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OBJECTIVE To investigate the possible stimulating mechanism of Huoxue Bushen Mixture (HXBSM), a traditional Chinese compound medicine, on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle. METHODS Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen. Ninety C57BL/6 mice were divided into 3 groups randomly: HXBSM group, Yangxue Shengfa Capsule (YXSFC, another traditional Chinese compound medicine) group and untreated group. The mice were fed with corresponding drugs after modeling. The hair growth of the mice was observed every day. Every ten mice out of each group were executed respectively at day 4, 11 and day 17. Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method. RESULTS The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 (P

We study a random system of cn linear equations over n variables in GF(2), where each equation contains exactly r variables; this is equivalent to r-XORSAT. Previous work has established a clustering threshold, c^*_r for this model: if c=c_r^*-\epsilon for any constant \epsilon>0 then with high probability all solutions form a well-connected cluster; whereas if c=c^*_r+\epsilon, then with high probability the solutions partition into well-connected, well-separated clusters (with probability tending to 1 as n goes to infinity). This is part of a general clustering phenomenon which is hypothesized to arise in most of the commonly studied models of random constraint satisfaction problems, via sophisticated but mostly non-rigorous techniques from statistical physics. We extend that study to the range c=c^*_r+o(1), and prove that the connectivity parameters of the r-XORSAT clusters undergo a smooth transition around the clustering threshold., Comment: 25 pages. A major part of this paper has appeared in the preprint arXiv:1309.6651

This paper is a continuation of the previous results on the stripping number of a random uniform hypergraph, and the maximum depth over all non-k-core vertices. The previous results focus on the supercritical case, whereas this work analyses these parameters in the subcritical regime and inside the critical window., 31 pages

Cyclic dinucleotides act as intracellular second messengers, modulating a variety of cellular activities including innate immune activation. Although phosphodiesterases (PDEs) hydrolyzing c-di-GMP and c-di-AMP have been identified, no PDEs for cGAMPs have been reported. Here we identified the first three cGAMP-specific PDEs in V. cholerae (herein designated as V-cGAP1/2/3). V-cGAPs are HD-GYP domain-containing proteins and specifically break 3'3'-cGAMP, but not other forms of cGAMP. 3'3'-cGAMP is first linearized by all three V-cGAPs to produce 5'-pApG, which is further hydrolyzed into 5'-ApG by V-cGAP1. In this two-step reaction, V-cGAP1 functions as both a PDE and a 5'-nucleotidase. In vivo experiments demonstrated that V-cGAPs play non-redundant roles in cGAMP degradation. The high specificity of V-cGAPs on 3'3'-cGAMP suggests the existence of specific PDEs for other cGAMPs, including 2'3'-cGAMP in mammalian cells. The absolute requirement of the GYP motif for 3'3'-cGAMP degradation suggests that HD domain-containing PDEs in eukaryotes are probably unable to hydrolyze cGAMPs. The fact that all V-cGAPs attack 3'3'-cGAMP on one specific phosphodiester bond suggests that PDEs for other cGAMPs would utilize a similar strategy. These results will provide valuable information for identification and characterization of mammalian 2'3'-cGAMP-specific PDEs in future studies.

Modelling of disc rotor is a key step in building a disc brake model for squeal analysis. While braking, the disc is rotating and other components are fixed and there are sliding contact between the pads and the disc. In the most common used complex eigenvalue analysis method, the moving load nature was normally ignored. In this paper a modal based rotating disc model is purposed. Modal parameters of stationary disc were calculated from finite element model. The frequency response function of rotating disc, under which the disc was excited and corresponding responses to be observed at spatial fixed points, was derived. The equivalent modal parameters, which represent the dynamic properties of rotating disc suffering moving loads, were studied. Because of rotating, each mode of the disc split to two complex modes and becomes the superposition of two travelling waves. The conclusion agrees with those from analytical method.

This chapter describes a project on the driving and controlling system of an automotive shock absorber tester. The system structures and key parameters are designed followed by the analysis of function partitioning and collaboration of a host personal computer (PC) and the controller. The communication protocol between controller and host PC is developed. Then, the structure and the flow chart of the controller program are presented. Finally, the performance test result using the tester with the developed drive system is given and compared with a qualified tester, which shows the accuracy of the new system.

Disc brake squeal remains an elusive problem in the automotive industry and developing a model that will predict unstable squeal-noise dynamics with reasonable accuracy is in urgent need. In this paper, a two stage validation method of closed-loop coupling disc brake model for squeal analysis using complex eigenvalue analysis is presented. At component level, finite element (FE) models are verified through the comparison of FE calculation and modal test results. At the system level, optimization method is adopted. Experiment modal analysis of stationary disc brake system with brake line pressure and brake torques applied is conducted. Then an optimization process is initiated to minimize the differences between modal frequencies predicted by the stationary model and those from test. Thus model parameters more close to real situation are found. Unstable mode prediction results of validated model are compared with those from brake noise bench test. The validated model can predict most of the squeal frequencies and the real part represent the occurrences of squeal. The method presented in this paper is proven to be valid and effective.

To examine the degree of contamination in the Dongting Lake ( ) area, surface sediments samples were collected and investigated in this study. This lake lies in the south of the middle Yangtze River, and it is the second largest fresh-water lake in China. These samples were analyzed for the concentrations of the following 6 elements (Cd, Cr, Cu, Ni, Pb and Zn) collected from 46 locations. The index of geo-accumulation was used to assess the degree of contamination of the total trace elements and the assessments showed that the contamination of Cd reached strong to very strong pollution. The speciation of metal in sediments was analyzed using the modified BCR (Community Bureau of Reference) sequential extraction technology and the water column-contamination risk was evaluated by the calculated contamination factors. The results of the speciation of metal indicated that more easily mobilized forms (exchangeable, water soluble, and acid soluble) were predominant for Cd, especially in the samples from East Dongting Lake. In contrast, the largest amount of lead was associated with the iron and manganese oxide fractions, and Cu, Zn, Cr, and Ni analyzed were mainly distributed in residual phase at an average percentage higher than 60% of the total metals. The potential risk to the lake's water contamination was the highest in East Dongting Lake based on the calculated contamination factors. The assessment results using geo-accumulation index were compared with the information obtained by trace metal speciation and both results were consistent.

Objective To assess the efficacy of Xianlong Capsule (XLC) in treating senile vascular dementia (VD).

The previously published version of this Article contained errors in Fig. 6. In panel h the units of the x axis were incorrectly given as mM and should have been given as µM. Also, the IC50s for RU.365, RU.332 and RU.521 within panel h were incorrectly given as mM and should have been given as µM. These errors have been corrected in both the PDF and HTML versions of the Article.

A model to study the effectiveness of potential chemopreventive agents that inhibit neoplastic process by different mechanisms has been used to test the efficacy of seven nitric oxide synthase (NOS) inhibitors. Five selective inducible NOS (iNOS) inhibitors: S-methyl isothiourea (S-MITU), S-2-aminoethyl isothiourea (S-2-AEITU), S-ethyl isothiourea (S-EITU), aminoguanidine (AG), 2-amino-4-methyl pyridine (2-AMP), and two non selective general NOS inhibitors: l-N(6)-(1-iminoethyl) lysine (IEL) and N(omega)-nitro-l-arginine (NNLA), were tested for efficacy against a carcinogen, benzo[a]pyrene (B[a]P)-induced primary rat tracheal epithelial (RTE) cell transformation assay. RTE cells were treated with B[a]P alone or with five nontoxic concentrations of an NOS inhibitor and the resulting foci at the end of 30 days were scored for inhibition of transformation. The results indicate that all three isothiourea compounds inhibited B[a]P-induced RTE foci in a dose-dependent manner. S-AEITU was the most effective inhibitor with an IC(50) (the molar concentration that inhibits transformation by 50%) of 9.1 microM and 100% inhibition at the highest dose tested (30 microM). However, both S-EITU and S-MITU showed a maximum percent inhibition of 81% and 100% at 1 mM with an IC(50) of 84 and 110 microM, respectively. 2-AMP did not show any dose-dependent response, but was highly effective (57% inhibition) at an intermediate dose of 30 microM and an IC(50) of 25 microM. Similar to thiourea compounds, AG exhibited good dose-dependent inhibition with a maximum inhibition of 86% at 1 mM. NNLA and IEL were negative in this assay. Based on the IC(50) values, NOS inhibitors were rated for efficacy from high to low as follows: S-2-AEITU

The reliability of smart substations has a great significance on the safety and stability of smart grid operation. Taking the protection system in smart substation as an example, this paper constructs comprehensive reliability models to evaluate the reliability of smart substations with different architectures. The paper first illustrates two important aspects which affect the reliability of the protection system, namely the network architecture and the maintenance strategy. To satisfy these two aspects, the paper then adopt the Monte Carlo simulation combined with the Reliability Block Diagram method to make quantitative reliability analysis. At last, reliability of four power transformer protection systems applying different maintenance strategies with alternative architectures is evaluated. The simulation results show clearly that advanced maintenance strategies such as conditional maintenance will play a critical role in enhancing the reliability and availability of smart substation. DOI : http://dx.doi.org/10.11591/telkomnika.v12i5.5109

Most of the existing reliability analysis is based on exponential distribution which is convenient to calculation, whereas most intelligent electronic devices exhibit Weibull distribution. What kind of influence will life distribution have on the reliability and availability of a smart substation. This paper compares the reliability and availability of systems with different life distributions based on reliability block diagram and Monte-Carlo simulation, by treating the smart substations as non-repairable and repairable systems respectively. Simulation results proves the feasibility of substituting Weibull distribution with exponential distribution in engineering practice when the smart substations are treated as repairable systems, thus the life data estimation as well as the reliability analysis and calculation will be greatly simplified. DOI : http://dx.doi.org/10.11591/telkomnika.v12i4.4833

A rapid, robust, and sensitive method has been developed to measure concentrations of deoxyribonucleoside triphosphates in individual, day 14 rat embryos by modifying and optimizing existing methods for cellular extracts. Significant changes include: (i) oxidative degradation of ribonucleoside triphosphates using methylamine at lower pH (decreased from 6.5 to 4.0) to improve poor HPLC peak shape of early eluting nucleotides; (ii) glass fiber disc solid-phase extraction of the reaction mixture, which dramatically reduces impurities that interfere with nucleotide measurement, eliminates the necessity of column regeneration, and allows mobile phase recycling; and (iii) lower ionic strength (reduced from 0.4 to 0.26 or 0.12 M ammonium phosphate) and higher pH (increased from 3.25 to 5.55 or 6.98, respectively) mobile phase, conditions which are less destructive to the column's bonded phase and silica support, thereby contributing to longer column life. Enhancements include: (i) filtration of the sample prior to HPLC injection and addition of an in-line filter, guard column, and saturating precolumn of silica in the mobile phase flow, which aids substantially in extending column life and improves chromatographic stability, and (ii) inclusion of an internal standard to correct for mechanical losses. Limits of determination at a signal to noise ratio of 6:1 range from 5.5 to 12 pmol on-column or 0.41 to 0.87 pmol/mg of embryonic tissue depending on the specific nucleotide. Recoveries are quantitative for all nucleotides, and interassay variabilities are between 5 and 7% when quantified by peak height. The method has also been applied successfully to analysis of murine erythroleukemic cell cultures and this, when coupled with the embryo results, suggests its general utility.

We study the asymptotic distribution of the number of matchings of size $\ell=\ell(n)$ in $G(n,p)$ for a wide range of $p=p(n)\in (0,1)$ and for every $1\le \ell\le \lfloor n/2\rfloor$. We prove that this distribution changes from normal to log-normal as $\ell$ increases, and we determine the critical value of $\ell$, as a function of $n$ and $p$, at which the transition of the limiting distribution occurs.

In this paper, we estimate the geometric Ramsey numbers of trees. Given a tree T n on n vertices and an outerplanar graph H m on m vertices, we estimate the minimum number M = M ( T n , H m ) such that, for any set of M points in the plane such that no three of them are collinear, and for any 2-colouring of the segments determined by the M points, either the first colour class contains a non-crossing copy of T n , or the second colour class contains a non-crossing copy of H m . We prove that M ( T n , H m ) = ( n - 1 ) ( m - 1 ) + 1 if (i) the points are in convex position, T n is a caterpillar and H m is Hamiltonian, or if (ii) the points are in general position, T n has at most two non-leaf vertices, and H m is Hamiltonian. We also prove several polynomial bounds for M ( T n , H m ) for other classes of T n and H m .

We prove that the geometric Ramsey numbers of the ladder graph on 2n vertices are bounded by O(n 3) and O(n 10), in the convex and general case, respectively. We also prove polynomial upper bounds of geometric Ramsey numbers of pathwidth-2 outerplanar triangulations in both convex and general cases.

Bromodichloromethane (BDCM), a carcinogenic water disinfection by-product, has been shown to be metabolized to intermediates that covalently bind to lipids and proteins, and this binding has been associated with trihalomethane-induced renal and hepatic toxicity. In this study, the effects of glutathione (GSH) on in vivo BDCM toxicity and in vitro BDCM macromolecular binding were evaluated. The in vivo toxicity of BDCM in animals pretreated with buthionine sulfoximine (BSO, a glutathione synthesis inhibitor) and in untreated male Fischer 344 rats was investigated. In another experiment, covalent binding to protein and lipid was quantified after [14C]BDCM was incubated with hepatic microsomal and S9 fractions and renal microsomes from F344 rats, under aerobic and anaerobic conditions, with and without added GSH. After oral dosing with BDCM, the BSO-pretreated animals had greatly increased levels of serum indicators of hepatotoxicity and serum and urinary indicators of nephrotoxicity compared to those in animals dosed solely with BDCM. Histopathological examination revealed that hepatic necrosis was more severe than renal necrosis in the BSO-treated rats. When GSH was added to an aerobic incubation, protein binding was decreased in hepatic microsomal and S9 fractions by 92 and 83%, respectively. GSH also decreased lipid binding by 55% in hepatic microsomal incubations carried out under anaerobic conditions. Addition of GSH decreased renal microsomal protein (aerobic) and lipid binding (anaerobic) by 20 and 43%, respectively. These data indicate that GSH is an important protective factor in the toxicity associated with BDCM.

Summary C2c1 is a newly identified guide RNA-mediated type V-B CRISPR-Cas endonuclease that site-specifically targets and cleaves both strands of target DNA. We have determined crystal structures of Alicyclobacillus acidoterrestris C2c1 (AacC2c1) bound to sgRNA as a binary complex and to target DNAs as ternary complexes, thereby capturing catalytically competent conformations of AacC2c1 with both target and non-target DNA strands independently positioned within a single RuvC catalytic pocket. Moreover, C2c1-mediated cleavage results in a staggered seven-nucleotide break of target DNA. crRNA adopts a pre-ordered five-nucleotide A-form seed sequence in the binary complex, with release of an inserted tryptophan, facilitating zippering up of 20-bp guide RNA:target DNA heteroduplex on ternary complex formation. Notably, the PAM-interacting cleft adopts a "locked" conformation on ternary complex formation. Structural comparison of C2c1 ternary complexes with their Cas9 and Cpf1 counterparts highlights the diverse mechanisms adopted by these distinct CRISPR-Cas systems, thereby broadening and enhancing their applicability as genome editing tools.

Cyclic GMP-AMP synthase (cGAS) plays a central role in sensing aberrantly localized cytoplasmic dsDNA. Upon binding dsDNA, cGAS synthesizes the cyclic dinucleotide cGAMP, which acts as a second messenger to initiate a signaling pathway for the induction of interferon genes. Given that cytoplasmic DNA can originate from bacteria or virus, cGAS is essential for innate immunity against pathogenic infection. Conversely, cGAS detection of mislocalized nuclear or mitochondrial DNA can lead to hyper-inflammation. Recent studies indicate that cGAS can potentiate autoimmunity in cases of lupus, Aicardi-Goutières syndrome, and other related diseases—suggesting that targeting cGAS activity may be therapeutically beneficial. We report the discovery of a first-in-class generation of cGAS small molecule inhibitor, RU.365, identified in a high-throughput screen. Its structure-activity relationship, and selectivity and potency in cellular assays, was characterized. Moreover, we solved the structure of cGAS in complex with dsDNA and RU.365 or its close structural analog within the active site. Finally, we demonstrate that the inhibitor can reduce constitutive expression of interferonin macrophages derived from a mouse model of autoimmunity. RU.365 will be useful towards understanding the biological roles of cGAS and can serve as a molecular scaffold for development of future autoimmune therapies. Note: This abstract was not presented at the conference. Citation Format: Pu Gao. Small molecule inhibition of cyclic GMP-AMP synthase reduces interferon expression in macrophages from an autoimmune mouse model [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B145.

The appearance of DNA in the cytoplasm is a very dangerous signal to cells. This could be caused by viral or bacterial infection, or as a result of cellular damage that leaks host DNA into the cytoplasm. Cytosolic DNA activates the host immune response, which is critically dependent on the newly identified cGAS-cGAMP-STING pathway. Structure-function studies from our laboratories have demonstrated that upon dsDNA binding, cGAS is activated through conformational transitions, resulting in formation of a catalytically competent and accessible nucleotide-binding pocket for generation of c[G(2',5')pA(3',5')p]. Further, cyclization occurs in a stepwise manner through initial generation of 5'-pppG(2',5')A prior to cyclization to c[G(2',5')pA(3',5')p], with the latter positioned precisely in the catalytic pocket. These studies established c[G(2',5')pA(3',5')p] as a founding member of a family of metazoan 2',5'-containing cyclic heteronucleotide second messengers distinct from bacterial 3',5' cyclic dinucleotides. Follow up structure-function studies from our laboratories have shown that human and mouse STING undergo an ‘open’ to ‘closed’ conformational transition upon binding c[G(2',5')pA(3',5')p] and the anti-viral agent DMXAA. Comparing hSTING to mSTING in cellular assays, 2',5'-linkage-containing cGAMP isomers were more specific triggers of the IFN pathway compared to the all 3',5'-linkage isomer counterparts. Our results highlight the critical role of the lid residue at position 230 (Gly in hSTING; Ile in mSTING) for the DMXAA species selectivity. Our structural and functional results also shed light on strategies to restore an efficient DMXAA-response of hSTING based on the binding pocket S162A and Q266I substitutions. Citation Format: Pu Gao, Manuel Ascano, Thomas Zillinger, Winfried Barchet, Thomas Tuschl, Dinshaw J. Patel. Structure-function studies of cytosolic DNA sensing pathway. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B030.

RecR is an important recombination mediator protein in the RecFOR pathway. RecR together with RecO and RecF facilitates RecA nucleoprotein filament formation and homologous pairing. Structural and biochemical studies of Thermoanaerobacter tengcongensis RecR (TTERecR) and its series mutants revealed that TTERecR uses the N-N dimer as a basic functional unit to interact with TTERecO monomer. Two TTERecR N-N dimers form a ring-shaped tetramer via an interaction between their C-terminal regions. The tetramer is a result of crystallization only. Hydrophobic interactions between the entire helix-hairpin-helix domains within the N-terminal regions of two TTERecR monomers are necessary for formation of a RecR functional N-N dimer. The TTERecR N-N dimer conformation also affects formation of a hydrophobic patch, which creates a binding site for TTERecO in the TTERecR Toprim domain. In addition, we demonstrate that TTERecR does not bind single-stranded DNA (ssDNA) and binds double-stranded DNA very weakly, whereas TTERecOR complex can stably bind DNA, with a higher affinity for ssDNA than double-stranded DNA. Based on these results, we propose an interaction model for the RecOR:ssDNA complex.

This paper considers the containment control of linear multi-agent system with weakly connected information topology. By defining the node-induced strongly connected subgraph as strong component, the agents contained in strong components with zero in-degree are called leaders and the others are called followers. Then, a sufficient and necessary condition is proposed for all agents to achieve containment by employing an observer-based protocol, where all followers finally converge to the convex hull formed by leaders and each strong component of leaders asymptotically achieve consensus. Since the number of leader agents in each strong component are always larger than one, the proposed scheme is more robust for the malfunction of leaders. Further, two LMIs are given to design the observer-based protocol. Numerical examples are included to illustrate the validity of the proposed results.

Agent solubility is a problem for aspiration of agents into lungs for chemopreventive efficacy evaluation, since many agents have to be dissolved in solvents. These solvents may be toxic to the lung epithelium. A study was conducted in female A/J mice to determine toxicity of different solvent concentrations by using saline, dimethyl sulfoxide (DMSO), ethanol, polyethylene glycol 400 (PEG-400), and labrasol for 1, 5, and 28 days via aspiration route. Toxicity was determined by measuring changes in body weight and bronchoalveolar lavage fluid (BALF). No significant difference was observed in body weight, differential cell counts, lactate dehydrogenase (LDH) and total protein in all solvent groups compared to saline by 28 days except 50% ethanol. However, myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) showed significant increase in 2% and 10% DMSO, 10% ethanol, 0.1% and 2% PEG-400, and 1% labrasol by longer dosing. All solvents except for 10% ethanol and 2% PEG-400 are suitable for agent aspiration.

We describe a general approach of determining the distribution of spanning subgraphs in the random graph $\G(n,p)$. In particular, we determine the distribution of spanning subgraphs of certain given degree sequences, which is a generalisation of the $d$-factors, of spanning triangle-free subgraphs, of (directed) Hamilton cycles and of spanning subgraphs that are isomorphic to a collection of vertex disjoint (directed) triangles., 17 pages, 2 figures

Type I DNA methyltransferases contain one specificity subunit (HsdS) and two modification subunits (HsdM). The electron microscopy model of M.EcoKI-M2S1 methyltransferase shows a reasonable closed state of this clamp-like enzyme, but the structure of the open state is still unclear. The 1.95 A crystal structure of the specificity subunit from Thermoanaerobacter tengcongensis (TTE-HsdS) shows an unreported open form inter-domain orientation of this subunit. Based on the crystal structure of TTE-HsdS and the closed state model of M.EcoKI-M2S1, we constructed a potential open state model of type I methyltransferase. Mutational studies indicated that two α-helices (aa30-59 and aa466-495) of the TTE-HsdM subunit are important inter-subunit interaction sites in the TTE-M2S1 complex. DNA binding assays also highlighted the importance of the C-terminal region of TTE-HsdM for DNA binding by the TTE-M2S1 complex. On the basis of structural analysis, biochemical experiments and previous studies, we propose a dynamic opening and closing mechanism for type I methyltransferase.

Previously, we developed a 30-day transformation assay (focus inhibition, FIA) of rat tracheal epithelial (RTE) cells to identify cancer preventive agents. This study reports nuclear density (ND) as a morphometric biomarker for efficacy evaluation of at an early stage before transformed foci appear. Positive (oltipraz, D-carvone, fumaric acid, and 2-amino-4-methylpyridine or 2-A-MPR) and negative agents (myristoleic acid, anethole trithione, hydrocortisone, and 3'-hydroxyflavanone), identified from FIA, were tested for their effect on ND. RTE cells plated for 24 h were treated with a carcinogen, benzo[a] pyrene (B[a]P) or plus a test agent. The data based on the number of nuclei in agent-treated and control cells at day 14 showed that all FIA-positive agents inhibited ND from 23-66% at 0.3-1000.0 microM and except for myristoleic acid, all of the FIA-negative compounds were also negative in the morphometry assay. As there is strong correlation between the FIA and morphometry data, morphometry analysis is useful for rapid screening of potential chemopreventive agents.

Caloric restriction is known to reduce chemically-induced tumor incidence in laboratory animals. The effect is believed to be mediated in part by modification of hepatic drug metabolism, including both phase I and phase II enzymes. Using aflatoxin B1 (AFB1) as a model carcinogen, we studied the effect of caloric restriction on the modification of rat liver nuclear DNA by AFB1 and DNA damage due to the formation of apurinic sites from the AFB1-DNA adduct removal process. Caloric restriction reduced the metabolic activation of AFB1 which resulted in a decrease of AFB1-DNA binding by more than 50%. The results of the study of the effect of caloric restriction on the AFB1-induced DNA strand breakage assayed by the alkaline unwinding technique showed that caloric restriction protected the formation of apurinic sites from the AFB1-DNA adducts and reduced the double strand DNA breakages by 1.3– 2.5-fold. Thus, the lower initial AFB1-DNA binding and less DNA damage, presumably by the less apurinic sites formed during the depurination process of AFB1-DNA adducts, contributed to the protective effect of caloric restriction.

Methylmalonyl-CoA is an important metabolic intermediate that exists in several key degradative and biosynthetic pathways.1 The pathway responsible for the degradation of branched amino acids and odd chain fatty acids involves three steps. In the first step, a biotindependent carboxylation produces the S-epimer of methylmalonyl-CoA. The third step, the B12-dependent methylmalonyl-CoA mutase converts the R-epimer of methylmalonyl-CoA to succinyl-CoA.1 This key epimerization between the two steps is carried out by the essential enzyme methylmalonyl-CoA epimerase (MMCE: EC number 5.1.99.1), which catalyzes the conversion of (2S)methylmalonyl-CoA to (2R)-methylmalonyl-CoA. In prokaryotes, MMCE participated in autotrophic CO2 fixation via the 3-hydroxypropionate pathway, in propionate fermentation, the regeneration of glyoxylate and in the biosynthesis of polyketide antibiotics.2–6 In animals, defects of this pathway can result in a buildup of methylmalonic acid, which causes severe acidosis and also damages the central nervous system.7,8 In this study, we determined the crystal structure of TTE0360 from Thermoanaerobacter tengcongensis to 2.0 A resolution using single-wavelength anomalous dispersion (SAD) by short cryo-soaking with a high concentration of potassium iodide.9,10 In GenBank database, the gene tte0360 is predicted to be glyoxalase I, a member of glyoxalase superfamily. However, the TTE0360 structure is very different than the released structures of glyoxalase I. A search for the 3D homologs using DALI11 shows that TTE0360 has significant structural similarity with the MMCE from Propionibacterium shermanii,12 which is also a member of glyoxalase superfamily. The fold type of the TTE0360 molecule belongs to the vicinal-oxygen-chelate superfamily (VOC).13 The similarities of structure folds, dimer formation, and active sites between TTE0360 and MMCE, suggest that the protein TTE0360 may be the MMCE from T. tengcongensis.

This paper considers the consensus problem of continuous-time sensor network in a noisy environment, in which both fixed topology case and switching topology case are considered. The main idea is based on the fact that the state of each agent has twofold identity, i.e., the state of itself and the control input of agents that take it as a neighbor. With this in mind, we first solely design unbiased Kalman filters for each agent such that the sensor network solves consensus problem when all information is contaminated by noises. Then, the convergence of the proposed algorithms is proved. All the proposed algorithms are fully distributed, unbiased, and use the least information. The validity of them is illustrated by the included numerical examples.

The pegging algorithm is a method of generating large random regular graphs beginning with small ones. The $\epsilon$-mixing time of the distribution of short cycle counts of these random regular graphs is the time at which the distribution reaches and maintains total variation distance at most $\epsilon$ from its limiting distribution. We show that this $\epsilon$-mixing time is not $o(\epsilon^{-1})$. This demonstrates that the upper bound $O(\epsilon^{-1})$ proved recently by the authors is essentially tight.

To clone human interleukin-26 (hIL-26) and express it in E. coli efficiently. Two pairs of primers were synthesized according to the hIL-26 gene reported on GenBank. The hIL-26 gene was cloned by nest PCR following the first round RT-PCR from human peripherial blood monocytes total RNA, and then the PCR product was cloned into pMD18-T vector. Colony PCR, restriction analysis and sequence analysis showed that the gene cloned was the same as the reported hIL-26. The recombinant was cut with BamHI and EcoR I to obtain the hIL-26 fragment, and then the fragment was inserted into pBV220 which was cut with the same enzymes. The recombinant expression vector was induced to express hIL-26 at 42 degrees C, SDS-PAGE analysis showed that the recombinant protein accounted for up to 20% of the whole protein of E. coli, and the protein was also confirmed by Western blotting. Purity of the protein was found to be above 90% after purified with molecular sieve. After renaturalized with glutathione buffer, the promoting effect of it on the production of IFN-y in PBMC was detected by RT-PCR. A recombinant bacterial strain for expressing hIL-26 with biological activity was constructed successfully.

This study explored the efficacy of oltipraz, a dithiolthione to prevent lung cancer by delivering it directly to the lung as inhaled particulates to obtain maximum efficacy with no toxicity. Two exposure regimens were used to compare the efficacies of early (Regimen-A) versus late (Regimen-B) intervention in prevention of lung tumorigenesis in A/J mice. Female A/J mice were exposed to 10, 30 and 100 mg/m(3) exposure concentrations of oltipraz for 1.0 h a day for 5 days per week for 4 weeks in Regimen A. During the second and third week, mice received totally 6 mg of B[a]P via gavage and after 16 weeks, they were killed for tumor counting and pathology. In Regimen B, mice were treated first with B[a]P and, after a gap of 4 weeks, exposed to oltipraz at 100 mg/m(3) for 16 additional weeks. At 22 weeks, animals were killed and necropsied for tumor scoring. The spontaneous tumors were few in untreated A/J mice (0.7 tumors/lung), whereas there was an average of 16.5 tumors per lung in the B[a]P group (20-fold induction). Evaluation of lung tumor multiplicity following exposure to oltipraz showed that oltipraz inhibited the tumor development in a dose-dependent manner (10-100 mg/m(3)) with inhibition ranging from 37 to 53% in Regimen A and 51% in Regimen B, when compared with the B[a]P group. Analysis of the tumor incidence showed that 81.5% of the animals had 10 or more tumors in the B[a]P group, whereas, in oltipraz exposure groups, there was a significant decrease in Regimen A (24-36%) and in Regimen B (42%). The data from this study show that oltipraz is an effective agent for lung cancer prevention, when it is delivered directly to the target tissue as aerosolized particulates.

This study was aimed to investigate the correlation of thrombosis with increased platelet turnover in essential thrombocythemia. According to presence or absence of thrombosis, 26 patients with ET were divided into two groups. Reticulated platelets (RP) were measured by flow cytometry and 26 healthy volunteers were selected as healthy controls. The ET patients with thrombosis were treated with hydroxyurea and interferon-alpha. The results demonstrated that the ET patients with thrombotic events had a significantly higher RP percentage (14.8% +/- 7.2%) than that in both asymptomatic ET patients (4.5% +/- 2.3%) and normal control (3.3% +/- 1.5%), (P0.05); the RP percentage in asymptomatic ET patients did not differ significantly from controls. ET patients with thrombosis also had a significantly higher absolute RP (ARP) count than those in ET patients without thrombosis [(176 +/- 37) x 10(9)/L vs (46 +/- 12) x 10(9)/L]. The ET patients with thrombosis were successfully treated with hydroxyurea plus INF-alpha, the RP percentage and ARP counts obviously reduced. In conclusion, when the ET patients had thrombotic events, those patients had a significantly higher RP percentage and ARP compared with patients without thrombosis and healthy controls. The ET patients with thrombosis were successfully treated with hydroxyurea plus INF-alpha.

Based on least squares support vector machines (LS-SVM) technique, a new method for airport freight traffic volume forecasting is proposed. The basic theory of regression LS-SVM is given, together with the brief review of SVM. The historical statistical data of airport freight traffic and pertinent indices from 1983 to 2003, which are provided by National Bureau of Statistics of China and Civil Aviation Administration of China, are used as the total data set of LS-SVM. RBF kernel function, polynomial kernel function, and linear kernel function are used as the kernel function of LS-SVM to perform freight traffic volume forecasting, respectively. After five-fold cross-validation, the LS-SVM of RBF kernel function has the best forecasting performance. Eventually, RBF function is selected as the kernel function of LS-SVM and its optimal parameters are /spl sigma//sup 2/=20 and /spl gamma/=13. The maximum absolute forecasting error is 12.4 and the maximum relative forecasting error is 5.66%. The results show that LS-SVM is a promising tool to perform airport freight traffic volume forecasting.

To study the effect of Runing II on expression of vascular endothelial growth factor (VEGF) in transplanted tumor of mammary cancer MA-891 in TA2 mice.The MA-981 mice mammary cancer cell cultivated in vivo was inoculated into the right axilla subcutaneously of TA2 mice to establish the transplanted tumor model, which were treated with Runing II.Runing II could inhibit the growth of transplanted tumor and the occurrence of lung metastasis (P0.05), reduce the expression of VEGF protein and mRNA in tumor tissue (P0.05).Runing II could reduce the expression of VEGF protein and mRNA, hence to inhibit the growth of tumor and lung metastasis.

To analyse the constitution of 5459 cleft lip and palate cases and to review the development of surgical treatment to them.The data of the 5459 cleft lip and palate cases were collected and classified. The ratio of sex and disease pattern were calculated and analyzed statistically. Also, by means of classification of the disease pattern, the operation methods and the operation time, the change of the surgical methods and the first operation age were analyzed.In the cleft lip and palate cases, the sex ratio is different. There were obvious differences in the first operative ages in different periods. The main repair methods for cleft lip and palate changed with time.The male is more than the female in the cleft lip and palate patients. The average first operation age has been decreased and the main repair methods have changed since 1980.

A two-degree-of-freedom system impacting a single stop is considered. Unusual routes form periodic impact to chaos are investigated by numerical simulation. The periodic impact motion and its period doubling bifurcation are obtained by experimental method. The global bifurcation process form periodic impact to chaos includes both period-doubling bifurcation and Hopf bifurcation. The routes to chaos are qualitatively very different to those in the usual consecutive maps. Grazing discontinuities in the Poincare map are likely to be a major cause of unusual routes to chaos for the vibro-impact system.© (2002) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Cancer prevention must be a leading public health objective, if we are to reduce cancer morbidity and mortality in the world. Cancer chemoprevention is defined as the use of chemical agents to prevent cancer and eliminate or reduce preinvasive, intraepithelial, precursor lesions that progress to invasive cancer. There are several thousand single agents and a large number of defined and undefined mixtures in the literature which either have epidemiological evidence of preventing cancer, have been shown to prevent cancer in experimental animals, to prevent cancer-related endpoints or to exhibit activity either in vivo or in vitro that are mechanistically related to cancer prevention.

While the developmental toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners has received considerable attention, the impact of advanced age on the biochemical effects and the pharmacokinetics of dioxins remains largely undetermined. In the present investigation, TCDD tissue distribution and cytochrome P4501A (CYP1A) induction were characterized in male C57BL/6N mice aged 10 weeks and 28 months at 7 days after administration of single oral [3H]TCDD doses ranging from 0.015 to 15 microgram/kg body wt. Determinations of hepatic marker enzyme activities for CYP1A1 (ethoxyresorufin O-deethylation, EROD) and 1A2 (acetanilide-4-hydroxylation, ACOH) indicated that the dose response curves for EROD induction by TCDD were nearly identical for the 2 age groups, but the ACOH induction response was greater in old mice. After receiving the 15 micrograms/kg dose, an increase (approximately 35%) in relative liver weight was observed 7 days after dosing in the 10-week mice, but not in the aged mice, and the hepatic concentration of TCDD was approximately 25% greater in young than old mice. No age difference was found in hepatic nuclear concentrations of TCDD. A dose-dependent increase in liver:fat tissue concentration ratios was noted at both ages, and adipose tissue and blood concentrations of TCDD did not vary significantly with age. In old mice however, TCDD concentrations in skin, kidney and muscle were all approximately twice those of young mice at the 15 micrograms/kg dose. These results suggest that advanced age may have differential effects on Ah receptor-mediated enzyme induction, while increased TCDD concentrations in certain tissues may have toxicological implications for older animals.