide
distribution. We develop the general formalism for the neutrino angular
distribution, and we present the inverse transformation which recovers the
terrestrial radioisotope distribution given a measurement of the neutrino
angular distribution. Thus, geoneutrinos not only allow a means to image the
Earth's interior, but offering a direct measure of the radioactive Earth, both
(1) revealing the Earth's inner structure as probed by radionuclides, and (2)
allowing for a complete determination of the radioactive heat generation as a
function of radius. We present the geoneutrino angular distribution for the
favored Earth model which has been used to calculate geoneutrino flux. In this
model the neutrino generation is dominated by decays in the Earth's mantle and
crust; this leads to a very ``peripheral'' angular distribution, in which 2/3
of the neutrinos come from angles > 60 degrees away from the downward vertical.
We note the possibility of that the Earth's core contains potassium; different
geophysical predictions lead to strongly varying, and hence distinguishable,
central intensities (< 30 degrees from the downward vertical). Other
uncertainties in the models, and prospects for observation of the geoneutrino
angular distribution, are briefly discussed. We conclude by urging the
development and construction of antineutrino experiments with angular
sensitivity. (Abstract abridged.)Comment: 25 pages, RevTeX, 7 figures. Comments welcom
Geo-neutrinos: A systematic approach to uncertainties and correlations
Geo-neutrinos emitted by heat-producing elements (U, Th and K) represent a
unique probe of the Earth interior. The characterization of their fluxes is
subject, however, to rather large and highly correlated uncertainties. The
geochemical covariance of the U, Th and K abundances in various Earth
reservoirs induces positive correlations among the associated geo-neutrino
fluxes, and between these and the radiogenic heat. Mass-balance constraints in
the Bulk Silicate Earth (BSE) tend instead to anti-correlate the radiogenic
element abundances in complementary reservoirs. Experimental geo-neutrino
observables may be further (anti)correlated by instrumental effects. In this
context, we propose a systematic approach to covariance matrices, based on the
fact that all the relevant geo-neutrino observables and constraints can be
expressed as linear functions of the U, Th and K abundances in the Earth's
reservoirs (with relatively well-known coefficients). We briefly discuss here
the construction of a tentative "geo-neutrino source model" (GNSM) for the U,
Th, and K abundances in the main Earth reservoirs, based on selected
geophysical and geochemical data and models (when available), on plausible
hypotheses (when possible), and admittedly on arbitrary assumptions (when
unavoidable). We use then the GNSM to make predictions about several
experiments ("forward approach"), and to show how future data can constrain - a
posteriori - the error matrix of the model itself ("backward approach"). The
method may provide a useful statistical framework for evaluating the impact and
the global consistency of prospective geo-neutrino measurements and Earth
models.Comment: 17 pages, including 4 figures. To appear on "Earth, Moon, and
Planets," Special Issue on "Neutrino Geophysics," Proceedings of Neutrino
Science 2005 (Honolulu, Hawaii, Dec. 2005
Educating for urban sustainability: A transdisciplinary approach
An understanding of sustainability issues should be a key component of degree programmes. It is widely regarded as being a central attribute to professional practice and responsible global citizenship, arguably more so for the training of teachers since they potentially influence their students. This issue was brought to the fore when responsibility for delivering the 'design and the environment' course was transferred to the building discipline at the University of Newcastle in Australia as a result of restructuring. The attractiveness of the subject as an elective, the need to make it accessible to distance learning students and the desirability of applying transdisciplinary approaches to solving environmental problems presented the course designers with both challenges and opportunities, particularly in devising an assessment context within which students from multiple disciplines could be exposed to, and learn from each other's professional environmental evaluation norms. This paper describes an innovative holistic, multi-criteria problem-solving course design that allows a diverse mix of undergraduates to develop a transdisciplinary understanding of sustainability issues through the use of learning contracts. It reports the experiences of staff and students involved with the course, highlighting the beneficial outcomes
Search for the Weak Decay of an H Dibaryon
We have searched for a neutral dibaryon decaying via and
. Our search has yielded two candidate events from which we set
an upper limit on the production cross section. Normalizing to the
inclusive production cross section, we find at 90% C.L., for an of mass
2.15 GeV/.Comment: 11 pages, 6 postscript figures, epsfig, aps, preprint, revte
A geoneutrino experiment at Homestake
A significant fraction of the 44TW of heat dissipation from the Earth's
interior is believed to originate from the decays of terrestrial uranium and
thorium. The only estimates of this radiogenic heat, which is the driving force
for mantle convection, come from Earth models based on meteorites, and have
large systematic errors. The detection of electron antineutrinos produced by
these uranium and thorium decays would allow a more direct measure of the total
uranium and thorium content, and hence radiogenic heat production in the Earth.
We discuss the prospect of building an electron antineutrino detector
approximately 700m^3 in size in the Homestake mine at the 4850' level. This
would allow us to make a measurement of the total uranium and thorium content
with a statistical error less than the systematic error from our current
knowledge of neutrino oscillation parameters. It would also allow us to test
the hypothesis of a naturally occurring nuclear reactor at the center of the
Earth.Comment: proceedings for Neutrino Sciences 2005, submitted to Earth, Moon, and
Planet
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