22 research outputs found

    Receptor-Mediated Endocytosis of a Cylindrical Nanoparticle in the Presence of Cytoskeleton Substrate

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    Internalization of particles by cells plays a crucial role for adsorbing nutrients and fighting infection. Endocytosis is one of the most important mechanisms of the particles uptake which encompass multiple pathways. Although endocytosis is a complex mechanism involving biochemical signaling and active force generation, the energetic cost associated to the large deformations of the cell membrane wrapping around the foreign particle is an important factor controlling this process, which can be studied using quantitative physical models. Of particular interest is the competition between membrane - cytoskeleton and membrane - target adhesion. Here, we explore the wrapping of a lipid membrane around a long cylindrical object in the presence of a substrate mimicking the cytoskeleton. Using discretization of the Helfrich elastic energy that accounts for the membrane bending rigidity and surface tension, we obtain a wrapping phase diagram as a function of the membrane-cytoskeleton and the membrane-target adhesion energy that includes unwrapped, partially wrapped and fully wrapped states. We provide an analytical expression for the boundary between the different regimes. While the transition to partial wrapping is independent of membrane tension, the transition to full wrapping is very much influenced by membrane tension. We also show that target wrapping may proceed in an asymmetric fashion in the full wrapping regime

    Theory of Nucleosome Corkscrew Sliding in the Presence of Synthetic DNA Ligands

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    Histone octamers show a heat-induced mobility along DNA. Recent theoretical studies have established two mechanisms that are qualitatively and quantitatively compatible with in vitro experiments on nucleosome sliding: Octamer repositiong through one-basepair twist defects and through ten-basepair bulge defects. A recent experiment demonstrated that the repositioning is strongly suppressed in the presence of minor-groove binding DNA ligands. In the present study we give a quantitative theory for nucleosome repositioning in the presence of such ligands. We show that the experimentally observed octamer mobilities are consistent with the picture of bound ligands blocking the passage of twist defects through the nucleosome. This strongly supports the model of twist defects inducing a corkscrew motion of the nucleosome as the underlying mechanism of nucleosome sliding. We provide a theoretical estimate of the nucleosomal mobility without adjustable parameters, as a function of ligand concentration, binding affinity, binding site orientiation, temperature and DNA anisotropy. Having this mobility at hand we speculate about the interaction between a nucleosome and a transcribing RNA polymerase and suggest a novel mechanism that might account for polymerase induced nucleosome repositioning.Comment: 23 pages, 4 figures, submitted to J. Mol. Bio

    Active Nucleosome Displacement: A Theoretical Approach

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    AbstractThree-quarters of eukaryotic DNA are wrapped around protein cylinders forming so-called nucleosomes that block the access to the genetic information. Nucleosomes need therefore to be repositioned, either passively (by thermal fluctuations) or actively (by molecular motors). Here we introduce a theoretical model that allows us to study the interplay between a motor protein that moves along DNA (e.g., an RNA polymerase) and a nucleosome that it encounters on its way. We aim at describing the displacement mechanisms of the nucleosome and the motor protein on a microscopic level to understand better the intricate interplay between the active step of the motor and the nucleosome-repositioning step. Different motor types (Brownian ratchet versus power-stroke mechanism) that perform very similarly under a constant load are shown to have very different nucleosome repositioning capacities

    Comparison of Cleaning Efficacy and Instrumentation Time in Primary Molars: Mtwo Rotary Instruments vs. Hand K-Files

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    Introduction: Pulpectomy is the preferred treatment for restorable primary teeth with symptomatic irreversible pulpitis or periradicular lesion. Considering the rather new application of rotary files for pulpectomy of primary teeth, the aim of this study was to compare the cleaning efficacy and instrumentation time of hand K-files and Mtwo rotary system for preparation of human primary molars. Methods and Materials: This experimental study was conducted on 100 extracted primary maxillary and mandibular intact molars with no resorption. Access cavities were prepared and India ink was injected into the root canal on a vibrator using an insulin syringe. Canals were then divided into 5 groups (n=20): in group I, canals were instrumented using K-files up to #25 for mesial and buccal canals and #30 for palatal and distal canals. In group II, canals were prepared using Mtwo rotary files (15/0.05, 20/0.06 and 25/0.06 for mesial and buccal canals and 15/0.05, 20/0.06, 25/0.06 and finally 30/0.05 for distal and palatal canals). In group III, root canals were only irrigated with saline. Groups IV and V were the positive and negative control groups, respectively. The time required for cleaning and preparation of the canals for each of the specimens in groups I, II and III was recorded. Results: The mean score of cleanliness of Mtwo was not significantly different from K-file group (P>0.05). However the mean instrumentation time in Mtwo group was significantly shorter (P<0.001). Conclusion: Although there were no differences regarding the cleaning efficacy of either system, Mtwo rotary files were far more time efficient.Keywords: Deciduous Tooth; Hand K-files; Mtwo; Primary Molars; Pulpectomy; Root Canal Preparation; Root Canal Therap

    Elastic Correlations in Nucleosomal DNA Structure

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    The structure of DNA in the nucleosome core particle is studied using an elastic model that incorporates anisotropy in the bending energetics and twist-bend coupling. Using the experimentally determined structure of nucleosomal DNA [T.J. Richmond and C.A. Davey, Nature {\bf 423}, 145 (2003)], it is shown that elastic correlations exist between twist, roll, tilt, and stretching of DNA, as well as the distance between phosphate groups. The twist-bend coupling term is shown to be able to capture these correlations to a large extent, and a fit to the experimental data yields a new estimate of G=25 nm for the value of the twist-bend coupling constant

    AdaBest: Minimizing Client Drift in Federated Learning via Adaptive Bias Estimation

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    In Federated Learning (FL), a number of clients or devices collaborate to train a model without sharing their data. Models are optimized locally at each client and further communicated to a central hub for aggregation. While FL is an appealing decentralized training paradigm, heterogeneity among data from different clients can cause the local optimization to drift away from the global objective. In order to estimate and therefore remove this drift, variance reduction techniques have been incorporated into FL optimization recently. However, these approaches inaccurately estimate the clients' drift and ultimately fail to remove it properly. In this work, we propose an adaptive algorithm that accurately estimates drift across clients. In comparison to previous works, our approach necessitates less storage and communication bandwidth, as well as lower compute costs. Additionally, our proposed methodology induces stability by constraining the norm of estimates for client drift, making it more practical for large scale FL. Experimental findings demonstrate that the proposed algorithm converges significantly faster and achieves higher accuracy than the baselines across various FL benchmarks.Comment: AdaBes

    Effect of Bending Anisotropy on the 3D Conformation of Short DNA Loops

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    The equilibrium three dimensional shape of relatively short loops of DNA is studied using an elastic model that takes into account anisotropy in bending rigidities. Using a reasonable estimate for the anisotropy, it is found that cyclized DNA with lengths that are not integer multiples of the pitch take on nontrivial shapes that involve bending out of planes and formation of kinks. The effect of sequence inhomogeneity on the shape of DNA is addressed, and shown to enhance the geometrical features. These findings could shed some light on the role of DNA conformation in protein--DNA interactions
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