Dynamics of a disc in a nematic liquid crystal.

We use lattice Boltzmann simulations to study the dynamics of a disc immersed in a nematic liquid crystal. In the absence of external torques, discs with homeotropic anchoring align with their surface normal parallel to the director of the nematic liquid crystal. In the presence of a weak magnetic field a ferromagnetic disc will rotate to equilibrate the elastic torque due to the distortion of the nematic director and the magnetic torque. When the magnetic field rotates the disc so that the angle θ between normal to the surface of the disc â and director of the liquid crystal n[combining circumflex] becomes greater than π/2, the disc flips around the axis perpendicular to the rotation axis so that â sweeps through π radians. An analysis of this behaviour was performed. In particular, we look at the impact of the disc thickness and edges on defect creation and the flipping transition. We also analyse the importance of backflow.

Sequence and structural variation in a human genome uncovered by short-read, massively parallel ligation sequencing using two-base encoding.

We describe the genome sequencing of an anonymous individual of African origin using a novel ligation-based sequencing assay that enables a unique form of error correction that improves the raw accuracy of the aligned reads to >99.9%, allowing us to accurately call SNPs with as few as two reads per allele. We collected several billion mate-paired reads yielding approximately 18x haploid coverage of aligned sequence and close to 300x clone coverage. Over 98% of the reference genome is covered with at least one uniquely placed read, and 99.65% is spanned by at least one uniquely placed mate-paired clone. We identify over 3.8 million SNPs, 19% of which are novel. Mate-paired data are used to physically resolve haplotype phases of nearly two-thirds of the genotypes obtained and produce phased segments of up to 215 kb. We detect 226,529 intra-read indels, 5590 indels between mate-paired reads, 91 inversions, and four gene fusions. We use a novel approach for detecting indels between mate-paired reads that are smaller than the standard deviation of the insert size of the library and discover deletions in common with those detected with our intra-read approach. Dozens of mutations previously described in OMIM and hundreds of nonsynonymous single-nucleotide and structural variants in genes previously implicated in disease are identified in this individual. There is more genetic variation in the human genome still to be uncovered, and we provide guidance for future surveys in populations and cancer biopsies.

Dynamics of disk pairs in a nematic liquid crystal.

We use a hybrid lattice Boltzmann method to study the behavior of sets of ferromagnetic colloidal disks in a nematic liquid crystal. When a weak rotating magnetic field acts on the system, the disks rotate following the magnetic field. This leads to a distortion in the liquid crystal that drives translational motion of the disks. If the concentration of disks is high, disks get locked together: a stable chain configuration is created, where each disk lays on the nearest neighbor. For intermediate concentrations of disks, a different behavior is observed. When disks are rotated by the magnetic field by more than 90^{∘} from their initial orientation, the distortion in the liquid crystal leads to a simultaneous flip of both disks. The final disk positions depends only weakly on the initial configuration. Consecutive rotations of magnetic field push disks towards an equidistant configuration. Periodicity of the systems studied and analysis of the flipping motion of a single disk imply that one can use weak rotating magnetic fields to create stable crystal structures of disks.

Development of personalized tumor biomarkers using massively parallel sequencing.

Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers with massively parallel sequencing revealed an average of nine rearranged sequences (range, 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints was able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.

Polymorphism discovery in high-throughput resequenced microarray-enriched human genomic loci.

Identifying genetic variants and mutations that underlie human diseases requires development of robust, cost-effective tools for routine resequencing of regions of interest in the human genome. Here, we demonstrate that coupling Applied Biosystems SOLiD system-sequencing platform with microarray capture of targeted regions provides an efficient and robust method for high-coverage resequencing and polymorphism discovery in human protein-coding exons.

Gene expression-based screening for inhibitors of PDGFR signaling.

Here we describe a proof-of-concept experiment designed to explore the possibility of using gene expression-based high-throughput screening (GE-HTS) to find inhibitors of a signaling cascade, using platelet derived growth factor receptor (PDGFR) signaling as the example. The previously unrecognized ability of aurintricarboxylic acid to inhibit PDGFR signaling, discovered through a screen of 1,739 compounds, demonstrates the feasibility and generalizability of GE-HTS for the discovery of small molecule modulators of any signaling pathway of interest.

A strategy for oligonucleotide microarray probe reduction.

BACKGROUND: One of the factors limiting the number of genes that can be analyzed on high-density oligonucleotide arrays is that each transcript is probed by multiple oligonucleotide probes. To reduce the number of probes required for each gene, a systematic approach to choosing the most representative probes is needed. A method is presented for reducing the number of probes per gene while maximizing the fidelity to the original array design. RESULTS: The methodology has been tested on a dataset comprising 317 Affymetrix HuGeneFL GeneChips. The performance of the original and reduced probe sets was compared in four cancer-classification problems. The results of these comparisons show that reduction of the probe set by 95% does not dramatically affect performance, and thus illustrate the feasibility of substantially reducing probe numbers without significantly compromising sensitivity and specificity of detection. CONCLUSIONS: The strategy described here is potentially useful for designing small, limited-probe genome-wide arrays for screening applications.