Sampling motifs on phylogenetic trees.

We present a method to find motifs by simultaneously using the overrepresentation property and the evolutionary conservation property of motifs. This method is applicable to divergent species where alignment is unreliable, which overcomes a major limitation of the current methods. The method has been applied to search regulatory motifs in four yeast species based on ChIP-chip data in Saccharomyces cerevisiae and obtained 20% higher accuracy than the best current methods.

A small-molecule inhibitor of Mps1 blocks the spindle-checkpoint response to a lack of tension on mitotic chromosomes.

The spindle checkpoint prevents chromosome loss by preventing chromosome segregation in cells with improperly attached chromosomes [1, 2 and 3]. The checkpoint senses defects in the attachment of chromosomes to the mitotic spindle [4] and the tension exerted on chromosomes by spindle forces in mitosis [5, 6 and 7]. Because many cancers have defects in chromosome segregation, this checkpoint may be required for survival of tumor cells and may be a target for chemotherapy.

The use of oscillatory signals in the study of genetic networks.

The structure of a genetic network is uncovered by studying its response to external stimuli (input signals). We present a theory of propagation of an input signal through a linear stochastic genetic network. We found that there are important advantages in using oscillatory signals over step or impulse signals and that the system may enter into a pure fluctuation resonance for a specific input frequency.

Role of epidermal growth factor receptor signaling in RAS-driven melanoma.

The identification of essential genetic elements in pathways governing the maintenance of fully established tumors is critical to the development of effective antioncologic agents. Previous studies revealed an essential role for H-RAS(V12G) in melanoma maintenance in an inducible transgenic model. Here, we sought to define the molecular basis for RAS-dependent tumor maintenance through determination of the H-RAS(V12G)-directed transcriptional program and subsequent functional validation of potential signaling surrogates.

Use of midazolam and ketamine as sedation for children undergoing minor operative procedures.

Objectives: We used intravenous midazolam and ketamine for children undergoing minor operative procedures with satisfactory results. We aimed to further evaluate its efficacy and adverse effects in pediatric ward setting.

Methods: This was a prospective study of all children undergoing minor operations with sedation in our pediatric general and oncology wards from July 1998 to June 1999.

Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection.

Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection.

Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo.

Heat shock proteins (HSPs) are thought to play a role in the development of cancer and to modulate tumor response to cytotoxic therapy. In this study, we have examined the expression of hsf and HSP genes in normal human prostate epithelial cells and a range of prostate carcinoma cell lines derived from human tumors. We have observed elevated expressions of HSF1, HSP60, and HSP70 in the aggressively malignant cell lines PC-3, DU-145, and CA-HPV-10.

A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese.

Objective: The programmed death 1 (PD-1) molecule is a negative regulator of T cells, and a genetic association between PD-1 and systemic lupus erythematosus and rheumatoid arthritis (RA) in Caucasians has been reported. The aim of this study was to investigate the association of PDCD1 polymorphisms and haplotypes with RA in the Chinese population.

Methods: Three single-nucleotide polymorphisms (SNPs), PD-1.

A boosting approach for motif modeling using ChIP-chip data.

Motivation: Building an accurate binding model for a transcription factor (TF) is essential to differentiate its true binding targets from those spurious ones. This is an important step toward understanding gene regulation.

Results: This paper describes a boosting approach to modeling TF-DNA binding.

Identification of viral genes essential for replication of murine gamma-herpesvirus 68 using signature-tagged mutagenesis.

Gamma-herpesviruses, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus are important human pathogens, because they are involved in tumor development. Murine gamma-herpesvirus-68 (MHV-68 or gammaHV-68) has emerged as a small animal model system for the study of gamma-herpesvirus pathogenesis and host-virus interactions. To identify the genes required for viral replication in vitro and in vivo, we generated 1,152 mutants using signature-tagged transposon mutagenesis on an infectious bacterial artificial chromosome of MHV-68.

Tight clustering: a resampling-based approach for identifying stable and tight patterns in data.

In this article, we propose a method for clustering that produces tight and stable clusters without forcing all points into clusters. The methodology is general but was initially motivated from cluster analysis of microarray experiments. Most current algorithms aim to assign all genes into clusters.

Comparative linkage analysis and visualization of high-density oligonucleotide SNP array data.

Background: The identification of disease-associated genes using single nucleotide polymorphisms (SNPs) has been increasingly reported. In particular, the Affymetrix Mapping 10 K SNP microarray platform uses one PCR primer to amplify the DNA samples and determine the genotype of more than 10,000 SNPs in the human genome. This provides the opportunity for large scale, rapid and cost-effective genotyping assays for linkage analysis.

GoSurfer: a graphical interactive tool for comparative analysis of large gene sets in Gene Ontology space.

Unlabelled: The analysis of complex patterns of gene regulation is central to understanding the biology of cells, tissues and organisms. Patterns of gene regulation pertaining to specific biological processes can be revealed by a variety of experimental strategies, particularly microarrays and other highly parallel methods, which generate large datasets linking many genes. Although methods for detecting gene expression have improved substantially in recent years, understanding the physiological implications of complex patterns in gene expression data is a major challenge.

GeneNotes--a novel information management software for biologists.

Background: Collecting and managing information is a challenging task in a genome-wide profiling research project. Most databases and online computational tools require a direct human involvement. Information and computational results are presented in various multimedia formats (e.

Evaluation of Streptomyces sp. strain g10 for suppression of Fusarium wilt and rhizosphere colonization in pot-grown banana plantlets.

Streptomyces sp. strain g10 exhibited strong antagonism towards Fusarium oxysporum f.sp.

Cytokine profiles in human immunodeficiency virus-infected children treated with highly active antiretroviral therapy.

Context: There have been few longitudinal studies of cytokine production in neonatally acquired HIV-1 infection and none in Asian or Chinese children.

Objective: To determine whether monitoring cytokine production could contribute to the better management of pediatric patients with HIV-1 infection.

Setting: Clinical Immunology Laboratory and Pediatrics Department, University Hospital, Hong Kong.

Extinction paradox and actual power scattered in light beam scattering: a two-dimensional study.

The extinction paradox is examined by applying partial-wave analysis to a two-dimensional light beam interacting with a long transverse cylinder without absorption, assuming always short wavelengths. We show that the (conventional) power scattered, Psca, except for a very narrow beam hitting a transparent cylinder on axis, is always double the power directly intercepted by the scatterer, Pitc, including a zero result for Psca when the incident beam is basically off the material surface. This contradicts the interpretation that attributes one half of Psca to edge diffraction by the scatterer.

Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform.

We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.

A double-blind, randomized, placebo-controlled trial of acupuncture for the treatment of childhood persistent allergic rhinitis.

Objective: To compare active acupuncture with sham acupuncture for the treatment of persistent allergic rhinitis among children.

Methods: Subjects with persistent allergic rhinitis were recruited from the pediatric outpatient clinic. They were randomized to receive either active acupuncture or sham acupuncture.

Differences between the negatively activating potassium conductances of Mammalian cochlear and vestibular hair cells.

Cochlear and type I vestibular hair cells of mammals express negatively activating potassium (K(+)) conductances, called g(K,n) and g(K,L) respectively, which are important in setting the hair cells' resting potentials and input conductances. It has been suggested that the channels underlying both conductances include KCNQ4 subunits from the KCNQ family of K(+) channels. In whole-cell recordings from rat hair cells, we found substantial differences between g(K,n) and g(K,L) in voltage dependence, kinetics, ionic permeability, and stability during whole-cell recording.

An optimal, cost-effective laparoscopic appendectomy technique for our surgical residents.

Since early 1999, we have implemented a standardized technique for laparoscopic appendectomy, which is simple, safe and easily learned and mastered by our residents. Besides superior ergonomics, it offers cosmetic advantages. It is inexpensive as only reusable instruments are used.

Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics.

Liver cirrhosis is a worldwide health problem. Reliable, noninvasive methods for early detection of liver cirrhosis are not available. Using a three-step approach, we classified sera from rats with liver cirrhosis following different treatment insults.

Detect and adjust for population stratification in population-based association study using genomic control markers: an application of Affymetrix Genechip Human Mapping 10K array.

Population-based association design is often compromised by false or nonreplicable findings, partially due to population stratification. Genomic control (GC) approaches were proposed to detect and adjust for this confounder. To date, the performance of this strategy has not been extensively evaluated on real data.

CisModule: de novo discovery of cis-regulatory modules by hierarchical mixture modeling.

The regulatory information for a eukaryotic gene is encoded in cis-regulatory modules. The binding sites for a set of interacting transcription factors have the tendency to colocalize to the same modules. Current de novo motif discovery methods do not take advantage of this knowledge.