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

Reversible stretching of homopolymers and random heteropolymers

We have analyzed the equilibrium response of chain molecules to stretching. For a homogeneous sequence of monomers, the induced transition from compact globule to extended coil below the $\theta$-temperature is predicted to be sharp. For random sequences, however, the transition may be smoothed by a prevalence of necklace-like structures, in which globular regions and coil regions coexist in a single chain. As we show in the context of a random copolymer, preferential solvation of one monomer type lends stability to such structures. The range of stretching forces over which necklaces are stable is sensitive to chain length as well as sequence statistics.Comment: 14 pages, 4 figure

Quasi-extinction risk and population targets for the Eastern, migratory population of monarch butterflies (Danaus plexippus)

The Eastern, migratory population of monarch butterflies (Danaus plexippus), an iconic North American insect, has declined by ~80% over the last decade. The monarch’s multi-generational migration between overwintering grounds in central Mexico and the summer breeding grounds in the northern U.S. and southern Canada is celebrated in all three countries and creates shared management responsibilities across North America. Here we present a novel Bayesian multivariate auto-regressive state-space model to assess quasi-extinction risk and aid in the establishment of a target population size for monarch conservation planning. We find that, given a range of plausible quasi-extinction thresholds, the population has a substantial probability of quasi-extinction, from 11–57% over 20 years, although uncertainty in these estimates is large. Exceptionally high population stochasticity, declining numbers, and a small current population size act in concert to drive this risk. An approximately 5-fold increase of the monarch population size (relative to the winter of 2014–15) is necessary to halve the current risk of quasi-extinction across all thresholds considered. Conserving the monarch migration thus requires active management to reverse population declines, and the establishment of an ambitious target population size goal to buffer against future environmentally driven variability

Mechanical response of random heteropolymers

We present an analytical theory for heteropolymer deformation, as exemplified experimentally by stretching of single protein molecules. Using a mean-field replica theory, we determine phase diagrams for stress-induced unfolding of typical random sequences. This transition is sharp in the limit of infinitely long chain molecules. But for chain lengths relevant to biological macromolecules, partially unfolded conformations prevail over an intermediate range of stress. These necklace-like structures, comprised of alternating compact and extended subunits, are stabilized by quenched variations in the composition of finite chain segments. The most stable arrangements of these subunits are largely determined by preferential extension of segments rich in solvophilic monomers. This predicted significance of necklace structures explains recent observations in protein stretching experiments. We examine the statistical features of select sequences that give rise to mechanical strength and may thus have guided the evolution of proteins that carry out mechanical functions in living cells.Comment: 10 pages, 6 figure

Estimating arthropod survival probability from field counts: a case study with monarch butterflies

Survival probability is fundamental for understanding population dynamics. Methods for estimating survival probability from field data typically require marking individuals, but marking methods are not possible for arthropod species that molt their exoskeleton between life stages. We developed a novel Bayesian state‐space model to estimate arthropod larval survival probability from stage‐structured count data. We performed simulation studies to evaluate estimation bias due to detection probability, individual variation in stage duration, and study design (sampling frequency and sample size). Estimation of cumulative survival probability from oviposition to pupation was robust to potential sources of bias. Our simulations also provide guidance for designing field studies with minimal bias. We applied the model to the monarch butterfly (Danaus plexippus), a declining species in North America for which conservation programs are being implemented. We estimated cumulative survival from egg to pupation from monarch counts conducted at 18 field sites in three landcover types in Iowa, USA, and Ontario, Canada: road right‐of‐ways, natural habitats (gardens and restored meadows), and agricultural field borders. Mean predicted survival probability across all landcover types was 0.014 (95% CI: 0.004–0.024), four times lower than previously published estimates using an ad hoc estimator. Estimated survival probability ranged from 0.002 (95% CI: 7.0E−7 to 0.034) to 0.058 (95% CI: 0.013–0.113) at individual sites. Among landcover types, agricultural field borders in Ontario had the highest estimated survival probability (0.025 with 95% CI: 0.008–0.043) and natural areas had the lowest estimated survival probability (0.008 with 95% CI: 0.009–0.024). Monarch production was estimated as adults produced per milkweed stem by multiplying survival probabilities by eggs per milkweed at these sites. Monarch production ranged from 1.0 (standard deviation [SD] = 0.68) adult in Ontario natural areas in 2016 to 29.0 (SD = 10.42) adults in Ontario agricultural borders in 2015 per 6809 milkweed stems. Survival estimates are critical to monarch population modeling and habitat restoration efforts. Our model is a significant advance in estimating survival probability for monarch butterflies and can be readily adapted to other arthropod species with stage‐structured life histories

Impact of propofol on mid-latency auditory-evoked potentials in children†

Background Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear. Therefore, we investigated the relationship between propofol and MLAEP in children undergoing anaesthesia. Methods Fourteen healthy children aged 4-16 yr received anaesthesia for elective surgery. Before surgery, propofol was administered in three concentrations (3, 6, 9 µg ml−1) through a target-controlled infusion pump using Kataria and colleagues' model. MLAEPs were recorded 5 min after having reached each target propofol concentration at each respective concentration. Additionally, venous propofol blood concentrations were assayed at each measuring time point. Results Propofol increased all four MLAEP peak latencies (peaks Na, Pa, Nb, P1) in a dose-dependent manner. In addition, the differences in amplitudes were significantly smaller with increasing propofol target concentrations. The measured propofol plasma concentrations correlated positively with the latencies of the peaks Na, Pa, and Nb. Conclusions Propofol affects MLAEP latencies and amplitudes in children in a dose-dependent manner. MLAEP measurement might therefore be a useful tool for monitoring depth of propofol anaesthesia in childre

Projet « cabinets de groupe » : collaboration entre médecine de premier recours et psychiatrie [« Group medical practices » project : collaboration between primary care medicine and institutional public psychiatry]

Collaboration between primary care medicine and psychiatry is a well-known challenge. In order to improve access to psychological care for patients undergoing primary care, the « group medical practices » project proposes a collaborative care model in which a psychiatrist employed by a public psychiatric institution integrates group medical practices in order to provide assistance to primary care physicians. It is thus able to evaluate patients directly in the practices and to offer supervision and consilium spaces to primary care physicians