Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from ...genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.
The benefits of coordinating activities and consolidating distribution points in supply chains are well highlighted and intuitively logical. However, the impact of these decisions on the overall ...performance of a complex supply chain may not be as obvious as usually perceived. This study models a relatively complex supply chain and evaluates the impact of simplifying demand and lead time assumptions under various supply chain configurations. Of particular interest is the investigation of the effect of risk pooling and the synchronization of production cycles in a multi-level multi-retailer supply chain under the influence of various parameters such as batch size, delivery frequency and ordering cycle. This study highlights the extent of complicated interaction effects among various factors exist in a complex supply chain and shows that that the intricacy of these effects can be better understood with a simulation model.
► Theoretical study of benzyl methyl ether production over a zeolite catalyst. ► Density functional theory and ONIOM approach were implemented for 3T and 36T cluster of zeolite, respectively. ► ...Results for ONIOM approach with PM3 and UFF method are comparable. ► The rate constants of the studied mechanism were calculated.
Benzyl methyl ether (BME) compounds are largely synthesized by the chemical industry for use as a starting material for the synthesis of other organic compounds. In order to achieve the target of green chemistry, BME can be synthesized from benzyl alcohol and dimethyl carbonate (DMC) using a zeolite catalyst. DMC is a good methylating and carboxymethylating agent that is, in contrast to other such agents, a relatively non-toxic compound. In this study, the methylation and carboxymethylation reactions of benzyl alcohol over a 3T cluster of zeolite and a 36T extended framework was investigated by density functional theory (DFT) and the ONIOM approach, respectively. Both frameworks revealed two pathways for the methylation reaction, the first involving two transition states (TSs) and the second only a single TS. Methylation via the two-TS pathway was found to be more kinetically stable than the single-TS pathway whilst the methylation reaction is kinetically favored over the carboxymethylation reaction. The rate constants with the 36T cluster were increased 104–106 fold compared to the 3T quantum cluster.
Optic neuropathy (ON), a serious complication of Graves ophthalmopathy, is often subclinical and masked by symptoms of orbitopathy. We examined herein bony and soft-tissue CT features associated with ...ON, including an angular assessment of orbital apex capacity, and their usefulness in the risk prediction of ON.
The CT scans of 41 patients with Graves ophthalmopathy (17 men, 24 women; mean age, 49.1 years) clinically diagnosed with (19 patients, 32 orbits) or without ON were evaluated by 2 independent raters. Quantitative linear and angular measurements of the orbital structures and bony walls and categoric scores of apical crowding and intracranial fat prolapse were assessed on a clinical workstation. Inter- and intrarater variability of these features was determined. The CT features of the 2 patient groups were compared, and multivariate logistic regression analysis was performed to evaluate the predictive features of ON.
Bony orbital angles (P < .005), length of the lateral orbital wall (P < .05), muscular diameters (P < .0005), muscular bulk of the medial rectus muscle relative to the bony orbit (P < .05), and apical crowding (P < .0005) were associated with clinical ON. Stepwise multivariate logistic regression analysis revealed the muscle diameter index and medial and lateral wall angles to be independent predictors. Combining these in a single multivariate equation yielded sensitivity, specificity, and positive and negative predictive values of 73%, 90%, 82%, and 85%, respectively.
Orbital wall angles, especially the medial wall, and muscular enlargement are independent risk predictors.
Objective. To assess the reliability, validity and sensitivity to change of a Chinese version of the 36-item Short-Form Health Survey (SF-36) in Chinese-speaking patients with rheumatoid arthritis ...(RA) in Singapore. Methods. The psychometric properties of the Chinese Hong Kong standard version of the SF-36 were assessed in 401 RA patients. The construct validity of the Chinese SF-36 was assessed by comparison with the American College of Rheumatology (ACR) functional status, a validated Chinese Health Assessment Questionnaire (C-HAQ) and markers of RA activity and severity. Results. The overall Cronbach's coefficient alpha was 0.921, reflecting excellent internal consistency. The instrument showed reasonable test–retest reliability except in the social functioning (SF) subscale. There was a significant ceiling effect in the role physical (RP), SF and role emotional (RE) subscales and a floor effect in the RP and RE subscales. Physical function (PF) and SF were strongly correlated with C-HAQ and patient's assessment of RA activity Pearson's correlation coefficient (r) ranging from −0.41 to −0.53 and moderately correlated with ACR functional status (r = −0.35 and −0.3, respectively). Weak correlations were also found between the Chinese SF-36 and markers of RA activity, deformed joint count and radiographic damage. PF and SF were the subscales most responsive to change in quality of life (QOL). Conclusion. The Chinese SF-36 showed reasonable reliability, criterion validity and responsiveness with limitations in certain subscales. Overall, the physical domains and PF in particular may be the most ideal psychometric measures of QOL in RA.
To evaluate the effect of parental myopia on eye size and growth in Chinese children.
A school-based, cross-sectional survey was performed in Chinese children 5 to 16 years of age. A longitudinal ...cohort study was conducted 1 year later. The effects of parental myopia, parental education level, and near work performed by the child on the refractive error and ocular biometry of the child were assessed.
There were 7560 children enrolled in the initial study (response rate: 76.3%). One year later, 4468 children (response rate: 75.9%) in the original cohort (with the exception of those who had completed primary schooling) were evaluated, to determine eye growth. Although children with a stronger parental history of myopia tended to be less hyperopic before the onset of myopia (spherical equivalent refraction SER = 0.43 D, 0.67 D, and 0.68 D in children with two, one, and no myopic parents respectively; P = 0.007), the axial lengths did not follow the same pattern (axial length AL = 23.11, 23.07, and 23.15 mm; P = 0.429). Eye growth and myopic shift in refraction occurred more rapidly among children with a stronger parental history of myopia (annual AL growth/myopia progression = 0.37 mm/-0.22 D, 0.26 mm/-0.07 D, and 0.20 mm/-0.02 D in children with two, one, and no myopic parents, respectively; P < 0.001).
Ocular biometric data in Chinese children suggest that parental history of myopia influences the growth rate of the eye, rather than its size before the onset of myopia, as previously reported in Caucasian children. Further longitudinal studies involving children of different ethnicities are warranted.
A conventional affinity protein purification system often requires a separate protease to separate the target protein from the affinity tag. This paper describes a unique protein purification system ...in which the target protein is fused to the C-terminus of a modified protein splicing element (intein). A small affinity tag is inserted in a loop region of the endonuclease domain of the intein to allow affinity purification. Specific mutations at the C-terminal splice junction of the intein allow controllable C-terminal peptide bond cleavage. The cleavage is triggered by addition of thiols such as dithiothreitol or free cysteine, resulting in elution of the target protein while the affinity-tagged intein remains immobilized on the affinity column. This system eliminates the need for a separate protease and allows purification of a target protein without the N-terminal methionine. We have constructed general cloning vectors and demonstrated single-column purification of several proteins. In addition, we discuss several factors that may affect the C-terminal peptide bond cleavage activity.
The role of the plasminogen activator/plasmin system in fibrinolysis has been well established. Indeed, clinicians worldwide have successfully utilized recombinant tissue‐type plasminogen activator ...as first‐line treatment of acute myocardial infarction for almost 2 decades. Outside the field of cardiology, there has been increasing excitement regarding the possible contribution of this system in many other important biological processes, including cell adhesion, cell migration, cell–cell signaling, tumor invasion and metastasis, ovulation, and wound healing. In this review, we present evidence in the current literature that the plasminogen activator/plasmin system does have a role in wound healing, looking at both normal and abnormal healing. Furthermore, the invaluable insights provided by numerous transgenic animal experiments are summarized. (WOUND REP REG 2003;11:239–247)
PDF
