Effect of local thermal fluctuations on folding kinetics: a study from the perspective of nonextensive statistical mechanics.

The search through the proteins conformational space is thought as an early independent stage of the folding process, governed mainly by the hydrophobic effect. Because of the nanoscopic size of proteins, we assume that the effects of local thermal fluctuations work like folding assistants, managed by the nonextensive parameter q. Using a 27-mer heteropolymer on a cubic lattice, we obtained--by Monte Carlo simulations--kinetic and thermodynamic amounts (such as the characteristic folding time and the native stability) as a function of temperature T and q for a few distinct native targets. We found that for each native structure, at a specific system temperature T, there exists an optimum q* that minimizes the folding characteristic time τ(min); for T=1, it is found that q* lies in the interval 1.15±0.05, even for native structures presenting significantly different topological complexities. The distribution of τ(min) obtained for specific q>1 (nonextensive approach) and temperature T can be fully reproduced for q=1 (Boltzmann approach), but only at higher temperatures T'>T. However, assuming that the complete set of proteins of each organism is optimized to work in a narrow range of temperature, we conclude that--for the present problem--the two approaches, namely, (T,q>1) and (T>T',q=1), cannot be equivalent; it is not a simple matter of reparametrization. Finally, by associating the nonextensive parameter q with the instantaneous degree of compactness of the globule, q becomes a dynamic variable, self-adjusted along the simulation. The results obtained through the q-variable approach are utterly consistent with those obtained by using a target-tuned parameter q*. However, in the former approach, q is automatically adjusted by the chain conformational evolution, eliminating the need to seek for a specific optimized value of q for each case. Besides, using the q-variable approach, different target structures are promptly characterized by inherent distributions of q, which reflect the overall complexity of their corresponding native topologies and energy landscapes.

A non-Gaussian model in polymeric network.

We investigate a finite chain approximation, the non-Gaussian Tsallis distribution, to the polymeric network, which gives an improvement to the Gaussian model. This distribution presents some necessary characteristics, like a cutoff to the maximum chain length and a continuous limit to the Gaussian one for a large number of monomers. It also presents a simple quadratic structure that allows to generalize the Gaussian properties such as exact-moments calculation and Wick theorem. We obtain the free-energy density in its full tensorial structure.

A randomised trial of compassionate care for the homeless in an emergency department.

Homeless adults often visit emergency departments and often leave dissatisfied. We tested whether compassionate care, by improving patient satisfaction, can alter subsequent use of emergency services. We identified 133 consecutive homeless adults visiting one inner-city emergency department who were not acutely psychotic, extremely intoxicated, unable to speak English, or medically unstable. Half were randomly assigned to receive compassionate contact from trained volunteers. All patients otherwise had usual care and were followed for repeat visits to emergency departments. We found that rates of use were high, with patients making an average of seven visits a year (0.60 per month). More than a third of all patients made two or more visits within two days of each other. The average number of visits per month after intervention was significantly lower for patients who received compassionate care (0.43 vs 0.65, p = 0.018). Analyses adjusting for each patient's previous rate of use confirmed that compassionate care led to a one third reduction in the number of return visits within one month (95% CI 14 to 40%). Compassionate management of selected homeless adults decreases repeat visits to the emergency department. One explanation is that patients tend to return frequently until they are satisfied with their treatment.