1,721,030 research outputs found
Cell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting
Get PDFMolecular recognition of proteins is key to their biological functions and processes such as protein–protein interactions (PPIs). The large binding interface involved and an often relatively flat binding surface make the development of selective protein-binding materials extremely challenging. A general method is reported in this work to construct protein-binding polymeric nanoparticles from cross-linked surfactant micelles. Preparation involves first dynamic covalent chemistry that encodes signature surface lysines on a protein template. A double molecular imprinting procedure fixes the binding groups on the nanoparticle for these lysine groups, meanwhile creating a binding interface complementary to the protein in size, shape, and distribution of acidic groups on the surface. These water-soluble nanoparticles possess excellent specificities for target proteins and sufficient affinities to inhibit natural PPIs such as those between cytochrome c (Cytc) and cytochrome c oxidase (CcO). With the ability to enter cells through a combination of energy-dependent and -independent pathways, they intervene apoptosis by inhibiting the PPI between Cytc and the apoptotic protease activating factor-1 (APAF1). Generality of the preparation and the excellent molecular recognition of the materials have the potential to make them powerful tools to probe protein functions in vitro and in cellulo.This article is published as Ghosh, Avijit, Mansi Sharma, and Yan Zhao. "Cell-penetrating protein-recognizing polymeric nanoparticles through dynamic covalent chemistry and double imprinting." Nature Communications 15, no. 1 (2024): 3731. doi: https://doi.org/10.1038/s41467-024-48131-5
New methods in computational systems biology
Get PDFSystems biology strives to reach greater understanding of biological function through an integrative, multidisciplinary approach utilizing experimentation, theory, and simulation in equal measures. Drawing from the traditionally distinct elds of biology, chemistry, physics, engineering, mathematics, computer science, informatics, and medicine, systems biology regards biological components as acting in tandem in a uni ed hierarchical system over a wide range of scales, from nano-scale (proteins and small molecules) to micro-scale (organelles and cells) to macro-scale (tissue and organs). Within this burgeoning eld, computational modeling of cell signaling serves not only to validate theoretical and experimental ndings, but also to provide quantitative and even predictive analysis of biochemical networks and intracellular machinery.In this thesis, a model of the canonical MAPK signal transduction pathway (well studied for its role in a large percentage of cancers) is analyzed using the custom simulation software package CellSim as a tool for predicting targets for e ective anti-cancer drugs, as well as predicting the e ects of such drugs on non-cancerous cells. Furthermore, computational tools and methods are developed for extending such purely kinetic models of intracellular signaling into the spatio-temporal realm, introducing locality, transport, and cell geometry.Ph.D., Physics -- Drexel University, 200
Automated sensitivity analysis on spatio-temporal biochemical systems
Get PDFIn silico models of signal transduction pathways have been highly successful in describing, quantitatively, how complex protein networks govern overall cell function. Understanding these signaling pathways helps us not only in understanding biology at its roots, but provides insight into how we can constructively manipulate biological functions, i.e., the developement of treatments of human diseases. However, the complexity of these signaling pathways or networks, characterized by feedback loops, cross-talk, redundancy, hinders the generation of new knowledge, strategies and breakthroughs for the regulation of cellular machinery. Sensitivity analysis, as one of the most effective approaches for studying mathematical models of biochemical systems, has the ability to identify dominant parameters, simplify models and answer “what if” questions. In this study, a stiff Rosenbrock integrator has been developed for sensitivity analysis using a direct sensitivity approach. Automated sparse Jacobian and Hessian calculations of the coupled system (the original model equations and the sensitivity equations) have been implemented in the freely available software package CellSim. The accuracy and efficiency of this newly developed R/DM method (Rosenbrock with direct method) are tested extensively on the complex MAPK (mitogen-activated protein kinase) pathway model of Bhalla et al. Both time-dependent concentration and parameter based sensitivity coefficients are measured using several integration schemes. The method is shown to perform sensitivity analysis in a manner that is both cost effective and accurate. It is several magnitudes faster than traditional integrators, such as adaptive Runge-Kutta, etc. The error control strategies between the DDM (decoupled direct method) and the R/DM are discussed and their computational accuracies are compared. The method is used to analyze the positive feedback loop within the MAPK signal transduction pathway.As systems biology models move from purely kinetic to spatio-temporal models, important analysis approaches such as sensitivity analysis must be appropriately expanded to fit this change. We have developed a fast integrator for the sensitivity analysis of spatiotemporal reaction-diffusion PDE systems. The method is an extension of the previously developed Rosenbrock integration method aimed for pure reaction systems. The expanded spatio-temporal sensitivity analysis method is successfully applied to the canonical Gray-Scott reaction-diffusion system. The mixture of this new integrator and the simulation together provide an efficient way to analyze the localization of a nonlinear system response at different times and locations as well as the pattern transitions between adjacent patterns.Ph.D., Biomedical Engineering -- Drexel University, 200
Algorithm-PYSWARM.ipynb
No full textThis is a PYSWARM based algorithm that performs the optimization task discussed in the paper Quantitative analysis of non-equilibrium systems from short-time experimental data, to infer entropy production from stationary, non-equilibrium trajectories.Reference: Quantitative analysis of non-equilibrium systems from short-time experimental data ( https://arxiv.org/abs/2102.11374 )Sreekanth K Manikandan, Subhrokoli Ghosh, Avijit Kundu, Biswajit Das, Vipin Agrawal, Dhrubaditya Mitra, Ayan Banerjee, Supriya Krishnamurthy</div
Algorithm.ipynb
No full textIn this Jupyter notebook we implement a particle-swarm algorithm that performs the optimization task discussed in the paper Quantitative analysis of non-equilibrium systems from short-time experimental data, to infer entropy production from stationary, non-equilibrium trajectories.Reference: Quantitative analysis of non-equilibrium systems from short-time experimental data ( https://arxiv.org/abs/2102.11374 )Sreekanth K Manikandan, Subhrokoli Ghosh, Avijit Kundu, Biswajit Das, Vipin Agrawal, Dhrubaditya Mitra, Ayan Banerjee, Supriya Krishnamurthy</div
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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