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Biomedical subjects

Xin Lu

Publications and source records attributed to Xin Lu.

At least 55 records · Page 3Linked to original sources
PubMed2005

Chromosome 1q loss of heterozygosity frequently occurs in sporadic insulinomas and is associated with tumor malignancy.

The pathogenesis of sporadic insulinomas is not clear, and there are no reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor. It was reported that 1q LOH might contribute to pathogenesis in gastrinomas and was correlated with tumor progression. However, little data are available on 1q LOH in sporadic insulinomas. In our study, we determine whether 1q LOH occurs in sporadic insulinomas and is associated with tumor malignancy by performing 1q allelotyping with 17 markers in 40 tumors and pair normal DNA. Thirty-five (88%) insulinomas had 1q LOH. Of the 35 insulinomas with 1q LOH, 14 (40%) had 1q21.3-23.2 LOH over a 7.5 cM region (SRO-1), whereas LOH in 21 tumors (60%) occurred at 1q31.3 over an 11.4 cM area (SRO-2). Of 24 tumors without MEN1 LOH, 20 had either SRO-1 or SRO-2 LOH (83%), whereas in 16 tumors with MEN1 LOH, 9 were shown to have LOH at either SRO-1 or SRO-2 (56%) (p = 0.065). This result suggests that LOH at 2 SRO might be MEN1 gene independent and may contribute to the pathogenesis in a subset of insulinomas without MEN1 gene LOH. The presence of 1q21.3-23.2 LOH is significantly associated with malignancy of insulinomas (p = 0.014). The high frequency of LOH at 1q 21.3-23.2 and 1q31.3 suggests these 2 areas may harbor putative tumor suppressor genes that may play an important role in the tumorigenesis of a subset of insulinomas. LOH at 1q21.3-23.2, which was associated with tumor malignancy, could be one of the genetic markers for identifying malignancy in sporadic insulinomas.

Adolescent↗
PubMed2005

ASPP--Apoptotic specific regulator of p53.

The p53 protein is one of the best-known tumor suppressors. The recently identified ASPP family (apoptosis-stimulating protein of p53) can interfere with the working of p53. Three members of ASPP family are proved to be apoptotic specific regulators of p53. The discovery of ASPP family may answer such questions as "how cells choose to die". Understanding the ASPP status in human cancer will allow us to develop better strategies to treat cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Quantitative determination of compounds in tobacco essential oils by comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry.

A quantitative analysis of the individual compounds in tobacco essential oils is performed by comprehensive two-dimensional gas chromatography (GC x GC) combined with flame ionization detector (FID). A time-of-flight mass spectrometer (TOF/MS) was coupled to GC x GC for the identification of the resolved peaks. The response of a flame ionization detector to different compound classes was calibrated using multiple internal standards. In total, 172 compounds were identified with good match and 61 compounds with high probability value were reliably quantified. For comparative purposes, the essential oil sample was also quantified by one-dimensional gas chromatography-mass spectrometry (GC/MS) with multiple internal standards method. The results showed that there was close agreement between the two analysis methods when the peak purity and match quality in one-dimensional GC/MS are high enough.

Gas Chromatography-Mass Spectrometry↗
PubMed2005

Deconvolution of overlapped peaks based on the exponentially modified Gaussian model in comprehensive two-dimensional gas chromatography.

Comprehensive two-dimensional gas chromatography (GC x GC) has attracted much attention for the analysis of complex samples. Even with a large peak capacity in GC x GC, peak overlapping is often met. In this paper, a new method was developed to resolve overlapped peaks based on the mass conservation and the exponentially modified Gaussian (EMG) model. Linear relationships between the calculated sigma, tau of primary peaks with the corresponding retention time (tR) were obtained, and the correlation coefficients were over 0.99. Based on such relationships, the elution profile of each compound in overlapped peaks could be simulated, even for the peak never separated on the second-dimension. The proposed method has proven to offer more accurate peak area than the general data processing method.

Chromatography, Gas↗
PubMed2005

Resolution prediction and optimization of temperature programme in comprehensive two-dimensional gas chromatography.

A model is developed for predicting the resolution of interested component pair and calculating the optimum temperature programming condition in the comprehensive two-dimensional gas chromatography (GC x GC). Based on at least three isothermal runs, retention times and the peak widths at half-height on both dimensions are predicted for any kind of linear temperature-programmed run on the first dimension and isothermal runs on the second dimension. The calculation of the optimum temperature programming condition is based on the prediction of the resolution of "difficult-to-separate components" in a given mixture. The resolution of all the neighboring peaks on the first dimension is obtained by the predicted retention time and peak width on the first dimension, the resolution on the second dimension is calculated only for the adjacent components with un-enough resolution on the first dimension and eluted within a same modulation period on the second dimension. The optimum temperature programming condition is acquired when the resolutions of all components of interest by GC x GC separation meet the analytical requirement and the analysis time is the shortest. The validity of the model has been proven by using it to predict and optimize GC x GC temperature programming condition of an alkylpyridine mixture.

Chromatography, Gas↗
PubMed2005

Structure and stability of binary transition-metal clusters (NbCo)n (n < or = 5): a relativistic density-functional study.

Equilibrium geometries and electronic properties of binary transition-metal clusters, (NbCo)n (n < or = 5), have been investigated by means of the relativistic density-functional approach. The metal-metal bonding and stability aspects of these clusters have been analyzed on the basis of calculations. Present results show that these clusters exhibit rich structural varieties on the potential-energy surfaces. The most stable structures have a compact conformation in relatively high symmetry, in which the Nb atoms prefer to form an inner core and Co atoms are capped to the facets of the core. Such building features in clustering of the Nb/Co system are related to the order of bond strength: Nb-Nb>Nb-Co>Co-Co. As the binary cluster size increases, the Nb-Co bond may become stronger than the Nb-Nb bond in the inner niobium core, which results in a remarkable increment of the Nb-Nb bond length. Amongst these binary transition-metal clusters, the singlet (NbCo)4 in T(d) symmetry has a striking high stability due to the presence of the spherical aromaticity and electronic shell closure. The size dependence of the bond length and stability of the cluster has been explored.

Journal Article↗
PubMed2005

Cell cycle-dependent nuclear retention of p53 by E2F1 requires phosphorylation of p53 at Ser315.

We show here that the cell cycle-dependent DNA-binding and transcriptional activity of p53 correlates with E2F expression in human primary fibroblasts. E2F1 binds and stimulates DNA-binding, transactivation and apoptotic functions of p53 but not p63 and p73. E2F1 binds residues 347-370 of p53 and enhances nuclear retention of Ser315 phosphorylated p53. This regulation of p53 by E2F1 is cell cycle dependent, as the cellular distribution of Ser315 phosphorylated p53 is associated with the periodic expression of E2F and cyclin A throughout the cell cycle. This is the first demonstration that the activities of p53 are regulated during the cell cycle by E2F/p53 interactions and that phosphorylation of p53 at Ser315 is required for this regulation.

Amino Acid Sequence↗
PubMed2005

Brönsted and Lewis acidity of the BF3/gamma-Al2O3 alkylation catalyst as revealed by solid-state NMR spectroscopy and DFT quantum chemical calculations.

Multinuclear solid-state NMR techniques and DFT quantum chemical calculations were employed to investigate the detailed structure of acid sites on the BF3/gamma-Al2O3 alkylation catalyst. The NMR experiment results indicate that gaseous BF3 is able to react with the hydroxyl groups present on the surface of gamma-Al2O3, leading to the formation of new Brönsted and Lewis acid sites. The 1H/11B and 1H/27Al TRAPDOR (TRAnsfer of Population in DOuble Resonance) experiments suggest that the 3.7 ppm signal in 1H NMR spectra of the BF3/gamma-Al2O3 catalyst is due to a bridging B-OH-Al group that acts as a Brönsted acid site of the catalyst. On the other hand, a Lewis acid site on the surface of the catalysts, as revealed by 31P MAS and 31P/27Al TRAPDOR NMR of adsorbed trimethylphosphine, is associated with three-coordinate -OBF2 species. 13C NMR of adsorbed 2-13C-acetone indicates that the Brönsted acid strength of the catalyst is slightly stronger than that of zeolite HZSM-5 but still weaker than that of 100% H2SO4, which is in good agreement with theoretical prediction. In addition, DFT calculations also reveal the detailed structure of various acid sites formed on the BF3/gamma-Al2O3 catalyst and the interaction of probe molecules with these sites.

Journal Article↗
PubMed2005

Isoflurane preserves energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation.

AIM: To investigate the protective effect of isoflurane on energy balance in isolated hepatocytes during in vitro anoxia/reoxygenation, and to compare isoflurane with halothane. METHODS: Hepatocytes freshly isolated from fed rats were suspended in Krebs-Henseleit buffer, and incubated in sealed flasks under O(2)/CO(2) or N(2)/CO(2) (95%/5%, V/V) for 30 or 60 min, followed by 5 or 10 min of reoxygenation, with an added volatile anesthetic or not. ATP, ADP, and adenosine monophosphate in hepatocytes were determined by high performance liquid chromatography, and energy charge was calculated. RESULTS: During 30 min of anoxia, the energy charge and total adenine nucleotide steadily increased with the isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration (MAC), then decreased from 2 to 3 MAC. In short incubations (30-35 min) at 1 MAC isoflurane, energy charge modestly decreased during anoxia, which was partially prevented by isoflurane and completely reversed by reoxygenation, and total adenine nucleotide did not decrease. In long incubations (60-70 min), both energy charge and total adenine nucleotide greatly decreased during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nucleotide during anoxia and reoxygenation. In addition, 1 MAC isoflurane obviously increased ATP/ADP, which could not be changed by 1 MAC halothane. CONCLUSION: Isoflurane partially protects isolated hepatocytes against decreases in both energy charge and total adenine nucleotide during short (reversible) or long (irreversible) anoxia.

Animals↗
PubMed2005

Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation.

Using various mutants of p53 and mdm2, we demonstrate here that both the DNA binding and transactivation function of p53 are required for ASPP1 and ASPP2 to stimulate the apoptotic functions of p53. Mdm2 and mdmx prevent ASPP1 and ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53. Importantly, mdm2 and mdmx can prevent the stimulatory effects of ASPP1 and ASPP2 without targeting p53 for degradation. These data provide a novel mechanism by which mdm2 and mdmx act as potent inhibitors of p53.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Gene expression profiling of NMU-induced rat mammary tumors: cross species comparison with human breast cancer.

Breast cancer is a complex genetic disease characterized by the accumulation of multiple molecular alterations. The NMU breast cancer model induced in the rat is used for the study of mammary carcinogenesis because it closely mimics human breast disease. To assess the validity of this model from a more global molecular perspective, and also to devise a general technique to compare animal profiles with human microarray studies, we have characterized 25 NMU-induced mammary tumors and 11 normal glands using a combination of immunohistochemical and microarray analyses. The rat mammary carcinomas were classified as non-invasive, ER-positive ductal carcinomas with a composition of differentiated epithelial and myoepithelial cell lineages. Gene expression profiles generated using rat Affymetrix arrays containing 15,866 genes demonstrated that the rat mammary tumors are homogeneous and that H-ras mutations did not confer a unique molecular signature. We compared the resulting rat profiles with those obtained from a human dataset by merging the raw microarray data, using an approach that involves a combination of cross-species and cross-platform analysis. Using this novel strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the classification of human tumors derived from human Affymetrix arrays. The gene expression profiles of the NMU-induced primary tumors were most similar to ER-positive, low to intermediate grade breast cancer. Our technique provides a means to correlate gene expression data from animal models of cancer to human cancer and disease states.

Animals↗
PubMed2005

Mechanisms of initial propane activation on molybdenum oxides: a density functional theory study.

We report the first detailed density functional theory study on the mechanisms of initial propane activation on molybdenum oxides. We consider 6 possible mechanisms of the C-H bond activation on metal oxides, leading to 17 transition states. We predict that hydrogen abstraction by terminal Mo=O is the most feasible reaction pathway. The calculated activation enthalpy and entropy are 32.3 kcal/mol and -28.6 cal/(mol/K), respectively, in reasonably good agreement with the corresponding experimental values (28.0 kcal/mol and -29.1 cal/(mol/K)). We find that activating the methylene C-H bond is 4.7 kcal/mol more favorable than activating the methyl C-H bond. This regioselectivity is correlated with the difference in strength between a methylene C-H bond and a methyl C-H bond. Our calculations suggest that a combined effect from both the methylene and the methyl C-H bond cleavages leads to the experimentally observed overall kinetic isotopic effects from propane to propylene on the MoO(x)/ZrO(2) catalysts.

Journal Article↗
PubMed2005

A boosting approach for motif modeling using ChIP-chip data.

MOTIVATION: Building an accurate binding model for a transcription factor (TF) is essential to differentiate its true binding targets from those spurious ones. This is an important step toward understanding gene regulation. RESULTS: This paper describes a boosting approach to modeling TF-DNA binding. Different from the widely used weight matrix model, which predicts TF-DNA binding based on a linear combination of position-specific contributions, our approach builds a TF binding classifier by combining a set of weight matrix based classifiers, thus yielding a non-linear binding decision rule. The proposed approach was applied to the ChIP-chip data of Saccharomyces cerevisiae. When compared with the weight matrix method, our new approach showed significant improvements on the specificity in a majority of cases.

Algorithms↗
PubMed2005

Mechanisms of methane activation and transformation on molybdenum oxide based catalysts.

We present a comprehensive survey of different C-H activation pathways over various kinds of active sites of terminal oxygens [=O] and bridge oxygens [-O-] by using Mo3O9 model systems. This allows us to provide some insights into fundamental issues concerning C-H activation by metal oxo species involved in many heterogeneous, homogeneous, and enzymatic processes. We show that H abstraction is the most feasible reaction pathway for the activation of a C-H bond on molybdenum oxides; and that [=O] is more active than [-O-]. Our calculations also suggest that (2+2) can be an alternative if M=O bond possesses a high polarity, while (5+2) can provide another effective pathway if two M=O bonds are in close proximity. Implications for the related heterogeneous, homogeneous, and enzymatic processes are discussed.

Journal Article↗
PubMed2005

Downregulated mRNA expression of ASPP and the hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type p53.

The p53 protein is one of the best-known tumour suppressors. Recently discovered ASPP1 and ASPP2 are specific activators of p53. To understand, if apoptosis-stimulating protein of p53 (ASPP) inactivation offers a selective advantage to tumors that have wild-type p53, we measured the mRNA expression of ASPP1 and ASPP2 in tumor cell lines retaining wide-type p53. In addition, the CpG island methylation status of ASPP1 gene and ASPP2 gene in the 5'-untranslated region was also investigated in order to understand the possible cause of abnormal expression of ASPP1 and ASPP2 in the tumor cell lines retaining wide-type p53. The data showed that mRNA expression of ASPP1 and ASPP2 is downregulated and CpG island tested is hypermethylated. These results indicated that ASPP CpG island aberrant methylation could be one molecular and genetic alteration in wild-type p53 tumours.

5' Untranslated Regions↗
PubMed2005

Polarization-dependent supercontinuum generation from light filaments in air.

We investigate polarization-dependent properties of the supercontinuum emission generated from filaments produced by intense femtosecond laser pulses propagating through air over a long distance. The conversion efficiency from the 800-nm fundamental to white light is observed to be higher for circular polarization than for linear polarization when the laser intensity exceeds the threshold of the breakdown of air.

Journal Article↗