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Biomedical subjects

D Huang

Publications and source records attributed to D Huang.

At least 19 recordsLinked to original sources

Enhancing density-based data reduction using entropy.

Data reduction algorithms determine a small data subset from a given large data set. In this article, new types of data reduction criteria, based on the concept of entropy, are first presented. These criteria can evaluate the data reduction performance in a sophisticated and comprehensive way. As a result, new data reduction procedures are developed. Using the newly introduced criteria, the proposed data reduction scheme is shown to be efficient and effective. In addition, an outlier-filtering strategy, which is computationally insignificant, is developed. In some instances, this strategy can substantially improve the performance of supervised data analysis. The proposed procedures are compared with related techniques in two types of application: density estimation and classification. Extensive comparative results are included to corroborate the contributions of the proposed algorithms.

Algorithms↗

A novel adenoviral vector which mediates hypoxia-inducible gene expression selectively in neurons.

Selective gene expression in neurons is still a challenge. We have developed several expression vectors using a combination of neuron restrictive silencer elements (NRSEs), hypoxia responsive elements (HREs) and CMV minimal promoter (CMVmp). These elements were packaged into replication defective adenovirus to target gene expression selectively in neurons in a hypoxia-regulated manner. Neuronal selectivity and responsiveness to hypoxia of these novel constructs were determined empirically in both neural cell lines and primary cerebellar granule neurons (CGNs). The construct p5HRE-3NRSE exhibited not only the highest level of reporter gene expression in neuronal cells but also in an oxygen concentration-dependent manner when compared with all other constructs. As expected, this construct did not elicit reporter gene expression in non-neuronal cells including human HEK293A and HT29 cells, rat NRK cells, mouse 3T6 cells and 3T3 L1 cells. This construct was packaged into a replication defective adenoviral vector (Ad/5HRE-3NRSE) to determine neuron-selective and hypoxia-inducible gene expression in cultured mouse postmitotic primary CGNs and differentiated human NT2 neurons (NT2/Ns). Remarkably, in response to hypoxia, Ad/5HRE-3NRSE showed strong hypoxia-inducible gene expression selectively in neurons (12-fold induction in CGNs and 22-fold in NT2/Ns), but not in glial cells. Taken together, this vector with restricted gene expression to neurons under the regulation of hypoxia will be a useful tool for investigations of mechanisms of neuronal damage caused by ischemic insult.

Adenoviridae↗

Estimating optimal feature subsets using efficient estimation of high-dimensional mutual information.

A novel feature selection method using the concept of mutual information (MI) is proposed in this paper. In all MI based feature selection methods, effective and efficient estimation of high-dimensional MI is crucial. In this paper, a pruned Parzen window estimator and the quadratic mutual information (QMI) are combined to address this problem. The results show that the proposed approach can estimate the MI in an effective and efficient way. With this contribution, a novel feature selection method is developed to identify the salient features one by one. Also, the appropriate feature subsets for classification can be reliably estimated. The proposed methodology is thoroughly tested in four different classification applications in which the number of features ranged from less than 10 to over 15,000. The presented results are very promising and corroborate the contribution of the proposed feature selection methodology.

Algorithms↗

Microdissection and molecular manipulation of single chromosomes in woody fruit trees with small chromosomes using pomelo (Citrus grandis) as a model. I. Construction of single chromosomal DNA libraries.

Construction of single chromosomal DNA libraries by means of chromosome microdissection and microcloning will be useful for genomic research, especially for those species that have not been extensively studied genetically. Application of the technology of microdissection and microcloning to woody fruit plants has not been reported hitherto, largely due to the generally small sizes of metaphase chromosomes and the difficulty of chromosome preparation. The present study was performed to establish a method for single chromosome microdissection and microcloning in woody fruit species using pomelo as a model. The standard karyotype of a pomelo cultivar ( Citrus grandis cv. Guanxi) was established based on 20 prometaphase photomicrographs. According to the standard karyotype, chromosome 1 was identified and isolated with fine glass microneedles controlled by a micromanipulator. DNA fragments ranging from 0.3 kb to 2 kb were acquired from the isolated single chromosome 1 via two rounds of PCR mediated by Sau3A linker adaptors and then cloned into T-easy vectors to generate a DNA library of chromosome 1. Approximately 30,000 recombinant clones were obtained. Evaluation based on 108 randomly selected clones showed that the sizes of the cloned inserts varied from 0.5 kb to 1.5 kb with an average of 860 bp. Our research suggests that microdissection and microcloning of single small chromosomes in woody plants is feasible.

Blotting, Southern↗

Microdissection and molecular manipulation of single chromosomes in woody fruit trees with small chromosomes using pomelo (Citrus grandis) as a model. II. Cloning of resistance gene analogs from single chromosomes.

Amplification of resistance gene analogs (RGAs) is both a useful method for acquiring DNA markers closely linked to disease resistance (R) genes and a potential approach for the rapid cloning of R genes in plants. However, the screening of target sequences from among the numerous amplified RGAs can be very laborious. The amplification of RGAs from specific chromosomes could greatly reduce the number of RGAs to be screened and, consequently, speed up the identification of target RGAs. We have developed two methods for amplifying RGAs from single chromosomes. Method 1 uses products of Sau3A linker adaptor-mediated PCR (LAM-PCR) from a single chromosome as the templates for RGA amplification, while Method 2 directly uses a single chromosomal DNA molecule as the template. Using a pair of degenerate primers designed on the basis of the conserved nucleotide-binding-site motifs in many R genes, RGAs were successfully amplified from single chromosomes of pomelo using both these methods. Sequencing and cluster analysis of RGA clones obtained from single chromosomes revealed the number, type and organization of R-gene clusters on the chromosomes. We suggest that Method 1 is suitable for analyzing chromosomes that are unidentifiable under a microscope, while Method 2 is more appropriate when chromosomes can be clearly identified.

Amino Acid Sequence↗

Difficulties in maintaining long-term partial nitritation of ammonium-rich sludge digester liquids in a moving-bed biofilm reactor (MBBR).

Nitrogen can be eliminated effectively from sludge digester effluents by anaerobic ammonium oxidation (anammox), but 55-60% of the ammonium must first be oxidized to nitrite. Although a continuous flow stirred tank reactor (CSTR) with suspended biomass could be used, its hydraulic dilution rate is limited to 0.8-1 d(-1) (30 degrees C). Higher specific nitrite production rates can be achieved by sludge retention, as shown here for a moving-bed biofilm reactor (MBBR) with Kaldnes carriers on laboratory and pilot scales. The maximum nitrite production rate amounted to 2.7 gNO2-Nm(-2)d(-1) (3 gO2m(-3)d(-1), 30.5 degrees C), thus doubling the dilution rate compared to CSTR operation with suspended biomass for a supernatant with 700 gNH4-Nm(-3). Whenever the available alkalinity was fully consumed, an optimal amount of nitrite was produced. However, a significant amount of nitrate was produced after 11 months of operation, making the effluent unsuitable for anaerobic ammonium oxidation. Because the sludge retention time (SRT) is relatively long in biofilm systems, slow growth of nitrite oxidizers occurs. None of the selection criteria applied - a high ammonium loading rate, high free ammonia or low oxygen concentration - led to selective suppression of nitrite oxidation. A CSTR or SBR with suspended biomass is consequently recommended for full-scale operation.

Bacteria, Anaerobic↗

The binding interface database (BID): a compilation of amino acid hot spots in protein interfaces.

SUMMARY: To make information about protein interactive function easily accessible, we are mining the primary scientific literature for detailed data about protein interfaces. The Binding Interface Database (BID) organizes the vast amount of protein interaction information into tables, graphical contact maps and descriptive functional profiles. Currently data on 170 interacting protein pairs are available with over 1300 mutations described. AVAILABILITY: The BID database is freely available at http://tsailab.org/BID/ To have your protein of interest entered, contact Tiffany Fischer (tiffbrink@neo.tamu.edu) or Jerry Tsai at the email below

Amino Acid Sequence↗

Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD and other autoimmune-prone mouse strains.

Interleukin (Il)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains that plays a key role in the induction of Th1 cells, a T cell subset involved in many autoimmune diseases. We report here the cDNA sequence encoding the IL-12 p40 subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which spontaneously develops type 1 diabetes. Compared with the C57BL/6 sequence, there are two base changes that lead to amino acid replacements. Other autoimmune-prone strains, but not the diabetes-resistant NOR strain, share the same allele as NOD. We found both trans- and cis- allele-dependent effects on levels of basal and induced IL-12p40 expression. Furthermore, we show that one of these changes results in a structural change in the p40 molecule, as evidenced by the failure of a monoclonal antibody to bind NOD IL-12. These findings have implications for the predisposition to autoimmune responses in NOD and other autoimmune-prone mouse strains.

Animals↗

A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced nitric oxide production.

Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promotor polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.

Animals↗

Analysis of intra-operative bleeding and recurrence of juvenile nasopharyngeal angiofibromas.

The purpose of this study is to present our experience with 34 patients diagnosed with juvenile nasopharyngeal angiofibromas and treated in the Chinese PLA General Hospital between 1986 and 1999, and to examine the factors influencing intra-operative bleeding and tumour recurrence. The age of the patient, the duration of symptoms and tumour stage were related to the amount of intra-operative bleeding. The tumours were totally resected in 30 patients and recurred in five patients (16.7%), with a mean follow-up time of 77 months. The mean time to tumour recurrence after operation was 3.2 months (1-6 months). The incidence of recurrence had no correlation with the age of the patient, duration of symptoms, peri-operative treatment or surgical approaches (P > 0.05); but strongly correlated with tumour stage (P < 0.05).

Adolescent↗

Survival effect of lung transplantation among patients with cystic fibrosis.

CONTEXT: Patients with cystic fibrosis (CF) are the second largest group of lung transplant recipients in the United States. The survival effect of transplantation on a general CF population has not previously been measured. OBJECTIVE: To determine the impact of bilateral lung transplantation on survival in patients with CF. DESIGN, SETTING, AND PATIENTS: Retrospective observational cohort study of 11 630 CF patients who did not undergo lung transplantation (controls) and 468 transplant recipients with CF from 115 CF centers in the United States, 1992-1998. Patients were stratified into 5 groups based on a 5-year survival prediction model (survival group 1: <30%; survival group 2: 30 to <50%; survival groups 3-5: 50 to <100%.) MAIN OUTCOME MEASURE: Five-year survival from date of transplantation in 1992-1997 in the transplant group and from January 1, 1993, in the control group. RESULTS: Lung transplantation increased 5-year survival of CF patients in survival group 1. Survival group 2 had equivocal survival effects, and groups 3-5 had negative survival effects from transplantation. From 1994-1997, there was a mean annual prevalence of 238 patients in survival group 1 and mean annual incidence of 154 patients entering the group, approximately 1.5 times the number of lung transplantations performed each year in CF patients (mean, 104). Use of the criterion of forced expiratory volume in 1 second of less than 30% resulted in an equivocal survival benefit and identified 1458 potential candidates for transplantation in 1993. CONCLUSIONS: Cystic fibrosis patients in group 1 have improved 5-year survival after lung transplantation. The majority of patients with CF have equivocal or negative survival effects from the procedure. Selection of patients with CF for transplantation based on group 1 survival predictions maximizes survival benefits to individuals and may reduce the demand for scarce donor organs.

Adult↗

E2F mediates induction of the Sp1-controlled promoter of the human DNA polymerase epsilon B-subunit gene POLE2.

The B-subunits of replicative DNA polymerases from Archaea to humans belong to the same protein family, suggesting that they share a common fundamental function. We report here the gene structure for the B-subunit of human DNA polymerase epsilon (POLE2), whose expression and transcriptional regulation is typical for replication proteins with some unique features. The 75 bp core promoter region, located within exon 1, contains an Sp1 element that is a critical determinant of promoter activity as shown by the luciferase reporter, electrophoretic mobility shift and DNase I footprinting assays. Two overlapping E2F elements adjacent to the Sp1 element are essential for full promoter activity and serum response. Binding sites for E2F1 and NF-1 reside immediately downstream from the core promoter region. Our results suggest that human POLE2 is regulated by two E2F-pocket protein complexes, one associated with Sp1 and the other with NF-1. So far, only one replicative DNA polymerase B-subunit gene promoter, POLA2 encoding the B-subunit of DNA polymerase alpha, has been characterized. Mitogenic activation of the POLE2 promoter by an E2F-mediated mechanism resembles that of POLA2, but the regulation of basal promoter activity is different between these two genes.

Base Sequence↗

BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.

Topoisomerase IIbeta-binding protein (TopBP1), a human protein with eight BRCT domains, is similar to Saccharomyces cerevisiae Dpb11 and Schizosaccharomyces pombe Cut5 checkpoint proteins and closely related to Drosophila Mus101. We show that human TopBP1 is required for DNA replication and that it interacts with DNA polymerase epsilon. In S phase TopBP1 colocalizes with Brca1 to foci that do not represent sites of ongoing DNA replication. Inhibition of DNA synthesis leads to relocalization of TopBP1 together with Brca1 to replication forks, suggesting a role in rescue of stalled forks. DNA damage induces formation of distinct TopBP1 foci that colocalize with Brca1 in S phase, but not in G(1) phase. We also show that TopBP1 interacts with the checkpoint protein hRad9. Thus, these results implicate TopBP1 in replication and checkpoint functions.

Animals↗

Interleukin-10 gene promoter polymorphisms in multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of malignant plasma cells in the bone marrow. It is unclear whether genetic background could have an etiological impact on MM or influence the course of the disease. Interleukin-10 (IL-10) has been implicated in the growth and differentiation of normal B cells, and has also been shown to enhance the proliferation of MM cells. To address the putative involvement of IL-10 genetic variation in MM, we analyzed previously defined loci for bi-allelic polymorphism at position -1082 and two microsatellite loci (IL10.G and IL10.R) in the IL-10 promoter region. Seventy-three patients with MM, 27 with monoclonal gammopathy of undetermined significance, and 109 ethnically matched individuals as controls were included in the study. Significantly increased frequencies of the IL10.G genotype 136/136 and the IL10.R genotype 112/114, in addition to a decreased frequency of the IL10.R genotype 114/116, were found among the MM patients. Increased production of IL-10 was detected in the supernatants of lipopolysaccharide-stimulated peripheral blood mononuclear cells from MM patients who were homozygotes (136/136) and heterozygotes (136/non-136) for the IL10.G allele 136, as compared with the other IL10.G genotype carriers (non-136/non-136). These results suggest that the genetic variation in the IL-10 promoter region may play a role in the development of MM.

Adult↗

An Arabidopsis mutant cex1 exhibits constant accumulation of jasmonate-regulated AtVSP, Thi2.1 and PDF1.2.

Jasmonates (JA) act as a regulator in plant growth as well as a signal in plant defense. The Arabidopsis vegetative storage protein (AtVSP) and plant defense-related proteins thionin (Thi2.1) and defensin (PDF1.2) have previously been shown to accumulate in response to JA induction. In this report, we isolated and characterized a novel recessive mutant, cex1, conferring constitutive JA-responsive phenotypes including JA-inhibitory growth and constitutive expression of JA-regulated AtVSP, Thi2.1 and PDF1.2. The plant morphology and the gene expression pattern of the cex1 mutant could be phenocopied by treatment of wild-type plants with exogenous JA, indicating that CEX1 might be a negative regulator of the JA response pathway.

Adenosine Triphosphatases↗

Noise properties in the Nagel-Schreckenberg traffic model.

The jamming transition in the stochastic traffic cellular automaton model of Nagel and Schreckenberg is examined. The behavior of the power spectrum is analyzed. Numerical results are presented. Satisfactory analytical approximations are established in both low frequency and high frequency regions. The intrinsic traffic states are revealed in the middle frequency range. A signature of 1/f noise is observed at the critical density of the transition.

Journal Article↗

Disruption of the IL-1beta gene diminishes acetylcholine receptor-induced immune responses in a murine model of myasthenia gravis.

Human autoimmune myasthenia gravis (MG) is associated with the IL-1beta TaqI RFLP allele 2. Individuals positive for this allele have high levels of inducible IL-1beta in their peripheral blood. Here, we have characterized MG induction and the immune response elicited by Torpedo acetylcholine receptor (AChR) immunization in wild-type and IL-1beta deficient (-/-) mice. Compared with wild-type mice, IL-1beta-/- mice were relatively resistant to induction of clinical experimental autoimmune myasthenia gravis (EAMG). Draining lymph node cells from IL-1beta-/- mice showed poor proliferative capacity upon AChR stimulation in vitro. Both Th1 (IFN-gamma, IL-2) and Th2 (IL-4) cytokine responses were reduced and levels of serum anti-AChR antibodies decreased in IL-1beta-/- mice compared to wild-type mice. Taken together, these results reveal a critical role for IL-1beta in the induction of MG in mice, and support a role for IL-1beta in the pathogenesis of MG in man.

Animals↗