Post-common envelope binary systems experiencing helium-shell-driven stable mass transfer

We evolve stellar models to study the common envelope (CE) interaction of an early asymptotic giant branch star of initial mass $5\,\rm M_{\odot}$ with a companion star of mass ranging from $0.1$ to $2\,\rm M_{\odot}$. We model the CE as a fast stripping phase in which the primary experiences rapid mass loss and loses about 80 per cent of its mass. The post-CE remnant is then allowed to thermally readjust during a Roche-lobe overflow (RLOF) phase and the final binary system and its orbital period are investigated. We find that the post-CE RLOF phase is long enough to allow nuclear burning to proceed in the helium shell. By the end of this phase, the donor is stripped of both its hydrogen and helium and ends up as carbon-oxygen white dwarf of mass about $0.8\,\rm M_{\odot}$. We study the sensitivity of our results to initial conditions of different companion masses and orbital separations at which the stripping phase begins. We find that the companion mass affects the final binary separation and that helium-shell burning causes the star to refill its Roche lobe leading to post-CE RLOF. Our results show that double mass transfer in such a binary interaction is able to strip the helium and hydrogen layers from the donor star without the need for any special conditions or fine tuning of the binary parameters

Binary stars in the Galactic thick disc

The combination of asteroseismologically-measured masses with abundances from detailed analyses of stellar atmospheres challenges our fundamental knowledge of stars and our ability to model them. Ancient red-giant stars in the Galactic thick disc are proving to be most troublesome in this regard. They are older than 5 Gyr, a lifetime corresponding to an initial stellar mass of about $1.2{\mathrm{M}_{\odot}}$. So why do the masses of a sizeable fraction of thick-disc stars exceed $1.3{\mathrm{M}_{\odot}}$, with some as massive as $2.3{\mathrm{M}_{\odot}}$ ? We answer this question by considering duplicity in the thick-disc stellar population using a binary population-nucleosynthesis model. We examine how mass transfer and merging affect the stellar mass distribution and surface abundances of carbon and nitrogen. We show that a few per cent of thick-disc stars can interact in binary star systems and become more massive than $1.3{\mathrm{M}_{\odot}}$. Of these stars, most are single because they are merged binaries. Some stars more massive than $1.3{\mathrm{M}_{\odot}}$ form in binaries by wind mass transfer. We compare our results to a sample of the APOKASC data set and find reasonable agreement except in the number of these thick-disc stars more massive than $1.3{\mathrm{M}_{\odot}}$. This problem is resolved by the use of a logarithmically-flat orbital-period distribution and a large binary fraction

Validation of Coevolving Residue Algorithms via Pipeline Sensitivity Analysis: ELSC and OMES and ZNMI, Oh My!

Correlated amino acid substitution algorithms attempt to discover groups of residues that co-fluctuate due to either structural or functional constraints. Although these algorithms could inform both ab initio protein folding calculations and evolutionary studies, their utility for these purposes has been hindered by a lack of confidence in their predictions due to hard to control sources of error. To complicate matters further, naive users are confronted with a multitude of methods to choose from, in addition to the mechanics of assembling and pruning a dataset. We first introduce a new pair scoring method, called ZNMI (Z-scored-product Normalized Mutual Information), which drastically improves the performance of mutual information for co-fluctuating residue prediction. Second and more important, we recast the process of finding coevolving residues in proteins as a data-processing pipeline inspired by the medical imaging literature. We construct an ensemble of alignment partitions that can be used in a cross-validation scheme to assess the effects of choices made during the procedure on the resulting predictions. This pipeline sensitivity study gives a measure of reproducibility (how similar are the predictions given perturbations to the pipeline?) and accuracy (are residue pairs with large couplings on average close in tertiary structure?). We choose a handful of published methods, along with ZNMI, and compare their reproducibility and accuracy on three diverse protein families. We find that (i) of the algorithms tested, while none appear to be both highly reproducible and accurate, ZNMI is one of the most accurate by far and (ii) while users should be wary of predictions drawn from a single alignment, considering an ensemble of sub-alignments can help to determine both highly accurate and reproducible couplings. Our cross-validation approach should be of interest both to developers and end users of algorithms that try to detect correlated amino acid substitutions

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe