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B He

Publications and source records attributed to B He.

At least 55 records · Page 3Linked to original sources
PubMed2001

High-resolution EEG: a new realistic geometry spline Laplacian estimation technique.

BACKGROUND: A new realistic geometry (RG) spline Laplacian estimation technique has been developed for high-resolution EEG imaging. METHODS: Estimation of the parameters associated with the spline Laplacian is formulated by seeking the general inverse of a transfer matrix. The number of spline parameters, which need to be determined through regularization, is reduced to one in the present approach, thus enabling easy implementation of the RG spline Laplacian estimator. RESULTS: Computer simulation studies have been conducted to test the feasibility of the new approach in a 3-concentric-sphere head model. The new technique has also been applied to human visual evoked potential data with a RG head model. CONCLUSIONS: The present numerical and experimental results demonstrate the feasibility of the new approach and indicate that the RG spline Laplacian can be estimated easily from the surface potentials and the scalp geometry.

Acoustic Stimulation↗
PubMed2001

Analysis of gene expression induced by irritant and sensitizing chemicals using oligonucleotide arrays.

Chemical-induced allergy continues to be an important occupational health problem. Despite decades of investigation, the molecular mechanisms underlying chemical-induced hypersensitivity and irritancy remain unclear because of the complex interplay between properties of different chemicals and the immune system. In this study, gene expression induced by toluene diisocyanate (TDI, a primarily IgE-inducing sensitizer), oxazolone (OXA, a cell-mediated hypersensitivity inducing sensitizer), or nonanoic acid (NA, a non-sensitizing irritant) was investigated using gene arrays. Female BALB/c mice were dermally exposed on the ears once daily for 4 consecutive days. On day 5, the lymph nodes draining the exposure sites were collected and used for RNA extraction and subsequent hybridization to Affymetrix Mu6500 oligonucleotide arrays. Of the 6519 genes on the arrays, there were 44, 13, and 51 genes in the TDI-, OXA-, and NA-exposed samples, respectively, that displayed a minimum of twofold change in expression level relative to the vehicle control. There were 32, 19, and 19 genes that were differentially expressed (with a minimum of twofold change) between TDI and OXA, TDI and NA, OXA and NA, respectively. The differentially expressed genes include immune response-related genes, transcriptional factors, signal transducing molecules, and Expressed Sequence Tags. Based on the gene array results, candidate genes were further evaluated using RT-PCR. There was only about 47% concordance between the gene array and RT-PCR results.

Animals↗
PubMed2001

A minimal product method and its application to cortical imaging.

In order to reduce the spatial blurring effect due to the head volume conductor, cortical imaging technique (CIT) can be used to reconstruct the cortical potential distribution from the scalp potential measurement with enhanced spatial resolution. To overcome the ill-posed nature of the inverse problem, Tikhonov regularization (TIK) and truncated Singular Value Decomposition (TSVD) are commonly used by choosing the appropriate regularization parameter and truncation parameter, respectively. We have developed a minimal product method (MINP) to determine the regularization and truncation parameters. The present computer simulation and experimental results indicate that the MINP can be easily implemented in both TIK and TSVD with satisfactory performance, and suggest the potential applications of the MINP method in determining the corner of the L-curve.

Algorithms↗
PubMed2001

Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis.

We have used interleukin (IL)-4 and -10-producing HSV-1 gamma(1)34.5 deletion viruses in gene therapy of a BALB/c model of experimental allergic encephalomyelitis (EAE), a T cell-mediated demyelinating disease of the central nervous system. It is known that in EAE of mice the Th2-type cytokines are down-regulated and the Th1-type cytokines up-regulated during the onset and relapse of the disease. Therefore, we tested two HSV-1 recombinants expressing the Th2-type cytokines IL-4 and IL-10. The recombinant viruses were injected intracranially (i.c.) in BALB/c mice 6 days after induction of EAE. As control groups we used mice without any infection, mice infected with backbone virus R3659 and mock-infected mice. Weights and symptoms of the mice were recorded daily and the tissue specimens were collected at specific time-points. The results indicate that the intracranial infection with IL-4-producing virus (1) precludes EAE symptoms, (2) protects the spinal cord from massive leukocyte infiltrations and (3) prevents demyelination and axonal loss. The IL-10-expressing virus R8308 did not have a similar favorable effect on the recovery of the mice as did the IL-4 virus R8306.

Animals↗
PubMed2001

A study of equivalent source techniques for high-resolution EEG imaging.

High-resolution EEG imaging has been an important topic in recent EEG research, and much work has been done on the two equivalent source imaging techniques: the equivalent distributed dipole-layer source imaging technique (EST) and the equivalent multipole source imaging technique (SAT). In this paper we first develop a forward density formula for a spherical equivalent distributed dipole layer of an arbitrary dipole in a three-concentric-sphere head model. It is clarified using the derived forward formula that the equivalent dipole-layer source and equivalent multipole source are interrelated in theory. Finally, simulation comparisons are conducted, the results of which suggest that EST has a higher spatial resolution than SAT when both of them are implemented by a truncated singular value decomposition algorithm. This is due to the different singularities of the inversion equations involved in the two techniques. An empirical VEP data study also shows that EST is better than SAT in providing higher spatial resolution EEG imaging.

Cerebral Cortex↗
PubMed2001

Localization of the site of origin of cardiac activation by means of a heart-model-based electrocardiographic imaging approach.

We have developed a new approach to solve the inverse problem of electrocardiography in terms of heart model parameters. The inverse solution of the electrocardiogram (ECG) inverse problem is defined, in the present study, as the parameters of the heart model, which are closely related to the physiological and pathophysiological status of the heart, and is estimated by using an optimization system of heart model parameters, instead of solving the matrix equation relating the body surface ECGs and equivalent cardiac sources. An artificial neural network based preliminary diagnosis system has been developed to limit the searching space of the optimization algorithm and to initialize the model parameters in the computer heart model. The optimal heart model parameters were obtained by minimizing the objective functions, as functions of the observed and model-generated body surface ECGs. We have tested the feasibility of the newly developed technique in localizing the site of origin of cardiac activation using a pace mapping protocol. The present computer simulation results show that, the present approach for localization of the site of origin of ventricular activation achieved an averaged localization error of about 3 mm [for 5-muV Gaussian white noise (GWN)] and 4 mm (for 10-muV GWN), with standard deviation of the localization errors of being about 1.5 mm. The present simulation study suggests that this newly developed approach provides a robust inverse solution, circumventing the difficulties of the ECG inverse problem, and may become an important alternative to other ECG inverse solutions.

Algorithms↗
PubMed2001

Imaging and visualization of 3-D cardiac electric activity.

Noninvasive imaging of cardiac electric activity is of importance for better understanding the underlying mechanisms and for aiding clinical diagnosis and intervention of cardiac abnormalities. We propose to image the three-dimensional (3-D) cardiac bioelectric source distribution from body-surface electrocardiograms. Cardiac electrical sources were modeled by a current dipole distribution throughout the entire myocardium, and estimated by using the Laplacian weighted minimum norm (LWMN) algorithm from body-surface potentials. The estimated inverse solution of the current distribution was further improved by using a recursive weighting strategy for localized sources, such as origins of cardiac arrhythmias. Computer simulations were conducted to test the feasibility of the proposed approach by using a 3-D ventricle model embedded in a realistically shaped torso model. The boundary element method was used to solve the forward problem from assumed cardiac sources to the body-surface potentials. Two testing dipoles were placed in the left and right ventricles, simulating the early activation associated with ventricular arrhythmias. The LWMN inverse solution showed an equivalent source distribution over the entity of both ventricles, with spread areas of activity overlying the positions of the testing dipoles. The sharpened inverse image provides well-localized focal sources near the testing dipole positions. In summary, the present computer simulation suggests that the proposed 3-D cardiac current source imaging and localization approach appears to be a promising candidate for localizing and imaging sites of origins of cardiac activation.

Algorithms↗
PubMed2001

Equivalent dipole source imaging of brain electric activity by means of parametric projection filter.

In the present study, spatial filters for inverse estimation of an equivalent dipole layer from the scalp-recorded potentials have been explored for their suitability in achieving high-resolution electroencephalogram (EEG) imaging. The performance of the parametric projection filter (PPF), which we propose to use for high-resolution EEG imaging, has been evaluated by computer simulations in the presence of a priori information on noise. An inhomogeneous three-concentric-sphere head model was used in the present simulation study to represent the head volume conductor. An equivalent dipole layer was used to model brain electric sources and estimated from the scalp potentials. Various noise conditions were simulated and the parametric projection filter was compared with standard regularization procedures such as the truncated singular value decomposition (TSVD) and the Tikhonov regularization (TKNV). The present simulation results suggest that the proposed method performs better than that of commonly used inverse regularization techniques, such as the general inverse using the TSVD and the TKNV, when the correlation between the original source distribution and the noise distribution is low, and performs similarly when the correlation is high. A method for determining the optimum regularization parameter, which can be applied to parametric inverse techniques, has also been developed.

Biomedical Engineering↗
PubMed2001

A self-coherence enhancement algorithm and its application to enhancing three-dimensional source estimation from EEGs.

In this paper a new algorithm is proposed to enhance the spatial resolution of solutions of the underdetermined EEG inverse problem. Termed the self-coherence enhancement algorithm (SCEA), the present algorithm provides a self-coherence solution, which is a function of the high order self-coherence estimate of an unbiased smooth estimate of the underdetermined EEG inverse solution. The order of the high order self-coherence function is determined by the blurring level of the actual source distribution as represented by a normalized blurring index. The proposed SCEA algorithm may be used to enhance the spatial resolution of an inverse solution obtained by any inverse reconstruction algorithm. Computer simulation studies have been conducted to evaluate the performance of the SCEA and to compare its performance to that of the LORETA and the FOCUSS algorithms.

Algorithms↗
PubMed2001

Single amino acid substitution in the V protein of simian virus 5 differentiates its ability to block interferon signaling in human and murine cells.

Previous work has demonstrated that the V protein of simian virus 5 (SV5) targets STAT1 for proteasome-mediated degradation (thereby blocking interferon [IFN] signaling) in human but not in murine cells. In murine BF cells, SV5 establishes a low-grade persistent infection in which the virus fluxes between active and repressed states in response to local production of IFN. Upon passage of persistently infected BF cells, virus mutants were selected that were better able to replicate in murine cells than the parental W3 strain of SV5 (wild type [wt]). Viruses with mutations in the Pk region of the N-terminal domain of the V protein came to predominate the population of viruses carried in the persistently infected cell cultures. One of these mutant viruses, termed SV5 mci-2, was isolated. Sequence analysis of the V/P gene of SV5 mci-2 revealed two nucleotide differences compared to wt SV5, only one of which resulted in an amino acid substitution (asparagine [N], residue 100, to aspartic acid [D]) in V. Unlike the protein of wt SV5, the V protein of SV5 mci-2 blocked IFN signaling in murine cells. Since the SV5 mci-2 virus had additional mutations in genes other than the V/P gene, a recombinant virus (termed rSV5-V/P N(100)D) was constructed that contained this substitution alone within the wt SV5 backbone to evaluate what effect the asparagine-to-aspartic-acid substitution in V had on the virus phenotype. In contrast to wt SV5, rSV5-V/P N(100)D blocked IFN signaling in murine cells. Furthermore, rSV5-V/P N(100)D virus protein synthesis in BF cells continued for significantly longer periods than that for wt SV5. However, even in cells infected with rSV5-V/P N(100)D, there was a late, but significant, inhibition in virus protein synthesis. Nevertheless, there was an increase in virus yield from BF cells infected with rSV5-V/P N(100)D compared to wt SV5, demonstrating a clear selective advantage to SV5 in being able to block IFN signaling in these cells.

Animals↗
PubMed2001

AlaArg motif in the carboxyl terminus of the gamma(1)34.5 protein of herpes simplex virus type 1 is required for the formation of a high-molecular-weight complex that dephosphorylates eIF-2alpha.

The gamma(1)34.5 protein of herpes simplex virus (HSV) type 1 functions to prevent the shutoff of protein synthesis mediated by the double-stranded-RNA-dependent protein kinase PKR. This is because gamma(1)34.5 associates with protein phosphatase 1 (PP1) through its carboxyl terminus, forming a high-molecular-weight complex that dephosphorylates the alpha subunit of translation initiation factor eIF-2 (eIF-2alpha). Here we show that Val193Glu and Phe195Leu substitutions in the PP1 signature motif of the gamma(1)34.5 protein abolished its ability to redirect PP1 to dephosphorylate eIF-2alpha and replication of mutant viruses was severely impaired. The gamma(1)34.5 protein, when expressed in Sf9 cells using a recombinant baculovirus, was capable of directing specific eIF-2alpha dephosphorylation. Deletions of amino acids 258 to 263 had no effect on activity of gamma(1)34.5. However, deletions of amino acids 238 to 258 abolished eIF-2alpha phosphatase activity but not PP1 binding activity. Interestingly, deletions in the AlaArg motif of the carboxyl terminus disrupted the high-molecular-weight complex that is required for dephosphorylation of eIF-2alpha. These results demonstrate that gamma(1)34.5 is functionally active in the absence of any other HSV proteins. In addition to a PP1 binding domain, the carboxyl terminus of gamma(1)34.5 contains an effector domain that is required to form a functional complex.

Alanine↗
PubMed2001

The SH integral membrane protein of the paramyxovirus simian virus 5 is required to block apoptosis in MDBK cells.

In some cell types the paramyxovirus simian virus 5 (SV5) causes little cytopathic effect (CPE) and infection continues productively for long periods of time; e.g., SV5 can be produced from MDBK cells for up to 40 days with little CPE. SV5 differs from most paramyxoviruses in that it encodes a small (44-amino-acid) hydrophobic integral membrane protein (SH). When MDBK cells were infected with a recombinant SV5 containing a deletion of the SH gene (rSV5DeltaSH), the MDBK cells exhibited an increase in CPE compared to cells infected with wild-type SV5 (recovered from cDNA; rSV5). The increased CPE correlated with an increase in apoptosis in rSV5DeltaSH-infected cells over mock-infected and rSV5-infected cells when assayed for annexin V binding, DNA content (propidium iodide staining), and DNA fragmentation (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay). In rSV5DeltaSH-infected MDBK cells an increase in caspase-2 and caspase-3 activities was observed. By using peptide inhibitors of individual caspases it was found that caspase-2 and caspase-3 were activated separately in rSV5DeltaSH-infected cells. Expression of caspase-2 and -3 in rSV5DeltaSH-infected MDBK cells appeared not to require STAT1 protein, as STAT1 protein could not be detected in SV5-infected MDBK cells. When mutant mice homologous for a targeted disruption of STAT1 were used as a model animal system and infected with the viruses it was found that rSV5DeltaSH caused less mortality than wild-type rSV5, consistent with the notion of clearance of apoptotic cells in a host species.

Animals↗
PubMed2001

Estimation of intra-cranial neural activities by means of regularized neural-network-based inversion techniques.

Artificial neural networks can be exploited to solve inverse problems arising from the estimation of neural activities in the brain. In this paper, we review the network inversion techniques for solving inverse problems with special attention directed towards electroencephalographic dipole localization and the improvement of positron emission tomography. In our regularized network inversion technique, for stabilizing the solution, we explicitly include the a priori knowledge by adding penalty terms to the energy function and/or build this knowledge into the architecture of the multi-layered neural networks that are used as an inverse problem solver. In the electroencephalogram analysis, the consensus term added to the energy function facilitated 3-dipole localization for visually evoked potentials. Effectiveness of our regularization is shown in improving the positron emission tomographic images and for generating metabolic images of the brain, under the constraints given by the a priori knowledge inherent to the measurement systems and physiological rules.

Algorithms↗
PubMed2001

Nuclear forms of parathyroid hormone-related peptide are translated from non-AUG start sites downstream from the initiator methionine.

PTH-related peptide (PTHrP), normally a secreted protein, exerts at least part of its biological functions via intracrine actions at the level of the cell nucleus/nucleolus. To gain insight into the mechanism whereby this peptide accesses the cytosol for subsequent nuclear import, we characterized its nuclear forms. In transfected COS-1 cells, three nuclear PTHrP species were produced, which were larger than the mature form of the protein but smaller than prepro-PTHrP and comprised both the amino- and carboxyl-terminal regions of the peptide. This suggested that nuclear PTHrP proteins contain part of the prepropeptide and likely arise from alternate initiation of translation at downstream non-AUG codons within the signal sequence. Transient expression of two PTHrP forms, one in which the unique initiator ATG was mutated to a noninitiator ATC codon, and another encompassing an engineered N-linked glycosylation site, generated peptides of size comparable to nuclear PTHrP proteins. These were inefficiently targeted to the ER, bypassed ER transit, and exclusively localized to nucleoli. Using a polyclonal antiserum against the pro-region of PTHrP, nuclear PTHrP species were shown to harbor the propeptide sequence. Hence, our data argue that nuclear PTHrP forms result from translation initiated at alternate, internal codons. This may constitute the first example of translation initiation at downstream non-AUG codons in a mammalian protein.

Animals↗
PubMed2001

Tissue-specific targeting of the pthrp gene: the generation of mice with floxed alleles.

PTH-related peptide (PTHrP) has been implicated in a variety of developmental and homeostatic processes. Although mice homozygous for the targeted disruption of the Pthrp gene have greatly expanded our capacity to investigate the developmental roles of the protein, the perinatal lethality of these animals has severely hindered the analysis of Pthrp's postnatal physiological effects. To overcome this obstacle, we have generated mice homozygous for a floxed Pthrp allele, i.e. two loxP sites flanking exon 4 of the Pthrp gene, which encodes most of the protein, with the aim of accomplishing cell type- and tissue-specific deletion of the gene. The ability of the Cre enzyme to cause recombination between the loxP sites and excision of the intervening DNA sequence was tested in vivo by crossing this strain to mice carrying a cre transgene under the transcriptional control of the human beta-actin promoter. The ubiquitous deletion of the floxed allele in the cre/loxP progeny resulted in perinatal lethality as a consequence of aberrant endochondral bone formation, fully recapitulating all the phenotypic abnormalities observed in the conventional Pthrp knockout mouse. The availability of the floxed Pthrp mice will serve as a valuable tool in genetic experiments that aim to investigate the physiological actions of Pthrp in the postnatal state.

Actins↗
PubMed2001

The furry gene of Drosophila is important for maintaining the integrity of cellular extensions during morphogenesis.

The Drosophila imaginal cells that produce epidermal hairs, the shafts of sensory bristles and the lateral extensions of the arista are attractive model systems for studying the morphogenesis of polarized cell extensions. We now report the identification and characterization of furry, an essential Drosophila gene that is involved in maintaining the integrity of these cellular extensions during morphogenesis. Mutations in furry result in the formation of branched arista laterals, branched bristles and a strong multiple hair cell phenotype that consists of clusters of epidermal hairs and branched hairs. By following the morphogenesis of arista laterals in pupae, we have determined that the branched laterals are due to the splitting of individual laterals during elongation. In genetic mosaics furry was found to act cell autonomously in the wing. The phenotypes of double mutant cells argue that furry functions independently of the frizzled planar polarity pathway and that it probably functions in the same pathway as the tricornered gene. We used a P-element insertion allele as a tag to clone the furry gene and found it to be a large and complicated gene that encodes a pair of large conserved proteins of unknown biochemical function.

Amino Acid Sequence↗