Exposure to toxic environments across the life course:consequences for development, DNA methylation and ageing

Early life exposure to cigarette smoke interferes with lung development and is in children associated with an increased risk of getting lung infections and asthma. In adult life, smoking is one of the exogenous stimuli that is linked with accelerated ageing of the lung and the development of chronic obstructive pulmonary disease (COPD). Similarly, in China, prenatal and childhood exposure to e-waste originated pollutants is associated with adverse birth outcomes, abnormal development and growth impairment. E-waste pollutants arise when in a primitive and unsafe manner electronics are recycled. This results in the contamination of the environment (air, soil and water) with a mixture of chemicals that are well known for their adverse health effects, such as lead, cadmium, manganese and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Pregnant women and young children that live in areas where electronics recycling takes place have a high risk of getting health problems. Risk factors for a particular disease can be hereditary and are then fixed in our genetic material, our DNA. In addition, environmental exposures during life induce changes in the use of the DNA. These are so-called epigenetic changes. Epigenetic mechanisms such as DNA methylation can be persistent and underlying chronic diseases and ageing.UMCG researcher Zhijun Zeng investigated the effect of (early life) smoke exposure on development and ageing in a mouse model of (maternal) smoking which was linked to Igf1 promoter methylation across 3 developmental stages, in liver and lung. The insulin-like growth factor (IGF) pathway has a pivotal role in (fetal) growth, development, and ageing. Prenatal smoke exposure induced differential Igf1 methylation in mouse offspring, which was persistent across the fetal stage to adulthood, and which was organ- and sex-specific. In addition, in offspring mice exposed to cigarette smoke for 12 weeks, the added effect of prenatal smoke exposure on smoke-induced lung ageing was only modest. The in China conducted study on prenatal exposure to e-waste-originated heavy metals showed an association with epigenome-wide differential methylation of 79 genes related to development and cell death. Childhood exposure to atmospheric e-waste was negatively associated with growth and linked with reduced plasma IGF1 levels

Design Space Exploration of Neural Network Activation Function Circuits

The widespread application of artificial neural networks has prompted researchers to experiment with FPGA and customized ASIC designs to speed up their computation. These implementation efforts have generally focused on weight multiplication and signal summation operations, and less on activation functions used in these applications. Yet, efficient hardware implementations of nonlinear activation functions like Exponential Linear Units (ELU), Scaled Exponential Linear Units (SELU), and Hyperbolic Tangent (tanh), are central to designing effective neural network accelerators, since these functions require lots of resources. In this paper, we explore efficient hardware implementations of activation functions using purely combinational circuits, with a focus on two widely used nonlinear activation functions, i.e., SELU and tanh. Our experiments demonstrate that neural networks are generally insensitive to the precision of the activation function. The results also prove that the proposed combinational circuit-based approach is very efficient in terms of speed and area, with negligible accuracy loss on the MNIST, CIFAR-10 and IMAGENET benchmarks. Synopsys Design Compiler synthesis results show that circuit designs for tanh and SELU can save between 3.13-7.69 and 4.45-8:45 area compared to the LUT/memory-based implementations, and can operate at 5.14GHz and 4.52GHz using the 28nm SVT library, respectively. The implementation is available at: https://github.com/ThomasMrY/ActivationFunctionDemo.Comment: 5 pages, 5 figures, 16 conferenc

Rogue peakon, well-posedness, ill-posedness and blow-up phenomenon for an integrable Camassa-Holm type equation

In this paper, we study an integrable Camassa-Holm (CH) type equation with quadratic nonlinearity. The CH type equation is shown integrable through a Lax pair, and particularly the equation is found to possess a new kind of peaked soliton (peakon) solution - called {\sf rogue peakon}, that is given in a rational form with some logarithmic function, but not a regular traveling wave. We also provide multi-rogue peakon solutions. Furthermore, we discuss the local well-posedness of the solution in the Besov space $B_{p,r}^{s}$ with $1\leq p,r\leq\infty$, $s>\max \left\{1+1/p,3/2\right\}$ or $B_{2,1}^{3/2}$, and then prove the ill-posedness of the solution in $B_{2,\infty}^{3/2}$. Moreover, we establish the global existence and blow-up phenomenon of the solution, which is, if $m_0(x)=u_0-u_{0xx}\geq(\not\equiv) 0$, then the corresponding solution exists globally, meanwhile, if $m_0(x)\leq(\not\equiv) 0$, then the corresponding solution blows up in a finite time.Comment: 23 pages, 6 figure

Weak Collocation Regression for Inferring Stochastic Dynamics with L\'{e}vy Noise

With the rapid increase of observational, experimental and simulated data for stochastic systems, tremendous efforts have been devoted to identifying governing laws underlying the evolution of these systems. Despite the broad applications of non-Gaussian fluctuations in numerous physical phenomena, the data-driven approaches to extracting stochastic dynamics with L\'{e}vy noise are relatively few. In this work, we propose a Weak Collocation Regression (WCR) to explicitly reveal unknown stochastic dynamical systems, i.e., the Stochastic Differential Equation (SDE) with both $\alpha$-stable L\'{e}vy noise and Gaussian noise, from discrete aggregate data. This method utilizes the evolution equation of the probability distribution function, i.e., the Fokker-Planck (FP) equation. With the weak form of the FP equation, the WCR constructs a linear system of unknown parameters where all integrals are evaluated by Monte Carlo method with the observations. Then, the unknown parameters are obtained by a sparse linear regression. For a SDE with L\'{e}vy noise, the corresponding FP equation is a partial integro-differential equation (PIDE), which contains nonlocal terms, and is difficult to deal with. The weak form can avoid complicated multiple integrals. Our approach can simultaneously distinguish mixed noise types, even in multi-dimensional problems. Numerical experiments demonstrate that our method is accurate and computationally efficient.Comment: 19 pages, 5 figures, 10 table

PAH exposure is associated with enhanced risk for pediatric dyslipidemia through serum SOD reduction

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) is linked to abnormal lipid metabolism, but evidence regarding PAHs as risk factors for dyslipidemia is lacking. Objective: To investigate the respective role and interaction of PAH exposure and antioxidant consumption in the risk for pediatric dyslipidemia. Methods: We measured the concentrations of serum lipids, superoxide dismutase (SOD) and urinary hydroxylated PAHs (OH-PAHs) in 403 children, of which 203 were from an e-waste-exposed area (Guiyu) and 200 were from a reference area (Haojiang). Biological interactions were calculated by additive models. Results: Guiyu children had higher serum triglyceride concentration and dyslipidemia incidence, and lower serum concentration of high-density lipoprotein (HDL) than Haojiang children. Elevated OH-PAH concentration, and concomitant SOD reduction, were both associated with lower HDL concentration and higher hypo-HDL risk (S3OH-Phes: B for lgHDL = 0.048, P <0.01; OR for hypo-HDL = 3.708, 95% CI: 1.200, 11.453; SOD: BT3 for lgHDL = 0.061, P <0.01; ORT3 for hypo-HDL = 0.168, 95% CI: 0.030, 0.941; all were adjusted for confounders). Biological interaction between phenanthrol exposure and SOD reduction was linked to dyslipidemia risk (RERI = 2.783, AP = 0.498, S = 2.537). Children with both risk factors (higher S3OH-Phes and lower SOD) had 5.594times (95% CI: 1.119, 27.958) the dyslipidemia risk than children with neither risk factors (lower S3OH-Phes and higher SOD). Conclusion: High PAH exposure combined with SOD reduction is recommended for predicting elevated risk for pediatric dyslipidemia. Risk assessment of PAH-related dyslipidemia should take antioxidant concentration into consideration

PM2.5-bound PAHs exposure linked with low plasma insulin-like growth factor 1 levels and reduced child height

Background: Exposure to atmospheric fine particle matter (PM2.5) pollution and the absorbed pollutants is known to contribute to numerous adverse health effects in children including to growth. Objective: The aim of this study was to evaluate exposure levels of atmospheric PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) in an electronic waste (e-waste) polluted town, Guiyu, and to investigate the associations between PM2.5-PAH exposure, insulin-like growth factor 1 (IGF-1) levels and child growth. Methods: This study recruited 238 preschool children (3–6 years of age), from November to December 2017, of which 125 were from Guiyu (an e-waste area) and 113 were from Haojiang (a reference area). Levels of daily PM2.5 and PM2.5-bound ∑16 PAHs were assessed to calculate individual chronic daily intakes (CDIs). IGF-1 and IGF-binding protein 3 (IGFBP-3) concentrations in child plasma were also measured. The associations and further mediation effects between exposure to PM2.5 and PM2.5-bound PAHs, child plasma IGF-1 concentration, and child height were explored by multiple linear regression models and mediation effect analysis. Results: Elevated atmospheric PM2.5-bound ∑16 PAHs and PM2.5 levels were observed in Guiyu, and this led to more individual CDIs of the exposed children than the reference (all P < 0.001). The median level of plasma IGF-1 in the exposed group was lower than in the reference group (91.42 ng/mL vs. 103.59 ng/mL, P < 0.01). IGF-1 levels were negatively correlated with CDIs of PM2.5, but not with CDIs of PM2.5-bound ∑16 PAHs after adjustment. An increase of 1 μg/kg of PM2.5 intake per day was associated with a 0.012 cm reduction of child height (95% CI: −0.014, −0.009), and similarly, an elevation of 1 ng/kg of PM2.5-bound ∑16 PAHs intake per day was associated with a 0.022 cm decrease of child height (95% CI: −0.029, −0.015), both after adjustment of several potential confounders (age, gender, family cooking oil, picky eater, eating sweet food, eating fruits or vegetables, parental education level and monthly household income). The decreased plasma IGF-1 concentration mediated 15.8% of the whole effect associated with PM2.5 exposure and 23.9% of the whole effect associated with PM2.5-bound ∑16 PAHs exposure on child height. Conclusion: Exposure to atmospheric PM2.5-bound ∑16 PAHs and PM2.5 is negatively associated with child height, and is linked to reduced IGF-1 levels in plasma. This may suggest a causative negative role of atmospheric PM2.5-bound exposures in child growth

A Targeted Lipidomic Reveals CYP450-Derived Oxylipin Linked to the Inflammatory Response by Polycyclic Aromatic Hydrocarbon Exposure in Children

Polycyclic aromatic hydrocarbon (PAH) exposure is a cause of chronic inflammation. The effect of PAHs on bioactive lipid mediators involved in the inflammatory process remains largely unknown. This study measured ten urinary monohydroxy-PAHs (OH-PAHs), 54 plasma oxylipins, and inflammation-related markers. Children with high PAH exposure had higher levels of ten OH-PAHs, (±)18-HETE, 19(S)-HETE, 5,6-DiHETrE, 9,10-DiHOME, more monocytes, interleukin (IL)-10, tumor necrosis factor (TNF)-α and IL-6 than those with low PAH exposure (all p &lt; 0.05). The ƩOH-PAHs were inversely correlated to the levels of anti-inflammatory oxylipins, including 5,6-EET (p for trend = 0.007), 11,12-EET (p for trend = 0.035), 14,15-EET (p for trend = 0.022), and 16(17)-EpDPE (p for trend = 0.043), but positively associated with pro-inflammatory 9,10-DiHOME (p for trend &lt; 0.001). Mediation analyses indicated that cytochrome P450 (CYP)-derived 9,10-DiHOME mediated a separate 42.7%, 31.1%, 57.8%, and 38.5% of the associations between OH-PAHs and monocytes, IL-6, IL-10, TNF-α (p = 0.017, 0.014, 0.005 and 0.012, respectively). Our study suggests that CYP-derived oxylipins can be considered sensitive lipid mediators to signal the early inflammation response to PAH exposure.</p

Synthesis and Application of Copper Nanowires and Silver Nanosheet-Coated Copper Nanowires as Nanofillers in Several Polymers

A large amount of copper (Cu) nanowires was synthesized through the reduction of Cu(OH)2 by hydrazine in an aqueous solution containing NaOH and ethylenediamine. Besides, Cu nanowires coated by silver nanosheet (denoted as Cu@Ag nanowires) were prepared with a facile transmetalation reaction method. In the meantime, the as‐prepared Cu and Cu@Ag nanowires were used as the nanofillers of polyvinyl chloride (PVC), ultra‐high molecular weight polyethylene (UHMWPE) and epoxy resin (EP), and their effects on the thermal properties and mechanical properties as well as friction and wear behavior of the polymer‐matrix composites nanocomposites were examined. Results indicate that the as‐prepared Cu@Ag nanowires consist of Cu nanowires core and Ag nanosheet shell. The Ag nanosheet shell can well inhibit the oxidation of the Cu nanowires core, thereby providing the as‐prepared Cu@Ag nanowires with good thermal stability even at an elevated temperature of 230°C. As compared with Cu nanowires, Cu@Ag nanowires could effectively increase the thermal stability of the PVC matrix composites. Moreover, due to the special morphology and microstructure, the as‐prepared Cu@Ag nanowires can effectively improve the mechanical properties and wear resistance of PVC, UHMWPE, and EP

Secure Batch Deduplication Without Dual Servers in Backup System

Cloud storage provides highly available and low cost resources to users. However, as massive amounts of outsourced data grow rapidly, an effective data deduplication scheme is necessary. This is a hot and challenging field, in which there are quite a few researches. However, most of previous works require dual-server fashion to be against brute-force attacks and do not support batch checking. It is not practicable for the massive data stored in the cloud. In this paper, we present a secure batch deduplication scheme for backup system. Besides, our scheme resists the brute-force attacks without the aid of other servers. The core idea of the batch deduplication is to separate users into different groups by using short hashes. Within each group, we leverage group key agreement and symmetric encryption to achieve secure batch checking and semantically secure storage. We also extensively evaluate its performance and overhead based on different datasets. We show that our scheme saves the data storage by up to 89.84%. These results show that our scheme is efficient and scalable for cloud backup system and can also ensure data confidentiality