The fractal globule state is a popular model for describing chromatin packing in eukaryotic nuclei. Here we provide a scaling theory and dissipative particle dynamics computer simulation for the thermal motion of monomers in the fractal globule state. Simulations starting from different entanglement-free initial states show good convergence which provides evidence supporting the existence of a unique metastable fractal globule state. We show monomer motion in this state to be subdiffusive described by with close to 0.4. This result is in good agreement with existing experimental data on the chromatin dynamics, which makes an additional argument in support of the fractal globule model of chromatin packing.
: Background. Community‐acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Risk stratification has previously been difficult.Methods. Markers of cardiac stress (B‐type natriuretic peptide, BNP) and inflammation (C‐reactive protein, white blood cell count, procalcitonin) as well as the pneumonia severity index (PSI) were determined in 302 consecutive patients presenting to the emergency department (ED) with CAP. The accuracy of these parameters to predict death was evaluated as the primary endpoint. Prediction of treatment failure was considered as the secondary endpoint.Results. B‐type natriuretic peptide levels increased with rising disease severity as classified by the PSI (P = 0.015). BNP levels were significantly higher in nonsurvivors compared to survivors [median 439.2 (IQR 137.1–1384.6) vs. 114.3 (51.3–359.6) pg mL−1, P < 0.001]. In a receiver operating characteristic analysis for the prediction of survival the area under the curve (AUC) for BNP was comparable to the AUC of the PSI (0.75 vs. 0.71, P = 0.52). Importantly, the combination of BNP and the PSI significantly improved the prognostic accuracy of the PSI alone (AUC 0.78 vs. 0.71; P = 0.02). The optimal cut‐off for BNP was 279 pg mL−1. The accuracy of BNP to predict treatment failure was identical to the accuracy to predict death (AUC 0.75).Conclusions. In patients with CAP, BNP levels are powerful and independent predictors of death and treatment failure. When used in conjunction with the PSI, BNP levels significantly improve the risk prediction when compared with the PSI alone.
Chromosomes are key players of cell physiology, their dynamics provides valuable information about its physical organization. In both prokaryotes and eukaryotes, the short-time motion of chromosomal loci has been described with a Rouse model in a simple or viscoelastic medium. However, little emphasis has been put on the influence of the folded organization of chromosomes on the local dynamics. Clearly, stress propagation, and thus dynamics, must be affected by such organization, but a theory allowing us to extract such information from data, e.g., on two-point correlations, is lacking. Here, we describe a theoretical framework able to answer this general polymer dynamics question. We provide a scaling analysis of the stress-propagation time between two loci at a given arclength distance along the chromosomal coordinate. The results suggest a precise way to assess folding information from the dynamical coupling of chromosome segments. Additionally, we realize this framework in a specific model of a polymer whose long-range interactions are designed to make it fold in a fractal way and immersed in a medium characterized by subdiffusive fractional Langevin motion with a tunable scaling exponent. This allows us to derive explicit analytical expressions for the correlation functions.
We present scaling estimates for characteristic times and of pulling ideal linear and randomly branched polymers of monomers into a small hole by a force . We show that the absorbtion process develops as sequential straightening of folds of the initial polymer configuration. By estimating the typical size of the fold involved into the motion, we arrive at the following predictions, and , and we also confirm them by the molecular dynamics experiment.
We analyze the mean time tapp that a randomly moving particle spends in a bounded domain (sphere) before it escapes through a small window in the domain’s boundary. A particle is assumed to diffuse freely in the bulk until it approaches the surface of the domain where it becomes weakly adsorbed, and then wanders diffusively along the boundary for a random time until it desorbs back to the bulk, etc. Using a mean-field approximation, we define tapp analytically as a function of the bulk and surface diffusion coefficients, the mean time it spends in the bulk between two consecutive arrivals to the surface and the mean time it wanders on the surface within a single round of the surface diffusion.