Just my luck: How children's causal attributions contribute to injury prevention.

Purpose: Traumatic injury in children, particularly adolescents, is both frequently and costly. In this study, we directly examined children's causal attributions for the recent traumas and asked them to propose prevention strategies of their own. We predict that children who attribute their injuries to their own actions, rather than an external force such as luck, will be more likely to develop strategies to avoid trauma in the future.

An in-depth examination of requirements for disclosure risk assessment.

The use of formal privacy to protect the confidentiality of responses in the 2020 Decennial Census of Population and Housing has triggered renewed interest and debate over how to measure the disclosure risks and societal benefits of the published data products. We argue that any proposal for quantifying disclosure risk should be based on prespecified, objective criteria. We illustrate this approach to evaluate the absolute disclosure risk framework, the counterfactual framework underlying differential privacy, and prior-to-posterior comparisons.

Comparative Analysis of the Measles Antibody Levels in Healthy Medical Personnel of Maternity Ward and Women in Labor.

It has been proven that post-vaccination immunity to measles virus after two doses of vaccine is not able to persistently protect against infection throughout life. The goal of this research was to determine the immune layer to the measles virus among women in labor and maternity ward personnel in the same medical institution. The levels of IgG antibodies to measles virus in the umbilical cord blood of 594 women in labor and 88 workers of the maternity ward were studied by ELISA.

Gender Differences in the Level of Antibodies to Measles Virus in Adults.

Individuals without a protective antibody level are susceptible to measles infection. There are differences in the persistence of antibodies after vaccination and infection, while the impact of gender on this process has not been sufficiently studied. Measles Ig G antibodies were measured in 1742 employees of a large hospital facility-403 men and 1339 women aged from 25 to 67 years; 15% participants had antibody levels less than the protective threshold of ≥0.

Low Force Unfolding of a Single-Domain Protein by Parallel Pathways.

Deviations from linearity in the dependence of the logarithm of protein unfolding rates, log (), as a function of mechanical force, , measurable in single molecule experiments, can arise for many reasons. In particular, upward curvature in log () as a function of implies that the underlying energy landscape must be multidimensional with the possibility that unfolding ensues by parallel pathways. Here, simulations using the SOP-SC model of a wild type β-sandwich protein and several mutants, with immunoglobulin folds, show upward curvature in the unfolding kinetics.

Symmetry, Rigidity, and Allosteric Signaling: From Monomeric Proteins to Molecular Machines.

Allosteric signaling in biological molecules, which may be viewed as specific action at a distance due to localized perturbation upon binding of ligands or changes in environmental cues, is pervasive in biology. Insightful phenomenological Monod, Wyman, and Changeux (MWC) and Koshland, Nemethy, and Filmer (KNF) models galvanized research in describing allosteric transitions for over five decades, and these models continue to be the basis for describing the mechanisms of allostery in a bewildering array of systems. However, understanding allosteric signaling and the associated dynamics between distinct allosteric states at the molecular level is challenging and requires novel experiments complemented by computational studies.

Protein collapse is encoded in the folded state architecture.

Folded states of single domain globular proteins are compact with high packing density. The radius of gyration, R, of both the folded and unfolded states increase as N where N is the number of amino acids in the protein. The values of the Flory exponent ν are, respectively, ≈⅓ and ≈0.

Force-dependent switch in protein unfolding pathways and transition-state movements.

Although it is known that single-domain proteins fold and unfold by parallel pathways, demonstration of this expectation has been difficult to establish in experiments. Unfolding rate, [Formula: see text], as a function of force f, obtained in single-molecule pulling experiments on src SH3 domain, exhibits upward curvature on a [Formula: see text] plot. Similar observations were reported for other proteins for the unfolding rate [Formula: see text].

Propensity to form amyloid fibrils is encoded as excitations in the free energy landscape of monomeric proteins.

Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation-prone (N(⁎)) states, which are rarely populated under force free native conditions but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration ([C]), mechanical force (f), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive N(⁎) states.

Theory of active transport in filopodia and stereocilia.

The biological processes in elongated organelles of living cells are often regulated by molecular motor transport. We determined spatial distributions of motors in such organelles, corresponding to a basic scenario when motors only walk along the substrate, bind, unbind, and diffuse. We developed a mean-field model, which quantitatively reproduces elaborate stochastic simulation results as well as provides a physical interpretation of experimentally observed distributions of Myosin IIIa in stereocilia and filopodia.

Computing free energy of a large-scale allosteric transition in adenylate kinase using all atom explicit solvent simulations.

During allosteric motions proteins navigate rugged energy landscapes. Hence, mapping of these multidimensional landscapes into lower dimensional manifolds is important for gaining deeper insights into allosteric dynamics. Using a recently developed computational technique, we calculated the free energy difference between the open and closed states of adenylate kinase, an allosteric protein which was extensively studied previously using both experimental and theoretical approaches.

Protein fluxes along the filopodium as a framework for understanding the growth-retraction dynamics: the interplay between diffusion and active transport.

We present a picture of filopodial growth and retraction from physics perspective, where we emphasize the significance of the role played by protein fluxes due to spatially extended nature of the filopodium. We review a series of works, which used stochastic simulations and mean field analytical modeling to find the concentration profile of G-actin inside a filopodium, which, in turn, determines the stationary filopodial length. In addition to extensively reviewing the prior works, we also report some new results on the role of active transport in regulating the length of filopodia.

Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework.

Energy landscape theories have provided a common ground for understanding the protein folding problem, which once seemed to be overwhelmingly complicated. At the same time, the native state was found to be an ensemble of interconverting states with frustration playing a more important role compared to the folding problem. The landscape of the folded protein - the native landscape - is glassier than the folding landscape; hence, a general description analogous to the folding theories is difficult to achieve.

Computing free energies of protein conformations from explicit solvent simulations.

We report a fully general technique addressing a long standing challenge of calculating conformational free energy differences between various states of a polymer chain from simulations using explicit solvent force fields. The main feature of our method is a special mapping variable, a path coordinate, which continuously connects two conformations. The path variable has been designed to preserve locality in the phase space near the path endpoints.

Design of active transport must be highly intricate: a possible role of myosin and Ena/VASP for G-actin transport in filopodia.

Recent modeling of filopodia--the actin-based cell organelles employed for sensing and motility--reveals that one of the key limiting factors of filopodial length is diffusional transport of G-actin monomers to the polymerizing barbed ends. We have explored the possibility of active transport of G-actin by myosin motors, which would be an expected biological response to overcome the limitation of a diffusion-based process. We found that in a straightforward implementation of active transport the increase in length was unimpressive, < or = 30%, due to sequestering of G-actin by freely diffusing motors.

Functional versus folding landscapes: the same yet different.

Protein functional landscapes are characterized by a modest number of states compared with the folding landscapes, allowing brute force sampling of these states for smaller proteins using computer simulations. On the other hand, because the functional landscape topographies are complicated, the native state dynamics are often difficult to interpret. Nevertheless, a number of experimental and computational techniques have recently emerged that are designed to reveal the essential features of the native landscape, such as the hierarchical organization of conformational substates.

Molecular noise of capping protein binding induces macroscopic instability in filopodial dynamics.

Capping proteins are among the most important regulatory proteins involved in controlling complicated stochastic dynamics of filopodia, which are dynamic finger-like protrusions used by eukaryotic motile cells to probe their environment and help guide cell motility. They attach to the barbed end of a filament and prevent polymerization, leading to effective filament retraction due to retrograde flow. When we simulated filopodial growth in the presence of capping proteins, qualitatively different dynamics emerged, compared with actin-only system.

Deconstructing the native state: energy landscapes, function, and dynamics of globular proteins.

Proteins are highly complex molecules with features exquisitely selected by nature to carry out essential biological functions. Physical chemistry and polymer physics provide us with the tools needed to make sense of this complexity. Upon translation, many proteins fold to a thermodynamically stable form known as the native state.

High resolution approach to the native state ensemble kinetics and thermodynamics.

Many biologically interesting functions such as allosteric switching or protein-ligand binding are determined by the kinetics and mechanisms of transitions between various conformational substates of the native basin of globular proteins. To advance our understanding of these processes, we constructed a two-dimensional free energy surface (FES) of the native basin of a small globular protein, Trp-cage. The corresponding order parameters were defined using two native substructures of Trp-cage.