860 research outputs found
The response of the tandem pore potassium channel TASK-3 (K2P9.1) to voltage : gating at the cytoplasmic mouth
Although the tandem pore potassium channel TASK-3 is thought to open and shut at its
selectivity filter in response to changes of extracellular pH, it is currently unknown whether the
channel also shows gating at its inner, cytoplasmic mouth through movements of membrane
helices M2 and M4.We used two electrode voltage clamp and single channel recording to show
that TASK-3 responds to voltage in a way that reveals such gating. In wild-type channels, Popen
was very low at negative voltages, but increased with depolarisation. The effect of voltage was
relatively weak and the gating charge small, ∼0.17.Mutants A237T (in M4) and N133A (in M2)
increased Popen at a given voltage, increasing mean open time and the number of openings per
burst. In addition, the relationship between Popen andvoltagewas shifted to lesspositive voltages.
Mutation of putative hinge glycines (G117A, G231A), residues that are conserved throughout
the tandem pore channel family, reduced Popen at a given voltage, shifting the relationship
with voltage to a more positive potential range. None of these mutants substantially affected
the response of the channel to extracellular acidification. We have used the results from single
channel recording to develop a simple kinetic model to show how gating occurs through two
classes of conformation change, with two routes out of the open state, as expected if gating
occurs both at the selectivity filter and at its cytoplasmic mouth
Adapting SAM for CDF
The CDF and D0 experiments probe the high-energy frontier and as they do so
have accumulated hundreds of Terabytes of data on the way to petabytes of data
over the next two years. The experiments have made a commitment to use the
developing Grid based on the SAM system to handle these data. The D0 SAM has
been extended for use in CDF as common patterns of design emerged to meet the
similar requirements of these experiments. The process by which the merger was
achieved is explained with particular emphasis on lessons learned concerning
the database design patterns plus realization of the use cases.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics
(CHEP03), La Jolla, Ca, USA, March 2003, 4 pages, pdf format, TUAT00
The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains
We have investigated the contribution to ionic
selectivity of residues in the selectivity filter and pore
helices of the P1 and P2 domains in the acid sensitive
potassium channel TASK-1. We used site directed mutagenesis
and electrophysiological studies, assisted by structural
models built through computational methods. We have
measured selectivity in channels expressed in Xenopus
oocytes, using voltage clamp to measure shifts in reversal
potential and current amplitudes when Rb+ or Na+ replaced
extracellular K+. Both P1 and P2 contribute to selectivity,
and most mutations, including mutation of residues in the
triplets GYG and GFG in P1 and P2, made channels nonselective.
We interpret the effects of these—and of other
mutations—in terms of the way the pore is likely to be
stabilised structurally. We show also that residues in the
outer pore mouth contribute to selectivity in TASK-1.
Mutations resulting in loss of selectivity (e.g. I94S, G95A)
were associated with slowing of the response of channels to
depolarisation. More important physiologically, pH sensitivity
is also lost or altered by such mutations. Mutations
that retained selectivity (e.g. I94L, I94V) also retained their
response to acidification. It is likely that responses both to
voltage and pH changes involve gating at the selectivity filter
Quasi-elastic and inelastic inclusive electron scattering from an oxygen jet target
The results of an experiment on inclusive electron scattering from an oxygen
jet target, performed in a wide range of energy and momentum transfer covering
both quasi-elastic and (1232) resonance regions, are reported. In the
former region the theoretical predictions, obtained including effects of
nucleon-nucleon correlations in both initial and final states, give a good
description of the experimental data. In the inelastic region a broadening as
well as a damping of the resonant part of the cross section with respect to the
free nucleon case is observed. The need of more detailed calculations including
nuclear structure effects on the electroproduction cross section of nucleon
resonances is highlighted.Comment: to appear in Nucl. Phys.
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Mitigating Cutting-Induced Plasticity Errors in the Determination of Residual Stress at Cold Expanded Holes Using the Contour Method
Background The split sleeve cold expansion process is widely used to improve the fatigue life of fastener holes in the civil and military aircraft industry. The process introduces beneficial compressive residual stresses around the processed hole, but uncertainties remain about the character of the stress field immediately adjacent to the bore of the hole.ObjectiveThe primary objective of this study was to implement the contour method with minimising error associated with cutting-induced plasticity to provide detailed and reliable characterisation of the residual stress introduced by the split sleeve cold expansion process.MethodsA systematic FE study of plasticity effects by simulating different contour cutting strategies (a single cut, two sequential cuts and a 6-cut sequence) for a cold expanded hole in an aluminium alloy coupon was conducted. The identified ‘optimum’ cutting strategy was then applied experimentally on coupons containing a hole that had been processed to 3.16% applied expansion. ResultsThe FE study of different cutting simulations show that the locations of the stress error is consistent with the location where cutting-induced plasticity accumulated and that the magnitude and locations of stress re-distribution plasticity can be controlled by an optimised cutting strategy. In order to validate this hypothesis a high quality contour measurement was performed, showing that accurate near bore stress results can be achieved by the proposed 6-cut approach that controls cutting induced plasticity.ConclusionsThe present work has demonstrated that detailed FE simulation analysis can be a very effective tool in supporting the development of an optimum cutting sequence and in making correct choices of boundary conditions. Through optimizing these key aspects of the cutting sequence one is much more likely to have a successful, low error contour residual stress result
The role of Comprehension in Requirements and Implications for Use Case Descriptions
Within requirements engineering it is generally accepted that in writing specifications (or indeed any requirements phase document), one attempts to produce an artefact which will be simple to comprehend for the user. That is, whether the document is intended for customers to validate requirements, or engineers to understand what the design must deliver, comprehension is an important goal for the author. Indeed, advice on producing ‘readable’ or ‘understandable’ documents is often included in courses on requirements engineering. However, few researchers, particularly within the software engineering domain, have attempted either to define or to understand the nature of comprehension and it’s implications for guidance on the production of quality requirements.
Therefore, this paper examines thoroughly the nature of textual comprehension, drawing heavily from research in discourse process, and suggests some implications for requirements (and other) software documentation. In essence, we find that the guidance on writing requirements, often prevalent within software engineering, may be based upon assumptions which are an oversimplification of the nature of comprehension. Hence, the paper examines guidelines which have been proposed, in this case for use case descriptions, and the extent to which they agree with discourse process theory; before suggesting refinements to the guidelines which attempt to utilise lessons learned from our richer understanding of the underlying discourse process theory. For example, we suggest subtly different sets of writing guidelines for the different tasks of requirements, specification and design
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