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Haitao Zhao

Publications and source records attributed to Haitao Zhao.

12 recordsLinked to original sources

Free energy of DNA duplex formation on short oligonucleotide microarrays.

DNA/DNA duplex formation is the basic mechanism that is used in genome tiling arrays and SNP arrays manufactured by Affymetrix. However, detailed knowledge of the physical process is still lacking. In this study, we show a free energy analysis of DNA/DNA duplex formation these arrays based on the positional-dependent nearest-neighbor (PDNN) model, which was developed previously for describing DNA/RNA duplex formation on expression microarrays. Our results showed that the two ends of a probe contribute less to the stability of the duplexes and that there is a microarray surface effect on binding affinities. We also showed that free energy cost of a single mismatch depends on the bases adjacent to the mismatch site and obtained a comprehensive table of the cost of a single mismatch under all possible combination of adjacent bases. The mismatch costs were found to be correlated with those determined in aqueous solution. We further demonstrate that the DNA copy number estimated from the SNP array correlates negatively with the target length; this is presumably caused by inefficient PCR amplification for long fragments. These results provide important insights into the molecular mechanisms of microarray technology and have implications for microarray design and the interpretation of observed data.

Base Pair Mismatch↗

Density functional theory studies on the mechanism of the reduction of CO2 to CO catalyzed by copper(I) boryl complexes.

The detailed reaction mechanism for the reduction of CO2 to CO catalyzed by (NHC)Cu(boryl) complexes (NHC = N-heterocyclic carbene) was studied with the aid of DFT by calculating the relevant intermediates and transition state structures. Our DFT calculations show that the reaction occurs through CO2 insertion into the Cu-B bond to give a Cu-OC(=O)-boryl species (i.e., containing Cu-O and C-B bonds), and subsequent boryl migration from C to O, followed by alpha-bond metathesis between pinB-Bpin (B2pin2, pin = pinacolate = OCMe2CMe2O) and (NHC)Cu(OBpin). The overall reaction is exergonic by 38.0 kcal/mol. It is the nucleophilicity of the Cu-B bond, a function of the very strong alpha-donor properties of the boryl ligand, rather than the oxophilicity of boron, which determines the direction of the CO2 insertion process. The boryl migration from C to O, which releases the product CO, is the rate-determining step and involves the "vacant" orbital orbital on boron. The (NHC)Cu(boryl) complexes show unique activity in the catalytic process. For the analogous (NHC)Cu(alkyl) complexes, the CO2 insertion into the Cu-C bond giving a copper acetate intermediate occurs with a readily achievable barrier. However, the elimination of CO from the acetate intermediate through a methyl migration from C to O is energetically inaccessible.

Boron↗

Application of bFGF and BDNF to improve angiogenesis and cardiac function.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a survival factor for endothelial cells and expresses in the ischemic myocytes. The purpose of this study was to assess whether the simultaneous application of basic fibroblast growth factor (bFGF) and BDNF incorporating gelatin hydrogels improves angiogenesis and cardiac function in ischemic myocardium compared with bFGF applied alone. MATERIALS AND METHODS: Direct intramyocardial injection of 100 microg of bFGF plus 25 microg of BDNF, 100 microg of bFGF, or saline were performed in canine infarct model. Colored microspheres were injected to assess the regional myocardial blood flow. Cardiac function was evaluated by cine magnetic resonance imaging (MRI). Immunohistochemical staining and enzyme linked immunosorbent assay (ELISA) were used to observe the localization and expression of bFGF and BDNF protein, and myocardial microvessel density was assessed by von Willebrand factor staining. RESULTS: Left ventricular ejection fraction (LVEF) was higher in bFGF plus BDNF group than in saline or bFGF group. Blood flow of the peri-infarct region was increased by bFGF plus BDNF treatment. The distribution of bFGF and BDNF-positive cardiomyocytes was similar in three groups. The expression of bFGF and BDNF protein and microvessel density in bFGF plus BDNF group was higher than in the other two groups. CONCLUSIONS: This study indicates that the sustained dual release of bFGF and BDNF incorporating gelatin hydrogels can improve angiogenesis and left ventricular function in the ischemic myocardium compared with bFGF applied alone. bFGF plus BDNF administration may be a promising therapeutic strategy for the treatment of ischemic myocardium.

Animals↗

Effects of basic fibroblast growth factor microspheres on angiogenesis in ischemic myocardium and cardiac function: analysis with dobutamine cardiovascular magnetic resonance tagging.

OBJECTIVE: Therapeutic angiogenesis with angiogenic growth factors has described as one of the promising methods for collateral formation in the treatment of ischemic heart diseases. The purpose of this study is to assess the value of intramyocardial injection of slow-released basic fibroblast growth factor microspheres on angiogenesis and cardiac function in the early period of acute infarcted myocardium with dobutamine cardiovascular magnetic resonance tagging. METHODS: Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. Immediately after coronary artery occlusion, 1 ml of saline containing 100 microg of basic fibroblast growth factor microspheres was injected into peri-infarct myocardial area in the basic fibroblast growth factor group, whereas only gelatin hydrogel microspheres with 1 ml of saline was given in control dogs. Cardiac function was evaluated by cine magnetic resonance imaging. Dobutamine cardiovascular magnetic resonance was performed at rest and during low doses of dobutamine to assess regional wall motion. Immunohistochemical study with von Willebrand factor was performed to observe angiogenesis. RESULTS: Left ventricular ejection fraction improved markedly 10 and 17 days after treatment in the basic fibroblast growth factor group. The basic fibroblast growth factor group had more viable myocardium. Microvessel density was higher in the basic fibroblast growth factor group than in the control group except the first day after treatment. CONCLUSIONS: Intramyocardial administration of basic fibroblast growth factor microspheres can promote the growth of microvessels and improve left ventricular function and myocardial viability in the early period of acute myocardial infarction.

Animals↗

HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma.

Tumor-associated antigens (TAAs) have been the most actively employed targets in the clinical diagnosis and treatment of human carcinoma, such as PSA in the diagnosis of prostate cancer and NY-ESO-1 in the immunotherapy of melanoma and other cancers. However, identification of TAAs has often been hampered by the complicated and laborsome laboratory procedures. In order to accelerate the process of tumor antigen discovery, and thereby improve diagnosis and treatment of human carcinoma, we have made an effort to establish a publicly available Human Potential Tumor Associated Antigen database (HPtaa) with potential TAAs identified by in silico computing (http://www.hptaa.org). Tumor specificity was chosen as the core of tumor antigen evaluation, together with other relevant clues. Various platforms of gene expression, including microarray, expressed sequence tag and SAGE data, were processed and integrated by several penalty algorithms. A total of 3518 potential TAAs have been included in the database, which is freely available to academic users. As far as we know, this database is the first one addressing human potential TAAs, and the first one integrating various kinds of expression platforms for one purpose.

Antigens, Neoplasm↗

A novel incremental principal component analysis and its application for face recognition.

Principal component analysis (PCA) has been proven to be an efficient method in pattern recognition and image analysis. Recently, PCA has been extensively employed for face-recognition algorithms, such as eigenface and fisherface. The encouraging results have been reported and discussed in the literature. Many PCA-based face-recognition systems have also been developed in the last decade. However, existing PCA-based face-recognition systems are hard to scale up because of the computational cost and memory-requirement burden. To overcome this limitation, an incremental approach is usually adopted. Incremental PCA (IPCA) methods have been studied for many years in the machine-learning community. The major limitation of existing IPCA methods is that there is no guarantee on the approximation error. In view of this limitation, this paper proposes a new IPCA method based on the idea of a singular value decomposition (SVD) updating algorithm, namely an SVD updating-based IPCA (SVDU-IPCA) algorithm. In the proposed SVDU-IPCA algorithm, we have mathematically proved that the approximation error is bounded. A complexity analysis on the proposed method is also presented. Another characteristic of the proposed SVDU-IPCA algorithm is that it can be easily extended to a kernel version. The proposed method has been evaluated using available public databases, namely FERET, AR, and Yale B, and applied to existing face-recognition algorithms. Experimental results show that the difference of the average recognition accuracy between the proposed incremental method and the batch-mode method is less than 1%. This implies that the proposed SVDU-IPCA method gives a close approximation to the batch-mode PCA method.

Algorithms↗

Diagnostic protein discovery using liquid chromatography/mass spectrometry for proteolytic peptide targeting.

A peptide targeting method has been developed for diagnostic protein discovery, which combines proteolytic digestion of fractionated plasma proteins and liquid chromatography coupled to electrospray time-of-flight mass spectrometry (LC/ESI-TOFMS) profiling. Proteolysis prior to profiling overcomes molecular weight limitations and compensates for the poor sensitivity of matrix-assisted laser desorption/ionization (MALDI) protein profiling. LC/MS increases the peak capacity compared to crude fractionation techniques or single sample MALDI analysis. Differentially expressed peptides are targeted in the mass chromatograms using bioinformatic techniques and subsequently sequenced with MALDI tandem MS. In a model study comparing pancreatic cancer patients to controls, 74% of the peptide targets were successfully sequenced. This profiling method was superior to previous experiments using single sample MALDI analysis for protein profiling or proteolytic peptide profiling, because more potential protein markers were identified.

Adult↗

The nonmetallicity of molybdenum clusters.

Molybdenum clusters consisting of 2-55 atoms were investigated using density functional theory calculations with a plane-wave basis set. The results show that the linear and planar molybdenum clusters have a strong tendency to form dimers. This tendency results in the formation of alternate short and long bonds within a linear cluster, in which the strength of these short bonds is covalent. Therefore, the linear and planar Mo clusters exhibit significant nonmetallic characteristics. Furthermore, the linear and planar Mo clusters show a strong even-odd effect in binding energy with the even-numbered clusters being more stable than their neighboring odd-numbered clusters. On the other hand, the even-odd effect in the energy gap between the highest occupied and the lowest unoccupied molecular orbitals, i.e., the HOMO-LUMO energy gap, for the linear and the planar clusters is different. The odd-numbered linear clusters and even-numbered planar clusters have larger HOMO-LUMO energy gaps than their corresponding neighboring clusters.

Journal Article↗

Diagnostic protein discovery using proteolytic peptide targeting and identification.

Plasma protein profiling with mass spectrometry is currently being evaluated as a diagnostic tool for cancer and other diseases. These experiments consist of three steps: plasma protein fractionation, analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), and comparisons of the MALDI profiles to develop diagnostic fingerprints using bioinformatic techniques. While preliminary results appear promising in small sample groups, the method is limited by the sensitivity of MALDI-MS for intact proteins, the limited mass range of MALDI-MS, and difficulties associated with isolating individual proteins for identification to validate the diagnostic fingerprint. Here we present an alternative and improved method directed toward diagnostic protein discovery, which incorporates proteolytic peptide profiling, bioinformatic targeting of ion signals, and MALDI tandem mass spectrometry (MS/MS) peptide sequencing, rather than fingerprinting. Pancreatic cancer patients, pancreatitis patients, and controls are used as the model system. Profiling peptides after enzymatic digestion improves sensitivity and extends the accessible protein molecular weight range when compared to intact protein profiling. The first step is to extract and fractionate the proteins from plasma. Each fraction is digested with trypsin and subsequently analyzed by MALDI-MS. Rather than using bioinformatic analysis as a pattern-matching technique, peptides are targeted based on the disease to control peak intensity ratios measured in the averages of all mass spectra in each group and t-tests of the intensity of each individual peak. The targeted peptide ion signals are subsequently identified using MALDI-MS/MS in quadrupole-TOF and tandem-TOF instruments. This study found not only the proteins targeted and identified by a previous protein profiling experiment, but also detected additional proteins. These initial results are consistent with the known biology of pancreatic cancer or pancreatitis, but are not specific to those diseases.

Adult↗

[Expression and clinical significance of MAGE-4 gene in human hepatocellular carcinoma].

OBJECTIVE: To explore the possibility of MAGE-4 gene encoding protein used as a target for immunotherapy in HCC patients. METHODS: The expression of MAGE-4 gene in tumor tissues and tumor adjacent non-HCC liver tissues was examined by the RT-PCR method. The relationship between positive expression rate of MAGE-4 gene and other clinical and lab data including AFP, AFU, anti-HCV, HBsAg, AFP mRNA, and the diameter of the tumors in HCC patients was also determined. RESULTS: The positive expression rate of MAGE-4 gene was significantly higher in the tumor than in tumor surrounding tissues (38.7% vs 0%, P<0.01), while the positive expression rate of MAGE-4 gene had no relationship with the clinical and lab data (P>0.05). CONCLUSIONS: The high frequency of MAGE-4 gene expression in HCC suggests the possibility of MAGE-4 gene encoding protein as a target for immunotherapy in HCC patients, but the expression has no relationship with the tumor metastasis and the recurrence of HCC.

Antigens, Neoplasm↗

A controlled study of the upper airway structure and function in patients with obstructive sleep apnea syndrome and normal adults.

OBJECTIVE: To investigate the major factors associated with the development of obstructive sleep apnea syndrome (OSAS) by logistic step regression analysis. METHOD: Fifty-nine patients with OSAS and 57 normal adults were included in the study. The dependent was whether the subject had OSAS, and the independents included age, sex, body mass index (BMI), as well as the measured data of palate, uvula, lingua and epiglottis by CT scan. Logistic regression was performed by using SPSS software. RESULTS: Among 40 independents, 8 were chosen by logistic regression as the major factors associated with the risk of developing OSAS. These factors were the increase of pharyngeal wall resilience in the uvula region, the thickness of the retropharyngeal soft tissue in the uvula and palate region, the increase of genioglossus width, the decrease of cross section of the palate region, the decrease of the coronal diameter of the uvula and lingual region, and a narrowed diameter of the uvula region. CONCLUSION: The results suggest that anatomic changes of the upper airway at different levels and an increase of the pharyngeal wall resilience in the uvula region are major etiological factors for OSAS.

Adult↗