Editorial overview: Folding and binding: In silico, in vitro and in cellula

The essence of any biological processes relies on the conformational states of macromolecules and their interactions. It comes therefore with no surprises that the study of folding and binding has been centre stage since the birth of structural biology. In this context, the collaborative efforts of experimen- talists and theoreticians have tremendously increased our current knowl- edge on macromolecular structure and recognition. Nevertheless, several challenges and open questions are still present and a multidisciplinary approach would appear the most appropriate means to shed light onto the mechanisms of folding and binding to the highest level of detail. This thematic issue brings together a collection of reviews describing our current understanding of folding and binding, looking at these fundamental pro- blems from a wide perspective ranging from the single molecule to the complexity of the living cell, drawing on approaches that span from compu- tational (in silico), to the test tube (in vitro) and cell cultures (in cellula)

Lifshitz holography with a probe Yang-Mills field

Taking as a probe an SU(2) gauge field with Yang-Mills action in a 3+1 dimensional Lifshitz black hole background, we use the gauge/gravity correspondence to discuss finite temperature effects in the dual theory defined on the boundary. In order to test the dependence of results on the anisotropic scaling exponent z we consider two analytical black hole solutions with z=2 and z=4. Apart from solving the equations of motion in the bulk using a numerical approach, we also apply an analytical approximation allowing the determination of the phase transition character, the critical exponent and the critical temperature behavior as a function of z.Comment: 12 pages, 3 figure

Gauged Lifshitz model with Chern-Simons term

We present a gauged Lifshitz Lagrangian including second and forth order spatial derivatives of the scalar field and a Chern-Simons term, and study non-trivial solutions of the classical equations of motion. While the coefficient beta of the forth order term should be positive in order to guarantee positivity of the energy, the coefficient alpha of the quadratic one need not be. We investigate the parameter domains finding significant differences in the field behaviors. Apart from the usual vortex field behavior of the ordinary relativistic Chern-Simons-Higgs model, we find in certain parameter domains oscillatory solutions reminiscent of the modulated phases of Lifshitz systems.Comment: 13 pages, 6 figure

InSiDDe: A server for designing artificial disordered proteins

InSiDDe (In Silico Disorder Design) is a program for the in silico design of intrinsically disordered proteins of desired length and disorder probability. The latter is assessed using IUPred and spans values ranging from 0.55 to 0.95 with 0.05 increments. One to ten artificial sequences per query, each made of 50 to 200 residues, can be generated by InSiDDe. We describe the rationale used to set up InSiDDe and show that an artificial sequence of 100 residues with an IUPred score of 0.6 designed by InSiDDe could be recombinantly expressed in E. coli at high levels without degradation when fused to a natural molecular recognition element (MoRE). In addition, the artificial fusion protein exhibited the expected behavior in terms of binding modulation of the specific partner recognized by the MoRE. To the best of our knowledge, InSiDDe is the first publicly available software for the design of intrinsically disordered protein (IDP) sequences. InSiDDE is publicly available online

Chern-Simons-Higgs Theory with Visible and Hidden Sectors and its N=2{\cal N}=2 SUSY Extension

We study vortex solutions in Abelian Chern-Simons-Higgs theories with visible and hidden sectors. We first consider the case in which the two sectors are connected through a BF-like gauge mixing term with no explicit interaction between the the two scalars. Since first order Bogomolny equations do not exist in this case, we derive the second order field equations. We then proceed to an ${\cal N}=2$ supersymmetric extension including a Higgs portal mixing among the visible and hidden charged scalars. As expected, Bogomolnyi equations do exist in this case and we study their string-like solutions numerically.Comment: 10 pages, 12 figures. Several typos fixed and the Gauss law is explicitly written, figures correctly shown. Accepted in PL

Strategic Debt in Vertical Relationships

We study a vertical relationship between two firms, and we show that the extent of the downstream firm's borrowing affects the contract offered by the upstream firm. We establish a negative relationship between the level of debt and the downstream firm's probability of bankrupt. We also show that, unless the interest rate is very high, there exists a conflict of interest between the upstream and the downstream firm: the latter wants to take on more debt than the former would like it to.We interpret this finding as an explanation of the constraint imposed by franchisors on the debt level of their franchisees.Contract Theory, Capital Structure, Franchise

Density of States and Critical Behavior of the Coulomb Glass

We present zero-temperature simulations for the single-particle density of states of the Coulomb glass. Our results in three dimensions are consistent with the Efros and Shklovskii prediction for the density of states. Finite-temperature Monte Carlo simulations show no sign of a thermodynamic glass transition down to low temperatures, in disagreement with mean-field theory. Furthermore, the random-displacement formulation of the model undergoes a transition into a distorted Wigner crystal for a surprisingly broad range of the disorder strength.Comment: 4 pages, 2 figures, 1 tabl

Monitoring the performance of residents during training in off-pump coronary surgery.

OBJECTIVE: Control charts (eg, cumulative sum charts) plot changes in performance with time and can alert a surgeon to suboptimal performance. They were used to compare performance of off-pump coronary artery bypass surgery between a consultant and four resident surgeons and to compare performance of off-pump coronary artery bypass surgery and conventional coronary artery bypass grafting within surgeons. METHODS: Data were analyzed for consecutive patients undergoing coronary artery bypass grafting who were operated on by one consultant or one of four residents. Conversions were analyzed by intention to treat. Perioperative death or one or more of 10 adverse events constituted failure. Predicted risks of failure for individual patients were derived from the study population. Variable life-adjusted displays and risk-adjusted sequential probability ratio test charts were plotted. RESULTS: Data for 1372 patients were analyzed; 769 of the procedures were off-pump coronary artery bypass operations (56.0%). The consultant operated on 382 patients (293 off-pump, 76.7%), and the residents operated on 990 (474 off-pump, 47.9%). Patients operated on by residents tended to be older, more obese, more likely to require an urgent operation, and more likely to need a circumflex artery graft but less likely to have triple-vessel disease. There were 7 conversions (consultant 5, residents 2). The overall failure rate was 8.5% (9.2% for consultant's operations and 8.2% for residents' operations), including 10 deaths (0.7%). Predicted and observed risks of failure were similar for all five surgeons. After 100 off-pump coronary artery bypass operations, performance was the same or better for the residents as for the consultant. For all surgeons, performance was the same or better for off-pump as for conventional coronary artery bypass grafting. CONCLUSIONS: Off-pump coronary artery bypass surgery can be safely taught to cardiothoracic residents. Implementation of continuous performance monitoring for residents is practicable