Understanding the dependence on the pulling speed of the unfolding pathway of proteins

The dependence of the unfolding pathway of proteins on the pulling speed is investigated. This is done by introducing a simple one-dimensional chain comprising $N$ units, with different characteristic bistable free energies. These units represent either each of the modules in a modular protein or each of the intermediate "unfoldons" in a protein domain, which can be either folded or unfolded. The system is pulled by applying a force to the last unit of the chain, and the units unravel following a preferred sequence. We show that the unfolding sequence strongly depends on the pulling velocity $v_{p}$. In the simplest situation, there appears a critical pulling speed $v_{c}$: for pulling speeds $v_{p}v_{c}$ it is the pulled unit that unfolds first. By means of a perturbative expansion, we find quite an accurate expression for this critical velocity.Comment: accepted for publication in JSTA

Thermally induced directed currents in hard rod systems

We study the non equilibrium statistical properties of a one dimensional hard-rod fluid undergoing collisions and subject to a spatially non uniform Gaussian heat-bath and periodic potential. The system is able to sustain finite currents when the spatially inhomogeneous heat-bath and the periodic potential profile display an appropriate relative phase shift, $\phi$. By comparison with the collisionless limit, we determine the conditions for the most efficient transport among inelastic, elastic and non interacting rods. We show that the situation is complex as, depending on shape of the temperature profile, the current of one system may outperform the others.Comment: 5 pages, 2 figure

Radio emission from satellite-Jupiter interactions (especially Ganymede)

Analyzing a database of 26 years of observations of Jupiter from the Nan\c{c}ay Decameter Array, we study the occurrence of Io-independent emissions as a function of the orbital phase of the other Galilean satellites and Amalthea. We identify unambiguously the emissions induced by Ganymede and characterize their intervals of occurrence in CML and Ganymede phase and longitude. We also find hints of emissions induced by Europa and, surprisingly, by Amalthea. The signature of Callisto-induced emissions is more tenuous.Comment: 14 pages, 7 figures, in "Planetary Radio Emissions VIII", G. Fischer, G. Mann, M. Panchenko and P. Zarka eds., Austrian Acad. Sci. Press, Vienna, in press, 201

Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock. a systematic review and meta-analysis

Sepsis-induced myocardial dysfunction is associated with poor outcomes, but traditional measurements of systolic function such as left ventricular ejection fraction (LVEF) do not directly correlate with prognosis. Global longitudinal strain (GLS) utilizing speckle-tracking echocardiography (STE) could be a better marker of intrinsic left ventricular (LV) function, reflecting myocardial deformation rather than displacement and volume changes. We sought to investigate the prognostic value of GLS in patients with sepsis and/or septic shock

Defining and identifying communities in networks

The investigation of community structures in networks is an important issue in many domains and disciplines. This problem is relevant for social tasks (objective analysis of relationships on the web), biological inquiries (functional studies in metabolic, cellular or protein networks) or technological problems (optimization of large infrastructures). Several types of algorithm exist for revealing the community structure in networks, but a general and quantitative definition of community is still lacking, leading to an intrinsic difficulty in the interpretation of the results of the algorithms without any additional non-topological information. In this paper we face this problem by introducing two quantitative definitions of community and by showing how they are implemented in practice in the existing algorithms. In this way the algorithms for the identification of the community structure become fully self-contained. Furthermore, we propose a new local algorithm to detect communities which outperforms the existing algorithms with respect to the computational cost, keeping the same level of reliability. The new algorithm is tested on artificial and real-world graphs. In particular we show the application of the new algorithm to a network of scientific collaborations, which, for its size, can not be attacked with the usual methods. This new class of local algorithms could open the way to applications to large-scale technological and biological applications.Comment: Revtex, final form, 14 pages, 6 figure

Refolding dynamics of stretched biopolymers upon force quench

Single molecule force spectroscopy methods can be used to generate folding trajectories of biopolymers from arbitrary regions of the folding landscape. We illustrate the complexity of the folding kinetics and generic aspects of the collapse of RNA and proteins upon force quench, using simulations of an RNA hairpin and theory based on the de Gennes model for homopolymer collapse. The folding time, $\tau_F$, depends asymmetrically on $\delta f_S = f_S - f_m$ and $\delta f_Q = f_m - f_Q$ where $f_S$ ($f_Q$) is the stretch (quench) force, and $f_m$ is the transition mid-force of the RNA hairpin. In accord with experiments, the relaxation kinetics of the molecular extension, $R(t)$, occurs in three stages: a rapid initial decrease in the extension is followed by a plateau, and finally an abrupt reduction in $R(t)$ that occurs as the native state is approached. The duration of the plateau increases as $\lambda =\tau_Q/\tau_F$ decreases (where $\tau_Q$ is the time in which the force is reduced from $f_S$ to $f_Q$). Variations in the mechanisms of force quench relaxation as $\lambda$ is altered are reflected in the experimentally measurable time-dependent entropy, which is computed directly from the folding trajectories. An analytical solution of the de Gennes model under tension reproduces the multistage stage kinetics in $R(t)$. The prediction that the initial stages of collapse should also be a generic feature of polymers is validated by simulation of the kinetics of toroid (globule) formation in semiflexible (flexible) homopolymers in poor solvents upon quenching the force from a fully stretched state. Our findings give a unified explanation for multiple disparate experimental observations of protein folding.Comment: 31 pages 11 figure

Cost-effectiveness of a quality improvement bundle for emergency laparotomy.

Background: The recent Emergency Laparotomy Pathway Quality Improvement Care (ELPQuiC) study showed that the use of a specific care bundle reduced mortality in patients undergoing emergency laparotomy. However, the costs of implementation of the ELPQuiC bundle remain unknown. The aim of this study was to assess the in-hospital and societal costs of implementing the ELPQuiC bundle. Methods: The ELPQuiC study employed a before-after approach using quality improvement methodology. To assess the costs and cost-effectiveness of the bundle, two models were constructed: a short-term model to assess in-hospital costs and a long-term model (societal decision tree) to evaluate the patient's lifetime costs (in euros). Results: Using health economic modelling and data collected from the ELPQuiC study, estimated costs for initial implementation of the ELPQuiC bundle were €30 026·11 (range 1794·64-40 784·06) per hospital. In-hospital costs per patient were estimated at €14 817·24 for standard (non-care bundle) treatment versus €15 971·24 for the ELPQuiC bundle treatment. Taking a societal perspective, lifetime costs of the patient in the standard group were €23 058·87, compared with €19 102·37 for patients receiving the ELPQuiC bundle. The increased life expectancy of 4 months for patients treated with the ELPQuiC bundle was associated with cost savings of €11 410·38 per quality-adjusted life-year saved. Conclusion: Implementation of the ELPQuiC bundle is associated with lower mortality and higher in-hospital costs but reduced societal costs