Biomedical subjects

Lei Xu

Publications and source records attributed to Lei Xu.

104 records · Page 6Linked to original sources

PubMed2002

Drosophila atrophin homolog functions as a transcriptional corepressor in multiple developmental processes.

Dentatorubral-pallidoluysian atrophy is a progressive neurodegenerative disease caused by the expansion of a polyglutamine repeats within the Atrophin-1 protein. The in vivo function of Atrophin-1 is unknown. We have characterized a Drosophila gene encoding an Atrophin family protein. Analysis of mutant phenotypes indicates that Drosophila Atrophin is required in diverse developmental processes including early embryonic patterning. Drosophila Atrophin genetically interacts with the transcription repressor even-skipped and is required for its repressive function in vivo. Drosophila Atrophin directly binds to Even-skipped in vitro. Furthermore, both human Atrophin-1 and Drosophila Atrophin repress transcription in vivo when tethered to DNA, and poly-Q expansion in Atrophin-1 reduces this repressive activity. We propose that Atrophin proteins function as versatile transcriptional corepressors and discuss a model that deregulation of transcription may contribute to the pathogenesis of neurodegeneration.

Animals↗

PubMed2002

Apomorphine induces trophic factors that support fetal rat mesencephalic dopaminergic neurons in cultures.

Apomorphine, the catechol-derived dopamine D1/D2 receptor agonist, is currently in use as an antiparkinsonian drug. It has previously been reported that apomorphine was able to elicit expression of the enzyme tyrosine hydroxylase, a marker for DA neurons, in the fetal rat cerebrocortical cultures whilst in the presence of brain-derived neurotrophic factor. The present study demonstrated that treatment of fetal rat ventral mesencephalic cultures with apomorphine caused a marked increase in the number of dopaminergic neurons. The action of apomorphine can be mimicked by dopamine receptor (D1 and D2) agonists or blocked by preincubation with D1/D2 receptor antagonists. Incubation of recipient mesencephalic cultures with the conditioned medium derived from apomorphine-stimulated donor mesencephalic cultures elicited a 3.72-fold increase in the number of TH-positive neurons. Increased mRNA expression levels of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were also found in the apomorphine-treated mesencephalic cells along with concomitant protein expression increases in the conditioned medium. Moreover, the trophic activity observed could be partially neutralized by antibodies against either brain-derived neurotrophic factor or glial cell line-derived neurotrophic factor. Cultured fetal striatal cells, but not hippocampal cells, also responded to apomorphine treatment. The membrane filtration studies revealed that both <30 kDa and >50 kDa fractions contained trophic activities. The latter characterization distinguishes them from most known neurotrophic factors. These results suggest that the apomorphine-modulated development of dopaminergic neurons may be mediated by activation of the dopamine receptor subtypes D1 and D2 thereby increasing the production of multiple growth factors.

Animals↗

PubMed2002

A Lagrange multiplier and Hopfield-type barrier function method for the traveling salesman problem.

A Lagrange multiplier and Hopfield-type barrier function method is proposed for approximating a solution of the traveling salesman problem. The method is derived from applications of Lagrange multipliers and a Hopfield-type barrier function and attempts to produce a solution of high quality by generating a minimum point of a barrier problem for a sequence of descending values of the barrier parameter. For any given value of the barrier parameter, the method searches for a minimum point of the barrier problem in a feasible descent direction, which has a desired property that lower and upper bounds on variables are always satisfied automatically if the step length is a number between zero and one. At each iteration, the feasible descent direction is found by updating Lagrange multipliers with a globally convergent iterative procedure. For any given value of the barrier parameter, the method converges to a stationary point of the barrier problem without any condition on the objective function. Theoretical and numerical results show that the method seems more effective and efficient than the softassign algorithm.

Journal Article↗

PubMed2002

Expression of metastasis-related genes in human epithelial ovarian tumors.

We examined the expression level of several genes that regulate distinct steps of metastasis in 55 formalin-fixed, paraffin-embedded, archival specimens of primary human ovarian carcinoma from patients undergoing curative surgery. The expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), basic fibroblast growth factor (bFGF), E-cadherin, type IV collagenase, matrix metalloproteinase (MMP-2 and MMP-9), and interleukin 8 (IL-8) was examined by a colorimetric in situ mRNA hybridization technique. The expression level of E-cadherin, MMP-2, MMP-9, VEGF, and IL-8 mRNA correlated with disease stages. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) increased with increasing stage of disease (p<0.0001). Death rates significantly increased with high MMP:E-cadherin ratio (p=0.0005). Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, even after adjustment for known prognostic factors, such as histology, stage, and age.

Adult↗

PubMed2002

Analysis on the environmental problems accompanying the high-speed urbanization of small towns in China.

The environmental problems accompanying the rapid urbanization of many small towns like Keqiao, Shaoxing County of China and their countermeasures are presented. To settle these problems rationally as well as effectively will not only conduce to boost the environmental quality and life quality of cities, but also help to promote the development of regional economy and the realization of sustainable development.

Animals↗

PubMed2002

Sequential H(2)(15)O PET studies in baboons: before and after amphetamine.

UNLABELLED: PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS: Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION: These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.

Anesthesia↗

PubMed2002

Study on the accuracy of automated hematology analyzers in Shanghai.

UNLABELLED: The objectives of this study were to research on the accuracy of automated hematology analyzers of various types from different manufacturers and to observe the deviation among these instruments. Fresh anticoagulated blood from healthy donors on 115 hematology analyzers in 114 different hospitals were determined. RESULTS: The maximum coefficients of variation (CVs. %) among instruments of three main manufacturers (Sysmex, Beckman Coulter and Abbott) of red blood cell count (RBC), hemoglobin (Hgb), hematocrit (Hct), white blood cell count (WBC) and platelet count (Plt) were 3.2%, 3.8%, 3.6%, 9.3% and 10.8%, respectively. The maximum deviations among these parameters of different instruments were 0.74%, 1.65%, 5.45%, 7.06% and 18.55%, respectively. By improving laboratory quality management, the results of hematology analyzer determination may be more reliable than manual methods. The difference among various manufacturers was very small about RBC, Hgb, Hct, WBC and Plt the results from all kinds of instruments will tend to be comparable.

China↗

PubMed2001

Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF.

Overexpression of vascular endothelial growth factor (VEGF) is associated with disease progression in human glioblastomas. We recently showed that VEGF promoter activity is inversely correlated with tumor extracellular pH (pH(o)) in vivo in the human glioma (U87 MG) xenografts. Here we show that substitution of the neutral culture medium (pH 7.3) with acidic pH medium (pH 6.6) up-regulates VEGF mRNA and protein production in human glioblastoma cells as reflected by Northern blot analysis and enzyme-linked immunosorbent assay. Functional analysis of the VEGF promoter reveals that the sequence between -961 bp and -683 bp upstream of the transcription start site is responsible for the transcriptional activation of the VEGF gene by acidic pH. This region contains the binding site for AP-1. Consequently, AP-1 luciferase reporter gene was activated by acidic pH. Gel-shift analysis confirmed that AP-1 DNA binding activity is induced under acidic pH. While investigating the upstream signaling pathways, we found that ERK1/2 MAPK is activated and translocates to the nucleus to activate Elk-1, and inhibition of the activation of ERK by specific inhibitors of MEK1 blocks the up-regulation of VEGF by low pH. Dominant negative forms of Ras and Raf abolished the activation of VEGF promoter by acidic pH. These results show that acidic pH activates Ras and the ERK1/2 MAPK pathway to enhance VEGF transcription via AP-1, leading to increased VEGF production.

Base Sequence↗

PubMed1999

Relationship between DNA ploidy,expression of ki-67 antigen and gastric cancer metastasis.

AIM:To evaluate the relationship between the expression of Ki-67 antigen and the pathobiological behaviours of gastric cancers especially their distant metastases.METHODS:Fifty-six specimens of gastric cancer routinely fixed in formalin and embedded in paraffin (FFEP) were studied by immunohistochemical method.RESULTS: Expression of Ki-67 antigen was significantly related to the distant metastases to liver, ovary and adrenal gland (P < 0.01), but not related to the histological type, growth pattern, depth of invasion, histological differentiation and the metastases to local lymph nodes (P > 0.05).Furthermore, the Ki-67 antigen expression was significantly related to the DNA aneuploidy pattern, which is closely related to poor prognosis (P < 0.05).CONCLUSION:Overexpression of Ki-67 can be used as an objectiv marker of the proliferative activity for predicting prognosis of gastric cancer and metastatic potential to distant organs.

Journal Article↗

PubMedDate not supplied

A comparative investigation on subspace dimension determination.

It is well-known that constrained Hebbian self-organization on multiple linear neural units leads to the same k-dimensional subspace spanned by the first k principal components. Not only the batch PCA algorithm has been widely applied in various fields since 1930s, but also a variety of adaptive algorithms have been proposed in the past two decades. However, most studies assume a known dimension k or determine it heuristically, though there exist a number of model selection criteria in the literature of statistics. Recently, criteria have also been obtained under the framework of Bayesian Ying-Yang (BYY) harmony learning. This paper further investigates the BYY criteria in comparison with existing typical criteria, including Akaike's information criterion (AIC), the consistent Akaike's information criterion (CAIC), the Bayesian inference criterion (BIC), and the cross-validation (CV) criterion. This comparative study is made via experiments not only on simulated data sets of different sample sizes, noise variances, data space dimensions, and subspace dimensions, but also on two real data sets from air pollution problem and sport track records, respectively. Experiments have shown that BIC outperforms AIC, CAIC, and CV while the BYY criteria are either comparable with or better than BIC. Therefore, BYY harmony learning is a more preferred tool for subspace dimension determination by further considering that the appropriate subspace dimension k can be automatically determined during implementing BYY harmony learning for the principal subspace while the selection of subspace dimension k by BIC, AIC, CAIC, and CV has to be made at the second stage based on a set of candidate subspaces with different dimensions which have to be obtained at the first stage of learning.

Air Pollution↗

PubMedDate not supplied

BYY harmony learning, structural RPCL, and topological self-organizing on mixture models.

The Bayesian Ying-Yang (BYY) harmony learning acts as a general statistical learning framework, featured by not only new regularization techniques for parameter learning but also a new mechanism that implements model selection either automatically during parameter learning or via a new class of model selection criteria used after parameter learning. In this paper, further advances on BYY harmony learning by considering modular inner representations are presented in three parts. One consists of results on unsupervisedmixture models, ranging from Gaussian mixture based Mean Square Error (MSE) clustering, elliptic clustering, subspace clustering to NonGaussian mixture based clustering not only with each cluster represented via either Bernoulli-Gaussian mixtures or independent real factor models, but also with independent component analysis implicitly made on each cluster. The second consists of results on supervised mixture-of-experts (ME) models, including Gaussian ME, Radial Basis Function nets, and Kernel regressions. The third consists of two strategies for extending the above structural mixtures into self-organized topological maps. All these advances are introduced with details on three issues, namely, (a) adaptive learning algorithms, especially elliptic, subspace, and structural rival penalized competitive learning algorithms, with model selection made automatically during learning; (b) model selection criteria for being used after parameter learning, and (c) how these learning algorithms and criteria are obtained from typical special cases of BYY harmony learning.

Bayes Theorem↗

PubMedDate not supplied

Improved system for object detection and star/galaxy classification via local subspace analysis.

The two traditional tasks of object detection and star/galaxy classification in astronomy can be automated by neural networks because the nature of the problems is that of pattern recognition. A typical existing system can be further improved by using one of the local Principal Component Analysis (PCA) models. Our analysis in the context of object detection and star/galaxy classification reveals that local PCA is not only superior to global PCA in feature extraction, but is also superior to gaussian mixture in clustering analysis. Unlike global PCA which performs PCA for the whole data set, local PCA applies PCA individually to each cluster of data. As a result, local PCA often outperforms global PCA for data of multi-modes. Moreover, since local PCA can effectively avoid the trouble of having to specify a large number of free elements of each covariance matrix of gaussian mixture, it can give a better description of local subspace structures of each cluster when applied on high dimensional data with small sample size. In this paper, the local PCA model proposed by Xu [IEEE Trans. Neural Networks 12 (2001) 822] under the general framework of Bayesian Ying Yang (BYY) normalization learning will be adopted. Endowed with the automatic model selection ability of BYY learning, the BYY normalization learning-based local PCA model can cope with those object detection and star/galaxy classification tasks with unknown model complexity. A detailed algorithm for implementation of the local PCA model will be proposed, and experimental results using both synthetic and real astronomical data will be demonstrated.

Astronomy↗

PubMedDate not supplied

Data smoothing regularization, multi-sets-learning, and problem solving strategies.

First, we briefly introduce the basic idea of data smoothing regularization, which was firstly proposed by Xu [Brain-like computing and intelligent information systems (1997) 241] for parameter learning in a way similar to Tikhonov regularization but with an easy solution to the difficulty of determining an appropriate hyper-parameter. Also, the roles of this regularization are demonstrated on Gaussian-mixture via smoothed versions of the EM algorithm, the BYY model selection criterion, adaptive harmony algorithm as well as its related Rival penalized competitive learning. Second, these studies are extended to a mixture of reconstruction errors of Gaussian types, which provides a new probabilistic formulation for the multi-sets learning approach [Proc. IEEE ICNN94 I (1994) 315] that learns multiple objects in typical geometrical structures such as points, lines, hyperplanes, circles, ellipses, and templates of given shapes. Finally, insights are provided on three problem solving strategies, namely the competition-penalty adaptation based learning, the global evidence accumulation based selection, and the guess-test based decision, with a general problem solving paradigm suggested.

Learning↗

PubMedDate not supplied

Surface stress on the erythrocyte under laser irradiation with finite-difference time-domain calculation.

The surface stress on the real shape (biconcave disklike) of an erythrocyte under laser irradiation is theoretically studied according to the finite-difference time-domain (FDTD) method. The distribution of the surface stresses depends on the orientation of erythrocytes in the laser beam. Typically when the erythrocyte was irradiated from the side direction (the laser beam was perpendicular to the normal of the erythrocyte plane), the surface stresses were so asymmetrical and nonuniform that the magnitude of the surface stress on the back surface was three times higher than that on the front surface, and the highest-to-lowest ratio of the stress reached 16 times. For comparison, the surface stress was also calculated according to the ray optics (RO) method. The tendency of the stress distribution from the RO calculation was roughly similar to that of the FDTD method. However the RO calculation produced some unphysical results, such as the infinite stress on some surface region and the zero stress on the most parts of the erythrocyte surface, which is due to the neglecting of light diffraction. The results obtained from the FDTD calculation are believed quantitatively reliable, because the FDTD method automatically takes into account of the diffraction and interference effects of the light wave. Thus, the FDTD method is more suitable than the RO method for the stress study of erythrocytes.

Animals↗