Bimodal and hysteretic expression in mammalian cells from a synthetic gene circuit

In order to establish cells and organisms with predictable properties, synthetic biology makes use of controllable, synthetic genetic devices. These devices are used to replace or to interfere with natural pathways. Alternatively, they may be interlinked with endogenous pathways to create artificial networks of higher complexity. While these approaches have been already successful in prokaryotes and lower eukaryotes, the implementation of such synthetic cassettes in mammalian systems and even animals is still a major obstacle. This is mainly due to the lack of methods that reliably and efficiently transduce synthetic modules without compromising their regulation properties. To pave the way for implementation of synthetic regulation modules in mammalian systems we utilized lentiviral transduction of synthetic modules. A synthetic positive feedback loop, based on the Tetracycline regulation system was implemented in a lentiviral vector system and stably integrated in mammalian cells. This gene regulation circuit yields a bimodal expression response. Based on experimental data a mathematical model based on stochasticity was developed which matched and described the experimental findings. Modelling predicted a hysteretic expression response which was verified experimentally. Thereby supporting the idea that the system is driven by stochasticity. The results presented here highlight that the combination of three independent tools/methodologies facilitate the reliable installation of synthetic gene circuits with predictable expression characteristics in mammalian cells and organisms

Spin Dynamics in the Magnetic Chains Arrays of Sr14Cu24O41: a Neutron Inelastic scattering Investigation

Below about 150 K, the spin arrangement in the chain arrays of Sr14Cu24O41 is shown to develop in two dimensions (2D). Both the correlations and the dispersion of the observed elementary excitations agree well with a model of interacting dimers. Along the chains, the intra- and inter-dimer distances are equal to 2 and about 3 times the distance (c) between neighboring Cu ions. While the intra-dimer coupling is J about 10 meV, the inter-dimer couplings along and between the chains are of comparable strenght, J// about -1.1 meV and Jperp about 1.7 meV, respectively. This remarkable 2D arrangement satisfies the formal Cu valence of the undoped compound. Our data suggest also that it is associated with a relative sliding of one chain with respect to the next one, which, as T decreases, develops in the chain direction. A qualitative analysis shows that nearest inter-dimer spin correlations are ferromagnetic, which, in such a 2D structure, could well result from frustration effects.Comment: 4 pages, 5 figures, submitted to Phys.Rev.B, date of receipt 29 June 199

Dynamic Spin Response for Heisenberg Ladders

We employ the recently proposed plaquette basis to investigate static and dynamic properties of isotropic 2-leg Heisenberg spin ladders. Simple non-interacting multi-plaquette states provide a remarkably accurate picture of the energy/site and dynamic spin response of these systems. Insights afforded by this simple picture suggest a very efficient truncation scheme for more precise calculations. When the small truncation errors are accounted for using recently developed Contractor Renormalization techniques, very accurate results requiring a small fraction of the computational effort of exact calculations are obtained. These methods allow us to determine the energy/site, gap, and spin response of 2x16 ladders. The former two values are in good agreement with density matrix renormalization group results. The spin response calculations show that nearly all the strength is concentrated in the lowest triplet level and that coherent many-body effects enhance the response/site by nearly a factor of 1.6 over that found for 2x2 systems.Comment: 9 pages with two enclosed postscript figure

Pathologies in International Policy Transfer:The Case of the OECD Tax Transparency Initiative

ABSTRACT The importance of international organizations to the development and diffusion of international policy norms is widely recognized but is increasingly tempered by an appreciation of the pathologies of policy transfer. Using a case study of the OECD’s campaign to promote transparency in global tax affairs, this paper identifies a new and relatively distinctive form of dysfunctional policy transfer. Specifically it argues that international organizations face bureaucratic incentives to promote weak or lowest common denominator standards in order to maximize their prospects of brokering successful international agreements. However the paper also notes that while international organizations may have a short-term interest in promoting weak standards, their longer-term legitimacy is often tied to the effectiveness of the standards they promote. It is argued that this dynamic often leads to incremental policy change

Phases of two coupled Luttinger liquids

A model of two interacting one--dimensional fermion systems (``Luttinger liquids'') coupled by single--particle hopping is investigated. Bosonization allows a number of exact statements to be made. In particular, for forward scattering only, the model contains two massless boson sectors and an Ising type critical sector. For general interactions, there is a spin excitation gap and either s-- or d--type pairing fluctuations dominate. It is shown that the same behavior is also found for strong interactions. A possible scenario for the crossover to a Fermi liquid in a many chain system is discussed.Comment: revised version, some changes, 11 pages, no figures, RexTeX3.

Nuclear spin relaxation rates in two-leg spin ladders

Using the transfer-matrix DMRG method, we study the nuclear spin relaxation rate 1/T_1 in the two-leg s=1/2 ladder as function of the inter-chain (J_{\perp}) and intra-chain (J_{|}) couplings. In particular, we separate the q_y=0 and \pi contributions and show that the later contribute significantly to the copper relaxation rate ^{63}(1/T_1) in the experimentally relevant coupling and temperature range. We compare our results to both theoretical predictions and experimental measures on ladder materials.Comment: Few modifications from the previous version 4 pages, 5 figures, accepted for publication in PR

Stability of the Haldane phase in anisotropic magnetic ladders

We have considered the properties of anisotropic two-leg ladder models with S=1/2 or S=1 spins on the rungs, using White's density matrix renormalization group method. We have generalized the method by taking into account the symmetries of the model in order to reduce the dimensions of the matrix to be diagonalized, thereby making possible to consider more states. The boundaries in the parameter space of the extended region, where the Haldane phase exists, are estimated.Comment: 19 pages, 5 figure

Dynamical Spin Response Functions for Heisenberg Ladders

We present the results of a numerical study of the 2 by L spin 1/2 Heisenberg ladder. Ground state energies and the singlet-triplet energy gaps for L = (4-14) and equal rung and leg interaction strengths were obtained in a Lanczos calculation and checked against earlier calculations by Barnes et al. (even L up to 12). A related moments technique is then employed to evaluate the dynamical spin response for L=12 and a range of rung to leg interaction strength ratios (0 - 5). We comment on two issues, the need for reorthogonalization and the rate of convergence, that affect the numerical utility of the moments treatment of response functions.Comment: Revtex, 3 figure

Modeling of the Magnetic Susceptibilities of the Ambient- and High-Pressure Phases of (VO)_{2}P_{2}O_{7}

The magnetic susceptibilities chi versus temperature T of powders and single crystals of the ambient-pressure (AP) and high-pressure (HP) phases of (VO)_{2}P_{2}O_{7} are analyzed using an accurate theoretical prediction of chi(T, J1, J2) for the spin-1/2 antiferromagnetic alternating-exchange (J1, J2) Heisenberg chain. The results are consistent with recent models with two distinct types of alternating-exchange chains in the AP phase and a single type in the HP phase. The spin gap for each type of chain is derived from the respective set of two fitted alternating exchange constants and the one-magnon dispersion relation for each of the two types of chains in the AP phase is predicted. The influences of interchain coupling on the derived intrachain exchange constants, spin gaps, and dispersion relations are estimated using a mean-field approximation for the interchain coupling. The accuracies of the spin gaps obtained using fits to the low-T chi(T) data by theoretical low-T approximations are determined. The results of these studies are compared with previously reported estimates of the exchange couplings and spin gaps in the AP and HP phases and with the magnon dispersion relations in the AP phase measured previously using inelastic neutron scattering.Comment: 25 two-column REVTeX pages, 16 embedded figures, 6 tables. Figures 9 and 10 and Sec. IIIC revised due to errors in Eq. (1) of Ref. 24 which gives the theoretical one-magnon dispersion relation for coupled alternating-exchange chains. Minor revisions also made in other section