Condensation and equilibration in an urn model

After reviewing the general scaling properties of aging systems, we present a numerical study of the slow evolution induced in the zeta urn model by a quench from a high temperature to a lower one where a condensed equilibrium phase exists. By considering both one-time and two-time quantities we show that the features of the model fit into the general framework of aging systems. In particular, its behavior can be interpreted in terms of the simultaneous existence of equilibrated and aging degrees with different scaling properties.Comment: 13 pages, 4 figures, Proceedings of the International Conference on Statistical Physics SigmaPhi, Rhodes 2014. v2: a footnote and one reference added, few typos correcte

Supersymmetric Langevin equation to explore free energy landscapes

The recently discovered supersymmetric generalizations of Langevin dynamics and Kramers equation can be utilized for the exploration of free energy landscapes of systems whose large time-scale separation hampers the usefulness of standard molecular dynamics techniques. The first realistic application is here presented. The system chosen is a minimalist model for a short alanine peptide exhibiting a helix-coil transition.Comment: 9 pages, 9 figures, RevTeX 4 v2: conclusive section enlarged, references adde

Recovery of free energy branches in single molecule experiments

We present a method for determining the free energy of coexisting states from irreversible work measurements. Our approach is based on a fluctuation relation that is valid for dissipative transformations in partially equilibrated systems. To illustrate the validity and usefulness of the approach, we use optical tweezers to determine the free energy branches of the native and unfolded states of a two-state molecule as a function of the pulling control parameter. We determine, within 0.6 kT accuracy, the transition point where the free energies of the native and the unfolded states are equal.Comment: To appear in Phys. Rev. Lett. 4 pages + Supp. Mat. (6 pages

Bio-molecular applications of recent developments in optical tweezers

In the past three decades, the ability to optically manipulate biomolecules has spurred a new era of medical and biophysical research. Optical tweezers (OT) have enabled experimenters to trap, sort, and probe cells, as well as discern the structural dynamics of proteins and nucleic acids at single molecule level. The steady improvement in OT\u2019s resolving power has progressively pushed the envelope of their applications; there are, however, some inherent limitations that are prompting researchers to look for alternatives to the conventional techniques. To begin with, OT are restricted by their one-dimensional approach, which makes it difficult to conjure an exhaustive three-dimensional picture of biological systems. The high-intensity trapping laser can damage biological samples, a fact that restricts the feasibility of in vivo applications. Finally, direct manipulation of biological matter at nanometer scale remains a significant challenge for conventional OT. A significant amount of literature has been dedicated in the last 10 years to address the aforementioned shortcomings. Innovations in laser technology and advances in various other spheres of applied physics have been capitalized upon to evolve the next generation OT systems. In this review, we elucidate a few of these developments, with particular focus on their biological applications. The manipulation of nanoscopic objects has been achieved by means of plasmonic optical tweezers (POT), which utilize localized surface plasmons to generate optical traps with enhanced trapping potential, and photonic crystal optical tweezers (PhC OT), which attain the same goal by employing different photonic crystal geometries. Femtosecond optical tweezers (fs OT), constructed by replacing the continuous wave (cw) laser source with a femtosecond laser, promise to greatly reduce the damage to living samples. Finally, one way to transcend the one-dimensional nature of the data gained by OT is to couple them to the other large family of single molecule tools, i.e., fluorescence-based imaging techniques. We discuss the distinct advantages of the aforementioned techniques as well as the alternative experimental perspective they provide in comparison to conventional OT

Tips and tricks for the diagnosis and management of biliary stenosis-state of the art review

Biliary stenosis may represent a diagnostic and therapeutic challenge resulting in a delay in diagnosis and initiation of therapy due to the frequent difficulty in distinguishing a benign from a malignant stricture. In such cases, the diagnostic flowchart includes the sequential execution of imaging techniques, such as magnetic resonance, magnetic resonance cholangiopancreatography, and endoscopic ultrasound, while endoscopic retrograde cholangiopancreatography is performed to collect tissue for histopathological/cytological diagnosis or to treat the stenosis by insertion of stent. The execution of percutaneous transhepatic drainage with subsequent biopsy has been shown to increase the possibility of tissue diagnosis after failure of the above techniques. Although the diagnostic yield of histopathology and imaging has increased with improvements in endoscopic ultrasound and peroral cholangioscopy, differential diagnosis between malignant and benign stenosis may not be easy in some patients, and strictures are classified as indeterminate. In these cases, a multidisciplinary workup including biochemical marker assays and advanced technologies available may speed up a diagnosis of malignancy or avoid unnecessary surgery in the event of a benign stricture. Here, we review recent advancements in the diagnosis and management of biliary strictures and describe tips and tricks to increase diagnostic yields in clinical routine

Direct single-molecule observation of calcium-dependent misfolding in human neuronal calcium sensor-1

Neurodegenerative disorders are strongly linked to protein misfolding, and crucial to their explication is a detailed understanding of the underlying structural rearrangements and pathways that govern the formation of misfolded states. Here we use single-molecule optical tweezers to monitor misfolding reactions of the human neuronal calcium sensor-1, a multispecific EF-hand protein involved in neurotransmitter release and linked to severe neurological diseases. We directly observed two misfolding trajectories leading to distinct kinetically trapped misfolded conformations. Both trajectories originate from an on-pathway intermediate state and compete with native folding in a calcium-dependent manner. The relative probability of the different trajectories could be affected by modulating the relaxation rate of applied force, demonstrating an unprecedented real-time control over the free-energy landscape of a protein. Constant-force experiments in combination with hidden Markov analysis revealed the free-energy landscape of the misfolding transitions under both physiological and pathological calcium concentrations. Remarkably for a calcium sensor, we found that higher calcium concentrations increased the lifetimes of the misfolded conformations, slowing productive folding to the native state. We propose a rugged, multidimensional energy landscape for neuronal calcium sensor-1 and speculate on a direct link between protein misfolding and calcium dysregulation that could play a role in neurodegeneration

Hamiltonian dynamics of homopolymer chain models

The Hamiltonian dynamics of chains of nonlinearly coupled particles is numerically investigated in two and three dimensions. Simple, off-lattice homopolymer models are used to represent the interparticle potentials. Time averages of observables numerically computed along dynamical trajectories are found to reproduce results given by the statistical mechanics of homopolymer models. The dynamical treatment, however, indicates a nontrivial transition between regimes of slow and fast phase space mixing. Such a transition is inaccessible to a statistical mechanical treatment and reflects a bimodality in the relaxation of time averages to corresponding ensemble averages. It is also found that a change in the energy dependence of the largest Lyapunov exponent indicates the theta-transition between filamentary and globular polymer configurations, clearly detecting the transition even for a finite number of particles.Comment: 11 pages, 8 figures, accepted for publication in Physical Review