Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway

BACKGROUND: Genome-scale RNA-interference (RNAi) screens are becoming ever more common gene discovery tools. However, whilst every screen identifies interacting genes, less attention has been given to how factors such as library design and post-screening bioinformatics may be effecting the data generated. RESULTS: Here we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen was carried out using a second-generation, computationally optimised dsRNA library and analysed using current methods and bioinformatic tools. To examine advances in RNAi screening technology, we compare this screen to a biologically very similar screen undertaken in 2005 with a first-generation library. Both screens used the same cell line, reporters and experimental design, with the SRSF screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which verified in a secondary screen and 16 verified with an independent probe design. Following reanalysis of the original screen data, comparisons of the two gene lists allows us to make estimates of false discovery rates in the SRSF data and to conduct an assessment of off-target effects (OTEs) associated with both libraries. We discuss the differences and similarities between the resulting data sets and examine the relative improvements in gene discovery protocols. CONCLUSIONS: Our work represents one of the first direct comparisons between first- and second-generation libraries and shows that modern library designs together with methodological advances have had a significant influence on genome-scale RNAi screens

Decoupling in the 1D frustrated quantum XY model and Josephson junction ladders: Ising critical behavior

A generalization of the one-dimensional frustrated quantum XY model is considered in which the inter and intra-chain coupling constants of the two infinite XY (planar rotor) chains have different strengths. The model can describe the superconductor to insulator transition due to charging effects in a ladder of Josephson junctions in a magnetic field with half a flux quantum per plaquette. From a fluctuation-effective action, this transition is expected to be in the universality class of the two-dimensional classical XY-Ising model. The critical behavior is studied using a Monte Carlo transfer matrix applied to the path-integral representation of the model and a finite-size-scaling analysis of data on small system sizes. It is found that, unlike the previous studied case of equal inter and intra-chain coupling constants, the XY and Ising-like excitations of the quantum model decouple for large interchain coupling, giving rise to pure Ising model critical behavior for the chirality order parameter and a superconductor-insulator transition in the universality class of the 2D classical XY model.Comment: 15 pages with figures, RevTex 3.0, INPE-93/00

Medium-range interactions and crossover to classical critical behavior

We study the crossover from Ising-like to classical critical behavior as a function of the range R of interactions. The power-law dependence on R of several critical amplitudes is calculated from renormalization theory. The results confirm the predictions of Mon and Binder, which were obtained from phenomenological scaling arguments. In addition, we calculate the range dependence of several corrections to scaling. We have tested the results in Monte Carlo simulations of two-dimensional systems with an extended range of interaction. An efficient Monte Carlo algorithm enabled us to carry out simulations for sufficiently large values of R, so that the theoretical predictions could actually be observed.Comment: 16 pages RevTeX, 8 PostScript figures. Uses epsf.sty. Also available as PostScript and PDF file at http://www.tn.tudelft.nl/tn/erikpubs.htm

Quantum Phase Transitions and Conserved Charges

The constraints on the scaling properties of conserved charge densities in the vicinity of a zero temperature ($T$), second-order quantum phase transition are studied. We introduce a generalized Wilson ratio, characterizing the non-linear response to an external field, $H$, coupling to any conserved charge, and argue that it is a completely universal function of $H/T$: this is illustrated by computations on model systems. We also note implications for transitions where the order parameter is a conserved charge (as in a $T=0$ ferromagnet-paramagnet transition).Comment: 19 pages, REVTEX 3.0, 8 uuencoded Postscript figues appended, YCTP-xxx

Parametric pumping at finite frequency

We report on a first principles theory for analyzing the parametric electron pump at a finite frequency. The pump is controlled by two pumping parameters with phase difference $\phi$. In the zero frequency limit, our theory predicts the well known result that the pumped current is proportional to $\sin\phi$. For the more general situation of a finite frequency, our theory predicts a non-vanishing pumped current even when the two driving forces are in phase, in agreement with the recent experimental results. We present the physical mechanism behind the nonzero pumped current at $\phi=0$, which we found to be due to photon-assisted processes

Feshbach resonance in a strictly two-dimensional atomic Bose gas

We discuss the atom-atom scattering problem across a Feshbach resonance in a two-dimensional dilute Bose gas at zero temperature, in the limit where the s-wave scattering length exceeds the width of the vertical confinement. We determine a tunable coupling-strength parameter and by controlling it we evaluate how the condensate wave function spreads out with increasing atom-atom repulsions. We also discuss the stability of the condensate in the magnetic-field regime where the coupling has become attractive.Comment: 9 pages, 1 figur

Strong-coupling perturbation theory for the two-dimensional Bose-Hubbard model in a magnetic field

The Bose-Hubbard model in an external magnetic field is investigated with strong-coupling perturbation theory. The lowest-order secular equation leads to the problem of a charged particle moving on a lattice in the presence of a magnetic field, which was first treated by Hofstadter. We present phase diagrams for the two-dimensional square and triangular lattices, showing a change in shape of the phase lobes away from the well-known power-law behavior in zero magnetic field. Some qualitative agreement with experimental work on Josephson-junction arrays is found for the insulating phase behavior at small fields.Comment: 7 pages, 5 figures include

Crystallization of a classical two-dimensional electron system: Positional and orientational orders

Crystallization of a classical two-dimensional one-component plasma (electrons interacting with the Coulomb repulsion in a uniform neutralizing positive background) is investigated with a molecular dynamics simulation. The positional and the orientational correlation functions are calculated for the first time. We have found an indication that the solid phase has a quasi-long-range (power-law) positional order along with a long-range orientational order. This indicates that, although the long-range Coulomb interaction is outside the scope of Mermin's theorem, the absence of ordinary crystalline order at finite temperatures applies to the electron system as well. The `hexatic' phase, which is predicted between the liquid and the solid phases by the Kosterlitz-Thouless-Halperin-Nelson-Young theory, is also discussed.Comment: 3 pages, 4 figures; Corrected typos; Double columne