Predicting Combinatorial Binding of Transcription Factors to Regulatory Elements in the Human Genome by Association Rule Mining

Cis-acting transcriptional regulatory elements in mammalian genomes typically contain specific combinations of binding sites for various transcription factors. Although some cisregulatory elements have been well studied, the combinations of transcription factors that regulate normal expression levels for the vast majority of the 20,000 genes in the human genome are unknown. We hypothesized that it should be possible to discover transcription factor combinations that regulate gene expression in concert by identifying over-represented combinations of sequence motifs that occur together in the genome. In order to detect combinations of transcription factor binding motifs, we developed a data mining approach based on the use of association rules, which are typically used in market basket analysis. We scored each segment of the genome for the presence or absence of each of 83 transcription factor binding motifs, then used association rule mining algorithms to mine this dataset, thus identifying frequently occurring pairs of distinct motifs within a segment. Results: Support for most pairs of transcription factor binding motifs was highly correlated across different chromosomes although pair significance varied. Known true positive motif pairs showed higher association rule support, confidence, and significance than background. Our subsets of high-confidence, high-significance mined pairs of transcription factors showed enrichment for co-citation in PubMed abstracts relative to all pairs, and the predicted associations were often readily verifiable in the literature. Conclusion: Functional elements in the genome where transcription factors bind to regulate expression in a combinatorial manner are more likely to be predicted by identifying statistically and biologically significant combinations of transcription factor binding motifs than by simply scanning the genome for the occurrence of binding sites for a single transcription factor.NIAAA Alcohol Training GrantNational Science FoundationCellular and Molecular Biolog

Variations in the Cyclotron Resonant Scattering Features during 2011 outburst of 4U 0115+63

We study the variations in the Cyclotron Resonant Scattering Feature (CRSF) during 2011 outburst of the high mass X-ray binary 4U 0115+63 using observations performed with Suzaku, RXTE, Swift and INTEGRAL satellites. The wide-band spectral data with low energy coverage allowed us to characterize the broadband continuum and detect the CRSFs. We find that the broadband continuum is adequately described by a combination of a low temperature (kT ~ 0.8 keV) blackbody and a power-law with high energy cutoff (Ecut ~ 5.4 keV) without the need for a broad Gaussian at ~ 10 keV as used in some earlier studies. Though winds from the companion can affect the emission from the neutron star at low energies (< 3 keV), the blackbody component shows a significant presence in our continuum model. We report evidence for the possible presence of two independent sets of CRSFs with fundamentals at ~ 11 keV and ~ 15 keV. These two sets of CRSFs could arise from spatially distinct emitting regions. We also find evidence for variations in the line equivalent widths, with the 11 keV CRSF weakening and the 15 keV line strengthening with decreasing luminosity. Finally, we propose that the reason for the earlier observed anti-correlation of line energy with luminosity could be due to modelling of these two independent line sets (~ 11 keV and ~ 15 keV) as a single CRSF.Comment: 12 pages, 8 figures (4 in colour), 6 tables. Accepted for publication in MNRAS. Typos corrected, Figure 8 changed and some changes to draf

The Frenet Serret Description of Gyroscopic Precession

The phenomenon of gyroscopic precession is studied within the framework of Frenet-Serret formalism adapted to quasi-Killing trajectories. Its relation to the congruence vorticity is highlighted with particular reference to the irrotational congruence admitted by the stationary, axisymmetric spacetime. General precession formulae are obtained for circular orbits with arbitrary constant angular speeds. By successive reduction, different types of precessions are derived for the Kerr - Schwarzschild - Minkowski spacetime family. The phenomenon is studied in the case of other interesting spacetimes, such as the De Sitter and G\"{o}del universes as well as the general stationary, cylindrical, vacuum spacetimes.Comment: 37 pages, Paper in Late

Dominance and Innovation

Do dominant or less dominant firms innovate more? Theoretically it has been shown that within an asymmetric mixed strategy game of a patent race, the less dominant firm invests more than the dominant firm. But the empirical data on patent races is divided. In this paper, we argue that the decisions that concern strategic choice in innovation may be influenced by expected relative returns. Our approach, which we call the returns-based beliefs approach, is based upon subjective probabilities. It combines a decision analytic solution concept and Luce’s (1959) probabilistic choice model. In particular, we show how the use of the returns-based beliefs approach provides support for the thesis that dominant firms invest more in R&D within an asymmetric mixed strategy game. Consequently, we argue that the returns-based beliefs approach is more in line with recent empirical studies of innovation. We also provide empirical evidence using UK R&D data across a range of industries from 2001-2006 that shows that firms’ spending on R&D is related more to their own profitability than that of their competitors, which is consistent with the returns-based beliefs approach. We discuss the managerial implications of our theoretical approach and the empirical findings

Beyond the basics: Access and equity in the expansion of post-compulsory schooling in Vietnam

Human capital development, including the expansion and improvement of schooling, has played a crucial role in Vietnam’s strong and relatively inclusive economic growth in recent years. Universal access to primary and lower secondary education have been achieved, but progression to upper secondary remains, for the most part, rationed by entrance examinations and the payment of fees. Both supply and access have improved strongly at upper secondary level since the 1990s, in line with rising demand for higher skilled school-leavers. However, it is less clear whether access to upper secondary schooling, and its wider social and economic benefits, is provided equitably. In this paper we employ a unique longitudinal dataset to examine the patterns of both access and attainment in upper secondary education in Vietnam. We consider their implications for equitable educational progression and the extent to which, in light of these patterns, the system can be described as meritocratic

Homogeneous Relaxation at Strong Coupling from Gravity

Homogeneous relaxation is a ubiquitous phenomenon in semiclassical kinetic theories where the quasiparticles are distributed uniformly in space, and the equilibration involves only their velocity distribution. For such solutions, the hydrodynamic variables remain constant. We construct asymptotically AdS solutions of Einstein's gravity dual to such processes at strong coupling, perturbatively in the amplitude expansion, where the expansion parameter is the ratio of the amplitude of the non-hydrodynamic shear-stress tensor to the pressure. At each order, we sum over all time derivatives through exact recursion relations. We argue that the metric has a regular future horizon, order by order in the amplitude expansion, provided the shear-stress tensor follows an equation of motion. At the linear order, this equation of motion implies that the metric perturbations are composed of zero wavelength quasinormal modes. Our method allows us to calculate the non-linear corrections to this equation perturbatively in the amplitude expansion. We thus derive a special case of our previous conjecture on the regularity condition on the boundary stress tensor that endows the bulk metric with a regular future horizon, and also refine it further. We also propose a new outlook for heavy-ion phenomenology at RHIC and ALICE.Comment: 60 pages, a section titled "Outlook for RHIC and ALICE" has been added, accepted for publication in Physical Review

Efficient simulations with electronic open boundaries

We present a reformulation of the Hairy Probe method for introducing electronic open boundaries that is appropriate for steady state calculations involving non-orthogonal atomic basis sets. As a check on the correctness of the method we investigate a perfect atomic wire of Cu atoms, and a perfect non-orthogonal chain of H atoms. For both atom chains we find that the conductance has a value of exactly one quantum unit, and that this is rather insensitive to the strength of coupling of the probes to the system, provided values of the coupling are of the same order as the mean inter-level spacing of the system without probes. For the Cu atom chain we find in addition that away from the regions with probes attached, the potential in the wire is uniform, while within them it follows a predicted exponential variation with position. We then apply the method to an initial investigation of the suitability of graphene as a contact material for molecular electronics. We perform calculations on a carbon nanoribbon to determine the correct coupling strength of the probes to the graphene, and obtain a conductance of about two quantum units corresponding to two bands crossing the Fermi surface. We then compute the current through a benzene molecule attached to two graphene contacts and find only a very weak current because of the disruption of the π-conjugation by the covalent bond between the benzene and the graphene. In all cases we find that very strong or weak probe couplings suppress the current