Search PubMed⌕ Search

Biomedical subjects

X Chen

Publications and source records attributed to X Chen.

At least 91 records · Page 5Linked to original sources

3-D correlation-based speckle tracking.

Widely-used 1-D/2-D speckle tracking techniques in elasticity imaging often experience significant speckle decorrelation in applications involving large elevational motion (i.e., out of plane motion). The problem is more pronounced for cardiac strain rate imaging (SRI) since it is very difficult to confine cardiac motion to a single image plane. Here, we present a 3-D correlation-based speckle tracking algorithm. Conceptually, 3-D speckle tracking is just an extension of 2-D phase-sensitive correlation-based speckle tracking. However, due to its high computational cost, optimization schemes, such as dynamic programming, decimation and two-path processing, are introduced to reduce the computational burden. To evaluate the proposed approach, a 3-D bar phantom under uniaxial compression was simulated for benchmark tests. A more sophisticated 3-D simulation of the left ventricle of the heart was also made to test the applicability of 3-D speckle tracking in cardiac SRI. Results from both simulations clearly demonstrated the feasibility of 3-D correlation-based speckle tracking. With the ability to follow 3-D speckle in 3-D space, 3-D speckle tracking outperforms lower-dimensional speckle tracking by minimizing decorrelation caused by pure elevational translation. In other words, 3-D tracking can push toward solely deformation-limited, decorrelation-optimized speckle tracking. Hardware implementation of the proposed 3-D speckle tracking algorithm using field programmable gate arrays (FPGA) is also discussed.

Algorithms↗

Control of relative tunneling rates in single molecule bipolar electron transport.

The influence of relative electron tunneling rates on electron transport in a double-barrier single-molecule junction is studied. The junction is defined by positioning a scanning tunneling microscope tip above a copper phthalocyanine molecule adsorbed on a thin oxide film grown on the NiAl(110) surface. By tuning the tip-molecule separation, the ratio of tunneling rates through the two barriers, vacuum and oxide, is controlled. This results in dramatic changes in the relative intensities of individual conduction channels, associated with different vibronic states of the molecule.

Journal Article↗

Integrated actions of transforming growth factor-beta1 and connective tissue growth factor in renal fibrosis.

Matrix accumulation in the renal tubulointerstitium is predictive of a progressive decline in renal function. Transforming growth factor-beta(1) (TGF-beta(1)) and, more recently, connective tissue growth factor (CTGF) are recognized to play key roles in mediating the fibrogenic response, independently of the primary renal insult. Further definition of the independent and interrelated effects of CTGF and TGF-beta(1) is critical for the development of effective antifibrotic strategies. CTGF (20 ng/ml) induced fibronectin and collagen IV secretion in primary cultures of human proximal tubule cells (PTC) and cortical fibroblasts (CF) compared with control values (P < 0.005 in all cases). This effect was inhibited by neutralizing antibodies to either TGF-beta or to the TGF-beta type II receptor (TbetaRII). TGF-beta(1) induced a greater increase in fibronectin and collagen IV secretion in both PTC (P < 0.01) and CF (P < 0.01) compared with that observed with CTGF alone. The combination of TGF-beta(1) and CTGF was additive in their effects on both PTC and CF fibronectin and collagen IV secretion. TGF-beta(1) (2 ng/ml) stimulated CTGF mRNA expression within 30 min, which was sustained for up to 24 h, with a consequent increase in CTGF protein (P < 0.05), whereas CTGF had no effect on TGF-beta(1) mRNA or protein expression. TGF-beta(1) (2 ng/ml) induced phosphorylated (p)Smad-2 within 15 min, which was sustained for up to 24 h. CTGF had a delayed effect on increasing pSmad-2 expression, which was evident at 24 h. In conclusion, this study has demonstrated the key dependence of the fibrogenic actions of CTGF on TGF-beta. It has further uniquely demonstrated that CTGF requires TGF-beta, signaling through the TbetaRII in both PTCs and CFs, to exert its fibrogenic response in this in vitro model.

Antibodies↗

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity.

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

Journal Article↗

Operon prediction by comparative genomics: an application to the Synechococcus sp. WH8102 genome.

We present a computational method for operon prediction based on a comparative genomics approach. A group of consecutive genes is considered as a candidate operon if both their gene sequences and functions are conserved across several phylogenetically related genomes. In addition, various supporting data for operons are also collected through the application of public domain computer programs, and used in our prediction method. These include the prediction of conserved gene functions, promoter motifs and terminators. An apparent advantage of our approach over other operon prediction methods is that it does not require many experimental data (such as gene expression data and pathway data) as input. This feature makes it applicable to many newly sequenced genomes that do not have extensive experimental information. In order to validate our prediction, we have tested the method on Escherichia coli K12, in which operon structures have been extensively studied, through a comparative analysis against Haemophilus influenzae Rd and Salmonella typhimurium LT2. Our method successfully predicted most of the 237 known operons. After this initial validation, we then applied the method to a newly sequenced and annotated microbial genome, Synechococcus sp. WH8102, through a comparative genome analysis with two other cyanobacterial genomes, Prochlorococcus marinus sp. MED4 and P.marinus sp. MIT9313. Our results are consistent with previously reported results and statistics on operons in the literature.

ATP-Binding Cassette Transporters↗

Hindered and enhanced coalescence of drops in stokes flows.

We analyze axisymmetric near-contact motion of two drops under the action of an external force or imposed flow. It is shown that hydrodynamic stresses in the near-contact region that are associated with the outer (drop-scale) flow can qualitatively affect the drainage of the thin fluid film separating the drops. If this far-field stress acts radially inward, film drainage is arrested at long times; exponential film drainage occurs if this stress acts outward. An asymptotic analysis of the stationary long-time film profile is presented for small-deformation conditions, and the critical strength of van der Waals attraction for film rupture is calculated. The effect of an insoluble surfactant is also considered. Hindered and enhanced drop coalescence are not predicted by the current theories, because the influence of the outer flow on film drainage is ignored.

Journal Article↗

Constraints on nucleon decay via invisible modes from the Sudbury Neutrino Observatory.

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to "invisible" modes, such as n-->3nu. The analysis was based on a search for gamma rays from the deexcitation of the residual nucleus that would result from the disappearance of either a proton or neutron from 16O. A limit of tau(inv)>2 x 10(29) yr is obtained at 90% confidence for either neutron- or proton-decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton-decay modes and 400 times more stringent than similar neutron modes.

Journal Article↗

Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice.

RATIONALE: No selective antagonists for the effects of MDMA have yet been identified. The structurally-similar, naturally-occurring plant alkaloid nantenine (9,10-methylenedioxy-1,2 dimethoxyaporphine) may represent such a compound. OBJECTIVES: To investigate the capacity of nantenine to block and/or reverse MDMA-induced hyperthermia, lethality, locomotor stimulation, and head twitches in mice, and to compare these actions with those of the selective alpha1 antagonist prazosin and the selective 5-HT2A antagonist M100907. METHODS: Pretreatments of either 10 mg/kg nantenine or 1 mg/kg prazosin were administered 15 min before 32 mg/kg MDMA; core temperature and locomotor stimulation were then monitored via radiotelemetry for at least 3 h. In further hyperthermia studies, 32 mg/kg MDMA was administered first and temperature was allowed to rise for 30 min; 10 mg/kg nantenine, 1 mg/kg prazosin, or 1 mg/kg M100907 was then administered in an attempt to reverse MDMA-induced hyperthermia. In lethality assays, percent lethality was quantified 2 h after MDMA injection in two distinct housing conditions, one or 12 mice per cage, with or without 15 min pretreatments of 10 mg/kg nantenine or 1 mg/kg prazosin. Drug elicited head twitches were quantified for 10 min following administration of either MDMA enantiomer, with and without pretreatments of 1 mg/kg nantenine, 0.1 mg/kg prazosin, or 0.001 mg/kg M100907. RESULTS: Nantenine blocked and rapidly reversed MDMA-induced hyperthermia, attenuated lethality in both housing conditions, and reduced MDMA-induced locomotor stimulation and head twitches in mice. Prazosin blocked, but did not reverse, MDMA-induced hyperthermia, attenuated lethality (more effectively in singly-housed animals), and reduced MDMA-induced locomotor stimulation and head twitches. M100907 did not reverse MDMA-induced hyperthermia, but effectively blocked drug-elicited head twitches. CONCLUSIONS: Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints.

Adrenergic alpha-Antagonists↗

Combined compression and elongation experiments and non-linear modelling of liver tissue for surgical simulation.

Uniaxial stress-strain data were obtained from in vitro experiments on 20 porcine livers for compressions, elongations and cycles of compression and then elongation. There were about 70 cylindrical samples, with diameter 7mm and varying height (4-11 mm). The combined compression and elongation test provide a unified framework for both compression and elongation for applications such as computer-aided surgical simulation. It enable the zero stress state of the experimental liver sample to be precisely determined. A new equation that combined both logarithmic and polynomial strain energy forms was proposed in modelling these experimental data. The assumption of incompressibility was justified from a preliminary Poisson's ratio for elongation and compression at 0.43+/-0.16 and 0.47+/-0.15, respectively. This equation provided a good fit for the observed mechanical properties of liver during compression-elongation cycles and for separate compressions or elongations. The root mean square errors were 91.92+/-17.43 Pa, 57.55+/-13.23 Pa and 29.78+/-17.67 Pa, respectively. In comparison with existing strain energy functions, this combined model was the better constitutive equation. Application of this theoretical model to small liver samples and other tissues demonstrated its suitability as the material model of choice for soft tissue.

Animals↗

The common and distinct target genes of the p53 family transcription factors.

p53 is the most commonly mutated gene in human cancer. After activation by cellular stresses such as DNA damage or oncogene activation, p53, a sequence-specific DNA-binding protein, induces the expression of target genes which mediate tumor suppression. Two recently identified p53 homologues, p63 and p73, appear to function similarly to p53, that is, they both activate target gene expression and suppress cell growth when overexpressed; however, the p63 and p73 genes are rarely mutated in human cancer and do not adhere to Knudson's classical model of a tumor suppressor gene. Recently, exciting observations suggest nonoverlapping functions for the family members. Herein, we outline the recent literatures identifying and characterizing both the common and distinct target genes of the p53 family transcription factors in relation to their signaling pathways.

Apoptosis↗

Orientation bias of the extraclassical receptive field of the relay cells in the cat's dorsal lateral geniculate nucleus.

The spatial properties of the extraclassical receptive fields (ECRF) of neurons responding to a stimulus restricted to it and its interaction with the classical receptive field (CRF) in visual information processing were investigated in 74 relay cells in the dorsal lateral geniculate nucleus (LGNd) of anesthetized cats. The results demonstrate that the ECRF of most relay cells in the LGNd responded preferentially to a grating stimulus of low spatial frequency through a mechanism of spatial summation. These biased cells showed a significant orientation bias which was relatively smaller than that of the CRF. The preferred orientations of the ECRF were not correlated with those of the CRF in most relay cells. The orientation biased ECRFs and CRFs interacted with each other in a non-linear way, resulting in a great diversity of response properties. Overall, the CRF played a more significant role than the ECRF in determining a cell's orientation bias and preferred orientation. The ECRF mostly showed a modulatory role mainly in suppressing and/or in partially facilitating the neural response to stimulation in the CRF although in some cases, the ECRF did determine a cell's responsiveness and orientation sensitivity. These results suggest that the ECRF might contribute to the ability of the LGNd neurons to detect some complex features such as texture segmentation and provide a subcortical contribution to the integrative field of visual cortical cells through receiving inputs from retinal ganglion cells with similar orientation biased extended surrounds [Neuroscience 98 (2000) 207].

Action Potentials↗

Spatiotemporal analysis of ERP during chinese idiom comprehension.

The objective of the present study was to elucidate the neural underpinning of Chinese idiom comprehension with spatiotemporal patterns of ERP. Thirteen subjects were required to decide whether the last character of each viewed Chinese four-character idiom was correct or not. Fuzzy c-means algorithm based on shape similarity was applied to segmenting spatiotemporal patterns of ERP. Statistical parametric map of t-statistic (SPM(t)) was performed after realignment according to the referential frame provided by fuzzy clustering in order to overcome temporal mismatch. Within 540 ms post-stimulus onset, the spatiotemporal patterns of ERP under both conditions could be segmented into 7 stages optimally and both share the first four microstates with variant membership functions and durations. SPM(t) presented significant differences in multiple regions in 3 stages: (1) during 120-150 ms, the early right hemispheric negativities (ERHN) inboth frontal and temporoparietal areas were likely to reflect both initial syntactic processing and visual word-form mismatch; (2) during 320-380 ms (the N400 stage), negative deflections in left frontal, left anterior temporal, centrofrontal regions might coordinate and integrate both syntactic and semantic analysis in extensive right hemisphere; (3) during 480-540 ms (the P600 stage), positive deflections in left temporoparietal and occipital regions seemed to reflect the reanalysis and the integration of word meanings to obtain the over all meaning of idioms. Our study has implicated the brain mechanism of language comprehension common to alphabetic language as well as that specialized in logographic language.

Adult↗

Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia.

Peritransplant toxicity and a delay in effective immune reconstitution have limited the utility of alternate donor transplantation for children with refractory severe aplastic anemia. We have assessed the effectiveness of infusing large numbers of highly purified haploidentical CD34+ cells after immunoablative conditioning in three patients who had failed intensive immunosuppression, lacked unrelated donors, and had active or recent serious infections. One patient rejected the first infusion, but engrafted after a second infusion from the same donor. This patient died 4 months after hematopoietic stem cell transplantation with no evidence of lymphoid reconstitution. Two patients experienced mixed chimerism requiring treatment with antibodies and/or donor lymphocyte infusion. Both currently survive more than 1 year after transplantation with normal blood counts, 100% donor engraftment, effective lymphoid reconstitution, and no chronic graft-versus-host disease. We observed functional thymopoiesis as measured by lymphocyte immunophenotyping, T cell receptor excision circles and T cell receptor Vbeta spectratyping complexity analysis. Further study is required to validate the initial promise of these preliminary observations.

Anemia, Aplastic↗

Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia.

Minimal residual disease (MRD) is an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). The most widely applied MRD assays in ALL are flow cytometric identification of leukemia immunophenotypes and polymerase chain reaction (PCR) amplification of antigen-receptor genes. We measured MRD by both assays in 227 patients with childhood B-lineage ALL. Of 1375 samples (736 bone marrow and 639 peripheral blood) examined, MRD was <0.01% in 1200, and > or =0.01% in 129 by both assays; MRD levels measured by the two methods correlated well. Of the remaining 46 samples, 28 had MRD > or =0.01% by flow cytometry but <0.01% by PCR. However, PCR (which had a consistent sensitivity of 0.001%) detected leukemic gene rearrangements in 26 of these 28 samples. Conversely, in 18 samples, MRD was > or =0.01% by PCR but <0.01% by flow cytometry. In nine of these samples, flow cytometry had a sensitivity of 0.001%, and detected aberrant immunophenotypes in eight samples. Therefore, the two most widely used methods for MRD detection in ALL yield concordant results in the vast majority of cases, although the estimated levels of MRD may vary in some. The use of the two methods in tandem ensures MRD monitoring in all patients.

Adolescent↗

Variants in the catechol-o-methyltransferase (COMT) gene are associated with schizophrenia in Irish high-density families.

The enzyme catechol-o-methyltransferase (COMT) transfers a methyl group from adenosylmethionine to catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. In this article, we reported our study of association of COMT with schizophrenia in Irish families with a high density of schizophrenia. Three single nucleotide polymorphisms (SNPs) were genotyped for the 274 such families and within-family transmission disequilibrium tests were performed. SNP rs4680, which is the functional Val/Met polymorphism, showed modest association with the disease by the TRANSMIT, FBAT and PDT programs, while the other two SNPs were negative. These SNPs showed lower level of LDs with each other in the Irish subjects than in Ashkenazi Jews. Haplotype analysis indicated that a haplotype, haplotype A-G-A for SNPs rs737865-rs4680-rs165599, was preferentially transmitted to the affected subjects. This was different from the reported G-G-G haplotype found in Ashkenazi Jews, but both haplotypes shared the Val allele. We concluded that COMT gene is associated with schizophrenia and carries a small but significant risk to the susceptibility in the Irish subjects.

Alleles↗

Linkage disequilibrium and haplotype architecture for two ABC transporter genes (ABCC1 and ABCG2) in Chinese population: implications for pharmacogenomic association studies.

Information about linkage disequilibrium (LD) patterns and haplotype structures for candidate genes is instructive for the design and analysis of genetic association studies for complex diseases and drug response. ABCC1 and ABCG2 are genes coding for two multidrug resistance (MDR) associated transporters; they are also related to some pathophysiological traits. To pinpoint the LD profiles of these MDR genes in Chinese, we systemically screened 27 unrelated individuals for single nucleotide polymorphisms (SNPs) in the coding and regulatory regions of these genes, and thereby characterized their haplotype structures. Despite marked variations in haplotype diversity, LD pattern and intragenic recombination intensity between the two genes, both loci could be partitioned into several LD blocks, in which a modest number of haplotypes accounted for a high fraction of the sampled chromosomes. We concluded that each locus has its own genomic LD profile, but that they still share a common segmental LD architecture with low haplotype diversity. Our data will benefit genetic association studies of complex traits and drug response possibly related to these genes.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation.

BACKGROUND: The presence of T and B cells in allogeneic grafts contributes to GvHD and to EBV-associated lymphoproliferative disease (LPD). Depletion of T and B cells from the graft decreases the risk of these complications. METHODS: T and B cells were depleted from mobilized peripheral stem cells from volunteer donors (n=5) using anti-CD3 and anti-CD19 Abs conjugated to magnetic microbeads, and the CliniMACS device. The function of the stem cells after depletion was evaluated using colony assays and non-obese diabetic (NOD)/SCID repopulating experiments. RESULTS: The mean mononuclear cell (MNC) count prior to T- and B-cell depletion was 2.19x10(10) (range 1.48-3.53). After depletion, the mean percentage of contaminating T cells was 0.02% (range 0.01-0.04%) with a mean log(10) depletion of 3.4 (range 3-3.8). The mean percentage of contaminating B cells was 0.1% (range 0.01-0.4%) with a mean log(10) depletion of 2.2 (range 1.4-3). The mean recovery of CD3- and CD19-negative MNCs after depletion was 70% (range 54-88%) and the mean recovery of CD34(+) stem cells was 69% (range 52-98%). The mean number of natural killer (NK) cells after T- and B-cell depletion was 5.2x10(8) (range 2-10x10(8)). In vitro colony assays and in vivo NOD/SCID repopulation assays showed no negative impact of this method on the function of the hematopoietic stem cells. DISCUSSION: Our results show that the CliniMACS system can be used to efficiently deplete PBSC of T and B cells simultaneously, without adverse effect on the graft.

Animals↗