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Biomedical subjects

Kui Zhang

Publications and source records attributed to Kui Zhang.

35 records · Page 2Linked to original sources

Effects of seawater salinity on nitrite accumulation in short-range nitrification to nitrite as end product.

The effect of seawater salinity on nitrite accumulation in short-range nitrification to nitrite as the end product was studied by using a SBR. Experimental results indicated that the growth of nitrobacteria was inhibited and very high levels of nitrite accumulation at different salinities were achieved under the conditions of 25-28 degrees C, pH 7.5-8.0, and the influent ammonia nitrogen of 40-70 mg/L when seawater flow used to flush toilet was less than 35% (salinity 12393 mg/L, Cl- 6778 mg/L) of total domestic wastewater flow, which is mainly ascribed to much high chlorine concentration of seawater. Results showed that high seawater salinity is available for short-range nitrification to nitrite as the end product. When the seawater flow used to flush toilet accounting for above 70% of the total domestic wastewater flow, the removal efficiency of ammonia was still above 80% despite the removal of organics declined obviously (less than 60%). It was found that the effect of seawater salinity on the removal of organics was negative rather than positive one as shown for ammonia removal.

Ammonia↗

[Leptin and clustering of the components of risk factors for metabolic syndrome].

OBJECTIVES: To evaluate relationship between serum level of leptin and the components of risk factors for metabolic syndrome and to analyze the characteristics and laws of clustering of the risk factors. METHODS: Totally, 795 non-diabetic adult Chinese subjects (691 men and 104 women, aged 40 - 75 years) from a diabetes prevalence survey in 2000 were involved in this study. Measurements included serum levels of true insulin (TI), leptin, fasting lipids, fasting glucose (FBG) and 2 h postchallenge glucose, as well as seated blood pressure (BP), body mass index (BMI), ratio of waist circumference to hip circumference (WHR), calculated quantitative insulin sensitivity check index (QUICKI), etc. Relationship between serum level of leptin and all the variables mentioned above was studied by statistical methods such as factor analysis, etc. RESULTS: Serum level of leptin in the study subjects increased with the number of components of abnormal metabolism they had. Detection rates of obesity, hypertension, dyslipidemia and metabolic syndrome were significantly higher in those with the upper tertile of serum leptin level than in those with the lower tertile. Factor analysis revealed that variation of the 11 variables including serum level of leptin was affected by the three factors, i.e., the central factor associated with BMI, WHR, FTI, QUICKI and higher serum level of triglyceride (TG) and lower serum level of high-density lipoprotein-cholesterol (HDL-C), the glucose intolerance factor loaded with blood glucose level, FTI, QUICKI and higher serum level of TG (in women only) and the hypertension factor loaded with blood pressure and BMI (in men only), which could explain 62.0% and 66.7% of total variance in men and women, respectively, and higher serum level of TI and insulin resistance also loaded with both the central factor and glucose tolerance factor. CONCLUSIONS: Serum level of leptin was significantly associated with the key markers of metabolic syndrome. Hyperleptinaemia could be a new component of metabolic syndrome. Clustering of the risk factors for metabolic syndrome could be affected by many factors, and although insulin resistance played an important role in it, insulin resistance alone could not explain its etiology.

Adult↗

Detecting susceptibility genes in case-control studies using set association.

Complex diseases are generally caused by intricate interactions of multiple genes and environmental factors. Most available linkage and association methods are developed to identify individual susceptibility genes assuming a simple disease model blind to any possible gene - gene and gene - environmental interactions. We used a set association method that uses single-nucleotide polymorphism markers to locate genetic variation responsible for complex diseases in which multiple genes are involved. Here we extended the set association method from bi-allelic to multiallelic markers. In addition, we studied the type I error rates and power for both approaches using simulations based on the coalescent process. Both bi-allelic set association (BSA) and multiallelic set association (MSA) tests have the correct type I error rates. In addition, BSA and MSA can have more power than individual marker analysis when multiple genes are involved in a complex disease. We applied the MSA approach to the simulated data sets from Genetic Analysis Workshop 13. High cholesterol level was used as the definitive phenotype for a disease. MSA failed to detect markers with significant linkage disequilibrium with genes responsible for cholesterol level. This is due to the wide spacing between the markers and the lack of association between the marker loci and the simulated phenotype.

Adult Children↗

Defining haplotype blocks and tag single-nucleotide polymorphisms in the human genome.

Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about their relative performance in real data or about the impact of allele frequencies and parameter choices on the detection of haplotype blocks and the markers that tag them. Here we present a formal comparison of two major algorithms, a linkage disequilibrium (LD)-based method and a dynamic programming algorithm (DPA), in three chromosomal regions differing in gene content and recombination rate. The two methods produced strikingly different results. DPA identified fewer and larger haplotype blocks as well as a smaller set of tag SNPs than the LD method. For both methods, the results were strongly dependent on the allele frequency. Decreasing the minor allele frequency led to an up to 3.7-fold increase in the number of haplotype blocks and tag SNPs. Definition of haploytpe blocks and tag SNPs was also sensitive to parameter changes, but the results could not be reconciled simply by parameter adjustment. These results show that two major methods for detecting haplotype blocks and tag SNPs can produce different results in the same data and that these results are sensitive to marker allele frequencies and parameter choices. More information is needed to guide the choice of method, marker allele frequencies, and parameters in the development of a haplotype map.

Algorithms↗

[Role of leptin in the pathogenesis of obesity-related hypertension].

OBJECTIVE: To assess the role of leptin in the pathogenesis of obesity-related hypertension and the relationship between blood pressure (BP), and body mass index (BMI), insulin resistance and leptin were examined. METHODS: 560 non-diabetic men, aged 35 - 75, selected from volunteers of health screening test during 2 000 were divided into hypertension group (n = 321, BP >or= 140/90 mm Hg without antihypertensive medication). and normal blood pressure group (n = 239). The body weight, waist hip ratio,BP, plasma glucose, serum lipids, true insulin (TI) and leptin were measured after overnight fast. Insulin sensitivity was assessed by the HOMA insulin resistance index (HOMA-R). RESULTS: Fasting leptin level showed good correlation with BMI, fasting TI, HOMA-R, BP and also triglycerides (all P < 0.01). After adjustment for age, BMI and HOMA-R, serum leptin was still positively correlated to SBP (r = 0.11, P < 0.05), and was significantly higher in hypertensive subjects than in normotensive subjects (geometric mean 6.4 vs 4.7 micro g/L, P < 0.001). Logistic regression analysis demonstrated that leptin remained significantly associated with hypertension after adjustment for potentially confounding factors. CONCLUSION: Leptin may play an important role in the pathogenesis of obesity related hypertension.

Adult↗

Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data.

Recent studies have shown that the human genome has a haplotype block structure such that it can be decomposed into large blocks with high linkage disequilibrium (LD) and relatively limited haplotype diversity, separated by short regions of low LD. One of the practical implications of this observation is that only a small fraction of all the single-nucleotide polymorphisms (SNPs) (referred as "tag SNPs") can be chosen for mapping genes responsible for human complex diseases, which can significantly reduce genotyping effort, without much loss of power. Algorithms have been developed to partition haplotypes into blocks with the minimum number of tag SNPs for an entire chromosome. In practice, investigators may have limited resources, and only a certain number of SNPs can be genotyped. In the present article, we first formulate this problem as finding a block partition with a fixed number of tag SNPs that can cover the maximal percentage of the whole genome, and we then develop two dynamic programming algorithms to solve this problem. The algorithms are sufficiently flexible to permit knowledge of functional polymorphisms to be considered. We apply the algorithms to a data set of SNPs on human chromosome 21, combining the information of coding and noncoding regions. We study the density of SNPs in intergenic regions, introns, and exons, and we find that the SNP density in intergenic regions is similar to that in introns and is higher than that in exons, results that are consistent with previous studies. We also calculate the distribution of block break points in intergenic regions, genes, exons, and coding regions and do not find any significant differences.

Chromosomes, Human, Pair 21↗

Prediction of protein function using protein-protein interaction data.

Assigning functions to novel proteins is one of the most important problems in the postgenomic era. Several approaches have been applied to this problem, including the analysis of gene expression patterns, phylogenetic profiles, protein fusions, and protein-protein interactions. In this paper, we develop a novel approach that employs the theory of Markov random fields to infer a protein's functions using protein-protein interaction data and the functional annotations of protein's interaction partners. For each function of interest and protein, we predict the probability that the protein has such function using Bayesian approaches. Unlike other available approaches for protein annotation in which a protein has or does not have a function of interest, we give a probability for having the function. This probability indicates how confident we are about the prediction. We employ our method to predict protein functions based on "biochemical function," "subcellular location," and "cellular role" for yeast proteins defined in the Yeast Proteome Database (YPD, www.incyte.com), using the protein-protein interaction data from the Munich Information Center for Protein Sequences (MIPS, mips.gsf.de). We show that our approach outperforms other available methods for function prediction based on protein interaction data. The supplementary data is available at www-hto.usc.edu/~msms/ProteinFunction.

Bayes Theorem↗

[Development of software system of medical monitoring equipment in spacecraft].

OBJECTIVE: To develop a software system that can gather, manage and transmit signals of electrocardiograms, respiration, body temperature and blood pressure at real time, in order to monitor physiological signals of astronauts. METHOD: Based on single-chip microprocessor, software system completed the A/D conversion, real-time signal processing, storage and transmission. RESULT: The software system realized data acquisition of electrocardiogram, respiration, body temperature and blood pressure, as well as heart rate extraction from electrocardiogram, storage of physiological data, and transmission of physiological parameters to spacecraft. CONCLUSION: The software system could meet the needs of medical monitoring during manned spaceflight.

Aerospace Medicine↗

[Development of impact acceleration measurement facility in return-cabin of spacecraft].

OBJECTIVE: To provide the basis for medical evaluation of spacecraft, and to measure the impact acceleration of return-cabin of spacecraft. METHOD: A facility to measure the impact acceleration of "SZ-3" and "SZ-4" during landing was developed and the acquired test data were analyzed. RESULT: The data of impact acceleration of return-cabins of "SZ-3" and "SZ-4" were accurately recorded during landing. Most reliable and scientific data were gotten. CONCLUSION: This facility could validate and evaluate the specifications of relevant systems of spacecraft, and provided the scientific basis for the decision if "SZ-5", the manned spacecraft, could be launched.

Acceleration↗

Haplotype block structure and its applications to association studies: power and study designs.

Recent studies have shown that the human genome has a haplotype block structure, such that it can be divided into discrete blocks of limited haplotype diversity. In each block, a small fraction of single-nucleotide polymorphisms (SNPs), referred to as "tag SNPs," can be used to distinguish a large fraction of the haplotypes. These tag SNPs can potentially be extremely useful for association studies, in that it may not be necessary to genotype all SNPs; however, this depends on how much power is lost. Here we develop a simulation study to quantitatively assess the power loss for a variety of study designs, including case-control designs and case-parental control designs. First, a number of data sets containing case-parental or case-control samples are generated on the basis of a disease model. Second, a small fraction of case and control individuals in each data set are genotyped at all the loci, and a dynamic programming algorithm is used to determine the haplotype blocks and the tag SNPs based on the genotypes of the sampled individuals. Third, the statistical power of tests was evaluated on the basis of three kinds of data: (1) all of the SNPs and the corresponding haplotypes, (2) the tag SNPs and the corresponding haplotypes, and (3) the same number of randomly chosen SNPs as the number of tag SNPs and the corresponding haplotypes. We study the power of different association tests with a variety of disease models and block-partitioning criteria. Our study indicates that the genotyping efforts can be significantly reduced by the tag SNPs, without much loss of power. Depending on the specific haplotype block-partitioning algorithm and the disease model, when the identified tag SNPs are only 25% of all the SNPs, the power is reduced by only 4%, on average, compared with a power loss of approximately 12% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. When the identified tag SNPs are approximately 14% of all the SNPs, the power is reduced by approximately 9%, compared with a power loss of approximately 21% when the same number of randomly chosen SNPs is used in a two-locus haplotype analysis. Our study also indicates that haplotype-based analysis can be much more powerful than marker-by-marker analysis.

Algorithms↗

A dynamic programming algorithm for haplotype block partitioning.

We develop a dynamic programming algorithm for haplotype block partitioning to minimize the number of representative single nucleotide polymorphisms (SNPs) required to account for most of the common haplotypes in each block. Any measure of haplotype quality can be used in the algorithm and of course the measure should depend on the specific application. The dynamic programming algorithm is applied to analyze the chromosome 21 haplotype data of Patil et al. [Patil, N., Berno, A. J., Hinds, D. A., Barrett, W. A., Doshi, J. M., Hacker, C. R., Kautzer, C. R., Lee, D. H., Marjoribanks, C., McDonough, D. P., et al. (2001) Science 294, 1719-1723], who searched for blocks of limited haplotype diversity. Using the same criteria as in Patil et al., we identify a total of 3,582 representative SNPs and 2,575 blocks that are 21.5% and 37.7% smaller, respectively, than those identified using a greedy algorithm of Patil et al. We also apply the dynamic programming algorithm to the same data set based on haplotype diversity. A total of 3,982 representative SNPs and 1,884 blocks are identified to account for 95% of the haplotype diversity in each block.

Algorithms↗

On a family-based haplotype pattern mining method for linkage disequilibrium mapping.

Linkage disequilibrium mapping is an important tool in disease gene mapping. Recently, Toivonen et al. [1] introduced a haplotype mining (HPM) method that is applicable to data consisting of unrelated high-risk and normal haplotypes. The HPM method orders haplotypes by their strength of association with trait values, and uses all haplotypes exceeding a given threshold of strength of association to predict the gene location. In this study, we extend the HPM method to pedigree data by measuring the strength of association between a haplotype and quantitative traits of interest using the Quantitative Pedigree Disequilibrium Test proposed by Zhang et al. [2]. This family-based HPM (F-HPM) method can incorporate haplotype information across a set of markers and allow both missing marker data and ambiguous haplotype information. We use a simulation procedure to evaluate the statistical significance of the patterns identified from the F-HPM method. When the F-HPM method is applied to analyze the sequence data from the seven candidate genes in the simulated data sets in the 12th Genetic Analysis Workshop, the association between genes and traits can be detected with high power, and the estimated locations of the trait loci are close to the true sites.

Chromosome Mapping↗

[The relationship between serum leptin, proinsulin, true insulin levels and insulin resistance in non-diabetic subjects: a population-based study].

OBJECTIVE: Leptin is involved in the regulation of body weight and metabolism. Previous data have suggested that leptin levels are related to insulin resistance and in a few reports with impaired insulin secretion. Some even revealed the existence of adipoinsular axis. However, little is known of these relations in Chinese population. With the availability of measurements of true insulin (TI), proinsulin (PI) and leptin, we examined the possible correlation of leptin with TI, PI and with insulin resistance (the HOMA model) in non-diabetic subjects of north China. We also evaluated whether leptin levels were associated with impaired insulin secretion, as evaluated by the fasting PI/TI ratio. METHODS: 902 non-diabetic subjects (670 with normal and 232 impaired glucose tolerance, aged 30 - 80 y) from a population of Beijing residents who underwent a diabetes survey in 2000 were studied. Fasting serum leptin, PI and TI levels were detected by sensitive and specific enzyme-linked immunosorbent assays (ELISA) which were all developed in our laboratory. RESULTS: Serum leptin values were higher in women. Correlation analysis showed that leptin levels were significantly correlated with fasting TI, PI and insulin resistance (HOMA-IR) (in men, n = 794, r = 0.345, 0.236 and 0.364 respectively; in women, n = 110, r = 0.574, 0.375 and 0.576 respectively, P < 0.001), but not with PI/TI ratio (r = -0.09, P < 0.01) in both sex. After adjustment for age, body mass index (BMI) and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with TI, PI and HOMA-IR, although the magnitude of the association was considerably attenuated. CONCLUSIONS: TI and PI levels were positively related to leptin levels independent of obesity and body fat distribution. Thus, subjects with increased insulin levels and/or insulin resistance may be relatively resistant to the effects of leptin, suggesting a dysfunction of leptin-insulin axis. However, leptin levels are not significantly associated with the fasting PI/TI ratio suggesting that leptin levels are not associated with an impairment in insulin secretion. The role of association between hyperinsulinemia/insulin resistance and hyperleptinemia/leptin resistance in the pathogenesis of insulin resistance-related diseases needs further study.

Adult↗

[Management of extensive closed internal degloving injury].

OBJECTIVE: To study the management of extensive closed internal degloving injury (CIDI). METHODS: From September 1987 to October 1999, 18 cases of CIDI were retrospectively reviewed. Of 18 cases, there were 7 cases in thigh, 6 cases in legs and 5 cases in pelvis, ranging from 15 cm x 12 cm to 38 cm x 25 cm in size. Various managements were adopted according to the severity of the injury, including vacuum drainage and adjuvant compression in 5 cases, regrafting of defatting fenestrated full-thickness skin by non-resection in 8 cases, and skin grafting with transfer of myocutaneous flap in 5 cases. Among them, there were 11 cases of bone and articular fixation or repair, 4 cases of principal vessels repair. All of the cases were evaluated clinically and followed up for 6 months to 3 years. RESULTS: In the 8 cases repaired by regrafting of defatting fenestrated full-thickness skin, only one case of skin necrosis, 5 cm x 2 cm in size, recovered after skin grafting; the others healed well. All of the patients recovered normal life and had normal limbs. CONCLUSION: It's crucial to make a careful assessment about the injury severity of CIDI, to stress on importance of management of both CIDI and deep injury, and to choose proper options after comprehensive assessment of the injury.

Adolescent↗

Prediction of protein function using protein-protein interaction data.

Assigning functions to novel proteins is one of the most important problems in the post-genomic era. Several approaches have been applied to this problem, including analyzing gene expression patterns, phylogenetic profiles, protein fusions and protein-protein interactions. We develop a novel approach that applies the theory of Markov random fields to infer a protein's functions using protein-protein interaction data and the functional annotations of its interaction protein partners. For each function of interest and a protein, we predict the probability that the protein has that function using Bayesian approaches. Unlike in other available approaches for protein annotation where a protein has or does not have a function of interest, we give a probability for having the function. This probability indicates how confident we are about the prediction. We apply our method to predict cellular functions (43 categories including a category "others") for yeast proteins defined in the Yeast Proteome Database (YPD), using the protein-protein interaction data from the Munich Information Center for Protein Sequences (MIPS, http://mips.gsf.de). We show that our approach outperforms other available methods for function prediction based on protein interaction data.

Amino Acid Sequence↗

Drinking and drinking patterns and health status in the general population of five areas of China.

AIMS: To understand drinking patterns, health status related to drinking and the level of unrecorded alcoholic beverage consumption for the general population living in five areas of China in 2001. METHODS: By cluster sampling, 24992 community residents aged 15 years or older were interviewed by trained psychiatrists using structured questionnaires provided by WHO. RESULTS: The 1-year drinking rate was 59.0%, and the point prevalence rate of dependence was 3.8%. The average annual consumption of pure alcohol was 4.47 l. The 1-year morbidity from gastritis/ulcer in the whole sample was 7.9%, which associated nonlinearly to alcohol intake, and heart disease and cerebral infarction/cerebral haemorrhage showed V-shaped curve relationships. CONCLUSIONS: The rate of alcohol use was higher in men than in women, and the annual alcohol consumption per capita was higher than that in the 1990s in the selected areas. Alcohol consumption plays a role in the development of alcohol-related physical diseases.

Adult↗