Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

Influence of geometric parameters on stress concentration factors of undermatched butt joint with single V-groove under three-point bending load

In order to improve the bending load-carrying capacity （BLCC） of undermatched butt joint under three-point bending load, the influence of joint geometric parameters on stress concentration factors （SCF） at the weld bottom center and the weld toe of uudermatched butt joint with single V-groove are studied respectively based on the finite element method in this paper. Results show that the reinforcement height and the cover pass width play decisive role in the BLCC for undermatched butt joint. BLCC of undermatched butt joint can be improved by choosing the appropriate joint geometric parameters.

Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Isolated single stage high power factor AC/DC converter

The problem of harmonic pollution has brought wide attention with the increase of power customers. The adoption of the technology of active power factor correction (APFC) with advanced high frequency power converter is a more efficient solution to the problem of harmonic pollution. A single stage isolated high power factor AC/DC converter, which features wide range DC output, high power factor, lower harmonic pollution in input current, and phase shift PWM full bridge circuit can achieve soft switching. The principle of the circuit topology and the reasons of voltage surges across the power switch are analyzed. Experiment results illustrate that this circuit has the advantages of high power factor and lower harmonic distortion.

Physical Models for Interactions Between Single Von Willebrand Factor A1 Domain and GPIbα

Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alternative understanding about the role of Al-GPlbαinteractions in the mechanism of hemostasis.

Study of effects of environmental factors on biochemical compositions of four species of marine single-celled algae

Photosynthetic rates (PR ) of four species of marine single- celled algae were determined by means of 14C-tracer method under the experimental modelling conditions. The effects of environmental factors, such as light, temperature and nutrients, on the biochemical compositions of the algae were studied. The results indicate that the suitable light intensities for the growth of Phaeodactylum tricorntum, Dunaliella spp, Skeletonema costatum and Isochrysis galbana are in the range from 5. 8 X 103 to 15 x 103 lx, showing an increasing trend of photosynthetic rates with the heightened light intensities. The irradiance response of Dunaliella spp. and Isochrysis galbana is significant. The contents of carbohydrate increase, but those of protein decrease, and the contents of lipids change very little. The optimum temperatures for the growth of the four species of algae are 14, 26, 21 and 26t respectively, characterized by the maxima of PR and the contents of carbohydrate, protein and lipid as well as their variations. The apparent activation energies in the photosynthesis process of Phaeodactylum tricornutum, Dunaliella spp., Skeletonema costatum and Isochrysis galbana are 23. 2, 38. 5, 22. 4 and 61. 7 kJ/mol respectively, and the temperature coefficients for the four algae are 1. 74, 1. 74, 1. 38 and 1. 69 respectively. The peaks of PR appeared in some culture media (N/P = 16 ) of Phaeodactylum tricornutum and Skeletonema costatum, and in other media (N/P = 28) of Dunaliella spp. and Isochurysis galbana. The contents and their variations of carbohydrate, protein and lipid of the four species of algae are all maximum when N/P is equal to 16 in culture media.

Single-stage active clamp power factor correction AC/DC converter

A simple single-stage AC/DC converter circuit with active clamp is presented. The operation theory and state are analyzed. The experimental results show that the voltage across main switch can be clamped to a certain value,and zero voltage switching (ZVS) can be achieved. The voltage stress and switching loss are both decreased. In range of the whole load,power factors can be always more than 97%,and the highest efficiency can reach 88%.

Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases(RTKs) and members of the fibroblast growth factor receptors(FGFR)-family. Singlenucleotide polymorphism(SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC.AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted.METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany.Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP.Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis.RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high"(+++) in 74(26%),"intermediate"(++) in 103(36.3%), and "low"(+) in 107(36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors(33.8%), 84 of them(29.6%) having a heterozygous and 12(4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage(P < 0.004), local metastasis(P < 0.0001) and reduced disease-free survival(P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival(P < 0.003).CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.

STATISTICAL ANALYSIS OF YARN APPEARANCE IN SINGLE PLATED WORK KNITTED ON LARGE DIAMETER CIRCULAR WEFT KNITTING MACHINE

In this paper the significance analysis has been made of the factors influencing the yarn appearing of single plated weft-knit fabrics knitted on large diameter machine by a mathematical statistical method. By means of orthogonal test and variance analysis, it is known that the feeding tension is the significant factor influencing the yarn appearance and the ground yarn tension should be larger than the face yarn tension. Through comparison, it is also known that the drawing off force should be regulated suitably, the carrier should be near the first closed needle, and the sinker should be out late slightly.

The exciton-longitudinal-optical-phonon coupling in InGaN/GaN single quantum wells with various cap layer thicknesses

This paper studies the exciton-longitudinal-optical-phonon coupling in InGaN/GaN single quantum wells with various cap layer thicknesses by low temperature photoluminescence （PL） measurements. With increasing cap layer thickness, the PL peak energy shifts to lower energy and the coupling strength between the exciton and longitudinal- optical （LO） phonon, described by Huang-Rhys factor, increases remarkably due to an enhancement of the internal electric field. With increasing excitation intensity, the zero-phonon peak shows a blueshift and the Huang-Rhys factor decreases. These results reveal that there is a large built-in electric field in the well layer and the exciton-LO-phonon coupling is strongly affected by the thickness of the cap layer.

An Analytical Theory of the Signal-to-Noise Ratio of Hall Plates with Four Contacts and a Single Mirror Symmetry

This work gives an analytical theory of the signal-to-thermal-noise ratio (SNR) of classical Hall plates with four contacts at small magnetic field. In contrast to previous works, the symmetry of the Hall plates is reduced to only a single mirror axis, whereby the average of potentials of the two output contacts off this mirror axis differs from the average of potentials at the two supply contacts on the mirror axis, i.e. the output common mode differs from 50%. Surprisingly, at fixed power dissipated in the Hall plate, the maximum achievable SNR is only 9% smaller for output common modes of 30% and 70% when compared to the overall optimum at output common modes of 50%. The theory is applied to Vertical Hall effect devices with three contacts on the top surface and one contact being the buried layer in a silicon BiCMOS process. Geometries are found with large contacts and only a moderate loss in SNR.

基于改进Single-Pass算法的话题发现技术研究

为了在海量的移动互联网数据中自动识别出新闻话题,分析经典Single-Pass聚类算法及其不足,提出针对性改进方法完成新闻话题发现。改进算法继承Single-Pass聚类算法的原理,通过对关键信息加权和引入时间因子提高算法的聚类精度;通过设置话题中心与待聚类文本比较来降低算法的计算开销。实验表明,改进后的算法相比于经典算法在准确率、召回率和F值三个指标上有所提高。

Average modeling of Single Stage Flyback PFC ＋ Flyback DC／DC converter

With the use of this novel average model for Single Stage Flyback PFC + Flyback DC/DC converter, voltage control mode, peak current control mode and average current control mode can be simulated easily by changing the model's parmneters. It can be used to do various analysis not only for small signal and static behavior but also for large signal and dynamic behavior of the converter. By using this average model the simulation speed can be improved by 2 orders of rrmgnitude above that obtained by using the conventional switched model. It can be applied to optimize the trade-off between high power factor, voltage stress, current stress and good output performance while designing this kind of single stage PFC converter. A 60W single stage power factor corrector was built to verify the proposed model. The modeling principle can be applied to other Single Stage PFC topologies.

Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer(NSCLC)

Background： Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism（SNP） loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods： Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results： Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC（0.681）/CT（0.319）, CC（0.660）/CG（0.340）, CC（0.681）/CA（0.319）, AA（0.984）/AT（0.016） and GG（1.000）/GA（0.000）, respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions： Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor（EGFR） targeted immunotherapy.

Single Chain Fragment Variables Antibody binding to EGF Receptor in the Surface of MCF7 Breast Cancer Cell Line: Application and Production Review

In this review, single-chain fragment variable construction using phage-display technology as a promising anticancer immunotherapy technology is described. Cloning and the specific bio-panning selection with phage display technology, as well as the use of the epidermal growth factor receptor (EGFR) at the surface of MCF-7 cells as the antigen for the straightforward specific selection of single chain Fvs, are discussed. Moreover, phage display technologies and their application are important for vaccine production and immunotherapy against viruses and cancers. Furthermore, expression of the gene will cause the production and expression of the protein in prokaryotic and eukaryotic cells, which can be used to detect anti-cancer single chain fragment variables (scFvs). Finally, homology modelling is described to show the three-dimensional scFv structure that verifies the Complementary-Determining-Regions (CDRs) on the surface of the model.

A Flux DC Bias Suppression Scheme of Single-stage Full-bridge PFC Converters Based on Dead Zone Adjustment

由于单级桥式功率因数校正（power factor correction,PFC）AC/DC变换技术电路的特点,导致高频变压器存在偏磁现象,影响了系统正常工作。传统方式通过增加变压器气隙或使用隔直电容来防止变压器出现偏磁,但是该类方案影响了系统性能,并增加了电路的复杂程度。结合有源钳位单级PFC变换器工作特点,提出一种基于死区调节的偏磁抑制策略,通过改变系统的开关时序,能够有效抑制偏磁,具有不增加主电路复杂程度、不影响系统性能、数字控制和模拟控制都能够实现等优点。在提出抑制策略的基础上,设计实现电路,给出死区设计方法及影响规律,最后进行实验研究。理论分析及实验结果表明,该策略能够在不影响系统性能的基础上,有效抑制单级桥式PFC变换器的高频变压器偏磁。

Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.