Lentiviral vectors with amplified beta cell-specific gene expression.

An important goal of gene therapy is to be able to deliver genes, so that they express in a pattern that recapitulates the expression of an endogenous cellular gene. Although tissue-specific promoters confer selectivity, in a vector-based system, their activity may be too weak to mediate detectable levels in gene-expression studies. We have used a two-step transcriptional amplification system to amplify gene expression from lentiviral vectors using the human insulin promoter. In this system, the human insulin promoter drives expression of a potent synthetic transcription activator (the yeast GAL4 DNA-binding domain fused to the activation domain of the Herpes simplex virus-1 VP16 activator), which in turn activates a GAL4-responsive promoter, driving the enhanced green fluorescent protein reporter gene. Vectors carrying the human insulin promoter did not express in non-beta-cell lines, but expressed in murine insulinoma cell lines, indicating that the human insulin promoter was capable of conferring cell specificity of expression. The insulin-amplifiable vector was able to amplify gene expression five to nine times over a standard insulin-promoter vector. In primary human islets, gene expression from the insulin-promoted vectors was coincident with insulin staining. These vectors will be useful in gene-expression studies that require a detectable signal and tissue specificity

Network inference using asynchronously updated kinetic Ising Model

Network structures are reconstructed from dynamical data by respectively naive mean field (nMF) and Thouless-Anderson-Palmer (TAP) approximations. For TAP approximation, we use two methods to reconstruct the network: a) iteration method; b) casting the inference formula to a set of cubic equations and solving it directly. We investigate inference of the asymmetric Sherrington- Kirkpatrick (S-K) model using asynchronous update. The solutions of the sets cubic equation depend of temperature T in the S-K model, and a critical temperature Tc is found around 2.1. For T < Tc, the solutions of the cubic equation sets are composed of 1 real root and two conjugate complex roots while for T > Tc there are three real roots. The iteration method is convergent only if the cubic equations have three real solutions. The two methods give same results when the iteration method is convergent. Compared to nMF, TAP is somewhat better at low temperatures, but approaches the same performance as temperature increase. Both methods behave better for longer data length, but for improvement arises, TAP is well pronounced.Comment: 6 pages, 4 figure

Expression of human adenosine deaminase in nonhuman primates after retrovirus-mediated gene transfer.

Primate bone marrow cells were infected with a retroviral vector carrying the genes for human adenosine deaminase (h-ADA) and bacterial neomycin resistance (neor). The infected cells were infused back into the lethally irradiated donor animals. Several monkeys fully reconstituted and were shown to express the h-ADA and neor genes at low levels in their recirculating hematopoietic cells for short periods of time

Degenerate ground states and nonunique potentials: breakdown and restoration of density functionals

The Hohenberg-Kohn (HK) theorem is one of the most fundamental theorems of quantum mechanics, and constitutes the basis for the very successful density-functional approach to inhomogeneous interacting many-particle systems. Here we show that in formulations of density-functional theory (DFT) that employ more than one density variable, applied to systems with a degenerate ground state, there is a subtle loophole in the HK theorem, as all mappings between densities, wave functions and potentials can break down. Two weaker theorems which we prove here, the joint-degeneracy theorem and the internal-energy theorem, restore the internal, total and exchange-correlation energy functionals to the extent needed in applications of DFT to atomic, molecular and solid-state physics and quantum chemistry. The joint-degeneracy theorem constrains the nature of possible degeneracies in general many-body systems

Ab Initio Calculation of Impurity Effects in Copper Oxide Materials

We describe a method for calculating, within density functional theory, the electronic structure associated with typical defects which substitute for Cu in the CuO2 planes of high-Tc superconducting materials. The focus is primarily on Bi2Sr2CaCu2O8, the material on which most STM measurements of impurity resonances in the superconducting state have been performed. The magnitudes of the effective potentials found for Zn, Ni and vacancies on the in-plane Cu sites in this host material are remarkably consistent with phenomenological fits of potential scattering models to STM resonance energies. The effective potential ranges are quite short, of order 1 A with weak long range tails, in contrast to some current models of extended potentials which attempt to fit STM data. For the case of Zn and Cu vacancies, the effective potentials are strongly repulsive, and states on the impurity site near the Fermi level are simply removed. The local density of states (LDOS) just above the impurity is nevertheless found to be a maximum in the case of Zn and a local minimum in case of the vacancy, in agreement with experiment. The Zn and Cu vacancy patterns are explained as due to the long-range tails of the effective impurity potential at the sample surface. The case of Ni is richer due to the Ni atom's strong hybridization with states near the Fermi level; in particular, the short range part of the potential is attractive, and the LDOS is found to vary rapidly with distance from the surface and from the impurity site. We propose that the current controversy surrounding the observed STM patterns can be resolved by properly accounting for the effective impurity potentials and wave-functions near the cuprate surface. Other aspects of the impurity states for all three species are discussed.Comment: 37 pp. pdf including figures, submitted to Phys. Rev.

Waterborne virus transport and the associated risks in a large lake

Waterborne enteric viruses in lakes, especially at recreational water sites, may have a negative impact on human health. However, their fate and transport in lakes are poorly understood. In this study, we propose a coupled water quality and quantitative microbial risk assessment (QMRA) model to study the transport, fate and infection risk of four common waterborne viruses (adenovirus, enterovirus, norovirus and rotavirus), using Lake Geneva as a study site. The measured virus load in raw sewage entering the lake was used as the source term in the water quality simulations for a hypothetical scenario of discharging raw wastewater at the lake surface. After discharge into the lake, virus inactivation was modeled as a function of water temperature and solar irradiance that varied both spatially and temporally during transport throughout the lake. Finally, the probability of infection, while swimming at a popular beach, was quantified and compared among the four viruses. Norovirus was found to be the most abundant virus that causes an infection probability that is at least 10 times greater than the other viruses studied. Furthermore, environmental inactivation was found to be an essential determinant in the infection risks posed by viruses to recreational water users. We determined that infection risks by enterovirus and rotavirus could be up to 1000 times lower when virus inactivation by environmental stressors was accounted for compared with the scenarios considering hydrodynamic transport only. Finally, the model highlighted the role of the wind field in conveying the contamination plume and hence in determining infection probability. Our simulations revealed that for beaches located west of the sewage discharge, the infection probability under eastward wind was 43% lower than that under westward wind conditions. This study highlights the potential of combining water quality simulation and virus-specific risk assessment for a safe water resources usage and management

Repeated games for eikonal equations, integral curvature flows and non-linear parabolic integro-differential equations

The main purpose of this paper is to approximate several non-local evolution equations by zero-sum repeated games in the spirit of the previous works of Kohn and the second author (2006 and 2009): general fully non-linear parabolic integro-differential equations on the one hand, and the integral curvature flow of an interface (Imbert, 2008) on the other hand. In order to do so, we start by constructing such a game for eikonal equations whose speed has a non-constant sign. This provides a (discrete) deterministic control interpretation of these evolution equations. In all our games, two players choose positions successively, and their final payoff is determined by their positions and additional parameters of choice. Because of the non-locality of the problems approximated, by contrast with local problems, their choices have to "collect" information far from their current position. For integral curvature flows, players choose hypersurfaces in the whole space and positions on these hypersurfaces. For parabolic integro-differential equations, players choose smooth functions on the whole space

Charge qubits in semiconductor quantum computer architectures: Tunnel coupling and decoherence

We consider charge qubits based on shallow donor electron states in silicon and coupled quantum dots in GaAs. Specifically, we study the feasibility of P$_2^+$ charge qubits in Si, focusing on single qubit properties in terms of tunnel coupling between the two phosphorus donors and qubit decoherence caused by electron-phonon interaction. By taking into consideration the multi-valley structure of the Si conduction band, we show that inter-valley quantum interference has important consequences for single-qubit operations of P$_2^+$ charge qubits. In particular, the valley interference leads to a tunnel-coupling strength distribution centered around zero. On the other hand, we find that the Si bandstructure does not dramatically affect the electron-phonon coupling and consequently, qubit coherence. We also critically compare charge qubit properties for Si:P$_2^+$ and GaAs double quantum dot quantum computer architectures.Comment: 10 pages, 3 figure

Quantum information entropies of the eigenstates and the coherent state of the P\"oschl-Teller potential

The position and momentum space information entropies, of the ground state of the P\"oschl-Teller potential, are exactly evaluated and are found to satisfy the bound, obtained by Beckner, Bialynicki-Birula and Mycielski. These entropies for the first excited state, for different strengths of the potential well, are then numerically obtained. Interesting features of the entropy densities, owing their origin to the excited nature of the wave functions, are graphically demonstrated. We then compute the position space entropies of the coherent state of the P\"oschl-Teller potential, which is known to show revival and fractional revival. Time evolution of the coherent state reveals many interesting patterns in the space-time flow of information entropy.Comment: Revtex4, 11 pages, 11 eps figures and a tabl

Theory of the optical conductivity of (TMTSF)2_2PF6_6 in the mid-infrared range

We propose an explanation of the mid-infrared peak observed in the optical conductivity of the Bechgaard salt (TMTSF)$_2$PF$_6$ in terms of electronic excitations. It is based on a numerical calculation of the conductivity of the quarter-filled, dimerized Hubbard model. The main result is that, even for intermediate values of $U/t$ for which the charge gap is known to be very small, the first peak, and at the same time the main structure, of the optical conductivity is at an energy of the order of the dimerization gap, like in the infinite $U$ case. This surprising effect is a consequence of the optical selection rules.Comment: 10 pages, 9 uuencoded figure