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• Exposure to PFOS and EtFOSAA affects urea cycle metabolism in maternal serum of pregnant women. • PFOS and EtFOSAA exhibit different association with key amino acid metabolites. • PFOS, but not EtFOSAA, activates energy metabolism pathways. High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk. [ABSTRACT FROM AUTHOR]

• Hierarchical community network to integrate exposome and metabolome. • Fatty acid and mitochondria related pathways are among associations with DDTs and PFASs. • Breast cancer risk in offspring positively associated with PCB compounds, negatively with PFASs. • Small number of metabolic phenotypes may account for large number of exposures. Even though the majority of population studies in environmental health focus on a single factor, environmental exposure in the real world is a mixture of many chemicals. The concept of "exposome" leads to an intellectual framework of measuring many exposures in humans, and the emerging metabolomics technology offers a means to read out both the biological activity and environmental impact in the same dataset. How to integrate exposome and metabolome in data analysis is still challenging. Here, we employ a hierarchical community network to investigate the global associations between the metabolome and mixed exposures including DDTs, PFASs and PCBs, in a women cohort with sera collected in California in the 1960s. Strikingly, this analysis revealed that the metabolite communities associated with the exposures were non-specific and shared among exposures. This suggests that a small number of metabolic phenotypes may account for the response to a large class of environmental chemicals. [ABSTRACT FROM AUTHOR]

• Maternal exposure to DDT and DDE is associated with changes in metabolome. • Differential metabolic pathways were linked to serum p , p '-DDT and p , p '-DDE levels. • Consistent changes in amino acid metabolism was found in DDT-treated mice. The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p , p '-DDT, o , p '-DDT and p , p '-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p , p '-DDT and p , p '-DDE. Amino acids such arginine had a strong association with p , p '-DDT and o , p '-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p , p '-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine and fatty acid metabolism on the causal disease pathway should be examined. [ABSTRACT FROM AUTHOR]

• Exposure to PFOS and EtFOSAA affects urea cycle metabolism in maternal serum of pregnant women. • PFOS and EtFOSAA exhibit different association with key amino acid metabolites. • PFOS, but not EtFOSAA, activates energy metabolism pathways. High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk. [ABSTRACT FROM AUTHOR]

Abstract Large diameter monopiles are typical foundation solutions for offshore wind turbines. In design of the monopile foundations in sand, it is necessary to understand the drainage conditions of the foundation soil under the design loading conditions as the soil performance (strength and stiffness) is highly dependent on the drainage conditions. This paper presents a numerical investigation into this issue, with a purpose to develop a simple design criterion for assessing the soil drainage conditions around a monopile in sand. It is found that for typical monopile foundations in sand, the drainage condition during a single load cycle is generally expected to be undrained. However, the current state-of-practice uses p-y springs derived for drained soil responses for monopile design. The impact of this discrepancy on monopile foundation design was evaluated and found to be insignificant due to the relatively low level of loading as compared to the capacity of the soil. [ABSTRACT FROM AUTHOR]

Abstract The paper presents a constitutive model to describe undrained cyclic stress-strain responses of soft clays based on the equivalent visco-elastic and creep theories. The hysteretic and nonlinear stress-strain responses of soft clays are described using the equivalent visco-elastic relationship and variations of the cyclic modulus and the damping ratio with the octahedral shear strain, respectively in the model. The cyclic accumulative strain is described using the Mises creeping potential function and the associated flow rule. The method determining the model parameters is given by static and cyclic triaxial tests. The finite element method to analyze deformation of anchor foundation in soft clay under static and cyclic loads is developed based on the model. For the method, a cyclic loading time history is divided into a series of incremental loading sub-processes which include one load cycle at least. The cyclic stress-strain responses of soil elements at any time are not tracked in detail and determined by the equivalent visco-elastic calculations for every loading sub-process. The accumulative deformation of anchor foundations is calculated using the initial strain algorithm. The method has been implemented in ABAQUS Software by developing interface programs. Model tests of the suction anchors are conducted and predicted using the method. Comparisons of predicted and model test results show that the method can be used to evaluate cyclic stability and reveal the failure process and mechanism of anchor foundations by analyzing deformation time-histories. [ABSTRACT FROM AUTHOR]

Canola meal (CM), a by-product of canola oil extraction, was modified by poly (styrene-co-glycidyl methacrylate) (PSG) and could potentially be used as a sustainable natural composite. Infrared analysis indicated that PSG could efficiently react with the proteins in CM and become covalently bonded. DSC results revealed that the modified CM composites showed new glass transition temperatures ( T g ) decreasing with the introduction of PSG, which were attributed to the disruption of intermolecular association. Torque curves and melt flow index tests showed the flow property of the modified CM composites increased due to interference by PSG of the hydrogen and disulfide bonding among the protein species. DMA results showed greater amorphous character for the modified CM composites and new glassy plateaus with increased storage moduli, indicating a change in molecular structure and enhancement in mechanical property and usability below T g . Furthermore, the thermostability, the tensile strength, and the elastic moduli of the modified CM composites increased because of the formation of cross-linked proteins in the CM composites, which will potentially increase the application value in some fields, such as single-use agricultural planting containers replacing high-impact polystyrene (HIPS) containers, and food or coffee trays. [ABSTRACT FROM AUTHOR]

To increase the usage value of canola meal (CM), a by-product of canola oil extraction, poly (styrene- co -maleic anhydride-co-glycidyl methacrylate) (PSMG) was prepared and used as a novel chain extender to modify CM. FTIR tests showed that cross-linking took place in the CM matrix and PSMG was covalent bonded with canola proteins; furthermore, the surface of fibers present in the CM composite was covered by proteins, attributed to the reactivity of anhydride groups on PSMG. The modified CM composites showed more apparent amorphous characteristic with the addition of PSMG, according to DSC results. DMA results suggested that cross-linked proteins could be further coupled by glycerol reacting with the anhydride groups remaining in the cross-linked proteins, and thus the storage moduli and the glass transition temperature ( T g ) of the modified CM composites increased with the addition of more PSMG. The reactions of proteins with proteins, proteins with fibers, and proteins with glycerol were further confirmed by TGA. SEM images showed that the CM matrix became much denser and the interfacial adhesion between fibers and the CM matrix was increased by the chemical modification, which also contributed to an increase in the tensile strength of the modified CM composites. [ABSTRACT FROM AUTHOR]

Background Plasmodium vivax is one of the leading causes of malaria worldwide. Infections with this parasite cause diverse clinical manifestations, and recent studies revealed that infections with P. vivax can result in severe and fatal disease. Despite these facts, biological traits of the host response and parasite metabolism during P. vivax malaria are still largely underexplored. Parasitemia is clearly related to progression and severity of malaria caused by P. falciparum , however the effects of parasitemia during infections with P. vivax are not well understood. Results We conducted an exploratory study using a high-resolution metabolomics platform that uncovered significant associations between parasitemia levels and plasma metabolites from 150 patients with P. vivax malaria. Most plasma metabolites were inversely associated with higher levels of parasitemia. Top predicted metabolites are implicated into pathways of heme and lipid metabolism, which include biliverdin, bilirubin, palmitoylcarnitine, stearoylcarnitine, phosphocholine, glycerophosphocholine, oleic acid and omega-carboxy-trinor-leukotriene B4. Conclusions The abundance of several plasma metabolites varies according to the levels of parasitemia in patients with P. vivax malaria. Moreover, our data suggest that the host response and/or parasite survival might be affected by metabolites involved in the degradation of heme and metabolism of several lipids. Importantly, these data highlight metabolic pathways that may serve as targets for the development of new antimalarial compounds. [ABSTRACT FROM AUTHOR]

Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D 3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D 3 (250,000 IU vitamin D 3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs. deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D 3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed ( P < 0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways—predominantly representing amino acid pathways—differed between the vitamin D 3 - and placebo-treated CF subjects over time ( P < 0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D 3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D 3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D 3 in this clinical setting. [ABSTRACT FROM AUTHOR]

Cross-linked canola protein isolate (CPI) films were prepared using a bisepoxide as a chain extender by wet cast followed by heat compression. By DSC measurements, it was verified that the cross-linking reaction took place in the CPI matrix and was completed in 10 min at 90 °C. FTIR analysis confirmed that the chain extenders were covalently bonded with CPI chains. The reaction led to the formation of a cross-linked architecture which was revealed by an increase in molecular weight of the modified CPI films. The newly formed chain architecture increased the thermostability of CPI as evaluated by TGA; furthermore, the thermostability increased with the increase in cross-linking degree of the modified CPI films. DMA results of the unmodified CPI film showed that microcosmic phase separation occurred between two major proteins, cruciferin and napin in CPI; however, the extent of phase separation decreased with the increase of chain extenders and finally disappeared because of the increased compatibility between cruciferin and napin. Elastomeric mechanical behavior was observed with the introduction of cross-linked architecture in the modified CPI films. At low humidity of 55%, the cross-linked CPI films showed an increase in tensile strength and a decrease in elongation at break. At high humidity of 98%, the increase in hydrophobicity of cross-linked CPI matrix resisted the decreasing tensile strength seen in unmodified films. [ABSTRACT FROM AUTHOR]

The bearing capacity of suction anchors subjected to inclined average and cyclic loads at the optimal loading point was researched using 35 model tests under 1 g condition. Results show that the cyclic bearing capacity of suction anchors depends on the average load and the number of load cycles to failure. The cyclic bearing capacity decreases with an increase of the number of load cycles to failure for a given average load. The cyclic bearing capacity decreased from 91% to 75% the static bearing capacity when the number of load cycles to failure increased from 100 to 1000 for the average load which was 0.5 times the static bearing capacity based on model test results. The cyclic bearing capacity increases with an increase of the average load for a given number of load cycles to failure when the average load varies from 0.5 to 0.7 times the static bearing capacity. The cyclic bearing capacity increased from 75% to 84% the static bearing capacity when the number of load cycles to failure was 1000 for vertical failure anchors based on model test results. The paper also presents a limiting equilibrium analysis method to calculate the cyclic bearing capacity of suction anchors using the cyclic shear strengths of soft clays determined by unconsolidated and undrained cyclic triaxial tests. Two procedures to determine the cyclic shear strength of the stratum around suction anchors were suggested for the method. For the first procedure, the normalized cyclic shear strength of each failure zone around anchors is determined based on the normalized average shear stress of the zone. The average shear stress of each failure zone is considered as constant and determined using static equilibrium conditions between the average load and resistances which are expressed by the average shear stress. For the second procedure, the normalized cyclic shear strength of the stratum is determined based on the normalized average shear stress of the stratum around anchors. The normalized average shear stress is determined based on the assumption which is that the ratio of the average shear stress and the cyclic shear strength is equal to the ratio of the average load and the sum of the average and cyclic loads. The relationship between the normalized cyclic shear strength of soft clays and the normalized average shear stress is determined by unconsolidated and undrained cyclic triaxial tests. The cyclic bearing capacity is determined using limiting equilibrium analyses. To check the validity of the calculation method, model test results were predicted using the method. Predicted results are generally less than model test results and most of relative errors between predicted and test results are less than 10%, which show that the method can be used to determine the cyclic bearing capacity of suction anchors in soft clays. [ABSTRACT FROM AUTHOR]

A water-soluble cationic diblock copolymer, CD-PAM-b-PMeDMA, was synthesized through atom transfer radical polymerization (ATRP) from a β-cyclodextrin (CD) macroinitiator with 10-active sites (10Br-β-CD). In order to reduce the cytotoxicity of the CD-PAM-b-PMeDMA, biocompatible polyacrylamide (PAM) was first introduced onto the surface of β-CD as a scaffold structure by ATRP using the 10Br-β-CD as a macroinitiator. The reaction conditions of AM were explored and optimized. The ATRP of [2-(methacryloyloxy)ethyl] trimethyl ammonium chloride (MeDMA) was also performed to synthesize the second cationic block using the resulting CD-PAM as a macroinitiator. The resulting diblock copolymer shows an increased hydrodynamic radius in aqueous solution with a pretty low concentration compared with β-CD. In addition, it appears a near-uniform coniform after being deposited on mica ascribed to the presence of an asymmetric 10-arm structure. [ABSTRACT FROM AUTHOR]

Highlights: [•] A permanently anti-microbe PP was prepared by a chemical bonding method. [•] The resulting PP showed enhanced killing activities against bacterium and fungi. [•] The antimicrobial PP kept antimicrobial activities after 10days water washing. [•] Guanidine-based antimicrobial polymers were dispersed in PP in a nanometer scale. [•] PP fabrics showed safe results in vivo and in vitro due to the chemical bonding. [Copyright &y& Elsevier]

Abstract: A novel strategy for introducing long chain branches (LCB) on commercial polypropylene (PP) was described using an extender agent, poly (hexamethylendiamine-guanidine hydrochloride) (PHGH), to couple with glycidyl methacrylate-grafted PP (PP-GMA). The presence of LCB was confirmed by GPC and melt strength measurements in two modified PP samples, MPP-1 and MPP-2. The foamability of LCB PPs and commercially linear PP (EPS) was investigated by foam extrudate. The results showed that the foamability of LCB PPs was significantly improved. To find out the difference in foamability of EPS and LCB PPs, some rheological properties were investigated. In the dynamic shear measurement, it was found that the elastic response of LCB PPs at low frequencies was distinctly enhanced in comparison with that of EPS, implying a presence of a long relaxation time mode that was not revealed in linear PP. The elongational rheology results showed that the strain hardening behaviors of LCB PPs were still intense even at higher strain rate of 1s−1; moreover, MPP-2 could sustain larger elongational stress and deformation, which helps to improve the foamability. In step-shear stress relaxation measurements, the fast and slow relaxation processes were observed over the entire ranges of strains, indicating the presence of two different relaxation time modes. Also, the strain dependence of slow damping function became weaker because of the introduction of LCB on linear PP. In addition, it was also found that the rheological behaviors characterizing the long relaxation time mode were further enhanced with the increase of the concentration of PHGH in the melt grafting reactions. [Copyright &y& Elsevier]

Abstract: Surface-initiated atom transfer radical polymerization (SI-ATRP) of butyl acrylate (BA) on cellulose microfibrils (CMF) was conducted to create controllable hydrophobic chains on CMF. The macroinitiator, CMF-Br, was prepared by the esterification of hydroxyl groups on CMF with 2-bromoisobutyrylbromide (BIBB); followed by the ATRP of BA using two catalyst systems, CuIBr/2,2′-bipyridine (BPY) and CuIBr/pentamethyl-diethylenetriamine (PMDETA). The molecular weight (MW) and polydispersity of the grafted PBA cleaved from CMF via hydrolysis was determined using GPC. The results indicated that the PMDETA system exhibited relatively poor control over the ATRP; whereas the BPY system produced the PBA with tailored chain lengths and relatively narrow polydispersities but experienced a rather slow polymerization process. To optimize the polymerization with the CuBr/PMDETA system, several influencing factors were investigated, including the type of solvents, reaction temperature and the use of co-catalyst CuIIBr2. The hydrophobic-modified CMF is of great potential as reinforcements biocomposites. [ABSTRACT FROM AUTHOR]

Abstract: To study the rheological properties of long chain branching (LCB) polypropylene (PP), long chain branches (LCB) were grafted onto the linear PP by melt grafting reaction in the presence of a novel chain extender, poly(hexamethylendiamine-guanidine hydrochloride) (PHGH). The branching reactions between the functionalized PP and PHGH were confirmed by transient torque curves and FTIR. By differential scanning calorimetry (DSC) and polarized microscope measurements, the presence of long chain branching structures was further confirmed. Also, the viscoelastic properties of the LCB PP and linear PP under shear flow were investigated for distinguishing LCB PP from linear PP. It was found that the elastic response of LCB PP at low frequencies was significantly enhanced in comparison with that of the linear PP, implying a presence of a long relaxation time mode that was not revealed in linear PP. Moreover, the branching levels of LCB PP were quantified using a detailed method, which was in correspondence with the molar amount of PHGH grafted on PP. [Copyright &y& Elsevier]

• A novel deep architecture to integrate attribute learning into person re-identification task in a different way to solve the part misalignment problem. • The proposed algorithm introduces the perceptual ability of attribute learning process which can be utilized as a part localizer to detect semantic human body parts and discriminative objects. • The learned and fused attribute information is further incorporated into part feature learning to refine the extracted local descriptors. • Extensive experiments and empirical analysis are provided to demonstrate the effectiveness of the proposed method. Person attributes are often exploited as mid-level human semantic information to help promote the performance of person re-identification task. In this paper, unlike most existing methods simply taking the attribute learning as a classification problem, we perform it in a different way with the motivation that attributes are related to specific local regions, which refers to the perceptual ability of attributes. We utilize the process of attribute detection to generate corresponding attribute-part detectors, whose invariance to many influences like poses and camera views can be guaranteed. With detected local part regions, our model extracts local part features to handle the body part misalignment problem, which is another major challenge for person re-identification. The local descriptors are further refined by fused attribute information to eliminate interferences caused by detection deviation. Finally, the refined local feature works together with a holistic-level feature to constitute our final feature representation. Extensive experiments on two popular benchmarks with attribute annotations demonstrate the effectiveness of our model and competitive performance compared with state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Objective: To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents.Study Design: This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD.Results: The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected.Conclusions: Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD. [ABSTRACT FROM AUTHOR]

In this paper, the influence of the structural parameters of subsea protective devices with asymmetric openings is studied through intelligent damage assessments. Moreover, three back propagation (BP) neural networks, the Levenberg‒Marquardt (LM) algorithm, Bayesian regularization (BR) algorithm and scaled conjugate gradient (SCG) algorithm, are selected to evaluate the damage to subsea protective facilities. Finite element models of subsea protective facilities without openings, square subsea protective facilities with openings and circular subsea protective facilities with openings are established, and finite element analysis is carried out to establish the database training algorithm. The accuracy of the database is ensured through testing to verify the finite element method. The influence of the opening, opening shape and structural damage on the damage assessment is analysed to find the most suitable intelligent damage assessment algorithm for subsea protective facilities with asymmetric openings. The results show that the opening will increase the error of damage identification, and the square opening will increase the maximum error. Meanwhile, structural damage will increase the damage evaluation error of subsea protective facilities with asymmetric openings but will reduce the damage stress evaluation error of subsea protective facilities without openings. In addition, the identification error of the BR neural network algorithm for each working condition, which is suitable for intelligent damage identification of subsea protective facilities, is very low. • The damage assessments of subsea protective facilities with asymmetric openings were investigated. • Three BP neural network algorithms, BR, LM and SCG, are selected to evaluate the damage of subsea protective facilities. • The BR algorithm is suitable for intelligent damage identification of subsea protective facilities. [ABSTRACT FROM AUTHOR]

Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m / z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2–10 ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers. [ABSTRACT FROM AUTHOR]