Transcriptome sequencing of the Microarray Quality Control (MAQC) RNA reference samples using next generation sequencing

<p>Abstract</p> <p>Background</p> <p>Transcriptome sequencing using next-generation sequencing platforms will soon be competing with DNA microarray technologies for global gene expression analysis. As a preliminary evaluation of these promising technologies, we performed deep sequencing of cDNA synthesized from the Microarray Quality Control (MAQC) reference RNA samples using Roche's 454 Genome Sequencer FLX.</p> <p>Results</p> <p>We generated more that 3.6 million sequence reads of average length 250 bp for the MAQC A and B samples and introduced a data analysis pipeline for translating cDNA read counts into gene expression levels. Using BLAST, 90% of the reads mapped to the human genome and 64% of the reads mapped to the RefSeq database of well annotated genes with e-values ≤ 10^-20. We measured gene expression levels in the A and B samples by counting the numbers of reads that mapped to individual RefSeq genes in multiple sequencing runs to evaluate the MAQC quality metrics for reproducibility, sensitivity, specificity, and accuracy and compared the results with DNA microarrays and Quantitative RT-PCR (QRTPCR) from the MAQC studies. In addition, 88% of the reads were successfully aligned directly to the human genome using the AceView alignment programs with an average 90% sequence similarity to identify 137,899 unique exon junctions, including 22,193 new exon junctions not yet contained in the RefSeq database.</p> <p>Conclusion</p> <p>Using the MAQC metrics for evaluating the performance of gene expression platforms, the ExpressSeq results for gene expression levels showed excellent reproducibility, sensitivity, and specificity that improved systematically with increasing shotgun sequencing depth, and quantitative accuracy that was comparable to DNA microarrays and QRTPCR. In addition, a careful mapping of the reads to the genome using the AceView alignment programs shed new light on the complexity of the human transcriptome including the discovery of thousands of new splice variants.</p

Superfield Approach to (Non-)local Symmetries for One-Form Abelian Gauge Theory

We exploit the geometrical superfield formalism to derive the local, covariant and continuous Becchi-Rouet-Stora-Tyutin (BRST) symmetry transformations and the non-local, non-covariant and continuous dual-BRST symmetry transformations for the free Abelian one-form gauge theory in four $(3 + 1)$-dimensions (4D) of spacetime. Our discussion is carried out in the framework of BRST invariant Lagrangian density for the above 4D theory in the Feynman gauge. The geometrical origin and interpretation for the (dual-)BRST charges (and the transformations they generate) are provided in the language of translations of some superfields along the Grassmannian directions of the six ($4 + 2)$-dimensional supermanifold parametrized by the four spacetime and two Grassmannian variables.Comment: LaTeX file, 23 page

The Dynamical Nonabelian Two-Form: BRST Quantization

When an antisymmetric tensor potential is coupled to the field strength of a gauge field via a $B\wedge F$ coupling and a kinetic term for $B$ is included, the gauge field develops an effective mass. The theory can be made invariant under a non-abelian vector gauge symmetry by introducing an auxiliary vector field. The covariant quantization of this theory requires ghosts for ghosts. The resultant theory including gauge fixing and ghost terms is BRST-invariant by construction, and therefore unitary. The construction of the BRST-invariant action is given for both abelian and non-abelian models of mass generation.Comment: 15 pages, revte

The return of the bursts: Thermonuclear flashes from Circinus X-1

We report the detection of 15 X-ray bursts with RXTE and Swift observations of the peculiar X-ray binary Circinus X-1 during its May 2010 X-ray re-brightening. These are the first X-ray bursts observed from the source after the initial discovery by Tennant and collaborators, twenty-five years ago. By studying their spectral evolution, we firmly identify nine of the bursts as type I (thermonuclear) X-ray bursts. We obtain an arcsecond location of the bursts that confirms once and for all the identification of Cir X-1 as a type I X-ray burst source, and therefore as a low magnetic field accreting neutron star. The first five bursts observed by RXTE are weak and show approximately symmetric light curves, without detectable signs of cooling along the burst decay. We discuss their possible nature. Finally, we explore a scenario to explain why Cir X-1 shows thermonuclear bursts now but not in the past, when it was extensively observed and accreting at a similar rate.Comment: Accepted for publication in The Astrophysical Journal Letters. Tables 1 & 2 merged. Minor changes after referee's comments. 5 pages, 4 Figure

Generalized Geometry and M theory

We reformulate the Hamiltonian form of bosonic eleven dimensional supergravity in terms of an object that unifies the three-form and the metric. For the case of four spatial dimensions, the duality group is manifest and the metric and C-field are on an equal footing even though no dimensional reduction is required for our results to hold. One may also describe our results using the generalized geometry that emerges from membrane duality. The relationship between the twisted Courant algebra and the gauge symmetries of eleven dimensional supergravity are described in detail.Comment: 29 pages of Latex, v2 References added, typos fixed, v3 corrected kinetic term and references adde

On the infrared behaviour of Gluons and Ghosts in Ghost-Antighost symmetric gauges

To investigate the possibility of a ghost-antighost condensate the coupled Dyson--Schwinger equations for the gluon and ghost propagators in Yang--Mills theories are derived in general covariant gauges, including ghost-antighost symmetric gauges. The infrared behaviour of these two-point functions is studied in a bare-vertex truncation scheme which has proven to be successful in Landau gauge. In all linear covariant gauges the same infrared behaviour as in Landau gauge is found: The gluon propagator is infrared suppressed whereas the ghost propagator is infrared enhanced. This infrared singular behaviour provides indication against a ghost-antighost condensate. In the ghost-antighost symmetric gauges we find that the infrared behaviour of the gluon and ghost propagators cannot be determined when replacing all dressed vertices by bare ones. The question of a BRST invariant dimension two condensate remains to be further studied.Comment: 34 pages, 6 figures, Version to be published in Phys. Rev.

On the Infrared Exponent for Gluon and Ghost Propagation in Landau Gauge QCD

In the covariant description of confinement, one expects the ghost correlations to be infrared enhanced. Assuming ghost dominance, the long-range behavior of gluon and ghost correlations in Landau gauge QCD is determined by one exponent kappa. The gluon propagator is infrared finite (vanishing) for kappa =1/2 (kappa > 1/2) which is still under debate. Here, we study critical exponent and coupling for the infrared conformal behavior from the asymptotic form of the solutions to the Dyson-Schwinger equations in an ultraviolet finite expansion scheme. The value for kappa is directly related to the ghost-gluon vertex. Assuming that it is regular in the infrared, one obtains kappa = 0.595. This value maximizes the critical coupling alpha_c(kappa), yielding alpha_c^max = (4 Pi/Nc) 0.709 approx. 2.97 for Nc=3. For larger kappa the vertex acquires an infrared singularity in the gluon momentum, smaller ones imply infrared singular ghost legs. Variations in alpha_c remain within 5% from kappa = 0.5 to 0.7. Above this range, alpha_c decreases more rapidly with alpha_c -> 0 as kappa -> 1 which sets the upper bound on kappa.Comment: 22 Pages, 10 Figures, LaTeX2e, revtex4, some notes and references added in response to communication

Component-wise incremental LTL model checking

Efficient symbolic and explicit-state model checking approaches have been developed for the verification of linear time temporal logic (LTL) properties. Several attempts have been made to combine the advantages of the various algorithms. Model checking LTL properties usually poses two challenges: one must compute the synchronous product of the state space and the automaton model of the desired property, then look for counterexamples that is reduced to finding strongly connected components (SCCs) in the state space of the product. In case of concurrent systems, where the phenomenon of state space explosion often prevents the successful verification, the so-called saturation algorithm has proved its efficiency in state space exploration. This paper proposes a new approach that leverages the saturation algorithm both as an iteration strategy constructing the product directly, as well as in a new fixed-point computation algorithm to find strongly connected components on-the-fly by incrementally processing the components of the model. Complementing the search for SCCs, explicit techniques and component-wise abstractions are used to prove the absence of counterexamples. The resulting on-the-fly, incremental LTL model checking algorithm proved to scale well with the size of models, as the evaluation on models of the Model Checking Contest suggests

Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde

Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping

Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505–180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533–182,688 kb) and PSARL (184,386 kb; 95% CI 184,356–184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10−7, p<10−10, and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia