Engineering orthogonal dual transcription factors for multi-input synthetic promoters

Synthetic biology has seen an explosive growth in the capability of engineering artificial gene circuits from transcription factors (TFs), particularly in bacteria. However, most artificial networks still employ the same core set of TFs (for example LacI, TetR and cI). The TFs mostly function via repression and it is difficult to integrate multiple inputs in promoter logic. Here we present to our knowledge the first set of dual activator-repressor switches for orthogonal logic gates, based on bacteriophage λ cI variants and multi-input promoter architectures. Our toolkit contains 12 TFs, flexibly operating as activators, repressors, dual activator–repressors or dual repressor–repressors, on up to 270 synthetic promoters. To engineer non cross-reacting cI variants, we design a new M13 phagemid-based system for the directed evolution of biomolecules. Because cI is used in so many synthetic biology projects, the new set of variants will easily slot into the existing projects of other groups, greatly expanding current engineering capacities

Scaling-up quantum heat engines efficiently via shortcuts to adiabaticity

The finite-time operation of a quantum heat engine that uses a single particle as a working medium generally increases the output power at the expense of inducing friction that lowers the cycle efficiency. We propose to scale up a quantum heat engine utilizing a many-particle working medium in combination with the use of shortcuts to adiabaticity to boost the nonadiabatic performance by eliminating quantum friction and reducing the cycle time. To this end, we first analyze the finite-time thermodynamics of a quantum Otto cycle implemented with a quantum fluid confined in a time-dependent harmonic trap. We show that nonadiabatic effects can be controlled and tailored to match the adiabatic performance using a variety of shortcuts to adiabaticity. As a result, the nonadiabatic dynamics of the scaled-up many-particle quantum heat engine exhibits no friction and the cycle can be run at maximum efficiency with a tunable output power. We demonstrate our results with a working medium consisting of particles with inverse-square pairwise interactions, that includes noninteracting and hard-core bosons as limiting cases.Comment: 15 pages, 3 figures; typo in Eq. (51) fixed. Feature paper in the Special Issue "Quantum Thermodynamics" edited by Prof. Dr. Ronnie Koslof

Numerical simulation of random paths with a curvature dependent action

We study an ensemble of closed random paths, embedded in R^3, with a curvature dependent action. Previous analytical results indicate that there is no crumpling transition for any finite value of the curvature coupling. Nevertheless, in a high statistics numerical simulation, we observe two different regimes for the specific heat separated by a rather smooth structure. The analysis of this fact warns us about the difficulties in the interpretation of numerical results obtained in cases where theoretical results are absent and a high statistics simulation is unreachable. This may be the case of random surfaces.Comment: 9 pages, LaTeX, 4 eps figures. Final version to appear in Mod. Phys. Lett.

An introduction to local Black Hole horizons in the 3+1 approach to General Relativity

We present an introduction to dynamical trapping horizons as quasi-local models for black hole horizons, from the perspective of an Initial Value Problem approach to the construction of generic black hole spacetimes. We focus on the geometric and structural properties of these horizons aiming, as a main application, at the numerical evolution and analysis of black hole spacetimes in astrophysical scenarios. In this setting, we discuss their dual role as an "a priori" ingredient in certain formulations of Einstein equations and as an "a posteriori" tool for the diagnosis of dynamical black hole spacetimes. Complementary to the first-principles discussion of quasi-local horizon physics, we place an emphasis on the "rigidity" properties of these hypersurfaces and their role as privileged geometric probes into near-horizon strong-field spacetime dynamics.Comment: 37 pages, 5 figures. Notes prepared for the course at the 2011 Shanghai Asia-Pacific School and Workshop on Gravitation (Shanghai Normal University, February 10-14, 2011

Analysis of regulatory network involved in mechanical induction of embryonic stem cell differentiation

Embryonic stem cells are conventionally differentiated by modulating specific growth factors in the cell culture media. Recently the effect of cellular mechanical microenvironment in inducing phenotype specific differentiation has attracted considerable attention. We have shown the possibility of inducing endoderm differentiation by culturing the stem cells on fibrin substrates of specific stiffness [1]. Here, we analyze the regulatory network involved in such mechanically induced endoderm differentiation under two different experimental configurations of 2-dimensional and 3-dimensional culture, respectively. Mouse embryonic stem cells are differentiated on an array of substrates of varying mechanical properties and analyzed for relevant endoderm markers. The experimental data set is further analyzed for identification of co-regulated transcription factors across different substrate conditions using the technique of bi-clustering. Overlapped bi-clusters are identified following an optimization formulation, which is solved using an evolutionary algorithm. While typically such analysis is performed at the mean value of expression data across experimental repeats, the variability of stem cell systems reduces the confidence on such analysis of mean data. Bootstrapping technique is thus integrated with the bi-clustering algorithm to determine sets of robust bi-clusters, which is found to differ significantly from corresponding bi-clusters at the mean data value. Analysis of robust bi-clusters reveals an overall similar network interaction as has been reported for chemically induced endoderm or endodermal organs but with differences in patterning between 2-dimensional and 3-dimensional culture. Such analysis sheds light on the pathway of stem cell differentiation indicating the prospect of the two culture configurations for further maturation. © 2012 Zhang et al