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

Structure-function mapping of a heptameric module in the nuclear pore complex.

The nuclear pore complex (NPC) is a multiprotein assembly that serves as the sole mediator of nucleocytoplasmic exchange in eukaryotic cells. In this paper, we use an integrative approach to determine the structure of an essential component of the yeast NPC, the ~600-kD heptameric Nup84 complex, to a precision of ~1.5 nm. The configuration of the subunit structures was determined by satisfaction of spatial restraints derived from a diverse set of negative-stain electron microscopy and protein domain-mapping data. Phenotypic data were mapped onto the complex, allowing us to identify regions that stabilize the NPC's interaction with the nuclear envelope membrane and connect the complex to the rest of the NPC. Our data allow us to suggest how the Nup84 complex is assembled into the NPC and propose a scenario for the evolution of the Nup84 complex through a series of gene duplication and loss events. This work demonstrates that integrative approaches based on low-resolution data of sufficient quality can generate functionally informative structures at intermediate resolution

Simulation of Lattice Polymers with Multi-Self-Overlap Ensemble

A novel family of dynamical Monte Carlo algorithms for lattice polymers is proposed. Our central idea is to simulate an extended ensemble in which the self-avoiding condition is systematically weakened. The degree of the self-overlap is controlled in a similar manner as the multicanonical ensemble. As a consequence, the ensemble --the multi-self-overlap ensemble-- contains adequate portions of self-overlapping conformations as well as higher energy ones. It is shown that the multi-self-overlap ensemble algorithm reproduce correctly the canonical averages at finite temperatures of the HP model of lattice proteins. Moreover, it outperforms massively a standard multicanonical algorithm for a difficult example of a polymer with 8-stickers. Alternative algorithm based on exchange Monte Carlo method is also discussed.Comment: 5 Pages, 4 Postscript figures, uses epsf.st

Reply to Comment on "Criterion that Determines the Foldability of Proteins"

We point out that the correlation between folding times and $\sigma = (T_{\theta } - T_{f})/T_{\theta }$ in protein-like heteropolymer models where $T_{\theta }$ and $T_{f}$ are the collapse and folding transition temperatures was already established in 1993 before the other presumed equivalent criterion (folding times correlating with $T_{f}$ alone) was suggested. We argue that the folding times for these models show no useful correlation with the energy gap even if restricted to the ensemble of compact structures as suggested by Karplus and Shakhnovich (cond-mat/9606037).Comment: 6 pages, Latex, 2 Postscript figures. Plots explicitly showing the lack of correlation between folding time and energy gap are adde

Lógica matemática: uma introdução ao cálculo proposicional

Competitiveness and economic development of the fruit sector are hampered by manifold conditions. In recent times, the creation of an exclusive fruit brand turns out to be a valid strategy to counteract such challenges. Specifically, the so-called \u201cvariety club\u201d leads the sector to benefit from an organizational model that relies upon a strong integration and a coordinated approach amongst actors. In this sense, it is an over-structure made up of the several subjects of the chain, which operate under formal contracts to be provided with exclusive goods and services and gain individual utilities. A large array of management schemes differ for levels of arrangements and control, with several forms in between. As a result, a complex structure emerges, depicting a dense and interconnected network of skills. Based on the general organizational structure of clubs, the study at hand is rather a concept paper, aimed exploring the subjects involved. Particularly, it elucidates various subjects who take part in the club model, explores strength relationships amongst them and sheds light on their bargaining power. Lastly, some insights are given for the improvement and future implementation of the model

Classification tree analysis of urban resource consumption

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Architecture, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 101-103).A study was carried out to develop a typology of urban metabolic (or resource consumption) profiles for 155 globally representative cities. Classification tree analysis was used to develop a model for determining how certain predictor (or independent) variables are related to levels of resource consumption. These predictor variables are: climate, city GDP, population, and population density. Classification trees and their corresponding decision rules were produced for the following major categories of material and energy resources: Total Energy, Electricity, Fossil fuels, Industrial Minerals & Ores, Construction Minerals, Biomass, Water, and Total Domestic Material Consumption. A tree was also generated for carbon dioxide emissions. Data at the city level was insufficient to include municipal solid waste generation in the analysis. Beyond just providing insight into the effects of the predictor variables on the consumption of different types of resources, the classification trees can also be used to predict consumption levels for cities that were not used in the model training data set. Urban metabolic profiles were also developed for each of the 155 cities, resulting in 15 metabolic types containing cities with identical or almost identical levels of consumption for all of the 8 resources and identical levels of carbon dioxide emissions. The important drivers of the differences in profile for each type include the dominant industries in the cities, as well as the presence of abundant natural resources in the countries in which the cities are the main economic centers.by Artessa Niccola D. Saldivar-Sali.S.M

A landslide risk rating system for the Baguio City, Philippines area

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2004.Includes bibliographical references (leaves 154-156).This research formulates a LANDSLIDE RISK RATING SYSTEM for the Greater Baguio area in the Philippines. It is hoped that the tool will be made a part of the physical/urban planning process when used by engineers and planners and used to address risks posed by landslides given the rapidly increasing concentration of population and the development of infrastructure and industry in the Baguio area. Reports and studies of individual landslides in the area are reviewed in order to discover the causal factors of mass movements and their interactions. The findings of these research works are discussed in the first portion of this paper. A description of the LANDSLIDE RISK RATING SYSTEM, remedial measures, and recommendations form the rest of the paper. This SYSTEM integrates different hazard (bedrock geology, slope gradients, vegetation) and risk (population, land use) factors. The selection of hazard factors takes into account the results of the analysis of causal factors of mass movements in the area. This analysis is based on the specific attributes of the subject study area, namely: a relatively extreme topographic relief, variable bedrock geology, and no significant differences in rainfall from one zone to another. The study assumes that the entire Greater Baguio area is subject to a uniform amount of rainfall during any given precipitation event. Although this study is area-specific it can have wider application.(cont.) Finally, the paper recommends that in future research work on this subject matter, soil and rock samples from various slopes be subjected to geomechanical testing to facilitate a mathematical analysis of slope failures. This can be the basis for a comprehensive database which can be used to create a Landslide Hazard Map where each slope in the Greater Baguio area can be rated. In addition, it would be beneficial to conduct an analysis of how Hazard Ratings may be reduced when particular remedial measures are in place. A site-specific preventive and remedial slope safety system for every slope in the Greater Baguio area would be the ultimate goal of future work.by Artessa Niccola D. Saldivar-Sali.M.Eng

Novel hemostatic patch achieves sutureless epicardial wound closure during complex cardiac surgery:A case report

Treatment of damaged cardiac tissue in patients with high bleeding tendency can be very challenging, damaged myocardial tissue has a high rupture risk when being sutured subsequently on-going bleeding is a major risk factor for poor clinical outcome. We present a case demonstrating the feasibility in using a novel haemostatic collagen sponge for the management of a myocardial wound. This report is the first description in cardiac surgery where Hemopatch (R) sponges are used to successfully seal a left ventricle wound. Our patient was diagnosed with endocarditis, had a low pre-operative haemoglobin count and underwent cardiac surgery for multiple valve repairs. The procedure was performed on cardiopulmonary bypass, which meant our patient had to be heparinized. Despite these major risk factors for bleeding Hemopatch (R) managed to contain bleeding and seal the wound, no sutures were needed