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Biomedical subjects

Hong Gu

Publications and source records attributed to Hong Gu.

At least 19 recordsLinked to original sources
PubMed2007

Assessing local influence in principal component analysis with application to haematology study data.

In many medical and health studies, high-dimensional data are often encountered. Principal component analysis (PCA) is a commonly used technique to reduce such data to a few components that includes most of the information provided by the original data. However, PCA is known to be very sensitive to some abnormal observations. Therefore, it is essential to assess such sensitivity in PCA. In this paper, the assessments of local influence based on generalized influence function are developed under the case-weights and additive perturbation schemes, along with a discussion of the perturbation scheme and the generalized influence function approach. When perturbing different variables of the data, it is noted that the directions of the largest joint local influence for the eigenvalues are all the same. Moreover, these directions are completely determined by the score values of the observations, to which an approximate cut-off point is given. The proposed methods are applied to analyse a set of haematology study data for illustration. Results add new insights in finding influential observations in the studied data set.

Health Status↗
PubMed2006

Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.

We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.

Animals↗
PubMed2006

A novel analytical method for in vivo phosphate tracking.

Genetically-encoded fluorescence resonance energy transfer (FRET) sensors for phosphate (P(i)) (FLIPPi) were engineered by fusing a predicted Synechococcus phosphate-binding protein (PiBP) to eCFP and Venus. Purified fluorescent indicator protein for inorganic phosphate (FLIPPi), in which the fluorophores are attached to the same PiBP lobe, shows P(i)-dependent increases in FRET efficiency. FLIPPi affinity mutants cover P(i) changes over eight orders of magnitude. COS-7 cells co-expressing a low-affinity FLIPPi and a Na(+)/P(i) co-transporter exhibited FRET changes when perfused with 100 microM P(i), demonstrating concentrative P(i) uptake by PiT2. FLIPPi sensors are suitable for real-time monitoring of P(i) metabolism in living cells, providing a new tool for fluxomics, analysis of pathophysiology or changes of P(i) during cell migration.

Animals↗
PubMed2006

Examining protein structure and similarities by spectral analysis technique.

The spectral envelope, a frequency based technique for analyzing categorical time series, is applied to amino acid sequences to examine their periodicity. The periodic signatures of such sequences is related to the secondary structure of the folding patterns in the gene. For a pair of sequences, we define a spectral envelope covariance which emphasizes the common periodicities in the two sequences. This is used to give a similarity measure for the two sequences which can then be used in a neighbour joining algorithm to construct a phylogeny. We apply the spectral methods to myoglobin sequences from primates and cetaceans. The spectral envelope reflects the structure of this protein and the tree constructed using spectral methods shows strong agreement with published trees. The spectral envelope can be used to explore similarities between and within different protein families. Since we do not require aligned sequences, the spectral methods can be used to create phylogenies across different protein families. We apply the method to 11 protein families from PANDIT obtaining a tree where the families are separated and the relationship among the families is given.

Algorithms↗
PubMed2006

Test a clade in phylogenetic trees.

We develop a new method for testing a portion of a tree (called a clade) based on multiple tests of many 4-taxon trees in this paper. This is particularly useful when the phylogenetic tree constructed by other methods have a clade that is difficult to explain from a biological point of view. The statement about the test of the clade can be made through the multiple P values from these individual tests. By controlling the familywise error rate or the false discovery rate (FDR), 4 different tree test methods are evaluated through simulation methods. It shows that the combination of the approximately unbiased (AU) test and the FDR-controlling procedure provides strong power along with reasonable type I error rate and less heavy computation.

Animals↗
PubMed2005

Noninvasive quantification of cerebral blood volume in humans during functional activation.

Like cerebral blood flow (CBF), cerebral blood volume (CBV) is an important physiological parameter closely associated with brain activity and thus, noninvasive quantification of CBV during brain activation provides another opportunity to investigate the relationship between neuronal activity and hemodynamic changes. In this paper, a new method is presented that is able to quantify CBV at rest and during activation. Specifically, using an inversion recovery pulse sequence, a set of brain images was collected at various inversion times (TIs). At each TI, functional images were acquired with a block-design visual stimulation paradigm. A biophysical model comprised of multiple tissue components was developed and was utilized for the determination of CBV using the visual stimulation data. MRI experiments on five healthy volunteers showed that CBV was 5.0 +/- 1.5 ml blood/100 ml brain during rest and increased to 6.6 +/- 1.8 ml blood/100 ml brain following visual stimulation. Furthermore, experiments with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases in CBV correlated with the strength of stimulation. This technique, with its ability to measure quantitative CBV values noninvasively, provides a valuable tool for quantifying hemodynamic signals associated with brain activation.

Algorithms↗
PubMed2005

Nonlinear responses of cerebral blood volume, blood flow and blood oxygenation signals during visual stimulation.

Hemodynamic-based functional magnetic resonance imaging (fMRI) techniques provide a great utility for noninvasive functional brain mapping. However, because the hemodynamic signals reflect underlying neural activity indirectly, characterization of these signals following brain activation is essential for experimental design and data interpretation. In this report, the linear (or nonlinear) responses to neuronal activation of three hemodynamic parameters based primarily on changes of cerebral blood volume, blood flow and blood oxygenation were investigated by testing these hemodynamic responses' additivity property. Using a recently developed fMRI technique that acquires vascular space occupancy (VASO), arterial spin labeling (ASL) perfusion and blood oxygenation level-dependent (BOLD) signals simultaneously, the additivity property of the three hemodynamic responses in human visual cortex was assessed using various visual stimulus durations. Experiments on healthy volunteers showed that all three hemodynamic-weighted signals responded nonlinearly to stimulus durations less than 4 s, with the degree of nonlinearity becoming more severe as the stimulus duration decreased. Vascular space occupancy and ASL perfusion signals showed similar nonlinearity properties, whereas the BOLD signal was the most nonlinear. These data suggest that caution should be taken in the interpretation of hemodynamic-based signals in fMRI.

Adult↗
PubMed2005

Development of recombinant VP2 vaccine for the prevention of infectious bursal disease of chickens.

The objective of the present study was to investigate the feasibility of a subunit vaccine and a live bacteria vaccine to protect chickens against infectious bursal disease virus (IBDV) infection. The gene for VP2 of a new wild-type very virulent IBDV (vvIBDV) strain was cloned into an Escherichia coli expression system. Following expression, the recombinant VP2 and the induced expression bacteria were used to vaccinate chickens against virulent IBDV (vIBDV). Three weeks after the vaccination, chickens were inoculated with IBDV strain BC 6/85 by intranasal route or eyedrop route, prior to challenge anti-IBDV serum antibody was detected by AGP. All chickens vaccinated with recombinant VP2 could be detected anti-IBDV antibody. The subunit vaccine of recombinant VP2 conferred protection for 90--100% chickens, live bacteria vaccine of recombinant VP2 conferred protection for 85.7% chickens. The results indicate that E. coli BL 21/pET 28 a-VP2 could be used to develop recombinant VP2 vaccine against infectious bursal disease in chickens.

Administration, Intranasal↗
PubMed2005

The comparison of the confidence regions in phylogeny.

In this paper, several different procedures for constructing confidence regions for the true evolutionary tree are evaluated both in terms of coverage and size without considering model misspecification. The regions are constructed on the basis of tests of hypothesis using six existing tests: Shimodaira Hasegawa (SH), SOWH, star form of SOWH (SSOWH), approximately unbiased (AU), likelihood weight (LW), generalized least squares, plus two new tests proposed in this paper: single distribution nonparametric bootstrap (SDNB) and single distribution parametric bootstrap (SDPB). The procedures are evaluated on simulated trees both with small and large number of taxa. Overall, the SH, SSOWH, AU, and LW tests led to regions with higher coverage than the nominal level at the price of including large numbers of trees. Under the specified model, the SOWH test gives accurate coverage and relatively small regions. The SDNB and SDPB tests led to the small regions with occasional undercoverage. These two procedures have a substantial computational advantage over the SOWH test. Finally, the cutoff levels for the SDNB test are shown to be more variable than those for the SDPB test.

Classification↗
PubMed2005

Telomere shortening in T lymphocytes of older individuals with Down syndrome and dementia.

Telomere shortening has been recently correlated with Alzheimer's disease status. Therefore, we hypothesized that a possible association might exist for adults with Down syndrome (DS). Using blind, quantitative telomere protein nucleic acid FISH analyses of metaphase and interphase preparations from 18 age-matched trisomy 21 female study participants with and without dementia, we have observed increased telomere shortening in adults with DS and dementia (p < .01). From this initial study, we conclude that telomere shortening is associated with dementia in this high-risk population and suggest that additional research may show that telomere shortening may be a biological marker of dementia status.

Chromosome Aberrations↗
PubMed2005

The intron 5/6 promoter region of the ship1 gene regulates expression in stem/progenitor cells of the mouse embryo.

The s-SHIP protein is a shorter isoform of the longer SHIP1 protein and lacks the N-terminal SH2 domain region contained in SHIP1. s-SHIP is expressed in ES cells and in enriched bone marrow stem cells, and may be controlled by a promoter within intron 5 of the ship1 gene. We therefore examined the potential specificity of promoter activity in ES cells of an intron 5/intron 6 ship1 genomic segment and its tissue specificity within transgenic mice expressing GFP from this promoter region. The results indicate that s-SHIP promoter activity is specific for ES cells in vitro and for known and presumptive stem/progenitor cells throughout embryo development of the transgenic mice. Specific GFP expression was observed in the blastocyst, primordial germ cells, thymus, arterioles, osteoblasts, and skin epidermis. The epidermis/epithelium is the progenitor for hair follicles, mammary tissue, and prostate. Interestingly, each of these latter tissues acquired a few GFP-positive cells in the course of their development from the epithelial layers, and these cells express marker proteins for stem/progenitor cells. These results identify potential stem cell populations, mark these cells for analyses in normal and cancer development, and implicate s-SHIP as an important protein in stem/progenitor cell function.

Animals↗
PubMed2005

Simultaneous perfusion and blood-oxygenation-level-dependent measurements using single-shot interleaved z-shim echo-planar imaging.

Single-shot interleaved z-shim EPI (SSIZS-EPI) was extended to a simultaneous perfusion and blood-oxygenation-level-dependent (BOLD) imaging technique that reduces susceptibility-induced signal loss while preserving rapid image acquisition. Experiments on human brains showed that images acquired with this technique had improved signal-to-noise ratio in the inferior prefrontal, meso-, and lateral-temporal lobes compared with a conventional EPI. Perfusion maps obtained from the SSIZS-EPI images at resting state illustrated substantial signal recovery in these brain areas. Perfusion and BOLD images collected with a sensorimotor paradigm demonstrated the feasibility of the technique to simultaneously measure cerebral blood flow and blood oxygenation signals associated with brain activation. Functional experiments with a neuropsychiatric paradigm showed increased brain activities in the periamygdalar regions in both perfusion and BOLD maps, consistent with a previous H(2) (15)O PET study. The proposed technique, with its advantages of reducing susceptibility artifacts and fast scanning speed, would be useful for obtaining more reliable measurements of functional signals, particularly in the brain regions with field inhomogeneities.

Artifacts↗
PubMed2004

Simultaneous MRI acquisition of blood volume, blood flow, and blood oxygenation information during brain activation.

Simultaneous acquisition of complementary functional hemodynamic indices reflecting different aspects of brain activity would be a valuable tool for functional brain-imaging studies offering enhanced detection power and improved data interpretation. As such, a new MRI technique is presented that is able to achieve concurrent acquisition of three hemodynamic images based primarily on the changes of cerebral blood volume, blood flow, and blood oxygenation, respectively, associated with brain activation. Specifically, an inversion recovery pulse sequence has been designed to measure VASO (vascular space occupancy), ASL (arterial spin labeling) perfusion, and BOLD (blood-oxygenation-level-dependent) signals in a single scan. The MR signal characteristics in this sequence were analyzed, and image parameters were optimized for the simultaneous acquisition of these functional images. The feasibility and efficacy of the new technique were assessed by brain activation experiments with visual stimulation paradigms. Experiments on healthy volunteers showed that this technique provided efficient image acquisition, and thus higher contrast-to-noise ratio per unit time, compared with conventional techniques collecting these functional images separately. In addition, it was demonstrated that the proposed technique was able to be utilized in event-related functional MRI experiments, with potential advantages of obtaining accurate transient information of the activation-induced hemodynamic responses.

Blood Flow Velocity↗
PubMed2003

High incidence of cardiac malformations in connexin40-deficient mice.

Gap junctions are intercellular channels formed by oligomerization of a protein called connexin (Cx). The heart expresses at least three connexin isotypes: Cx40, Cx43, and Cx45. A possible role for Cx40 in cardiac morphogenesis remains to be determined. We have characterized the anatomy and histology of fetal and newborn hearts obtained from crossing Cx40-deficient mice of mixed genetic background (C57BL/6x129Sv). Hearts were serial-sectioned (5 microm) along the coronal plane, stained with hematoxylin-eosin, and visualized by conventional light microscopy. Cardiac malformations in mice lacking Cx40 in one allele (Cx40+/-) included bifid atrial appendage, ventricular septal defect, tetralogy of Fallot (TOF), and an aortic arch abnormality. In Cx40-/- mice resulting from crossing of Cx40+/- mice, the most common cardiac malformations were double-outlet right ventricle (DORV), TOF, and endocardial cushion defects. Overall incidence of cardiac malformations was 6/33 (18%) in Cx40+/- mice and 4/12 (33%) in Cx40-/- mice. No cardiac malformations were observed in 15 wild-type mice studied. In addition, we examined 39 hearts from offspring of Cx40-/- matings. Frequency of cardiac malformations was even higher in this group (44%). Over one third of the hearts (14 of 39) showed conotruncal malformations corresponding to either DORV or TOF. Endocardial cushion defects were found in 3 out of 39 hearts. Our results suggest that Cx40 participates in cardiac morphogenesis, likely in association with other (unknown) products whose expression may vary with the genetic background of the mice.

Animals↗
PubMed2003

Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients.

A method is presented for mapping intravoxel fiber structures using spectral decomposition onto a circular distribution of measured apparent diffusion coefficients (ADCs). The zeroth-, second-, and fourth-order harmonic components of the ADC distribution on the circle spanned by the major and median eigenvectors of the diffusion tensor can be used to provide quantitative indices for isotropic, linear, and fiber-crossing diffusion, respectively. A diffusion-weighted MRI technique with 90 encoding orientations was implemented to estimate the circular ADC distribution and calculate the circular spectrum. A digital phantom was used to simulate various diffusion patterns. Comparisons were made between the circular spectrum and regular DTI-based index maps. The results indicated that the zeroth- and second-order circular spectrum maps exhibited a strong consistency with the DTI-based mean diffusivity and linear indices, respectively, and the fourth-order circular spectrum map was able to identify the fiber crossings. MRI experiments were performed on seven healthy human brains using a 3T scanner. The in vivo fourth-order maps showed significantly higher densities in several brain regions, including the corpus callosum, cingulum bundle, superior longitudinal fasciculus, corticospinal tract, and middle cerebellar peduncle, which indicated the existence of fiber crossings in these regions.

Adult↗
PubMed2003

Single-shot MR imaging using trapezoidal-gradient-based Lissajous trajectories.

A novel single-shot trapezoidal-gradient-based Lissajous trajectory is described and implemented on a 3-tesla magnetic resonance (MR) scanner. A feature of this trajectory is that its sampling points are located on a nonequidistant rectangular grid, which permits the usage of one-dimensional optimal algorithms to increase the robustness and speed of image reconstruction. Another advantage of the trajectory is that two images with different effective echo times can be obtained within a single excitation, which might be used for fast T2* mapping, in functional MR imaging scanning of brain activity associated with mental processes. Potential artifacts in reconstructed images were investigated and methods for suppressing these artifacts were developed. Experiments on normal subjects at rest and during brain activation were performed to demonstrate the feasibility of the new sequence.

Algorithms↗
PubMed2002

Role of the carboxyl terminal of connexin43 in transjunctional fast voltage gating.

Previous studies show that chemical regulation of connexin43 (Cx43) gap junction channels depends on the integrity of the carboxyl terminal (CT) domain. Experiments using Xenopus oocytes show that truncation of the CT domain alters the time course for current inactivation; however, correlation with the behavior of single Cx43 channels has been lacking. Furthermore, whereas chemical gating is associated with a "ball-and-chain" mechanism, there is no evidence whether transjunctional voltage regulation for Cx43 follows a similar model. We provide data on the properties of transjunctional currents from voltage-clamped pairs of mammalian tumor cells expressing either wild-type Cx43 or a mutant of Cx43 lacking the carboxyl terminal domain (Cx43M257). Cx43 transjunctional currents showed bi-exponential decay and a residual steady-state conductance of approximately 35% maximum. Transjunctional currents recorded from Cx43M257 channels displayed a single, slower exponential decay. Long transjunctional voltage pulses caused virtual disappearance of the residual current at steady state. Single channel data revealed disappearance of the residual state, increase in the mean open time, and slowing of the transition times between open and closed states. Coexpression of CxM257 with Cx43CT in a separate fragment restored the lower conductance state. We propose that Cx43CT is an effector of fast voltage gating. Truncation of Cx43CT limits channel transitions to those occurring across the higher energy barrier that separates open and closed states. We further propose that a ball-and-chain interaction provides the fast component of voltage-dependent gating between CT domain and a receptor affiliated with the pore.

Animals↗