Analysis of the variations in IL-28RA gene and their association with allergic rhinitis

IL-28RA is one of the important candidate genes for complex trait of genetic diseases, but there is no published information of the genetic variation in this gene. We scanned the seven exons and their boundary introns sequence of IL-28RA including the promoter regions to analyze genetic variation sites, and identified eighteen single nucleotide polymorphisms (SNPs) and two variation sites. We chose seven SNPs (g.-1193 A>C, g.-30 C>T, g.17654 C>T, g.27798 A>G, g.31265 C>T, g.31911 C>T and g.32349 G>A) of them for large sample size genotyping, and assessed the association of genotype and allele frequencies of these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. We also compared the genotype frequencies between Korean controls and Han Chinese control or Korean Chinese control. We investigated the frequencies of haplotype constructed by these SNPs between allergic rhinitis patients and non-allergic rhinitis controls. Our results suggested that the g.32349 G>A polymorphism of IL-28RA might be associated with susceptibility to allergic rhinitis (P=0.032), but seems to have no relationship with serum total IgE levels. The haplotype frequencies by these SNPs also show significant association between controls and allergic rhinitis patients.     

Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.     

Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection

Transforming growth factor-beta1 (TGF-beta1) can act as both a tumor suppressor and a stimulator of tumor progression. We have examined the relationship between polymorphisms of the TGF-beta1 gene and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. A total of 1,237 Korean subjects were prospectively enrolled; 1,046 patients with chronic HBV infection and 191 healthy controls with no evidence of recent or remote HBV infection. The patients were divided into two groups: those without (n = 809) and those with HCC (n = 237). Single nucleotide polymorphisms (SNPs) of TGF-beta1 were searched for and genotyped using the single base extension method. In Korean subjects, only two SNPs were found among the seven known polymorphisms of TGF-beta1, at position -509 and in codon 10. The risk of HCC was significantly lower in patients with the T/T or C/T genotypes than in those with the C/C genotypes at position -509 (P < 0.02), and also lower among those with the Pro/Pro or Leu/Pro genotypes than in those with the Leu/Leu genotypes in codon 10 (P < 0.007). Haplotype analysis revealed that the possession of [-509C > T; L10P] conferred a decreased likelihood of HCC (OR = 0.74; 95% CI, 0.59-0.93; P = 0.008). In conclusion, the presence of the TGF-beta1 -509C > T promoter or of the L10P polymorphism, and the combination of both [-509C > T; L10P] as a haplotype were strongly associated with a reduced risk of HCC in patients with chronic HBV infection.     

Impact of Interleukin-28B Polymorphism on Response to Treatment in Chinese Hepatitis C Patients

The candidate polymorphism rs12979860 of interleukin 28B(IL28B) gene was genotyped by means of polymerase chain reaction(PCR) amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism(SNP) in the response to the treatment of 172 Chinese patients with hepatitis C virus(HCV) chronic infection was analyzed. The results show that the frequencies of major homozygotes(CC) and heterozygotes(CT) of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes(TT) wasn't found in this cohort. A highly significant association was found between the CC genotype and sustained virological response(SVR) in HCV genotype 1 infected patients(P<0.001) but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response(RVR) in both HCV genotype 1 infected patients(P<0.001) and non-genotype 1 infected patients(P<0.001). Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C(CHC) patients.     

Common interleukin 10 polymorphism associated with decreased risk of tuberculosis

Interleukin 10 (IL10) is a powerful TH2-cell cytokine that inhibits lymphocyte replication and secretion of inflammatory cytokines. The genetic associations of polymorphisms in IL10 with clinical manifestations of tuberculosis (TB) were examined in a large number of patients with clinical TB infection (n = 459) and normal controls (n = 871). One common promoter SNP (IL10 -592 A>C) was found to be significantly associated with decreased risk of TB manifestation. The frequency of the "C"-bearing genotype was higher in normal controls than in patients with clinical TB infection (P = 0.005, OR = 0.69). A summary of the genetic effect of IL10 -1082 A>G, the other nearby promoter SNP, in other ethnic groups is also presented.     

Molecular variations in Th1-specific cell surface gene Tim-3

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.     

Theoretical Evidence for the Stronger Ability of Thymine to Disperse SWCNT than Cytosine and Adenine: self-stacking of DNA bases vs their cross-stacking with SWCNT

Self-stacking of four DNA bases, adenine (A), cytosine (C), guanine (G) and thymine (T), and their cross-stacking with (5,5) as well as (10,0) single walled carbon nanotubes (SWCNTs) were extensively investigated with a novel hybrid DFT method, MPWB1K/cc-pVDZ. The binding energies were further corrected with MP2/6-311++G(d,p) method in both gas phase and aqueous solution, where the solvent effects were included with conductor-like polarized continuum model (CPCM) model and UAHF radii. The strongest self-stacking of G and A takes displaced anti-parallel configuration, but un-displaced or "eclipsed" anti-parallel configuration is the most stable for C and T. In gas phase the self-stacking of nucleobases decreases in the sequence G>A>C>T, while because of quite different solvent effects their self-stacking in aqueous solution exhibits a distinct sequence A>G>T>C. For a given base, cross-stacking is stronger than self-stacking in both gas phase and aqueous solution. Binding energy for cross-stacking in gas phase varies as G>A>T>C for both (10,0) and (5,5) SWCNTs, and the binding of four nucleobases to (10,0) is slightly stronger than to (5,5) SWCNT by a range of 0.1-0.5 kcal/mol. The cross-stacking in aqueous solution varies differently from that gas phase: A>G>T>C for (10,0) SWCNT and G>A>T>C for (5,5) SWCNT. It is suggested that the ability of nucleobases to disperse SWCNT depends on relative strength [Formula: see text] of self-stacking and cross-stacking with SWCNT in aqueous solution. Of the four investigated nucleobases thymine (T) exhibits the highest [Formula: see text] which can well explain the experimental finding that T more efficiently functionalizes SWCNT than C and A.     

The association of eotaxin-2 and eotaxin-3 gene polymorphisms in a Korean population with ulcerative colitis

The eotaxin gene family (eotaxin, eotaxin-2 and eotaxin-3) have been implicated in the recruitment of eosinophils, basophiles and helper T (Th) 2 lymphocytes that is a central aspect of allergic disease. We previously suggested that Eo2+179T>C and Eo2 +275C>T of the eotaxin-2, and Eo3 +2497T>G of the eotaxin-3 were significantly associated with susceptibility to asthma. To determine whether the single nucleotide polymorphisms (SNPs) of eotaxin-2 and eotaxin-3 gene family are associated with the susceptibility of ulcerative colitis (UC), we analyzed the genotype of 119 patients with UC and 303 controls using single-base extension (SBE) method. We also calculated the haplotype frequencies among Eo2 +179T>C and Eo2 +275C >T of the eotaxin-2 and Eo3 +2497T>G of the eotaxin-3 in both control and UC patients. The genotype frequency of Eo2 +179T>C and Eo2 +275C>T between UC patients and controls were significantly different (P=0.006 and 0.022, respectively). The genotype and allele frequencies of EoA2497T>G in UC patients were not significantly different from those in the controls without UC patients. Our results suggest that Eo2 +179T>C and Eo2 +275C>T of eotaxin-2 might be associated with the susceptibility of UC.     

Serum exosomal microRNAs as novel biomarkers for hepatocellular carcinoma

Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 μl of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.     

Theoretical Study of Decomposition Mechanism of Azoisobutyronitrile

The decomposition mechanisms of azoisobutyronitrile were systematically investigated. Density function theory B3LYP/6-311G*, B3LYP/6-311+G* and BHandH/6-31+G** methods were employed to optimize the geometry parameters of the reactants, transition states, possible intermediates and products based on the detailed potential energy surfaces scanned with AM1. The reaction mechanisms were also analyzed theoretically. The results indicate that the decomposition of azoisobutyronitrile is a two-bond (three body) synchronouscleavage process in the ground state (CH3)2CNC-N=N-CCN(CH3)2→2(CH3)2CNC·+N2; and is a twobond asynchronous cleavage process while in the triple state (CH3)2CNCN=N-CCN(CH3)2→(CH3)2CNCN=N· · ·CCN(CH3)2→2(CH3)2CNC·+N2. The calculations rationalize and verify all experimental facts.     

线性氟代烷烃电子相关能的基团加和性

应用Meld 程序在MP2-OPT2/6-311++G(d)水平计算了线性氟代烷烃分子CH3(CH2)mF(m=0-5)中—CH3、—CH2—和—F基团电子相关能贡献值. 计算结果表明, 在CH3(CH2)mF(m=0-5)体系中, 端基—F、—CH3基团电子相关能贡献值Ecorr(—F)和Ecorr(—CH3)随着m的增大而逐渐减小. 分子中α位置—CH2—基团电子相关能贡献值Ecorr(—CH2—)大于其他位置的贡献值. 通过计算结果可以推断, 在CH3(CH2)mF体系中随着m的逐渐增大, 远离端基—F的—CH2—基团电子相关能贡献值逐渐减小并将趋于不变, 此—CH2—基团可看作一个标准的亚甲基且其Ecorr(—CH2—)的数值在CH3(CH2)mF体系中具有传递性. 应用Meld程序在MP2-OPT2/6-311++G(d)水平对CH3(CH2)mF(m=2-5)体系的计算结果和应用Gaussian 98程序在MP2/6-311++G(d)//HF/6-311++G(d)水平对CH3(CH2)mF(m=2-10)体系的计算结果均表明, 体系总电子相关能与体系中(m-1)数值呈线性关系.     

Carbon-to-carbon identity proton transfer from allene, ketene, ketenimine, and thioketene to their respective conjugate anions in the gas phase. An ab initio study.

Gas-phase acidities of CH2=C=X (X = CH2, NH, O, and S) and barriers for the identity proton transfers (X=C=CH2 + HC triple bond C-X- right harpoon over left harpoon -X-C triple bond CH + CH2=C=X) as well as geometries and charge distributions of CH2=C=X, HC triple bond C-X- and the transition states of the proton transfer were determined by ab initio methods at the MP2/6-311+G(d,p)//MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory. The acidities were also calculated at the CCSD(T)/6-311+G(2df,p) level. A major objective of this study was to examine how the enhanced unsaturation of CH2=C=X compared to that of CH3CH=X may affect acidities, transition state imbalances, and intrinsic barriers of the identity proton transfer. The results show that the acidities are all higher while the barriers are lower than for the corresponding CH3CH=X series. The transition states are all imbalanced but less so than for the reactions of CH3CH=X.     

Gas phase generation of the neutrals H2CCCCO, HCCCCDO and CCCHCHO from anionic precursors. Rearrangements of HCCCCDO and CCCHCHO. A joint experimental and theoretical study

The reaction between O-. and MeO-CH2-C identical to C-CDO in the ion source of a VG ZAB 2HF mass spectrometer gives a number of product anions including [H2CCCCO]-. and [HCCCCDO]-. (in the ratio 1:5). Neutralisation-reionisation (NR+) of [H2CCCCO]-. results in the sequential two-electron vertical oxidation [H2CCCCO]-.-->H2CCCCO-->[H2CCCCO](+.). Singlet H2CCCCO lies 158 kJ mol-1 below the triplet [at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-31G(d) level of theory]. The majority of neutrals H2CCCCO are stable for the microsecond duration of the NR experiment, but some are energized and decompose to give H2CCC and CO. A similar NR+ experiment with [HCCCCDO]-. yields neutrals HCCCCDO, some of which are excited and rearrange. Calculations show that it is the singlet form of HCCCCHO which rearranges (the singlet lies 36 kJ mol-1 above the ground state triplet): the rearrangement occurs by the sequential H transfer process, HCCCCHO-->HCC(CH)CO<--H2CCCCO. Neutral HCCCCHO needs an excess energy of only 43 kJ mol-1 to effect this reaction, which is exothermic by 230 kJ mol-1. Both HCC(CH)CO and H2CCCCO formed in this way should have sufficient excess energy to cause some loss of CO. The anions [CC(CH)CHO]-. and [CC(CD)CHO]-. are formed in the ion source of the mass spectrometer by the reactions of HO- with Me3SiC identical to C-CH = CHOMe and Me3SiC identical to C-CD = CHOMe respectively. NR+ of these anions indicate that energized forms of CC(CH)CHO and CC(CD)CHO may rearrange to isomer(s) which decompose by loss of CO. Singlet CC(CH)CHO rearranges to HCC(CH)CO and H2CCCCO, both of which are energized and fragment by loss of CO.     

Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients

Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry‐based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto‐identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC–MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.     

Carbon-to-carbon identity proton transfers from propyne, acetimide, thioacetaldehyde, and nitrosomethane to their respective conjugate anions in the gas phase. An ab initio study.

Gas-phase acidities of CH3Y (Y: NO, C identical to CH, CH=NH, and CH=S), barriers to the identity proton-transfer CH3Y + CH2=Y- reversible CH2=Y- + CH3Y, as well as geometries and charge distributions of CH3Y, CH2=Y- and the transition states of the proton transfers were determined by ab initio methods at the MP2/6-311 + G(d,p)//MP2/6-311 + G(d,p), B3LYP/6-311 + G(d,p), and BPW-91/6-311 + G-(d,p) levels of theory. The acidities were also calculated at the CCSD(T)/6-311 + G(2df,2p) level. To make more meaningful comparisons, the same quantities for previously studied systems (Y: H, CH=CH2, CH=O, CN, NO2) were recalculated at the levels used in the present work. The geometric parameters as well as the group charges indicate that the transition states for all the reactions are imbalanced, although there is no correlation between the degree of imbalance and the pi-acceptor strength of the Y group. Based on multi-parameter correlations with the field (sigma F), resonance (sigma R), and polarizability effect (sigma alpha) substituent constants, the contributions of each of these effects to the acidities and barriers were evaluated. For the Y groups whose sigma F, sigma R, and sigma alpha are unknown (CH=NH, CH=S, C identical to CH), a method for estimating these substituent constants is proposed. The barriers for the CH3Y/CH2=Y- systems are all lower than for the CH4/CH3- system; this contrasts with the situation in solution where the Y groups lead to an increase in the barrier. The reasons for this reversal are analyzed. We also make an attempt to clarify the issue as to why the transition states of these reactions are imbalanced, a question which continues to draw attention in the literature.     

Interaction and protection mechanism between Li@C(60) and nucleic acid bases (NABs): performance of PM6-DH2 on noncovalent interaction of NABs-Li@C60

To discuss the protection mechanism of DNA from radiation as well as assess the performance of PM6-DH2 on noncovalent interactions, the interaction of four nucleic acid bases (NABs) such as adenine (A), cytosine (C), guanine (G), and thymine (T), with Li@C(60) was extensively investigated with the-state-of-art theoretical methods describing noncovalent systems, like M06-2x, PBE-D, and PM6-DH2 methods. In the gas phase, the binding strength of NABs to Li@C(60) from M06-2x decreases in the sequence, G>C>A>T. As dispersion was explicitly included, PBE-D relatively enhances the binding of A and T and corrects the sequence to, G>A>C～T. PM6-DH2 predicted similar binding energies to those from PBE-D within 0.5 kcal/mol and the same binding sequence, suggesting that the PM6-DH2 method is promising for nano-scale systems. In the aqueous solution, binding of NABs-Li@C(60) is considerably decreased, and the M06-2X and PM6-D methods yield a different sequence from the gas phase, G>A>T>C. The encapsulation of Li atom results in a lower IP for Li@C(60) than those of NABs, and the dominant localization of single-occupied molecular orbital on Li@C(60) moiety of the complexes NABs-Li@C(60) further indicates that an electron would be ejected from Li@C(60) upon radiation and Li@C(60) is therefore able to protect DNA bases from radiation. In addition, it was revealed that Li prefers coordination with the hexagonal ring at Li@C(60) , which clarifies the existing controversy in this respect. Finally, Yang's reduced density gradient approach clearly shows that the weak and strong noncovalent interaction regions in the complexes, NABs-Li@C(60) and (NABs-Li@C(60) )(+).     

Synthesis and surface properties of new ureas and amides at different interfaces

The influence of the urea and amide group in the alkyl chain of methyl nonadecanoate on the surface properties is investigated and compared. For that purpose, the ureas CH3O2C-(CH2)m-NHCONH-(CH2)n-CH3 (n + m = 14) [1 (m = 2), 3 (m = 3), and 5 (m = 4)] and the amides CH3O2C-(CH2)m-NHCO-(CH2)n-CH3 (n + m = 15) [2(m = 2), 4 (m = 3), and 6 (m = 4)] were synthesized. The pi/A isotherms of the ureas show up to the attainable temperature of 313 K no LE phase, which indicates a very stable LC phase. The amides exhibit a two phase plateau region, with the exception of 2. The different behavior is connected with the hydrogen bond energies, which are stronger with the ureas in the LC than in the LE phase, whereas those of the amides have a similar strength in both phases. The effect of hydrogen bonds in self-assembled molecules of N,N'-dialkylurea CH3-(CH2)m-NHCONH-(CH2)n-CH3 (m + n = 14) [7 (n = 2)] was visualized by STM at the octylbenzene/graphite interface. Compound 7 forms a lamella structure with a periodicity of one molecule length. The tilt angle of 86 degrees +/- 2 degrees to the edge of the lamella points to a nearly orthogonal arrangement of the molecules. It indicates two equivalent bonds between the aza-hydrogens and the carbonyl oxygen. A similar arrangement is proposed for the LC phase of the ureas at the air/water interface.     

Structural and spectral characteristics of the electrogenerated tetracyanoethylene dianion

Structural and spectral characteristics of the electrogenerated tetracyanoethylene dianion (TCNE2-) were experimentally and theoretically examined. Spectroelectrochemistry of TCNE gives the spectra of TCNE2- in CH3CN at 220 nm, and in CH2Cl2 at 300 nm. These spectral characteristics are well explained by CIS/6-31G(d) and semiempirical CNDO/S-CI calculations. The bands in CH3CN and in CH2Cl2 are assigned to the degenerate 1E<--1A1 transition at the D2d structure and the 1B2u<--1Ag transition at the D2h structure, respectively. The rotation barrier of the C=C bond in TCNE2- is estimated by Hartree-Fock (HF), second-order M?ller-Plesset perturbation (MP2) and fourth-order MP (MP4) calculations with 6-31G(d), 6-31+G(d) and 6-311+G(d) basis sets as 42-51 kJ mol(-1). The D2d structure is most stable, and the D2h structure represents the transition state of the internal rotation. The calculations reveal that the two-electron addition to the antibonding LUMO of TCNE causes an easy rotation around the C=C bond of TCNE2- characterized by the formal single bond. These results show that TCNE2- preferentially adopts D2d and D2h structures in solvents depending upon the solvent nature by virtue of the easy rotation around the C=C bond.     

N-甲硝胺异构化和分解反应机理和动力学的理论研究

The complex potential energy surface and reaction mechanisms for the unimolecular isomerization and decomposition of methyl-nitramine (CH3NHNO2) were theoretically probed at the QCISD(T)/6-311+G*//B3LYP/6-311+G* level of theory. The results demonstrated that there are four low-lying energy channels: (i) the NN bond fission pathway; (ii) a sequence of isomerization reactions via CH3NN(OH)O; (IS2a); (iii) the HONO elimination pathway; (iv) the isomerization and the dissociation reactions via CH3NHONO (IS3). The rate constants of each initial step (rate-determining step) for these channels were calculated using the canonical transition state theory. The Arrhenius expressions of the channels over the temperature range 298-2000 K are k6(T)=1014:8e-46:0=RT , k7(T)=1013:7e-42:1=RT , k8(T)=1013:6e-51:8=RT and k9(T)=1015:6e-54:3=RT s-1, respectively. The calculated overall rate constants is 6.9￡10-4 at 543 K, which is in good agreement with the experimental data. Based on the analysis of the rate constants, the dominant pathway is the isomerization reaction to form CH3NN(OH)O at low temperatures, while the NN bond fission and the isomerization reaction to produce CH3NHONO are expected to be competitive with the isomerization reaction to form CH3NN(OH)O at high temperatures.