A Stochastic Single-Molecule Event Triggers Phenotype Switching of a Bacterial Cell

By monitoring fluorescently labeled lactose permease with single-molecule sensitivity, we investigated the molecular mechanism of how an Escherichia coli cell with the lac operon switches from one phenotype to another. At intermediate inducer concentrations, a population of genetically identical cells exhibits two phenotypes: induced cells with highly fluorescent membranes and uninduced cells with a small number of membrane-bound permeases. We found that this basal-level expression results from partial dissociation of the tetrameric lactose repressor from one of its operators on looped DNA. In contrast, infrequent events of complete dissociation of the repressor from DNA result in large bursts of permease expression that trigger induction of the lac operon. Hence, a stochastic single-molecule event determines a cell's phenotype.Chemistry and Chemical Biolog

Optimized modeling and experiment test of a fluid inerter

This paper presents the fluid structure of the third passive vibration isolation element inerter. The fluid inerter ideally has the same characteristic that the force applying to the two terminals is proportional to the relative acceleration as the ball-screw inerter and rack-and-pinion inerter. An optimized nonlinear model of the fluid inerter is introduced, and the effect of nonlinearities compromising friction, oil density and viscosity of the fluid are discussed and analyzed. Simulations show that the friction has a great effect on the dynamic performance of fluid inerter in low frequency and the influence of the viscosity is not negligible. The damping force and the inertia force will become larger with the increase of the frequency and the inertia force will become more and more apparent in higher frequency. Furthermore, experiments are carried out to test the effectiveness of the fluid inerter. Results show that the optimized nonlinear model of the fluid inerter is deemed effective

PRMT2 promotes dextran sulfate sodium-induced colitis by inhibiting SOCS3 via histone H3R8 asymmetric dimethylation

BACKGROUND AND PURPOSE: There is emerging evidence for critical roles of epigenetic modifiers in development of inflammatory bowel disease (IBD). Protein arginine methyltransferase 2 (PRMT2) is responsible for methylation of arginine residues on histones and targets transcription factors critically involved in many cellular processes, including gene transcription, mRNA splicing, cell proliferation and differentiation. However, its role in colitis remains unknown. In this study, the role and underlying mechanisms of PRMT2 in colitis was studied. EXPERIMENTAL APPROACH: A mouse dextran sulfate sodium (DSS)-induced experimental colitis model was applied to study PRMT2 in colitis. Lentivirus induced PRMT2 silencing or overexpression in vivo was applied to address the role of PRMT2 in colitis. Detailed western blot and expression analysis was done to understand epigenetic changes induced by PRMT2 in colitis. KEY RESULTS: PRMT2 is highly expressed in patients with IBD, inflamed colon of mice and TNF-α stimulated mice gut epithelial cells. PRMT2 overexpression aggravates while knockdown alleviates DSS-induced colitis in mice, suggesting that PRMT2 is a pivotal mediator of colitis development. Mechanistically, PRMT2 mediates colitis by increasing repressive histone mark H3R8 asymmetric methylation (H3R8me2a) at the promoter region of the suppressor of cytokine signaling 3 (SOCS3) promoter. Resultant inhibition of SOCS3 expression and SOCS3-mediated degradation of TNF receptor associated factor 5 (TRAF5) via ubiquitination led to elevated TRAF5 expression and TRAF5-mediated downstream NF-κB/MAPK activation. CONCLUSION AND IMPLICATIONS: Our study demonstrates that PRMT2 acts as a transcriptional co-activator for proinflammatory genes during colitis. Hence targeting PRMT2 may provide a novel therapeutic approach for colitis

Multi-key Fully Homomorphic Encryption Scheme with Compact Ciphertexts

Multi-Key fully homomorphic encryption (MKFHE) allows computations on data encrypted by different parties. One disadvantage of previous MKFHE schemes is that the ciphertext size increases linearly or squarely with respect to the number of parties. It incurs a heavy communication and computation burden for the homomorphic evaluation, especially when the number of involved parties is large. In this paper, we propose the first method to construct MKFHE scheme while keeping the size of the ciphertext and corresponding evaluation key to be independent of the number of parties during the homomorphic evaluation. Specifically, we construct efficient compact MKFHE schemes with various advantages. On the one hand, we show how to construct compact MKFHE schemes which support the homomorphic encryption of ring elements and are friendly to floating point numbers. On the other hand, we give a compact MKFHE scheme that supports high efficient bootstrapping. In our paper, we show a novel method to reduce the cost of generating these evaluation keys from a quadratic time to a linear time with respect to the number of parties

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cumulative Effect, Targeted Poverty Alleviation, and Firm Value: Evidence from China

This paper studies the influence of the annual cumulative earnings of Chinese listed TPA (targeted poverty alleviation) companies before 2004 on the companies’ value using data from 2012 to 2019, measures the long-term earnings persistence of these companies with the variable of the cumulative earnings averaged by the market price of each company at the current year’s end, and obtains a model of the company’s value combined with each company’s earnings persistence and the long-term competitive strength of its products. The cumulative data from 2004 to 2012, 2005 to 2013…, and 2011 to 2019 provide the data used for regression from 2012 to 2019. The TPA companies’ value is affected by long-term cumulative net profits and long-term competitive advantage. The higher the company’s accumulated net profit, the longer the duration of the long-term competitive advantage, the more stable the company’s value increase, and the higher the quality of the value increase

Stability analysis of semi-active inerter-spring-damper suspensions based on time-delay

To analyze the variation rule of the critical instability time-delay of the semi-active ISD suspension, a general solution was proposed and applied into two three-element-structure ISD suspensions. The dynamical response and the performance of the semi-active ISD suspension in various time-delays indicated that different structures had different suspension performance. The time-delay deteriorated the performance of all of the suspensions which were analyzed. The stability of the semi-active ISD suspension would seriously weaken with the critical time-delay. This paper provided a general solution for parameters selection in semi-active ISD suspension design to avoid the negative effect of the time-delay

Modeling and Optimization of Vehicle Suspension Employing a Nonlinear Fluid Inerter

An ideal inerter has been applied to various vibration engineering fields because of its superior vibration isolation performance. This paper proposes a new type of fluid inerter and analyzes the nonlinearities including friction and nonlinear damping force caused by the viscosity of fluid. The nonlinear model of fluid inerter is demonstrated by the experiments analysis. Furthermore, the full-car dynamic model involving the nonlinear fluid inerter is established. It has been detected that the performance of the vehicle suspension may be influenced by the nonlinearities of inerter. So, parameters of the suspension system including the spring stiffness and the damping coefficient are optimized by means of QGA (quantum genetic algorithm), which combines the genetic algorithm and quantum computing. Results indicate that, compared with the original nonlinear suspension system, the RMS (root-mean-square) of vertical body acceleration of optimized suspension has decreased by 9.0%, the RMS of pitch angular acceleration has decreased by 19.9%, and the RMS of roll angular acceleration has decreased by 9.6%

Task Embedded Coordinate Update: A Realizable Framework for Multivariate Non-Convex Optimization

We in this paper propose a realizable framework TECU, which embeds task-specific strategies into update schemes of coordinate descent, for optimizing multivariate non-convex problems with coupled objective functions. On one hand, TECU is capable of improving algorithm efficiencies through embedding productive numerical algorithms, for optimizing univariate sub-problems with nice properties. From the other side, it also augments probabilities to receive desired results, by embedding advanced techniques in optimizations of realistic tasks. Integrating both numerical algorithms and advanced techniques together, TECU is proposed in a unified framework for solving a class of non-convex problems. Although the task embedded strategies bring inaccuracies in sub-problem optimizations, we provide a realizable criterion to control the errors, meanwhile, to ensure robust performances with rigid theoretical analyses. By respectively embedding ADMM and a residual-type CNN in our algorithm framework, the experimental results verify both efficiency and effectiveness of embedding task-oriented strategies in coordinate descent for solving practical problems