A Comparative Study of Cluster Detection Algorithms in Protein–Protein Interaction for Drug Target Discovery and Drug Repurposing

The interactions between drugs and their target proteins induce altered expression of genes involved in complex intracellular networks. The properties of these functional network modules are critical for the identification of drug targets, for drug repurposing, and for understanding the underlying mode of action of the drug. The topological modules generated by a computational approach are defined as functional clusters. However, the functions inferred for these topological modules extracted from a large-scale molecular interaction network, such as a protein–protein interaction (PPI) network, could differ depending on different cluster detection algorithms. Moreover, the dynamic gene expression profiles among tissues or cell types causes differential functional interaction patterns between the molecular components. Thus, the connections in the PPI network should be modified by the transcriptomic landscape of specific cell lines before producing topological clusters. Here, we systematically investigated the clusters of a cell-based PPI network by using four cluster detection algorithms. We subsequently compared the performance of these algorithms for target gene prediction, which integrates gene perturbation data with the cell-based PPI network using two drug target prioritization methods, shortest path and diffusion correlation. In addition, we validated the proportion of perturbed genes in clusters by finding candidate anti-breast cancer drugs and confirming our predictions using literature evidence and cases in the ClinicalTrials.gov. Our results indicate that the Walktrap (CW) clustering algorithm achieved the best performance overall in our comparative study

Creating, moving and merging Dirac points with a Fermi gas in a tunable honeycomb lattice

Dirac points lie at the heart of many fascinating phenomena in condensed matter physics, from massless electrons in graphene to the emergence of conducting edge states in topological insulators [1, 2]. At a Dirac point, two energy bands intersect linearly and the particles behave as relativistic Dirac fermions. In solids, the rigid structure of the material sets the mass and velocity of the particles, as well as their interactions. A different, highly flexible approach is to create model systems using fermionic atoms trapped in the periodic potential of interfering laser beams, a method which so far has only been applied to explore simple lattice structures [3, 4]. Here we report on the creation of Dirac points with adjustable properties in a tunable honeycomb optical lattice. Using momentum-resolved interband transitions, we observe a minimum band gap inside the Brillouin zone at the position of the Dirac points. We exploit the unique tunability of our lattice potential to adjust the effective mass of the Dirac fermions by breaking inversion symmetry. Moreover, changing the lattice anisotropy allows us to move the position of the Dirac points inside the Brillouin zone. When increasing the anisotropy beyond a critical limit, the two Dirac points merge and annihilate each other - a situation which has recently attracted considerable theoretical interest [5-9], but seems extremely challenging to observe in solids [10]. We map out this topological transition in lattice parameter space and find excellent agreement with ab initio calculations. Our results not only pave the way to model materials where the topology of the band structure plays a crucial role, but also provide an avenue to explore many-body phases resulting from the interplay of complex lattice geometries with interactions [11, 12]

Quality Assessment of Printable Strain Hardening Cementitious Composites Manufactured in Two Different Printing Facilities

Over the past few years, several studies have shown the potential of three-dimensional concrete printing (3DCP) for applications in building and civil engineering. However, only a few studies have compared the properties of the fresh printing material and the quality of the printed elements from different printing facilities. Variations in the manufacturing conditions caused by the mixing procedures, the pumping device and the nozzle shape and/or dimensions may influence the quality of the printed elements. This study investigates the differences in the fresh and hardened properties of a printing material tested in two different printing facilities. The pump pressure and temperature experienced by the printing material during the printing session are monitored real-time. Hardened properties are measured for the printed elements, such as the bending capacity, the apparent density, and the air void content. The research shows that two different printing facilities may result in printed elements with relative differences in flexural strength and volumetric density of 49% and 7%, respectively

The Halo Occupation Distribution of Active Galactic Nuclei

Using a fully cosmological hydrodynamic simulation that self-consistently incorporates the growth and feedback of supermassive black holes and the physics of galaxy formation, we examine the effects of environmental factors (e.g., local gas density, black hole feedback) on the halo occupation distribution of low luminosity active galactic nuclei (AGN). We decompose the mean occupation function into central and satellite contribution and compute the conditional luminosity functions (CLF). The CLF of the central AGN follows a log-normal distribution with the mean increasing and scatter decreasing with increasing redshifts. We analyze the light curves of individual AGN and show that the peak luminosity of the AGN has a tighter correlation with halo mass compared to instantaneous luminosity. We also compute the CLF of satellite AGN at a given central AGN luminosity. We do not see any significant correlation between the number of satellites with the luminosity of the central AGN at a fixed halo mass. We also show that for a sample of AGN with luminosity above 10^42 ergs/s the mean occupation function can be modeled as a softened step function for central AGN and a power law for the satellite population. The radial distribution of AGN inside halos follows a power law at all redshifts with a mean index of -2.33 +/- 0.08. Incorporating the environmental dependence of supermassive black hole accretion and feedback, our formalism provides a theoretical tool for interpreting current and future measurements of AGN clustering.Comment: 14 pages, 11 figures, 2 Tables (Matches the MNRAS accepted version

Artificial graphene as a tunable Dirac material

Artificial honeycomb lattices offer a tunable platform to study massless Dirac quasiparticles and their topological and correlated phases. Here we review recent progress in the design and fabrication of such synthetic structures focusing on nanopatterning of two-dimensional electron gases in semiconductors, molecule-by-molecule assembly by scanning probe methods, and optical trapping of ultracold atoms in crystals of light. We also discuss photonic crystals with Dirac cone dispersion and topologically protected edge states. We emphasize how the interplay between single-particle band structure engineering and cooperative effects leads to spectacular manifestations in tunneling and optical spectroscopies.Comment: Review article, 14 pages, 5 figures, 112 Reference

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

Foundations of Black Hole Accretion Disk Theory

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).Comment: 91 pages, 23 figures, final published version available at http://www.livingreviews.org/lrr-2013-

Orbital excitation blockade and algorithmic cooling in quantum gases

Interaction blockade occurs when strong interactions in a confined few-body system prevent a particle from occupying an otherwise accessible quantum state. Blockade phenomena reveal the underlying granular nature of quantum systems and allow the detection and manipulation of the constituent particles, whether they are electrons, spins, atoms, or photons. The diverse applications range from single-electron transistors based on electronic Coulomb blockade to quantum logic gates in Rydberg atoms. We have observed a new kind of interaction blockade in transferring ultracold atoms between orbitals in an optical lattice. In this system, atoms on the same lattice site undergo coherent collisions described by a contact interaction whose strength depends strongly on the orbital wavefunctions of the atoms. We induce coherent orbital excitations by modulating the lattice depth and observe a staircase-type excitation behavior as we cross the interaction-split resonances by tuning the modulation frequency. As an application of orbital excitation blockade (OEB), we demonstrate a novel algorithmic route for cooling quantum gases. Our realization of algorithmic cooling utilizes a sequence of reversible OEB-based quantum operations that isolate the entropy in one part of the system, followed by an irreversible step that removes the entropy from the gas. This work opens the door to cooling quantum gases down to ultralow entropies, with implications for developing a microscopic understanding of strongly correlated electron systems that can be simulated in optical lattices. In addition, the close analogy between OEB and dipole blockade in Rydberg atoms provides a roadmap for the implementation of two-qubit gates in a quantum computing architecture with natural scalability.Comment: 6 pages, 4 figure

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Theory of disk accretion onto supermassive black holes

Accretion onto supermassive black holes produces both the dramatic phenomena associated with active galactic nuclei and the underwhelming displays seen in the Galactic Center and most other nearby galaxies. I review selected aspects of the current theoretical understanding of black hole accretion, emphasizing the role of magnetohydrodynamic turbulence and gravitational instabilities in driving the actual accretion and the importance of the efficacy of cooling in determining the structure and observational appearance of the accretion flow. Ongoing investigations into the dynamics of the plunging region, the origin of variability in the accretion process, and the evolution of warped, twisted, or eccentric disks are summarized.Comment: Mostly introductory review, to appear in "Supermassive black holes in the distant Universe", ed. A.J. Barger, Kluwer Academic Publishers, in pres