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Biomedical subjects

Wei Pan

Publications and source records attributed to Wei Pan.

At least 19 recordsLinked to original sources

Incorporating prior information via shrinkage: a combined analysis of genome-wide location data and gene expression data.

Transcriptional control is a critical step in regulation of gene expression. Understanding such a control on a genomic level involves deciphering the mechanisms and structures of regulatory programmes and networks. A difficulty arises due to the weak signal and high noise in various sources of data while most current approaches are limited to analysis of a single source of data. A natural alternative is to improve statistical efficiency and power by a combined analysis of multiple sources of data. Here we propose a shrinkage method to combine genome-wide location data and gene expression data to detect the binding sites or target genes of a transcription factor. Specifically, a prior 'non-target' gene list is generated by analysing the expression data, and then this information is incorporated into the subsequent binding data analysis via a shrinkage method. There is a Bayesian justification for this shrinkage method. Both simulated and real data were used to evaluate the proposed method and compare it with analysing binding data alone. In simulation studies, the proposed method gives higher sensitivity and lower false discovery rate (FDR) in detecting the target genes. In real data example, the proposed method can reduce the estimated FDR and increase the power to detect the previously known target genes of a broad transcription regulator, leucine responsive regulatory protein (Lrp) in Escherichia coli. This method can also be used to incorporate other information, such as gene ontology (GO), to microarray data analysis to detect differentially expressed genes.

Bayes Theorem↗

Imaging brain activity during natural vision using CASL perfusion fMRI.

Functional MRI (fMRI) has begun to be used to explore human brain activity during ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI provides an appealing approach for imaging sustained brain activity during natural conditions because of its long-term temporal stability and ability to noninvasively quantify absolute cerebral blood flow (CBF). The present study used ASL perfusion fMRI to measure brain activation patterns associated with natural vision by concurrently recording CBF and blood oxygen level-dependent (BOLD) contrasts while subjects were freely viewing a cartoon movie. Reliable quantitative whole-brain CBF values ( approximately 60 mL/100g/min) as well as regional CBF values (45 approximately 80 mL/100g/min) were measured during movie viewing and resting states. The perfusion contrast revealed CBF increases in multiple visual pathway areas and frontal areas, and CBF decreases in ventromedial frontal cortex and superior temporal cortex during movie viewing compared to resting states. Concurrent BOLD contrast revealed similar but weaker activation and deactivation patterns. Regression analyses of both CBF data and BOLD data showed significant associations between activation in the middle temporal (MT) region and subjects' perception of motion. Region of interest analysis based on a priori literature-defined MT demonstrated significant monotonic stepwise associations between the intensity of motion perception and the CBF and BOLD signal changes. These results demonstrate the feasibility of using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural activation during natural and ecologically valid situations, and support the notion of maintained functional segregation and specialization during natural vision.

Adult↗

Semi-supervised learning via penalized mixture model with application to microarray sample classification.

MOTIVATION: It is biologically interesting to address whether human blood outgrowth endothelial cells (BOECs) belong to or are closer to large vessel endothelial cells (LVECs) or microvascular endothelial cells (MVECs) based on global expression profiling. An earlier analysis using a hierarchical clustering and a small set of genes suggested that BOECs seemed to be closer to MVECs. By taking advantage of the two known classes, LVEC and MVEC, while allowing BOEC samples to belong to either of the two classes or to form their own new class, we take a semi-supervised learning approach; for high-dimensional data as encountered here, we propose a penalized mixture model with a weighted L1 penalty to realize automatic feature selection while fitting the model. RESULTS: We applied our penalized mixture model to a combined dataset containing 27 BOEC, 28 LVEC and 25 MVEC samples. Analysis results indicated that the BOEC samples appeared to form their own new class. A simulation study confirmed that, compared with the standard mixture model with or without initial variable selection, the penalized mixture model performed much better in identifying relevant genes and forming corresponding clusters. The penalized mixture model seems to be promising for high-dimensional data with the capability of novel class discovery and automatic feature selection.

Algorithms↗

Calcium-regulated phosphorylation of soybean serine acetyltransferase in response to oxidative stress.

Glycine max serine acetyltransferase 2;1 (GmSerat2;1) is a member of a family of enzymes that catalyze the first reaction in the biosynthesis of cysteine from serine. It was identified by interaction cloning as a protein that binds to calcium-dependent protein kinase. In vitro phosphorylation assays showed that GmSerat2;1, but not GmSerat2;1 mutants (S378A or S378D), were phosphorylated by soybean calcium-dependent protein kinase isoforms. Recombinant GmSerat2;1 was also phosphorylated by soybean cell extract in a Ca2+-dependent manner. Phosphorylation of recombinant GmSerat2;1 had no effect on its catalytic activity but rendered the enzyme insensitive to the feedback inhibition by cysteine. In transient expression analyses, fluorescently tagged GmSerat2;1 localized in the cytoplasm and with plastids. Phosphorylation state-specific antibodies showed that an increase in GmSerat2;1 phosphorylation occurred in vivo within 5 min of treatment of soybean cells with 0.5 mM hydrogen peroxide, whereas GmSerat2;1 protein synthesis was not significantly induced until 1 h after oxidant challenge. Internal Ca2+ was required in the induction of both GmSerat2;1 phosphorylation and synthesis. Treatment of cells with calcium antagonists showed that externally derived Ca2+ was important for retaining GmSerat2;1 at a basal level of phosphorylation but was not necessary for its hydrogen peroxide-induced synthesis. Protein phosphatase type 1, but not type 2A or alkaline phosphatase, dephosphorylated native GmSerat2;1 in vitro. These results support the hypothesis that GmSerat2;1 is regulated by calcium-dependent protein kinase phosphorylation in vivo and suggest that increased GmSerat2;1 synthesis and phosphorylation in response to active oxygen species could play a role in anti-oxidative stress response.

Amino Acid Sequence↗

Aqueous-organic phase-transfer of highly stable gold, silver, and platinum nanoparticles and new route for fabrication of gold nanofilms at the oil/water interface and on solid supports.

A simple but effective aqueous-organic phase-transfer method for gold, silver, and platinum nanoparticles was developed on the basis of the decrease of the PVP's solubility in water with the temperature increase. The present method is superior in the transfer efficiency of highly stable nanoparticles to the common phase-transfer methods. The gold, silver, and platinum nanoparticles transferred to the 1-butanol phase dispersed well, especially silver and platinum particles almost kept the previous particle size. Electrochemical synthesis of gold nanoparticles in an oil-water system was achieved by controlling the reaction temperature at 80 degrees C, which provides great conveniences for collecting metal particles at the oil/water interface and especially for fabricating dense metal nanoparticle films. A technique to fabricate gold nanofilms on solid supports was also established. The shapes and sizes of gold nanoparticles as the building blocks may be controllable through changing reaction conditions.

Journal Article↗

Proactive telephone counseling as an adjunct to minimal intervention for smoking cessation: a meta-analysis.

Proactive telephone counseling is an effective adjunct to minimal intervention for smoking cessation, but its effect has not been quantitatively synthesized thoroughly. The present meta-analysis reviewed 22 studies published between January 1990 and December 2003 and found that there was a heterogeneous, significant adjunct effect of proactive telephone counseling for smoking cessation. This meta-analytic review also found that the following study characteristics explained most of the variation in the adjunct effect: year of publication, follow-up time, mean age of participants, proportion of female participants, participants' readiness to quit smoking and number of cigarettes smoked per day before intervention. In other words, based on the 22 studies, proactive telephone counseling is effective as an adjunct to other minimal interventions for younger, male, light-smoking participants. The results of this meta-analytic review imply that researchers and health care providers may need to focus on participants as much as on intervention process to obtain more effective interventions.

Counseling↗

Operon information improves gene expression estimation for cDNA microarrays.

BACKGROUND: In prokaryotic genomes, genes are organized in operons, and the genes within an operon tend to have similar levels of expression. Because of co-transcription of genes within an operon, borrowing information from other genes within the same operon can improve the estimation of relative transcript levels; the estimation of relative levels of transcript abundances is one of the most challenging tasks in experimental genomics due to the high noise level in microarray data. Therefore, techniques that can improve such estimations, and moreover are based on sound biological premises, are expected to benefit the field of microarray data analysis RESULTS: In this paper, we propose a hierarchical Bayesian model, which relies on borrowing information from other genes within the same operon, to improve the estimation of gene expression levels and, hence, the detection of differentially expressed genes. The simulation studies and the analysis of experiential data demonstrated that the proposed method outperformed other techniques that are routinely used to estimate transcript levels and detect differentially expressed genes, including the sample mean and SAM t statistics. The improvement became more significant as the noise level in microarray data increases. CONCLUSION: By borrowing information about transcriptional activity of genes within classified operons, we improved the estimation of gene expression levels and the detection of differentially expressed genes.

Animals↗

Effects of unwanted feedback on synchronized chaotic optical communications.

The effects of unwanted external optical feedback on synchronized chaotic optical communication systems are studied numerically. We consider an open-loop configuration consisting of a transmitter laser with double external optical feedbacks and a receiver laser with optical injection from the transmitter laser. First, including the effects of unwanted optical feedback, the synchronization performances of both the complete synchronization and the generalized synchronization are examined. Then the encoding and decoding performances of the generalized synchronization and the effects of the introduced feedback are investigated, respectively. Finally, we study the control of the unwanted feedback on the dynamics of the transmitter laser and briefly discuss the system security when the transmitter laser is driven to operate in a steady state or periodic oscillation state by the additional feedback.

Journal Article↗

Resveratrol prevents CsA inhibition of proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through an ER/NO/cGMP pathway.

The purpose of this study was to investigate the in vitro effects of resveratrol (RSVL) and cyclosporin A (CsA) on proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cell (BMSC) cultures. Application of RSVL (10(-8) -10(-6) mol l(-1)) resulted in a dose-dependent increase in [3H]-thymidine incorporation, alkaline phosphatase (ALP) activity and calcium deposition of BMSCs cultures, which was accompanied with the increase of NO production and cGMP content. Concurrent treatment with the estrogen receptor antagonist ICI182,780 (10(-7) mol l(-1)) or the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (6 x 10(-3) mol l(-1)) abolished the RSVL (10(-6) mol l(-1))-induced increase in NO production and cGMP content and eliminated the RSVL-induced increase in proliferation and osteoblastic differentiation of BMSCs. In contrast, CsA (10(-6) -10(-5) mol l(-1)) dose-dependently decreased [3H]-thymidine incorporation, ALP activity and calcium deposition of BMSCs cultures, which was accompanied with the reduction of NO production in the conditioned media. Concurrent treatment with RSVL (10(-6) mol l(-1)) significantly reversed the CsA (3 x 10(-6) mol l(-1))-mediated decrease in NO production and restored the proliferation and differentiation potential of BMSCs. Our data suggest that (1) the NO/cGMP pathway may play an important role in both RSVL-induced and CsA-inhibited proliferation and osteoblastic differentiation of mouse BMSCs, and (2) RSVL may act through an ER/NO/cGMP pathway to reverse the inhibitory effect of CsA on BMSC cultures. Taken together, the data suggest that RSVL may prevent osteoporosis induced by CsA.

Animals↗

Incorporating biological knowledge into distance-based clustering analysis of microarray gene expression data.

MOTIVATION: Because co-expressed genes are likely to share the same biological function, cluster analysis of gene expression profiles has been applied for gene function discovery. Most existing clustering methods ignore known gene functions in the process of clustering. RESULTS: To take advantage of accumulating gene functional annotations, we propose incorporating known gene functions into a new distance metric, which shrinks a gene expression-based distance towards 0 if and only if the two genes share a common gene function. A two-step procedure is used. First, the shrinkage distance metric is used in any distance-based clustering method, e.g. K-medoids or hierarchical clustering, to cluster the genes with known functions. Second, while keeping the clustering results from the first step for the genes with known functions, the expression-based distance metric is used to cluster the remaining genes of unknown function, assigning each of them to either one of the clusters obtained in the first step or some new clusters. A simulation study and an application to gene function prediction for the yeast demonstrate the advantage of our proposal over the standard method.

Algorithms↗

Incorporating gene functions as priors in model-based clustering of microarray gene expression data.

MOTIVATION: Cluster analysis of gene expression profiles has been widely applied to clustering genes for gene function discovery. Many approaches have been proposed. The rationale is that the genes with the same biological function or involved in the same biological process are more likely to co-express, hence they are more likely to form a cluster with similar gene expression patterns. However, most existing methods, including model-based clustering, ignore known gene functions in clustering. RESULTS: To take advantage of accumulating gene functional annotations, we propose incorporating known gene functions as prior probabilities in model-based clustering. In contrast to a global mixture model applicable to all the genes in the standard model-based clustering, we use a stratified mixture model: one stratum corresponds to the genes of unknown function while each of the other ones corresponding to the genes sharing the same biological function or pathway; the genes from the same stratum are assumed to have the same prior probability of coming from a cluster while those from different strata are allowed to have different prior probabilities of coming from the same cluster. We derive a simple EM algorithm that can be used to fit the stratified model. A simulation study and an application to gene function prediction demonstrate the advantage of our proposal over the standard method. CONTACT: weip@biostat.umn.edu

Algorithms↗

Profile of machine safety in small metal fabrication businesses.

BACKGROUND: Metal working has been identified as an industry with one of the highest rates of non-fatal injury in the United States. However, the systematic evaluation of machine-related hazards is lacking. METHODS: The Minnesota Machine Guarding Study evaluates the effectiveness of a peer-based technical and educational intervention designed to reduce exposure to amputation hazards among workers in small machining/metal working businesses. The data presented here provide a profile of machine guarding in small (5-100 employees) metal fabrication businesses in Minnesota. A set of checklists to quantify machine-guarding practices were developed. Up to 25 randomly selected machines were evaluated in each facility. In addition, walk-through surveys were conducted to assess machine-related safety practices and programs (e.g., lock out-tag out). RESULTS: A total of 824 machines were evaluated. Overall, 55% (SD 11%) of items addressing machine guarding were present. No single machine complied with all critical safety requirements. Shops with safety committees tended to have better scores than did shops without safety committees. Thirty-five percent of all businesses had established machine guarding procedures and 17% provided training in machine guarding (e.g., use of machine guards and devices in daily operations) to their employees. CONCLUSIONS: These data indicate that machine guarding and related safety programs in small metal fabrication businesses were inadequate. The data also suggest that safety committees are an important component in improving machine safety and related programs in small businesses.

Equipment Safety↗

Combining gene annotations and gene expression data in model-based clustering: weighted method.

It has been increasingly recognized that incorporating prior knowledge into cluster analysis can result in more reliable and meaningful clusters. In contrast to the standard modelbased clustering with a global mixture model, which does not use any prior information, a stratified mixture model was recently proposed to incorporate gene functions or biological pathways as priors in model-based clustering of gene expression profiles: various gene functional groups form the strata in a stratified mixture model. Albeit useful, the stratified method may be less efficient than the global analysis if the strata are non-informative to clustering. We propose a weighted method that aims to strike a balance between a stratified analysis and a global analysis: it weights between the clustering results of the stratified analysis and that of the global analysis; the weight is determined by data. More generally, the weighted method can take advantage of the hierarchical structure of most existing gene functional annotation systems, such as MIPS and Gene Ontology (GO), and facilitate choosing appropriate gene functional groups as priors. We use simulated data and real data to demonstrate the feasibility and advantages of the proposed method.

Algorithms↗

Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity.

BACKGROUND: Despite the fact that obesity is a known risk factor for cardiovascular disease, many studies have failed to demonstrate that obesity is independently associated with an increased risk of cardiovascular morbidity and mortality in nondiabetic patients undergoing coronary artery bypass graft surgery. The authors investigated the influence of obesity on adverse postoperative outcomes in diabetic and nondiabetic patients after primary coronary artery bypass surgery. METHODS: A retrospective cohort study of patients undergoing primary coronary artery bypass surgery (n = 9,862) between January 1995 and December 2004 at the Texas Heart Institute was performed. Diabetic (n = 3,374) and nondiabetic patients (n = 6,488) were classified into five groups, according to their body mass index: normal weight (n = 2,148), overweight (n = 4,257), mild obesity (n = 2,298), moderate obesity (n = 785), or morbid obesity (n = 338). Multivariate, stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications to determine whether obesity was independently associated with an increased risk of adverse postoperative outcomes. RESULTS: Obesity in nondiabetic patients was not independently associated with an increased risk of adverse postoperative outcomes. In contrast, obesity in diabetic patients was independently associated with a significantly increased risk of postoperative respiratory failure (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.41-3.61; P < 0.001), ventricular tachycardia (OR, 2.27; 95% CI, 1.18-4.35; P < 0.02), atrial fibrillation (OR, 1.56; 95% CI, 1.03-2.38; P < 0.04), atrial flutter (OR, 2.38; 95% CI, 1.29-4.40; P < 0.01), renal insufficiency (OR, 1.66; 95% CI, 1.10-3.41; P < 0.03), and leg wound infection (OR, 5.34; 95% CI, 2.27-12.54; P < 0.001). Obesity in diabetic patients was not independently associated with an increased risk of mortality, stroke, myocardial infarction, sepsis, or sternal wound infection. CONCLUSION: Obesity in diabetic patients is an independent predictor of worsened postoperative outcomes after primary coronary artery bypass graft surgery.

Adult↗

[Chemical forms of cadmium in industrial contaminated soil and its phytoremediation].

The study showed that the adsorbed cadmium in soil could be dissolved in water, and the lower the soil pH, the higher and stronger the dissolving rate and mobility, and the more uptake by crops. The water-soluble, exchangeable and complexed cadmium contents in the contaminated soil were lower when the soil was chemically neutral, with the values being 0.68%, 12.70% and 12.40%, respectively, while the insoluble (granulated) cadmium content was 74.40%. Radish caudex in the contaminated soil could absorb cadmium, and be considered as the hyperaccumulator of soil cadmium.

Biodegradation, Environmental↗

[Serum levels of IFN-gamma and IL-4 in children with Mycoplasmal pneumonia at the acute phase].

OBJECTIVE: Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) are typical cytokines produced by CD4(+) T cells under antigenic stimulations, and the changes of serum levels of the two cytokines can indirectly reflect the immune state and the progress of inflammation. The aim of this study was to investigate the changes of IFN-gamma and IL-4 in peripheral blood of children with Mycoplasmal pneumonia. METHODS: The peripheral blood concentrations of IFN-gamma and IL-4 were measured using ELISA in 40 children with Mycoplasmal pneumonia at the acute stage. The samples from 40 healthy children were used as the Control group. RESULTS: The serum concentrations of IFN-gamma and IL-4 in the Mycoplasmal pneumonia group were 99.43 +/- 13.18 and 44.61 +/- 17.46 pg/mL, respectively, which were higher than those in the Control group (86.23 +/- 6.31 and 25.97 +/- 9.40 pg/mL respectively; P < 0.05). CONCLUSIONS: There was an imbalance in cytokine secretion in children with Mycoplasmal pneumonia at the acute phase, suggesting that adjuvant immunological therapy is needed for Mycoplasmal pneumonia.

Acute Disease↗