Presence Of Multiple Minima Research Articles

Application of new measures of nonlinearity to parameter estimation and simulations in individual pharmacokinetic analyses.

Since simulation studies are widely used in pharmacokinetics, it is necessary to ascertain their validity. An important, well-documented, concern that may negatively impact the validity of estimated parameters in pharmacokinetic models is existence of multiple minima of the criterion used in estimation. A presence of multiple minima causes instability of the estimates, dependence of the parameter estimates on the initial values, and bimodal (or, generally, multimodal) distributions of the estimated parameters. This paper offers a method to identify when these issues may occur by applying two new measures of nonlinearity.

Spin-valley lifetimes in a silicon quantum dot with tunable valley splitting

Although silicon is a promising material for quantum computation, the degeneracy of the conduction band minima (valleys) must be lifted with a splitting sufficient to ensure the formation of well-defined and long-lived spin qubits. Here we demonstrate that valley separation can be accurately tuned via electrostatic gate control in a metal-oxide-semiconductor quantum dot, providing splittings spanning 0.3-0.8 meV. The splitting varies linearly with applied electric field, with a ratio in agreement with atomistic tight-binding predictions. We demonstrate single-shot spin read-out and measure the spin relaxation for different valley configurations and dot occupancies, finding one-electron lifetimes exceeding 2 s. Spin relaxation occurs via phonon emission due to spin-orbit coupling between the valley states, a process not previously anticipated for silicon quantum dots. An analytical theory describes the magnetic field dependence of the relaxation rate, including the presence of a dramatic rate enhancement (or hot-spot) when Zeeman and valley splittings coincide.

Conformational Heterogeneity of an Equilibrium Folding Intermediate Quantified and Mapped by Scanning Mutagenesis

It is challenging to experimentally define an energy landscape for protein folding that comprises multiple partially unfolded states. Experimental results are often ambiguous as to whether a non-native state is conformationally homogeneous. Here, we tested an approach combining systematic mutagenesis and a Brønsted-like analysis to reveal and quantify conformational heterogeneity of folding intermediate states. Using this method, we resolved an otherwise apparently homogeneous equilibrium folding intermediate of Borrelia burgdorferi OspA into two conformationally distinct species and determined their relative populations. Furthermore, we mapped the structural differences between these intermediate species, which are consistent with the non-native species that we previously proposed based on native-state hydrogen exchange studies. When treated as a single state, the intermediate ensemble exhibited fractional Φ-values for mutations and Hammond-type behaviors that are often observed for folding transition states. We found that a change in relative population of the two species within the intermediate ensemble explains these properties well, suggesting that fractional Φ-values and Hammond-type behaviors exhibited by folding intermediates and transition states may arise more often from conformational heterogeneity than from a single partial structure. Our results are consistent with the presence of multiple minima in a rugged energy landscape predicted from theoretical studies. The method described here provides a promising means to probe a complex folding energy landscape.

κ-(BEDT-TTF)2Cu[N(CN)2]Cl: magnet and superconductor. High pressure and high magnetic field experiments

Abstract In this paper, we have surveyed the current status of an experimental study of κ-(BEDT-TTF)2Cu[N(CN)2]Cl having revealed that the interplay between magnetism and superconductivity in this 2-d organic crystal is not described by a simple scheme letting the only single phase to exist at certain fixed pressure and temperature. In contrast, it has been discovered that the magnetism and SC both coexist in the same crystal sample in a wide pressure range, from 1 bar to at least 1.5 kbar. Delicate balance between two competing states depends not only on pressure and temperature but also on the magnetic field treatment and thermal history. Both magnetic and electron transport behavior suggests the presence of multiple minima in the free energy possibly associated with a modification of molecular arrangement.

A versatile method for the Monte Carlo optimization of stochastic systems

The paper discusses a versatile family of Monte Carlo methods for the sequential optimization of stochastic systems. The method selects a sequence of successive one-dimensional search directions, defines a (stochastic) search in each of the directions, where the data used for both the one-dimensional search and the direction determination are merely noise-corrupted observations on the system. The method is more general than stochastic approximation, it converges to a stationary point even in the presence of multiple minima, and it uses rather natural logics. A convergence theorem is proved.