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Toll-like receptor 5 (TLR5) binding to bacterial flagellin activates signaling through the transcription factor NF-κB and triggers an innate immune response to the invading pathogen. To elucidate the structural basis and mechanistic implications of TLR5-flagellin recognition, we determined the crystal structure of zebrafish TLR5 (as a variable lymphocyte(More)
Measurements were made of two components of the average and fluctuating velocities, and of the local self-diffusion coefficients in a flow of granular material. The experiments were performed in a 1 m-high vertical channel with roughened sidewalls and with polished glass plates at the front and the back to create a two-dimensional flow. The particles used(More)
Unlike reversible quiescence, cellular senescence is characterized by a large flat cell morphology, β-gal staining and irreversible loss of regenerative (i.e., replicative) potential. Conversion from proliferative arrest to irreversible senescence, a process named geroconversion, is driven in part by growth-promoting pathways such as mammalian target of(More)
In normal human cells, oncogene-induced senescence (OIS) depends on induction of DNA damage response. Oxidative stress and hyperreplication of genomic DNA have been proposed as major causes of DNA damage in OIS cells. Here, we report that down-regulation of deoxyribonucleoside pools is another endogenous source of DNA damage in normal human fibroblasts(More)
For a graph (<i>V, E</i>), existing compact linear formulations for the minimum cut problem require &Theta;(|<i>V</i>||<i>E</i>|) variables and constraints and can be interpreted as a composition of |<i>V</i>|--1 polyhedra for minimum <i>s-t</i> cuts in much the same way as early approaches to finding globally minimum cuts relied on |<i>V</i>|--1 calls to a(More)
It is widely believed that aging results from the accumulation of molecular damage, including damage of DNA and mitochondria and accumulation of molecular garbage both inside and outside of the cell. Recently, this paradigm is being replaced by the "hyperfunction theory", which postulates that aging is caused by activation of signal transduction pathways(More)
Chronic inflammation is associated with increased cancer risk. Furthermore, the transcription factor NF-κB, a central regulator of inflammatory responses, is constitutively active in most tumors. To determine whether active NF-κB inherently contributes to malignant transformation, we isolated a set of NF-κB-activating genetic elements and tested their(More)
Keywords: Data-based modeling Elastic net Lasso Monte Carlo methods Biopharmaceutical manufacturing Regularization methods a b s t r a c t Biopharmaceutical manufacturing involves multiple process steps that can be challenging to model. Oftentimes, operating conditions are studied in bench-scale experiments and then fixed to specific values during(More)