Cyclic Density Functional Theory : A route to the first principles simulation of bending in nanostructures

We formulate and implement Cyclic Density Functional Theory (Cyclic DFT) -- a self-consistent first principles simulation method for nanostructures with cyclic symmetries. Using arguments based on Group Representation Theory, we rigorously demonstrate that the Kohn-Sham eigenvalue problem for such systems can be reduced to a fundamental domain (or cyclic unit cell) augmented with cyclic-Bloch boundary conditions. Analogously, the equations of electrostatics appearing in Kohn-Sham theory can be reduced to the fundamental domain augmented with cyclic boundary conditions. By making use of this symmetry cell reduction, we show that the electronic ground-state energy and the Hellmann-Feynman forces on the atoms can be calculated using quantities defined over the fundamental domain. We develop a symmetry-adapted finite-difference discretization scheme to obtain a fully functional numerical realization of the proposed approach. We verify that our formulation and implementation of Cyclic DFT is both accurate and efficient through selected examples. The connection of cyclic symmetries with uniform bending deformations provides an elegant route to the ab-initio study of bending in nanostructures using Cyclic DFT. As a demonstration of this capability, we simulate the uniform bending of a silicene nanoribbon and obtain its energy-curvature relationship from first principles. A self-consistent ab-initio simulation of this nature is unprecedented and well outside the scope of any other systematic first principles method in existence. Our simulations reveal that the bending stiffness of the silicene nanoribbon is intermediate between that of graphene and molybdenum disulphide. We describe several future avenues and applications of Cyclic DFT, including its extension to the study of non-uniform bending deformations and its possible use in the study of the nanoscale flexoelectric effect.Comment: Version 3 of the manuscript, Accepted for publication in Journal of the Mechanics and Physics of Solids, http://www.sciencedirect.com/science/article/pii/S002250961630368

Management of Hepatitis C Antiviral Therapy Adverse Effects

Hepatitis C is one of the leading causes of liver disease in the United States, affecting more than 4 million individuals. The current treatment regimen involves pegylated interferon in combination with ribavirin. Although antiviral treatment has been associated with a greater than 50% sustained viral response rate, the adverse effects have proven to be detrimental to quality of life and therapy adherence, and consequently lead to lower sustained viral response rates. This article identifies the most frequently described complications associated with pegylated interferon and ribavirin. The active management of these complications is discussed, including both preventive and empiric treatments

Improving trafficking and kinetics of a synthetic light-gated Potassium channel

BLINK1 is a synthetic light-gated potassium (K+) channel reversibly activated by blue light, encoded by a single gene, whose activity does not need the addition of cofactors. Transient ectopic expression of BLINK1 reversibly inhibits the escape response in light-exposed two-days-old Zebrafish larvae, confirming in vivo applicability of BLINK1 as a single-component optogenetic tool that can establish sustained, physiological hyperpolarization of cells at K+ electrochemical potential (EK). In HEK293 cells, we record a measurable BLINK1 current in less than 10% of the transfected cells. Immunolocalization experiments confirmed a very low frequency of BLINK1-specific signal on the plasma membrane (PM) of transfected cells and retention of the protein in inner cellular compartments. To fix this problem, we have added to the channel C-terminal region diacidic ER export signals from other K+ channels (mKir2.1, KAT1), plasma membrane trafficking sequences (YXX\u3a6 motifs) and mode III 14-3-3 binding sites found in other channels and pumps (TASK channels, MHA2 H+-ATP-ase, KAT1). In most cases, addition of trafficking motifs increased BLINK1 presence at the PM up to 30-40 % (cells with measurable current on the total of transfected cells) but the channel lost its light regulation. The best results were obtained with the clone renamed BLINK2, that shows a moderate improvement of expression rate (26% of transfected HEK 293T cells) but intact light regulation of the current. However, BLINK2 has slower kinetics (t1/2 on= 5 min; t1/2 off= 8 min) than the parental channel BLINK1 (\uf074on= 87s; \uf074off 168 s) and a 60 to 90 s delay in opening after light on. To improve channel kinetics, we have introduced mutations known to tune the LOV domain photocycle: BLINK2 Q513D shows indeed a reduced delay in opening (30 sec). BLINK2 and BLINK2 Q513D are currently under investigation for optogenetic applicability in vivo, both in zebrafish and mouse models

Phase Sensitivity and Entrainment in a Modeled Bursting Neuron

A model of neuron R15 in Aplysia was used to study the mechanisms determining the phase-response curve (PRC) of the cell in response to both extrinsic current pulses and modeled synaptic input and to compare entrainment predictions from PRCs with those from actual simulations. Over the range of stimulus parameters studied, the PRCs of the model exhibited minimal dependence upon stimulus amplitude, and a strong dependence upon stimulus duration. State-space analysis of the effect of transient current pulses provided several important insights into the relationship between the PRC and the underlying dynamics of the model, such as a correlation between the prestimulus concentration of Ca(2+) and the poststimulus phase of the oscillation. The system nullclines were also found to provide well-defined limits upon the perturbatory extent of a hyperpolarizing input. These results demonstrated that experimentally applied current pulses are sufficient to determine the shape of the PRC in response to a synaptic input, provided that the duration of the current pulse is of a duration similar to that of the evoked synaptic current. Furthermore, we found that predictions of phase-locked 1:m entrainment from PRCs were valid, even when the duration of the periodically applied pulses were a significant portion of the control limit cycle