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Biomedical subjects

Xin Lu

Publications and source records attributed to Xin Lu.

At least 37 records · Page 2Linked to original sources

Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data.

BACKGROUND: Like microarray-based investigations, high-throughput proteomics techniques require machine learning algorithms to identify biomarkers that are informative for biological classification problems. Feature selection and classification algorithms need to be robust to noise and outliers in the data. RESULTS: We developed a recursive support vector machine (R-SVM) algorithm to select important genes/biomarkers for the classification of noisy data. We compared its performance to a similar, state-of-the-art method (SVM recursive feature elimination or SVM-RFE), paying special attention to the ability of recovering the true informative genes/biomarkers and the robustness to outliers in the data. Simulation experiments show that a 5%- approximately 20% improvement over SVM-RFE can be achieved regard to these properties. The SVM-based methods are also compared with a conventional univariate method and their respective strengths and weaknesses are discussed. R-SVM was applied to two sets of SELDI-TOF-MS proteomics data, one from a human breast cancer study and the other from a study on rat liver cirrhosis. Important biomarkers found by the algorithm were validated by follow-up biological experiments. CONCLUSION: The proposed R-SVM method is suitable for analyzing noisy high-throughput proteomics and microarray data and it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features. The multivariate SVM-based method outperforms the univariate method in the classification performance, but univariate methods can reveal more of the differentially expressed features especially when there are correlations between the features.

Algorithms↗

Pericyclic transition-state-like aromaticity in the inorganic ions Se2i4(2+) and S2O4(2-).

We show, by means of quantum chemical calculations, that the inorganic ions Se2I4(2+) and S2O4(2-), whose structures have been long-known and well-characterized, have aromaticity resulting from through-space conjugation, analogous to the aromaticity in the transition states of some pericyclic reactions, such as Cope rearrangements and Diels-Alder reactions.

Journal Article↗

La2@C72 and Sc2@C72: computational characterizations.

The La2@C72 and Sc2@C72 metallofullerenes have been characterized by systematic density functional computations. On the basis of the most stable geometry of 39 C72 hexaanions and the computed energies of the best endofullerene candidates, the experimentally isolated La2@C72 species was assigned the structure coded #10611. The good agreement between the computed and the experimental 13C chemical shifts for La2@C72 further supports the literature assignment (Kato, H.; Taninaka, A.; Sugai, T.; Shinohara, H. J. Am. Chem. Soc. 2003, 125, 7782). The geometry, IR vibrational frequencies, and 13C chemical shifts of Sc2@C72 were predicted to assist its future experimental characterization.

Journal Article↗

Electronic structure and redox properties of the open-shell metal-carbide endofullerene Sc3C2@C80: a density functional theory investigation.

Density functional theory calculations have shown that the open-shell metal-carbide endofullerene Sc3C2@C80 has the valence state (Sc3+)3(C2)(3-)@C80(6-). A lot of low-lying isomers differing in geometries and locations of the endohedral [(Sc3+)3(C2)(3-)] cluster have been located, indicating unusual dual intramolecular dynamic behaviors of this endofullerene at room temperature. The electrochemical redox properties of this endofullerene have been elucidated in terms of electronic structure theory. Its redox states are found to follow the general charge-state formula (Sc3+)3C2(3-q)-@C80(6-) (q is the charge of the whole molecule ranging from +1 to -3), demonstrating the high charge flexibility of the endohedral metal-carbide cluster. The structure of the endohedral [(Sc3+)3C2(3-q)-)] cluster varies with the redox processes, shifting from a planar structure (for q = 0 and -1) to a trifoliate structure (for q = +1, -2, -3).

Journal Article↗

Determination of agmatine in biological samples by capillary electrophoresis with chemiluminescence detection.

A fast and simple method based on capillary electrophoresis (CE) with chemiluminescence (CL) detection has been developed for the determination of agmatine, a recently identified neurotransmitter/modulator. The CE run time was approximately 2 min for each sample injected. CL detection employed a lab-built reaction flow cell and a photon counter. The CL reagents used were luminol and NaBrO. The optimized conditions for the CL detection were 5 x 10(-4)M luminol added to the CE running buffer and 5.0 x 10(-4)M NaBrO in 100 mM NaCO3-NaOH buffer solution at pH 12.5 introduced post column. Detection limit for agmatine was 4.3 x 10(-6)M (S/N=3). The precision (R.S.D.) on peak height (at 1 x 10(-5)M agmatine) and migration time were 3.7 and 2.5%, respectively. The present CE-CL method was evaluated with the determination of agmatine in tissue samples taken from rat brain, and rat and monkey stomachs. Samples were directly injected into the CE-CL system after the removal of proteins. A higher level of agmatine was detected in the stomach samples. Agmatine concentrations in the tissue samples taken from rat and monkey stomachs were similar at approximately 1950 ng/g wet tissue.

Agmatine↗

Interaction of light filaments generated by femtosecond laser pulses in air.

The interaction of two light filaments propagating in air is simulated. Simulations show that the interaction of the two light filaments displays interesting features such as attraction, fusion, repulsion, and spiral propagation, depending on the relative phase shift and the crossing angle between them. A long and stable channel can be formed by fusing two in-phase light filaments. The channel becomes unstable with the increase of the crossing angle and phase shift. The interaction of two light filaments in different planes is studied and the spiral propagation is observed.

Journal Article↗

CE-based analysis of hemoglobin and its applications in clinical analysis.

This review focuses on the developments and trends in CE including CIEF, CZE, MEKC, two-dimensional conjunction of CIEF-capillary gel electrophoresis, and MEKC-CZE on microfluidic devices coupled to different detection approaches, such as UV absorbance, LIF, MS, and chemiluminescence etc. for performing analysis of hemoglobin (Hb), also with an emphasis on its applications in clinical analysis. Analysis of human Hb is of important clinical sense for numerous hemoglobinopathies associated with the congenital defects and abnormal contents of Hb. The diversiform modes render CE a comprehensive primary clinical tool for Hb analysis, which is rapid, sensitive, high-resolution, and not labor-intensive.

Electrophoresis, Capillary↗

X chromosomal abnormalities in basal-like human breast cancer.

Sporadic basal-like cancers (BLC) are a distinct class of human breast cancers that are phenotypically similar to BRCA1-associated cancers. Like BRCA1-deficient tumors, most BLC lack markers of a normal inactive X chromosome (Xi). Duplication of the active X chromosome and loss of Xi characterized almost half of BLC cases tested. Others contained biparental but nonheterochromatinized X chromosomes or gains of X chromosomal DNA. These abnormalities did not lead to a global increase in X chromosome transcription but were associated with overexpression of a small subset of X chromosomal genes. Other, equally aneuploid, but non-BLC rarely displayed these X chromosome abnormalities. These results suggest that X chromosome abnormalities contribute to the pathogenesis of BLC, both inherited and sporadic.

Alleles↗

Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery.

Breast cancer is the most common nonskin malignancy affecting women. Currently, no simple, blood-based diagnostic test exists to complement radiological screening and increase sensitivity of detection. To screen plasma specimens and identify biomarkers that detect HER2-positive breast cancer, automated robotic sample processing followed by surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectroscopy was used. Multiple statistical algorithms were used to select biomarkers that segregate cancer patients versus controls and produced average CV rates ranging from 20% to 29%. A set of seven biomarkers were validated on an independent test data set and achieved the best error rate of 19.1%. A permutation test indicated a p-value for CV error less than 0.002. Moreover, a ROC curve using these biomarkers achieved an area-under-the-curve value of 0.95 on an independent test data set. The marker responsible for most of the resolving power was identified as a fragment of Fibrinogen Alpha (FGA) encompassing residues 605-629. This marker was present at lower levels in cancer patients as compared to controls. The importance of this biomarker was validated in a longitudinal study comparing pre- and post-operative levels and was shown to revert to normal levels after surgery. This fragment may serve as a useful diagnostic and treatment-monitoring marker.

Amino Acid Sequence↗

ASPP [corrected] and cancer.

One of the most frequently mutated genes in human cancers, tumour suppressor p53 (TP53), can induce cell-cycle arrest and apoptosis. The apoptotic function of p53 is tightly linked to its tumour-suppression function and the efficacy of many cancer therapies depends on this. The identification of a new family of proteins, known as ASPPs (ankyrin-repeat-, SH3-domain- and proline-rich-region-containing proteins), has led to the discovery of a novel mechanism that selectively regulates the apoptotic function, but not the cell-cycle-arrest function, of p53, and gives an insight into how p53 responds to different stress signals. ASPPs might be new molecular targets for cancer therapy.

Apoptosis↗

Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells.

Although glycogen synthase kinase-3 (GSK-3) might act as a tumor suppressor since its inhibition is expected to mimic the activation of Wnt-signaling pathway, GSK-3beta may contribute to NF-kappaB activation in cancer cells leading to increased cancer cell proliferation and survival. Here we report that GSK-3beta activity was involved in the proliferation of human ovarian cancer cell both in vitro and in vivo. Inhibition of GSK-3 activity by pharmacological inhibitors suppressed proliferation of the ovarian cancer cells. Overexpressing constitutively active form of GSK-3beta induced entry into the S phase, increased cyclin D1 expression and facilitated the proliferation of ovarian cancer cells. Furthermore, GSK-3 inhibition prevented the formation of the tumor in nude mice generated by the inoculation of human ovarian cancer cells. Our findings thus suggest that GSK-3beta activity is important for the proliferation of ovarian cancer cells, implicating this kinase as a potential therapeutic target in ovarian cancer.

Animals↗

[The effect of HCV core protein on the expression of cyclooxygenase 2 (COX-2) in HepG2 cells].

AIM: To investigate the effect of Hepatitis C virus (HCV) core protein on the expression of cyclooxygenase 2 (COX-2). METHODS: The genes encoded HCV core protein were amplified from plasmid containing full length genome of HCV strain H77 using PCR, and were cloned into eukaryotic expression vector pcDNA3.1. The recombinant HCV-C/pcDNA3.1 was transiently co-transfected into HepG2 cells with luciferase reporter vector containing COX-2 promotor (COX2pro1.5 kb/luc). The luciferase activity and COX-2 protein expression were detected. RESULTS: The recombinants HCV-C/pcDNA3.1 have been constructed successfully. The luciferase activity of COX-2 promotor was activated by the expressed HCV core, and the increased protein expression of COX-2 in transfected HepG2 cells was detected by Western blot. CONCLUSION: HCV core protein can activate the COX-2 promotor and induce its expression, which provides a new experimental basis for further research on relationship between COX-2 and HCV pathogenesis.

Blotting, Western↗

[Methodological study on magnetic enzymic immunoassay for detecting free hCGbeta subunit].

AIM: To establish a novel magnetic enzyme immunoassay (MEIA) for detecting human choriogonadotropin free beta subunit (hCGbeta). METHODS: Two monoclonal antibodies (mAb) were used for conjugating with FITC and with alkaline phosphatase(AP) respectively, which incorporated magnetic solid phase separation. Magnetic beads were coupled with sheep anti-FITC antibody as solid phase, and phenolphthalein monophosphate was used as substrate to set up MEIA for detecting hCGbeta. RESULTS: The sensitivity of hCGbeta MEIA kit reached 0.1 IU/L. The intraassay variation and inter-assay variation was 8.5% and 14% respectively, with the average recovery rate of dilution of 92.5%. The kit showed no cross reactivity to LH, TSH and FSH, while a cross reactivity of 1.2% to intact hCG at concentration of 1000 IU/L. The time of efficacy of hCGbeta MEIA kit was longer than 14 months. CONCLUSION: hCGbeta MEIA kit is better than hCGbeta radio immunoassay and ELISA kit, which can provide a high-qualitative and cheap hCGbeta kit for market.

Antibodies, Monoclonal↗

[Diagnosis and treatment of primitive neuroectodermal tumors of pancreas].

OBJECTIVE: To improve the diagnosis and treatment of primitive neuroectodermal tumors (PNET) of the pancreas. METHODS: One patient with PNET of the pancreas was reported in this article. The corresponding literatures on the diagnosis and treatment was reviewed. RESULTS: The patient was diagnosed as pancreatic PNET by her clinical, microscopic, and immunohistochemical features as well as cytogenetic analysis after the resection of the tumor located in the uncinate process in PUMC Hospital. Radiochemotherapy was given after the operation for 8 months and no recurrence was observed. Since PNET of pancreas have no specific clinical symptoms and most patients have jaundice and/or abdominal pain, the diagnosis depended on the immunohistochemical features of positive P30/32(MIC2) and at least two of the neural markers. The cytogenetic analysis showed translocation mainly harbored the characteristic t (11; 22) (q24; q12). Since pancreatic PNET were highly aggressive, early chemotherapy, close follow-up, and immediate surgical interventions were required as early as possible. CONCLUSION: PNET can occur in pancreas, and diagnosis and treatment should be made as early as possible to improve the outcome.

Child↗

PET of human prostate cancer xenografts in mice with increased uptake of 64CuCl2.

UNLABELLED: Our objective was to determine whether human prostate cancer xenografts in mice can be localized by PET using 64CuCl2 as a probe (64Cu PET). METHODS: Athymic mice bearing human prostate cancer xenografts were subjected to 64Cu PET, followed by quantitative analysis of the tracer concentrations and immunohistochemistry study of human copper transporter 1 expression in the tumor tissues. RESULTS: Human prostate cancer xenografts expressing high levels of human copper transporter 1 were well visualized on the PET images obtained 24 h after injection but not on the images obtained 1 h after injection. PET quantitative analysis demonstrated a high concentration of 64CuCl2 in the tumors in comparison to that in the left shoulder regions (percentage injected dose per gram of tissue: 3.6 +/- 1.3 and 0.6 +/- 0.3, respectively; P = 0.004), at 24 h after injection. CONCLUSION: The data from this study suggested that locally recurrent prostate cancer might be localized with 64Cu PET using 64CuCl2 as a probe.

Animals↗

Dicarboxylic degradation products of nonylphenol polyethoxylates. Determination and structural elucidation in water samples by solid-phase extraction and gas chromatography-mass spectrometry after methylation.

A reliable method combining solid-phase extraction, derivatization and gas chromatography-chemical ionization mass spectrometry (GC-CI-MS) was developed for the measurement, in river and sewage effluent water, of four select model compounds of dicarboxylic metabolites (dm-CA(5-8)P1EC) and other dicarboxylic metabolites (CA(5-8)P1ECs) of nonylphenol polyethoxylates. These selected isomers were referred as dm-CA(5-8)P1ECs because they have an alpha,alpha-dimethyl configuration (expressed as "dm"), five to eight C atoms and a carboxyl group in the alkyl chain, and an ethoxy acetic acid group. The derivatization of terminal carboxyl groups was successful with (trimethylsilyl)diazomethane. The best extraction conditions were obtained using an Oasis HLB cartridge as a sorbent bed and 4 ml of MTBE/methanol (9:1, v/v) elution mixture. The method detection limits of 0.03-0.07 microg/l for dm-CA(5-8)P1ECs were attained in 500 ml pure water. The recovery was then evaluated for pure water, river and sewage effluent water samples. The high recoveries of typically >89% for each isomer indicated the high performance of the method. Although dm-CA(5-8)P1ECs were not detected in the collected water samples, 21 isomers of CA(5-8)P1ECs were identified by CI-MS and the tentative structures of six out of them were elucidated, mainly limited to the branch at alpha-C atom, by studying the EI-mass spectra. The relative concentrations of individual CA(5-8)P1EC metabolites were calculated based on dm-CA(5-8)P1ECs. The results showed that the main degradation on the nonyl chain occurred via the elimination of two carbon-units and the concentrations in Japan were much lower than those in Taiwan and Italy.

Chemical Fractionation↗