Adsorption of symmetric random copolymer onto symmetric random surface: the annealed case

Adsorption of a symmetric (AB) random copolymer (RC) onto a symmetric (ab) random heterogeneous surface (RS) is studied in the annealed approximation by using a two-dimensional partially directed walk model of the polymer. We show that in the symmetric case, the expected a posteriori compositions of the RC and the RS have correct values (corresponding to their a priori probabilities) and do not change with the temperature, whereas second moments of monomers and sites distributions in the RC and RS change. This indicates that monomers and sites do not interconvert but only rearrange in order to provide better matching between them and, as a result, a stronger adsorption of the RC on the RS. However, any violation of the system symmetry shifts equilibrium towards the major component and/or more favorable contacts and leads to interconversion of monomers and sites.Comment: 15 pages, 7 figure

Theory of mechanical unfolding of homopolymer globule: all-or-none transition in force-clamp mode vs phase coexistence in position-clamp mode

Equilibrium mechanical unfolding of a globule formed by long flexible homopolymer chain collapsed in a poor solvent and subjected to an extensional force f (force-clamp mode) or extensional deformation D (position-clamp mode) is studied theoretically. Our analysis, like all previous analysis of this problem, shows that the globule behaves essentially differently in two modes of extension. In the force-clamp mode, mechanical unfolding of the globule with increasing applied force occurs without intramolecular microphase segregation, and at certain threshold value of the pulling force the globule unfolds as a whole ("all-or-none" transition). The value of the threshold force and the corresponding jump in the distance between the chain ends increase with a deterioration of the solvent quality and/or with an increase in the degree of polymerization. In the position-clamp mode, the globule unfolding occurs via intramolecular microphase coexistence of globular and extended microphases followed by an abrupt unraveling transition. Reaction force in the microphase segregation regime demonstrates an "anomalous" decrease with increasing extension. Comparison of deformation curves in force and position-clamp modes demonstrates that at weak and strong extensions the curves for two modes coincide, differences are observed in the intermediate extension range. Another unfolding scenario is typical for short globules: in both modes of extension they unfold continuously, without jumps or intramolecular microphase coexistence, by passing a sequence of uniformly elongated configurations.Comment: 19 pages, 13 figures, 1 tabl

A Quantitative Theory of Mechanical Unfolding of a Homopolymer Globule

We propose the quantitative mean-field theory of mechanical unfolding of a globule formed by long flexible homopolymer chain collapsed in poor solvent and subjected to extensional deformation. We demonstrate that depending on the degree of polymerization and solvent quality (quantified by the Flory-Huggins $\chi$ parameter) the mechanical unfolding of the collapsed chain may either occur continuously (by passing a sequence of uniformly elongated configurations) or involves intra-molecular micro-phase coexistence of a collapsed and a stretched segment followed by an abrupt unraveling transition. The force-extension curves are obtained and quantitatively compared to our recent results of numerical self-consistent field (SCF) simulations. The phase diagrams for extended homopolymer chains in poor solvent comprising one- and two-phase regions are calculated for different chain length or/and solvent quality.Comment: 24 pages, 18 figure

Vertical sleeve gastrectomy improves ventilatory drive through a leptin-dependent mechanism

Obesity hypoventilation syndrome (OHS) is a serious disorder characterized by daytime hypercapnia, disordered breathing, and a reduction in chemosensitivity. Vertical sleeve gastrectomy (VSG), a bariatric surgical procedure resulting in weight loss and weight-independent improvements in glucose metabolism, has been observed to substantially improve sleep-disordered breathing. However, it is unclear if the ventilatory effects of VSG are secondary to weight loss or the marked change in metabolic physiology. Using preclinical mouse models, we found that VSG leads to an improvement in the hypercapnic ventilatory response (HCVR) and reductions in circulating leptin levels independent of reductions in body mass, fat mass, and caloric intake. In the absence of leptin, VSG continues to improve body mass, fat mass, and glucose tolerance in ob/ob mice but no longer affects HCVR. However, the HCVR of ob/ob mice can be returned to wild-type levels with leptin treatment. These data demonstrate that VSG improves chemosensitivity and ventilatory drive via a leptin-dependent mechanism. Clinically, these data downgrade the relative contribution of physical, mechanical load in the pathogenesis of OHS, and instead point to physiological components of obesity, including alterations in leptin signaling, as key drivers in OHS

Adsorption of Multi-block and Random Copolymer on a Solid Surface: Critical Behavior and Phase Diagram

The adsorption of a single multi-block $AB$-copolymer on a solid planar substrate is investigated by means of computer simulations and scaling analysis. It is shown that the problem can be mapped onto an effective homopolymer adsorption problem. In particular we discuss how the critical adsorption energy and the fraction of adsorbed monomers depend on the block length $M$ of sticking monomers $A$, and on the total length $N$ of the polymer chains. Also the adsorption of the random copolymers is considered and found to be well described within the framework of the annealed approximation. For a better test of our theoretical prediction, two different Monte Carlo (MC) simulation methods were employed: a) off-lattice dynamic bead-spring model, based on the standard Metropolis algorithm (MA), and b) coarse-grained lattice model using the Pruned-enriched Rosenbluth method (PERM) which enables tests for very long chains. The findings of both methods are fully consistent and in good agreement with theoretical predictions.Comment: 27 pages, 12 figure

Mild Transient Hypercapnia as a Novel Fear Conditioning Stimulus Allowing Re-Exposure during Sleep

Introduction:Studies suggest that sleep plays a role in traumatic memories and that treatment of sleep disorders may help alleviate symptoms of posttraumatic stress disorder. Fear-conditioning paradigms in rodents are used to investigate causal mechanisms of fear acquisition and the relationship between sleep and posttraumatic behaviors. We developed a novel conditioning stimulus (CS) that evoked fear and was subsequently used to study re-exposure to the CS during sleep.Methods:Experiment 1 assessed physiological responses to a conditioned stimulus (mild transient hypercapnia, mtHC; 3.0% CO2; n = 17)+footshock for the purpose of establishing a novel CS in male FVB/J mice. Responses to the novel CS were compared to tone+footshock (n = 18) and control groups of tone alone (n = 17) and mild transient hypercapnia alone (n = 10). A second proof of principle experiment re-exposed animals during sleep to mild transient hypercapnia or air (control) to study sleep processes related to the CS.Results:Footshock elicited a response of acute tachycardia (30-40 bpm) and increased plasma epinephrine. When tone predicted footshock it elicited mild hypertension (1-2 mmHg) and a three-fold increase in plasma epinephrine. When mtHC predicted footshock it also induced mild hypertension, but additionally elicited a conditioned bradycardia and a smaller increase in plasma epinephrine. The overall mean 24 hour sleep-wake profile was unaffected immediately after fear conditioning.Discussion:Our study demonstrates the efficacy of mtHC as a conditioning stimulus that is perceptible but innocuous (relative to tone) and applicable during sleep. This novel model will allow future studies to explore sleep-dependent mechanisms underlying maladaptive fear responses, as well as elucidate the moderators of the relationship between fear responses and sleep. © 2013 McDowell et al