Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

A statistically self-consistent fatigue damage accumulation model including load sequence effects under spectrum loading

A probabilistic methodology is proposed to evaluate fatigue damage accumulation and fatigue lives of specimens under variable amplitude loading. With probabilistic modifications in the present model, the calculative consistency is achieved between fatigue damage and fatigue life. The load sequence effects on fatigue damage accumulation are properly accounted for variable amplitude loading. The developed damage model overcomes the inherent deficiencies in the linear damage accumulation rule, but still preserves its simplicity for engineering application. Based on the Monte Carlo sampling method, numerical verification of this model is conducted under two kinds of spectrum loading. The predicted probabilistic distributions of fatigue lives are validated by fatigue tests on Al-alloy straight lugs.&nbsp

Weight Function Method for computations of crack face displacements and stress intensity factors of center cracks

The weight function method provides a powerful and reliable tool for the determination of the stress intensity factor around the crack tip in a linearly elastic cracked solid subjected to arbitrary loading conditions. However, it is difficult to exactly compute the crack face displacement whose partial derivative is responsible for the weight function calculation. In the present paper, only one reference stress intensity factor is used for the purpose of establishing a general expression of the crack face displacement. Then, the generalized and simple expression is applied to calculate the weight function and the stress intensity factor of the center crack configuration. The calculation of the weight function is reduced to the simple integration of the correction function and of the partial derivative of the crack face displacement. It is shown that the present expressions for the computations of the crack face displacement and its partial derivative are in good agreement with their exact solutions

Function of TRP channels in monocytes/macrophages

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium. These TRP channels may also intermingle with macrophage activation signals to jointly regulate the occurrence and development of diseases. Here, we summarize recent findings on the expression and function of TRP channels in macrophages and discuss their role as modulators of macrophage activation and function. As research on TRP channels in health and disease progresses, it is anticipated that positive or negative modulators of TRP channels for treating specific diseases may be promising therapeutic options for the prevention and/or treatment of disease

DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use

A residual life prediction method of mine-used cable

For problems of complex modeling, difficult invalid data collection and low prediction precision of existing residual life prediction methods of mine-used cable, a residual life prediction method of mine-used cable was proposed which was based on gray prediction and multi-scale quantum harmonic oscillator algorithm(MQHOA). Dielectric dissipation factors and aging time under different temperature are collected firstly in accelerated hygrothermal aging test. Then residual life prediction model of mine-used cable is established by use of gray prediction GM(1,1) model and the collected data, which takes dielectric dissipation factor of 5% as ending criterion of cable life. Finally, MQHOA is used to optimize parameter of the GM(1,1) model to improve prediction precision. The test result shows that the method has short test time and higher correctness

Dynamic Analysis of Planar 3-RRR Flexible Parallel Robots with Dynamic Stiffening

In consideration of the second-order coupling quantity of the axial displacement caused by the transverse displacement of flexible beam, the first-order approximation coupling model of planar 3-RRR flexible parallel robots is presented, in which the rigid body motion constraints, elastic deformation motion constraints, and dynamic constraints of the moving platform are considered. Based on the different speed of the moving platform, numerical simulation results using the conventional zero-order approximation coupling model and the proposed firstorder approximation coupling model show that the effect of “dynamic stiffening” term on dynamic characteristics of the system is insignificant and can be neglected, and the zero-order approximation coupling model is enough precisely for catching essentially dynamic characteristics of the system. Then, the commercial software ANSYS 13.0 is used to confirm the validity of the zero-order approximation coupling model

Are Older Adults More Willing to Donate? The Roles of Donation Form and Social Relationship

Objectives: Whether older adults are more prosocial than younger adults has been under debate. In the current study, we investigated how age differences in prosocial behaviors varied across different contextual factors, that is, donation form, kinship, and social distance. Methods: To achieve this purpose, 89 younger and 66 older adults took part in a hypothetical donation task in which they were asked to donate money and time to relatives and nonrelatives at various social distances. Results: The results showed that, compared to younger adults, (a) older adults donated less to nonrelatives (regardless of the donation form), but donated a similar amount (in money) or even donated more (in time) to relatives; (b) older adults displayed higher levels of kin selection (favoring relatives over nonrelatives) in both monetary and time donations; and (c) older adults showed higher levels of social discounting (favoring socially close over distant others) in monetary but not time donation. Discussion: The study underscored the importance of contextual factors in understanding age differences in prosocial behaviors such as donation

Optimizing Production Schedule of Coalbed Methane Wells Using a Stochastic Evolution Algorithm

Production optimization of coalbed methane (CBM) is a complex constrained nonlinear programming problem. Finding an optimal decision is challenging since the coal seams are generally heterogeneous with widespread cleats, fractures, and matrix pores, and the stress sensitivities are extremely strong; the production of CBM wells needs to be adjusted dynamically within a reasonable range to fit the complex physical dynamics of CBM reservoirs to maximize profits on a long-term horizon. To address these challenges, this paper focuses on the step-down production strategy, which reduces the bottom hole pressure (BHP) step by step to expand the pressure drop radius, mitigate the formation damage, and improve CBM recovery. The mathematical model of CBM well production schedule optimization problem is formulated. The objective of the optimization model is to maximize the cumulative gas production and the variables are chosen as BHP declines of every step. BHP and its decline rate constraints are also considered in the model. Since the optimization problem is high dimensional, nonlinear with many local minima and maxima, covariance matrix adaptation evolution strategy (CMA-ES), a stochastic, derivative-free intelligent algorithm, is selected. By integrating a reservoir simulator with CMA-ES, the optimization problem can be solved successfully. Experiments including both normal wells and real featured wells are studied. Results show that CMA-ES can converge to the optimal solution efficiently. With the increase of the number of variables, the converge rate decreases rapidly. CMA-ES needs 3 or even more times number of function evaluations to converge to 100% of the optimum value comparing to 99%. The optimized schedule can better fit the heterogeneity and complex dynamic changes of CBM reservoir, resulting a higher production rate peak and a higher stable period production rate. The cumulative production under the optimized schedule can increase by 20% or even more. Moreover, the effect of the control frequency on the production schedule optimization problem is investigated. With the increases of control frequency, the converge rate decreases rapidly and the production performance increases slightly, and the optimization algorithm has a higher risk of falling into local optima. The findings of this study can help to better understanding the relationship between control strategy and CBM well production performance and provide an effective tool to determine the optimal production schedule for CBM wells