Identifiability, reducibility, and adaptability in allosteric macromolecules

The ability of macromolecules to transduce stimulus information at one site into conformational changes at a distant site, termed “allostery,” is vital for cellular signaling. Here, we propose a link between the sensitivity of allosteric macromolecules to their underlying biophysical parameters, the interrelationships between these parameters, and macromolecular adaptability. We demonstrate that the parameters of a canonical model of the mSlo large-conductance Ca2+-activated K+ (BK) ion channel are non-identifiable with respect to the equilibrium open probability-voltage relationship, a common functional assay. We construct a reduced model with emergent parameters that are identifiable and expressed as combinations of the original mechanistic parameters. These emergent parameters indicate which coordinated changes in mechanistic parameters can leave assay output unchanged. We predict that these coordinated changes are used by allosteric macromolecules to adapt, and we demonstrate how this prediction can be tested experimentally. We show that these predicted parameter compensations are used in the first reported allosteric phenomena: the Bohr effect, by which hemoglobin adapts to varying pH

A General Backwards Calculus of Variations via Duality

We prove Euler-Lagrange and natural boundary necessary optimality conditions for problems of the calculus of variations which are given by a composition of nabla integrals on an arbitrary time scale. As an application, we get optimality conditions for the product and the quotient of nabla variational functionals.Comment: Submitted to Optimization Letters 03-June-2010; revised 01-July-2010; accepted for publication 08-July-201

Convolutional higher order matching pursuit

We introduce a greedy generalised convolutional algorithm to efficiently locate an unknown number of sources in a series of (possibly multidimensional) images, where each source contributes a localised and low-dimensional but otherwise variable signal to its immediate spatial neighbourhood. Our approach extends convolutional matching pursuit in two ways: first, it takes the signal generated by each source to be a variable linear combination of aligned dictionary elements; and second, it executes the pursuit in the domain of high-order multivariate cumulant statistics. The resulting algorithm adapts to varying signal and noise distributions to flexibly recover source signals in a variety of settings

Dedicated front-end electronics for the next generation of linear collider electromagnetic calorimeter

This paper describes an R&D electronic program for the next generation of linear collider electromagnetic calorimeter. After a brief presentation of the requirements, a global scheme of the electronics is given. Then, we describe the three different building blocks developed in 0.35\mum CMOS technology: an amplifier, a comparator and finally the pipelined AD

Score-matching estimators for continuous-time point-process regression models

We introduce a new class of efficient estimators based on score matching for probabilistic point process models. Unlike discretised likelihood-based estimators, score matching estimators operate on continuous-time data, with computational demands that grow with the number of events rather than with total observation time. Furthermore, estimators for many common regression models can be obtained in closed form, rather than by iteration. This new approach to estimation may thus expand the range of tractable models available for event-based data

Avoidance Control on Time Scales

We consider dynamic systems on time scales under the control of two agents. One of the agents desires to keep the state of the system out of a given set regardless of the other agent's actions. Leitmann's avoidance conditions are proved to be valid for dynamic systems evolving on an arbitrary time scale.Comment: Revised edition in JOTA format. To appear in J. Optim. Theory Appl. 145 (2010), no. 3. In Pres

R-matrix approach to integrable systems on time scales

A general unifying framework for integrable soliton-like systems on time scales is introduced. The $R$-matrix formalism is applied to the algebra of $\delta$-differential operators in terms of which one can construct infinite hierarchy of commuting vector fields. The theory is illustrated by two infinite-field integrable hierarchies on time scales which are difference counterparts of KP and mKP. The difference counterparts of AKNS and Kaup-Broer soliton systems are constructed as related finite-field restrictions.Comment: 21 page

The mixed analog/digital shaper of the LHCb preshower

The LHCb preshower signals show so many fluctuations at low energy that a classical shaping is not usable at all. Thanks to the fact that the fraction of the collected energy during a whole LHC beam crossing time is 85%, we studied the special solution we presented at Snowmass 1999 workshop. This solution consists of 2 interleaved fast integrators, one being in integrate mode when the other is digitally reset. Two track-and-hold systems and an analog multiplexer are used to give at the output 85% of the signal plus 15% of the previous one. These 15% are digitally computed from the previous sample, and subtracted. A completely new design of this solution had to be made. This new design is described, including new methods to decrease the supply voltage and the noise, as well as to increase the quality of the reset and the linearity. An output stage, consisting of an AB class push-pull using only NPN transistors is also described. Laboratory and beam test results are given. (5 refs)

Dedicated front-end electronics for the next generation of linear collider electromagnetic calorimeter

présenté par S. ManenThis paper describes an R&D electronic program for the next generation of linear collider electromagnetic calorimeter. After a brief presentation of the requirements, a global scheme of the electronics is given. Then, we describe the three different building blocks developed in 0.35\mum CMOS technology: an amplifier, a comparator and finally the pipelined AD