Biomedical subjects

Bin He

Publications and source records attributed to Bin He.

At least 55 records · Page 3Linked to original sources

PubMed2005

Classification of motor imagery tasks for brain-computer interface applications by means of two equivalent dipoles analysis.

We have developed a novel approach using source analysis for classifying motor imagery tasks. Two-equivalent-dipoles analysis was proposed to aid classification of motor imagery tasks for brain-computer interface (BCI) applications. By solving the electroencephalography (EEG) inverse problem of single trial data, it is found that the source analysis approach can aid classification of motor imagination of left- or right-hand movement without training. In four human subjects, an averaged accuracy of classification of 80% was achieved. The present study suggests the merits and feasibility of applying EEG inverse solutions to BCI applications from noninvasive EEG recordings.

Action Potentials↗

PubMed2005

Herpes simplex virus 1 infection activates the endoplasmic reticulum resident kinase PERK and mediates eIF-2alpha dephosphorylation by the gamma(1)34.5 protein.

The gamma(1)34.5 protein of herpes simplex virus (HSV) plays a crucial role in virus infection. Although the double-stranded RNA-dependent protein kinase (PKR) is activated during HSV infection, the gamma(1)34.5 protein inhibits the activity of PKR by mediating dephosphorylation of the translation initiation factor eIF-2alpha. Here we show that HSV infection also induces phosphorylation of an endoplasmic reticulum (ER) resident kinase PERK, a hallmark of ER stress response. The virus-induced phosphorylation of PERK is blocked by cycloheximide but not by phosphonoacetic acid, suggesting that the accumulation of viral proteins in the ER is essential. Notably, the maximal phosphorylation of PERK is delayed in PKR+/+ cells compared to that seen in PKR-/- cells. Further analysis indicates that hyperphosphorylation of eIF-2alpha caused by HSV is greater in PKR+/+ cells than in PKR-/- cells. However, expression of the gamma(1)34.5 protein suppresses the ER stress response caused by virus, dithiothreitol, and thapsigargin as measured by global protein synthesis. Interestingly, the expression of GADD34 stimulated by HSV infection parallels the status of eIF-2alpha phosphorylation. Together, these observations suggest that regulation of eIF-2alpha phosphorylation by the gamma(1)34.5 protein is an efficient way to antagonize the inhibitory activity of PKR as well as PERK during productive infection.

Animals↗

PubMed2005

Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the interdomain interaction.

Gene activation by steroid hormone receptors involves the recruitment of the steroid receptor coactivator (SRC)/p160 coactivator LXXLL motifs to activation function 2 (AF2) in the ligand binding domain. For the androgen receptor (AR), AF2 also serves as the interaction site for the AR NH(2)-terminal FXXLF motif in the androgen-dependent NH(2)-terminal and carboxyl-terminal (N/C) interaction. The relative importance of the AR AF2 site has been unclear, since the AR FXXLF motif interferes with coactivator recruitment by competitive inhibition of LXXLL motif binding. In this report, we identified the X chromosome-linked melanoma antigen gene product MAGE-11 as an AR coregulator that specifically binds the AR NH(2)-terminal FXXLF motif. Binding of MAGE-11 to the AR FXXLF alpha-helical region stabilizes the ligand-free AR and, in the presence of an agonist, increases exposure of AF2 to the recruitment and activation by the SRC/p160 coactivators. Intracellular association between AR and MAGE-11 is supported by their coimmunoprecipitation and colocalization in the absence and presence of hormone and by competitive inhibition of the N/C interaction. AR transactivation increases in response to MAGE-11 and the SRC/p160 coactivators through mechanisms that include but are not limited to the AF2 site. MAGE-11 is expressed in androgen-dependent tissues and in prostate cancer cell lines. The results suggest MAGE-11 is a unique AR coregulator that increases AR activity by modulating the AR interdomain interaction.

Amino Acid Motifs↗

PubMed2005

Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34.

Mice heterozygous for targeted disruption of Pthrp exhibit, by 3 months of age, diminished bone volume and skeletal microarchitectural changes indicative of advanced osteoporosis. Impaired bone formation arising from decreased BM precursor cell recruitment and increased apoptotic death of osteoblastic cells was identified as the underlying mechanism for low bone mass. The osteoporotic phenotype was recapitulated in mice with osteoblast-specific targeted disruption of Pthrp, generated using Cre-LoxP technology, and defective bone formation was reaffirmed as the underlying etiology. Daily administration of the 1-34 amino-terminal fragment of parathyroid hormone (PTH 1-34) to Pthrp+/- mice resulted in profound improvement in all parameters of skeletal microarchitecture, surpassing the improvement observed in treated WT littermates. These findings establish a pivotal role for osteoblast-derived PTH-related protein (PTHrP) as a potent endogenous bone anabolic factor that potentiates bone formation by altering osteoblast recruitment and survival and whose level of expression in the bone microenvironment influences the therapeutic efficacy of exogenous PTH 1-34.

Animals↗

PubMed2005

Increased efficacy of an interleukin-12-secreting herpes simplex virus in a syngeneic intracranial murine glioma model.

Long-term survivors of glioblastoma multiforme, the most common form of primary intracranial malignancy in adults, are extremely rare. Experimental animal models that more closely resemble human disease are essential for the identification of effective novel therapies. We report here an extensive analysis of the 4C8 glioma model to assess its suitability for evaluating novel type 1 herpes simplex virus (HSV-1) therapies of malignant glioma. We first determined that expression of major histocompatibility complex I and II and of alphavbeta3 in the 4C8 model was comparable to that seen in human glioma cells. Next, using a panel of Delta(gamma1)34.5 HSVs, we demonstrated that, in vitro, 4C8 cells were as sensitive as human glioma cells to both infection and lysis and that the 4C8 cells supported the production of foreign gene products. Replication competence of HSV was demonstrated in vitro. Finally, 4C8 intracranial gliomas were established in immunologically competent syngeneic B6D2F1 mice, treated by intratumoral injection of selected engineered HSVs, including the interleukin-12-expressing virus, M002. Survival data from these studies demonstrated that 4C8 cells in vivo are sensitive to both direct oncolysis and HSV-mediated interleukin-12 expression. Fluorescence-activated cell sorting analyses of immune-related infiltrating cells supported the concept that survival was prolonged in part because of antitumor actions of these cells. We conclude that the 4C8/B6D2F1 syngeneic glioma model is suitable for preclinical evaluation of HSV-based therapies and that M002 is a superior virus for the treatment of murine glioma in this model.

Animals↗

PubMed2005

Use of 3-D magnetic resonance electrical impedance tomography in detecting human cerebral stroke: a simulation study.

We have developed a new three dimensional (3-D) conductivity imaging approach and have used it to detect human brain conductivity changes corresponding to acute cerebral stroke. The proposed Magnetic Resonance Electrical Impedance Tomography (MREIT) approach is based on the J-Substitution algorithm and is expanded to imaging 3-D subject conductivity distribution changes. Computer simulation studies have been conducted to evaluate the present MREIT imaging approach. Simulations of both types of cerebral stroke, hemorrhagic stroke and ischemic stroke, were performed on a four-sphere head model. Simulation results showed that the correlation coefficient (CC) and relative error (RE) between target and estimated conductivity distributions were 0.9245+/-0.0068 and 8.9997%+/-0.0084%, for hemorrhagic stroke, and 0.6748+/-0.0197 and 8.8986%+/-0.0089%, for ischemic stroke, when the SNR (signal-to-noise radio) of added GWN (Gaussian White Noise) was 40. The convergence characteristic was also evaluated according to the changes of CC and RE with different iteration numbers. The CC increases and RE decreases monotonously with the increasing number of iterations. The present simulation results show the feasibility of the proposed 3-D MREIT approach in hemorrhagic and ischemic stroke detection and suggest that the method may become a useful alternative in clinical diagnosis of acute cerebral stroke in humans.

Brain Ischemia↗

PubMed2005

Determination of 3-chloropropane-1,2-diol in liquid hydrolyzed vegetable proteins and soy sauce by solid-phase microextraction and gas chromatography/mass spectrometry.

Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography/mass spectrometry (GC/MS) method was developed to determine 3-chloropropane-1,2-diol (3-MCPD) in hydrolyzed vegetable protein and Chinese soy sauce. The 3-MCPD was firstly derivativized with phenylboronic acid in aqueous solution at 90 degrees C for 10 min, then extracted by HS-SPME and finally detected with GC/MS, parameters related to both the derivative reaction and the HS-SPME process were optimized. The proposed method has a linear range of 0.0194-394 microg g(-1), a detection limit of 3.87 ng g(-1) (S/N = 3), and a precision of RSD = 7.5% (n = 5). Seventeen real samples, including four HVPs and thirteen soy sauce samples, were analyzed to examine the feasibility of the proposed procedure; with a concentration of 3-MCPD and acceptable recoveries at 0.71 microg g(-1) spiked levels were obtained. Being simpler, faster and more environmentally benign than the existing methods, this method is accurate and suitable for routine analysis.

Boronic Acids↗

PubMed2005

[Study on the role of angiogenesis and related factors in leukemias].

OBJECTIVE: To observe the bone marrow angiogenesis in leukemia and evaluate the expression and role of endostatin (ES), vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in leukemia patients. METHODS: Bone marrow angiogenesis was assayed by vWF immunohistochemical method. The ES and VEGF concentrations in plasma were detected by ELISA. The expression of VEGFR in leukemia cells was determined by flow cytometry (FCM). RESULTS: The bone marrow microvessel density (MVD) in 26 cases of acute leukemia (AL) [(20.78 +/- 7.75)/high-power field (HP)] and 5 chronic myelogenous leukemia (CML) [(28.67 +/- 7.32)/HP] at newly diagnosed stage was significantly higher than that in the control group [(9.29 +/- 3.53)/HP, P < 0.01]. The bone marrow MVD in the complete remission (CR) groups, (11.33 +/- 5.66)/HP for AL and (17.00 +/- 8.04)/HP for CML, was significantly lower than that of newly diagnosed groups (P < 0.05 and < 0.01). No significant difference was found between the remission groups and the control group (P > 0.05). The plasma ES and VEGF concentrations of newly diagnosed AL and CML groups were significantly higher than those of the control group (P < 0.05). The levels of plasma ES and VEGF in AL CR group and plasma ES in CML CR group decreased to levels comparable to normal values (P > 0.05), but the plasma VEGF in CML CR group was still higher than that in control (P < 0.01). AL bone marrow mononuclear cells had higher expression of VEGFR at various levels whereas CML and control samples had lower levels of VEGFR. CONCLUSIONS: Leukemia patients at newly diagnosed stage had remarkable angiogenesis in bone marrow and elevated plasma ES and VEGF concentrations. VEGFR was expressed at different levels in AL cells.

Acute Disease↗

PubMed2005

[Study on the relationship between LOH and MI of FHIT gene and the development of cervical carcinoma].

OBJECTIVE: To explore the relationship of loss of heterozygosity (LOH) and microsatellite instability (MI) of fragile histidine triad (FHIT) gene to the development of cervical carcinoma. METHODS: Two sites of microsatellite polymophism in FHIT gene were selected to detect LOH and MI in 60 cases of primary invasive cervical carcinoma and 35 cases of cervical intra-epithelial neoplasia (CIN). RESULTS: At D3S1234 and D3S1300, the LOH rates of primary invasive cervical carcinomas were 45.0% (27/60) and 38.3% (23/60), the MI rates were 18.3% (11/60) and 11.7% (7/60), respectively. The LOH rates of CINs were 42.9% (15/35) and 37.1% (13/35), the MI rates were 11.4% (4/35), 8.6% (3/35), respectively. There were no significant differences between invasive cervical carcinomas and CINs in respect to their positive rates of LOH and MI at D3S1234 and D3S1300 (P>0.05). There were significant differences in LOH rates at D3S1234 and D3S1300 between the well/moderately differentiated cervical carcinomas and the poorly differentiated invasive cervical carcinomas (P<0.05). Significant differences were noted between the invasive cervical carcinomas with lymph node metastasis and those without lymph node metastasis in regard to their LOH and MI at the two sites (P < 0.05). The positive rates of LOH and MI for CIN III and noninvasive cervical carcinomas were higher than those for CIN I-II. CONCLUSION: The FHIT gene change is a relatively late event in CINs. The detection of the LOH of FHIT gene might be helpful to the early diagnosis and the screening of cervical carcinoma. It might also be useful for predicting the prognosis of cervical carcinoma.

Acid Anhydride Hydrolases↗

PubMed2004

Highly enantioselective cyanosilylation of aldehydes catalyzed by novel beta-amino alcohol-titanium complexes.

The beta-amino alcohol 1b-Ti(Oi-Pr)(4) complex has been shown to catalyze the enantioselective cyanosilylation of aldehydes efficiently. In the presence of 5 mol % of 1b-Ti(Oi-Pr)(4) complex catalyst, the aromatic, conjugated, heteroaromatic, and aliphatic aldehydes were converted to their corresponding trimethylsilyl ethers of cyanohydrins in 90-99% yields with up to 94% ee under mild conditions.

Journal Article↗

PubMed2004

Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance.

The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily.

Amino Acid Motifs↗

PubMed2004

Motor imagery classification by means of source analysis for brain-computer interface applications.

We report a pilot study of performing classification of motor imagery for brain-computer interface applications, by means of source analysis of scalp-recorded EEGs. Independent component analysis (ICA) was used as a spatio-temporal filter extracting signal components relevant to left or right motor imagery (MI) tasks. Source analysis methods including equivalent dipole analysis and cortical current density imaging were applied to reconstruct equivalent neural sources corresponding to MI, and classification was performed based on the inverse solutions. The classification was considered correct if the equivalent source was found over the motor cortex in the corresponding hemisphere. A classification rate of about 80% was achieved in the human subject studied using both the equivalent dipole analysis and the cortical current density imaging analysis. The present promising results suggest that the source analysis approach could manifest a clearer picture on the cortical activity, and thus facilitate the classification of MI tasks from scalp EEGs.

Algorithms↗

PubMed2004

Synergistic activation of the CMV promoter by NF-kappaB P50 and PKG.

Several DNA binding NF-kappaB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-kappaB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-kappaB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-kappaB sites. These interactions may be relevant for the activation of viral gene expression.

Animals↗

PubMed2004

Mathematical algorithm for discovering states of expression from direct genetic comparison by microarrays.

Highly specific direct genome-scale expression discovery from two biological samples facilitates functional discovery of molecular systems. Here, expression data from cDNA arrays are ranked and curve-fitted. The algorithm uses filters based on the derivatives (slopes) of the curve fits. The rules are set to (i) filter the largest number of artifactual ratios from same-to-same datasets and (ii) maximize discovery from direct comparisons of different samples. The unsupervised discovery is optimized without lowering specificity. The false discovery rates are significantly lower than other methods. The discovered states of genetic expression facilitate functional discovery and are validated by real-time RT-PCR. Better quality improves sensitivity.

Algorithms↗

PubMed2004

A second-order finite element algorithm for solving the three-dimensional EEG forward problem.

A finite element algorithm has been developed to solve the electroencephalogram (EEG) forward problem. A new computationally efficient approach to calculate the stiffness matrix of second-order tetrahedral elements has been developed for second-order tetrahedral finite element models. The present algorithm has been evaluated by means of computer simulations, by comparing with analytic solutions in a multi-spheres concentric head model. The developed finite element method (FEM) algorithm has also been applied to address questions of interest in the EEG forward problem. The present simulation study indicates that the second-order FEM provides substantially enhanced numerical accuracy and computational efficiency, as compared with the first-order FEM for comparable numbers of tetrahedral elements. The anisotropic conductivity distribution of the head tissue can be taken into account in the present FEM algorithm. The effects of dipole eccentricity, size of finite elements and local mesh refinement on solution accuracy are also addressed in the present simulation study.

Algorithms↗

PubMed2004

An androgen receptor NH2-terminal conserved motif interacts with the COOH terminus of the Hsp70-interacting protein (CHIP).

The NH2-terminal sequence of steroid receptors is highly variable between different receptors and in the same receptor from different species. In this study, a primary sequence homology comparison identified a 14-amino acid NH2-terminal motif of the human androgen receptor (AR) that is common to AR from all species reported, including the lower vertebrates. The evolutionarily conserved motif is unique to AR, with the exception of a partial sequence in the glucocorticoid receptor of higher species. The presence of the conserved motif in AR and the glucocorticoid receptor and its absence in other steroid receptors suggests convergent evolution. The function of the AR NH2-terminal conserved motif was suggested from a yeast two-hybrid screen that identified the COOH terminus of the Hsp70-interacting protein (CHIP) as a binding partner. We found that CHIP functions as a negative regulator of AR transcriptional activity by promoting AR degradation. In support of this, two mutations in the AR NH2-terminal conserved motif previously identified in the transgenic adenocarcinoma of mouse prostate model reduced the interaction between CHIP and AR. Our results suggest that the AR NH2-terminal domain contains an evolutionarily conserved motif that functions to limit AR transcriptional activity. Moreover, we demonstrate that the combination of comparative sequence alignment and yeast two-hybrid screening using short conserved peptides as bait provides an effective strategy to probe the structure-function relationships of steroid receptor NH2-terminal domains and other intrinsically unstructured transcriptional regulatory proteins.

Amino Acid Motifs↗

PubMed2004

Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.

In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC(50)'s as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity. Substitutents at the C3-position can incorporate a variety of different groups. The synthesis and primary structure-activity relationship of this new series of potent PDE5 inhibitors are described.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

An alternative subspace approach to EEG dipole source localization.

In the present study, we investigate a new approach to electroencephalography (EEG) three-dimensional (3D) dipole source localization by using a non-recursive subspace algorithm called FINES. In estimating source dipole locations, the present approach employs projections onto a subspace spanned by a small set of particular vectors (FINES vector set) in the estimated noise-only subspace instead of the entire estimated noise-only subspace in the case of classic MUSIC. The subspace spanned by this vector set is, in the sense of principal angle, closest to the subspace spanned by the array manifold associated with a particular brain region. By incorporating knowledge of the array manifold in identifying FINES vector sets in the estimated noise-only subspace for different brain regions, the present approach is able to estimate sources with enhanced accuracy and spatial resolution, thus enhancing the capability of resolving closely spaced sources and reducing estimation errors. The present computer simulations show, in EEG 3D dipole source localization, that compared to classic MUSIC, FINES has (1) better resolvability of two closely spaced dipolar sources and (2) better estimation accuracy of source locations. In comparison with RAP-MUSIC, FINES' performance is also better for the cases studied when the noise level is high and/or correlations among dipole sources exist.

Algorithms↗