Hongyan Wang

Shanghai Jiao Tong University, Shanghai, Shanghai Shi, China

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Publications (34)144.43 Total impact

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    ABSTRACT: Fluorine atoms were introduced into the molecular chain of a phenolic resin (PR) by a two-step acid synthesis process to improve its thermal and hydrophobic properties. The successful synthesis of a fluorinated phenolic resin/phenolic resin blend (F-PR/PR) was proven by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance 19F (19F-NMR). The thermal properties of F-PR/PR were analyzed by differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) and the results indicate that the F-PR/PR had good thermal stability. The hydrophobic properties of PR were effectively modified as demonstrated by the water drop contact angles. The flexural and tribological properties of F-PR/PR were also investigated. The fluorine atom, by virtue of its electronegativity, size and bond strength with carbon, can be used to create composites from F-PR/PR with remarkable properties. For comparison, two other resin blends were also synthesized.
    No preview · Article · Dec 2015 · Journal of Macromolecular Science Part B
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    ABSTRACT: Background: Ventricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs. Methods: We analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis. Results: Among 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD. Among these 15 genes, 7 genes were in "abnormal interventricular septum morphology" derived from the MGI (mouse genome informatics) database, and nine genes were associated with cardiovascular system development (GO:0072538). We also found that these VSD-related candidate genes are enriched in chromatin binding and transcription regulation, which are the biological processes underlying heart development. Conclusions: Our study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in VSD patients. Additionally, gene enrichment and pathway analysis helped us to implicate VSD related candidate genes.
    Preview · Article · Dec 2015 · BMC Medical Genomics
  • XiaoHong Gong · HongYan Wang
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    ABSTRACT: Autism spectrum disorders (ASD) are highly heterogeneous pediatric developmental disorders with estimated heritability more than 70%. Although the genetic factors in ASD are mainly unknown, a large number of gene mutations have been found, especially in genes involved in neurogenesis. The Neurexin-Neuroligin-Shank (NRXN-NLGN-SHANK) pathway plays a key role in the formation, maturation and maintenance of synapses, consistent with the hypothesis of neurodevelopmental abnormality in ASD. Presynaptic NRXNs interact with postsynaptic NLGNs in excitatory glutamatergic synapses. SHANK proteins function as core components of the postsynaptic density (PSD) by interacting with multiple proteins. Recently, deletions and point mutations of the SHANK1 gene have been detected in ASD individuals, indicating the involvement of SHANK1 in ASD. This review focuses on the function of SHANK1 protein, Shank1 mouse models, and the molecular genetics of the SHANK1 gene in human ASD.
    No preview · Article · Sep 2015 · Science China. Life sciences
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    ABSTRACT: WNT5A is one of the most highly investigated non-canonical Wnt ligands and is involved in the embryonic heart development, especially in formation of the cardiac conotruncal region by regulating the migration and differentiation of cardiac neural crest (CNC) and second heart field (SHF) cells. No study to date has comprehensively characterized the WNT5A regulatory variants in patients with congenital heart malformations (CHMs). The association between regulatory variants of the WNT5A gene and CHMs was examined in case-control association study in 1,210 CHMs and 798 controls. Individuals carrying a homozygous genotype CC (rs524153) or GG (rs504849) had a similarly reduced risk of conotruncal malformations. The homozygous genotypes (CC for rs524153 and GG for rs504849) were associated with a lower WNT5A transcriptional level compared with the transcriptional level of those with wild-type genotypes. Further functional analysis revealed that an additional upstream single nucleotide polymorphisms (SNP) rs371954924 (-5244GCCA > CC) in a linkage disequilibrium (LD) block with the above genotyped SNPs decreased WNT5A expression through the attenuated binding affinity with the transcription factor SOX9. This is the first demonstration that genetic variants in the regulatory regions of WNT5A play a vital role in sporadic conotruncal malformations susceptibility through the changeable expression of the WNT5A gene.
    Full-text · Article · Aug 2015 · Scientific Reports
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    ABSTRACT: Despite repeated exposures to HIV-1, some individuals remain uninfected, suggesting that genetic factors confer host resistance to HIV-1 acquisition. The chemokine receptors CCR5, CXCR4 and the principal ligand SDF1 of CXCR4 play an important role for the entry of HIV-1 to target cells. To explore the relationship between genetic variants and HIV-1 infection, 11 common SNPs in CCR5, CXCR4 and SDF1 were genotyped in 921 male intravenous drug users (IDUs), of which 263 individuals were HIV-1-exposed seropositive (HESP) and 658 were HIV-1-exposed seronegative (HESN). According to the situation of syringe-sharing, the whole cohort was divided into two subgroups: syringe-sharing (SS) and syringe-not-sharing (SNS). We found that in the SNS subgroup rs17540465 of SDF1 showed significant difference of allele and genotype frequencies between HESP IDUs and HESN IDUs, but not in the SS subgroup. HESP with SNS carried significantly less allele A compared with HESN with SNS, indicating a protective role of allele A against HIV-1 infection. Syringe-sharing IDUs are supposed to be exposed highly to HIV-1 infection risk due to the direct transfer of HIV-1 infected blood to another. For syringe-not-sharing IDUs, sexual contact may be the major route of HIV-1 transmission. Considering the different route of HIV-1 transfection between two subgroups, we speculate that SDF1 may contribute susceptibility to HIV-1 infection in the route of sexual intercourse. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: Background: Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. Methods: We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multicenter series of 42 persons with 16p11.2 deletions. Results: We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10(-6)). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10(-6)). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. Conclusions: Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. (Funded by the National Basic Research Program of China and others.).
    Full-text · Article · Jan 2015 · New England Journal of Medicine
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    Xin Zhang · Renqian Du · Shilin Li · Feng Zhang · Li Jin · Hongyan Wang
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    ABSTRACT: Copy Number Variations (CNVs) are usually inferred from Single Nucleotide Polymorphism (SNP) arrays by use of some software packages based on given algorithms. However, there is no clear understanding of the performance of these software packages; it is therefore difficult to select one or several software packages for CNV detection based on the SNP array platform.We selected four publicly available software packages designed for CNV calling from an Affymetrix SNP array, including Birdsuite, dChip, Genotyping Console (GTC) and PennCNV. The publicly available dataset generated by Array-based Comparative Genomic Hybridization (CGH), with a resolution of 24 million probes per sample, was considered to be the "gold standard". Compared with the CGH-based dataset, the success rate, average stability rate, sensitivity, consistence and reproducibility of these four software packages were assessed compared with the "gold standard". Specially, we also compared the efficiency of detecting CNVs simultaneously by two, three and all of the software packages with that by a single software package. Simply from the quantity of the detected CNVs, Birdsuite detected the most while GTC detected the least. We found that Birdsuite and dChip had obvious detecting bias. And GTC seemed to be inferior because of the least amount of CNVs it detected. Thereafter we investigated the detection consistency produced by one certain software package and the rest three software suits. We found that the consistency of dChip was the lowest while GTC was the highest. Compared with the CNVs detecting result of CGH, in the matching group, GTC called the most matching CNVs, PennCNV-Affy ranked second. In the non-overlapping group, GTC called the least CNVs. With regards to the reproducibility of CNV calling, larger CNVs were usually replicated better. PennCNV-Affy shows the best consistency while Birdsuite shows the poorest. We found that PennCNV outperformed the other three packages in the sensitivity and specificity of CNV calling. Obviously, each calling method had its own limitations and advantages for different data analysis. Therefore, the optimized calling methods might be identified using multiple algorithms to evaluate the concordance and discordance of SNP array-based CNV calling.
    Full-text · Article · Feb 2014 · BMC Bioinformatics

  • No preview · Article · Jan 2014
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    ABSTRACT: SMAD7 is a general antagonist of TGF-β signaling and has been found to be involved in cardiogenesis in mouse models, but its role in human congenital heart disease (CHD) has yet to be investigated. To examine if SMAD7 is associated with CHD, we conducted a case-control study in the Han Chinese population. Exon1 and exon4 of SMAD7, which encode the functional MH1 and MH2 domains, were directly sequenced in 1,201 sporadic CHD patients and 1,116 control individuals. A total of 18 sequence variations were identified. Two common variants rs3809922 and rs3809923 are located at exon4 of SMAD7, and were found in strong linkage disequilibrium with each other (r (2) = 0.93). We analyzed the association of these two loci with CHD in 3 independent subgroup case-control studies, and found that in some subgroups, rs3809922 and rs3809923 were significantly associated with CHD through genetic model analysis. In the combined data set, TT genotype in rs3809922 significantly increased the risk of CHD compared with CC and CT, while GG genotype in rs3809923 significantly increased the risk of CHD compared with CC and CG, particularly in the recessive model. In addition, haplotype analyses showed that haplotype TG significantly increased the risk of CHD (P = 6.9×10(-6)); this finding supports the results from the analyses based on single locus. According to data from the 1000 Genomes Project, the frequencies of the two risk alleles varied greatly between populations worldwide, which indicate the identified associations might have a population difference. To our knowledge, this is the first report that genetic variants in SMAD7 influence susceptibility to CHD risk.
    Full-text · Article · Sep 2013 · PLoS ONE
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    ABSTRACT: Crosslinked fluorinated polyimides (CFPI) were successfully synthesized to study and explore the effect of cross-linkage on the migration of fluorinated segments and on the adhesion strength. Characterization by dynamic thermomechanical analysis (DMA) and thermo gravimetric analysis (TGA) confirmed good thermal properties of CFPI. X-ray photoelectron spectroscopy (XPS) results showed that the ratio of fluorinated component (6FDA-ODA) concentration of the surface to the bulk decreased with the crosslink density. The water contact angle of CFPI was lower than that of non-crosslinked fluorinated polyimide, indicating that the migration of fluorinated groups to the surface was reduced by the presence of cross-linkage. Therefore, CFPI, with no fluorine segregation on the surface, exhibited excellent wetting of adherent surfaces and adhesion strength, which was proved by lap shear strength (LSS) measurements and scanning electron microscopy.
    No preview · Article · Jun 2013 · Journal of Macromolecular Science Part B
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    ABSTRACT: Congenital heart disease (CHD) is one of the most prevalent developmental anomalies and the leading cause of noninfectious morbidity and mortality in newborns. Despite its prevalence and clinical significance, the etiology of CHD remains largely unknown. GATA4 is a highly conserved transcription factor that regulates a variety of physiological processes and has been extensively studied, particularly on its role in heart development. With the combination of TBX5 and MEF2C, GATA4 can reprogram postnatal fibroblasts into functional cardiomyocytes directly. In the past decade, a variety of GATA4 mutations were identified and these findings originally came from familial CHD pedigree studies. Given that familial and sporadic CHD cases allegedly share a basic genetic basis, we explore the GATA4 mutations in different types of CHD. In this study, via direct sequencing of the GATA4 coding region and exon-intron boundaries in 384 sporadic Chinese CHD patients, we identified 12 heterozygous non-synonymous mutations, among which 8 mutations were only found in CHD patients when compared with 957 controls. Six of these non-synonymous mutations have not been previously reported. Subsequent functional analyses revealed that the transcriptional activity, subcellular localization and DNA binding affinity of some mutant GATA4 proteins were significantly altered. Our results expand the spectrum of GATA4 mutations linked to cardiac defects. Together with the newly reported mutations, approximately 110 non-synonymous mutations have currently been identified in GATA4. Our future analysis will explore why the evolutionarily conserved GATA4 appears to be hypermutable.
    Full-text · Article · Apr 2013 · PLoS ONE
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    ABSTRACT: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules , and scaffolding proteins and . Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes and in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5'/3' untranslated regions (UTR) and the entire coding region of in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in were identified in our cohort. Association analysis of 6 common SNPs in did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.
    Full-text · Article · Feb 2013 · PLoS ONE
  • Pei Liu · Renguo Lu · Hongyan Wang · Ting Huang · Tongsheng Li
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    ABSTRACT: A series of composites with Twaron fabric as reinforcement and PTFE as matrix were fabricated with various contents of PTFE, viz. 30, 40, 50, 60 and 70 vol%. The Rockwell hardness and tensile strength of the composites were tested according to the corresponding standards. The composites were also evaluated for their tribological behaviors on an MPX-2000A friction and wear tester. The worn surface and wear debris of the composites were observed by scanning electron microscopy (SEM) and the mechanism is discussed. The PTFE content in the composites had a great influence on both the mechanical and tribological properties. The composite with 40 vol% PTFE provided the proper wetting of the fibers and the best load transfer efficency and, hence, showed the best mechanical properties and tribological behaviors.
    No preview · Article · Sep 2012 · Journal of Macromolecular Science Part B
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    ABSTRACT: AbstractA novel curing agent, poly (amide‐amidic acid) (PAA), was used to cure tetraglycidyl 4,4′‐diaminodiphenylmethane (TGDDM). The initial cure and exothermic peak temperatures increased with increase in PAA content. The mechanism for the cure of TGDDM/PAA was proposed which involved, besides TGDDM cure, PAA imidization in the system. Examination of the morphology of the fractured surface using scanning electron microscopy showed that curing with PAA improved more the fracture toughness as compared to the conventional 4,4′‐diaminodiphenylsulfone (DDS), and rendered TGDDM more fire resistant with higher char yield. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
    No preview · Article · Aug 2012 · Journal of Applied Polymer Science
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    ABSTRACT: The chemokine receptors and ligand CCR5, CXCR4 and SDF-1 play important roles in the entry of HIV-1 into host cells. Genetic polymorphisms such as CCR5-Δ32 and SDF-1 3'A have been reported to be associated with HIV-1 susceptibility and the progression of AIDS. Considering the remarkable difference in CCR5-Δ32 allele frequency among worldwide populations, we aimed to survey the genetic variations in CCR5, CXCR4 and SDF-1 in different Chinese populations. The open reading frames and regulatory regions of CCR5, CXCR4 and SDF-1 were sequenced in 141 Chinese individuals from three ethnic groups: Han, Mongol and Uyghur. Ninety-six variants were identified, 41 of which were newly identified (NI) in Chinese populations. A novel non-synonymous variant c.459 C>T (Trp153Cys) within CCR5 was identified in one Han individual. Of NI variants, 11 were common polymorphisms with a minor allele frequency (MAF) >5%. The polymorphism CCR5-Δ32 was found in three Uyghur individuals but was absent in Han and Mongol groups. The linkage disequilibrium (LD) analysis of CCR5 and SDF-1 and frequency of CCR5 haplotypes showed considerable divergence among three ethnic groups. Our results show the great genetic heterogeneity within CCR5, CXCR4 and SDF-1 in Chinese ethnic populations.
    Full-text · Article · Jul 2012 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
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    ABSTRACT: Reinforced phenolic resin (PF) was prepared by in situ polymerization of different fractions of carbon nanotubes (CNTs) that had undergone oxidation. The compressive strength and hardness of the material, according to mechanical property testing, was improved by the modified CNTs. The tribological properties of PF composites were investigated by a block-on-ring friction and wear tester. The results indicated that CNTs reinforced PF showed lower friction coefficient and higher wear resistance, compared with pure PF. The morphologies of the worn surfaces, debris, and transfer films were observed by scanning electron microscopy (SEM) and optical microscopy (OM). A continuous and thinner transfer film formed during the friction test of the composites led to the significant improvement of the tribological properties.
    No preview · Article · Jun 2012 · Journal of Macromolecular Science Part B
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    ABSTRACT: Intellectual disability (ID) is a heterogeneous disorder caused by chromosomal abnormalities, monogenic factors and environmental factors. 22q13 deletion syndrome is a genetic disorder characterized by severe ID. Although the frequency of 22q13 deletions in ID is unclear, it is believed to be largely underestimated. To address this issue, we used Affymetrix Human SNP 6.0 array to detect the 22q13 deletions in 234 Chinese unexplained ID patients and 103 controls. After the Quality Control (QC) test of raw data, 22q13 deletions were found in four out of 230 cases (1.7%), while absent in parents of the cases and 101 controls. A review of genome-wide microarray studies in ID was performed and the frequency of 22q13 deletions from the literatures was 0.24%, much lower than our report. The overlapping region shared by all 4 cases encompasses the gene SHANK3. A heterozygous de novo nonsense mutation Y1015X of SHANK3 was identified in one ID patient. Cortical neurons were prepared from embryonic mice and were transfected with a control plasmid, shank3 wild-type (WT) or mutant plasmids. Overexpression of the Y1015 mutant in neurons significantly affected neurite outgrowth compared with shank3 WT. These findings suggest that 22q13 deletions may be a more frequent cause for Chinese ID patients than previously thought, and the SHANK3 gene is involved in the neurite development.
    Full-text · Article · Apr 2012 · PLoS ONE
  • Pei Liu · Renguo Lu · Ting Huang · Hongyan Wang · Tongsheng Li
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    ABSTRACT: Carbon fabric reinforced polytetrafluoroethylene (PTFE) composites with different PTFE content, viz. 30, 40, 50, 60, and 70 vol%, were fabricated by a dispersion impregnation technique followed by a hot-press process. The composites were evaluated for their mechanical and tribological properties. The tribological tests were conducted on a friction and wear tester with a ring-on-block arrangement. The mechanical properties were also tested and their relationship with tribological properties was analyzed. The worn surface and wear debris were analyzed by a scanning electron microscope (SEM) to study the wear mechanism. It was found that the resin content had a great influence on both the mechanical properties and the tribological properties, and the tribological properties were correlated with the mechanical properties. The composite with 50 vol% PTFE showed promising tribological behaviors under the selected test conditions.
    No preview · Article · Apr 2012 · Journal of Macromolecular Science Part B
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    ABSTRACT: Soluble guanylate cyclase (sGC) mediates NO signaling for a wide range of physiological effects in the cardiovascular system and the central nervous system. The α1β1 isoform is ubiquitously distributed in cytosolic fractions of tissues, whereas α2β1 is mainly found in the brain. The major occurrence and the unique characteristic of human sGC α2β1 indicate a special role in the mediation of neuronal communication. We have efficiently purified and characterized the recombinant heme-binding domain of the human sGC α2 subunit (hsGC α2H) and heterodimeric α2β1 (hsGC β1H–α2H) by UV–vis spectroscopy, circular dichrosim spectroscopy, EPR spectroscopy, and homology modeling. The heme dissociation and related NO/CO binding/dissociation of both hsGC α2H and hsGC β1H–α2H were investigated. The two truncated proteins interact with heme noncovalently. The CO binding affinity of hsGC α2H is threefold greater than that of human sGC α1H, whereas the dissociation constant k 1 for dissociation of NO from hsGC α2H is sevenfold larger than that for dissociation of NO from hsGC α1H, although k 2 is almost identical. The results indicate that in comparison with the α1β1 isoform, the brain α2β1 isoform exhibits a distinctly different CO/NO affinity and binding rate in favor of NO signaling, and this is consistent with its physiological role in the activation and desensitization. Molecular modeling and sequence alignments are consistent with the hypothesis that His105 contributes to the different CO/NO binding properties of different isoforms. This valuable information is helpful to understand the molecular mechanism by which human sGC α2β1 mediates NO/CO signaling.
    No preview · Article · Mar 2012 · European Journal of Biochemistry
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    ABSTRACT: In this work, poly(amide‐amidic acid) (PAA) was used to modify tetraglycidyl 4,4′‐diaminodiphenylmethane (TGDDM)/4,4′‐diaminodiphenylsulfone (DDS) system. Results of non‐isothermal differential scanning calorimetry analysis indicated that PAA played a role of catalyst during the process of the curing reaction. The curing mechanism was studied by Fourier transform infrared spectroscopy, showing that the PAA acted as a co‐curing agent in the system. The glass transition temperature decreased firstly and then increased with the increase of the PAA content. PAA equally rendered TGDDM more fire resistant with higher char yield. On examining the fracture surface morphology using scanning electron microscopy, it was observed that there was no obvious phase separation when the content of PAA was less than 20 phr (per hundred weight of TGDDM/DDS resin), however, phase separation was observed when the content of PAA was 25 and 30 phr. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
    No preview · Article · Jan 2012 · Journal of Applied Polymer Science

Publication Stats

391 Citations
144.43 Total Impact Points

Institutions

  • 2015
    • Shanghai Jiao Tong University
      Shanghai, Shanghai Shi, China
  • 2009-2015
    • Fudan University
      • • Key Laboratory for Contemporary Anthropology
      • • School of Life Sciences
      • • Institutes of Biomedical Sciences
      Shanghai, Shanghai Shi, China