Intermodulation electrostatic force microscopy for imaging surface photo-voltage

We demonstrate an alternative to Kelvin Probe Force Microscopy for imaging surface potential. The open-loop, single-pass technique applies a low-frequency AC voltage to the atomic force microscopy tip while driving the cantilever near its resonance frequency. Frequency mixing due to the nonlinear capacitance gives intermodulation products of the two drive frequencies near the cantilever resonance, where they are measured with high signal to noise ratio. Analysis of this intermodulation response allows for quantitative reconstruction of the contact potential difference. We derive the theory of the method, validate it with numerical simulation and a control experiment, and we demonstrate its utility for fast imaging of the surface photo-voltage on an organic photo-voltaic material.Comment: 4 pages, 3 figures, peer-reviewed, preprin

Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit

Modeling the evolution of a classic genetic switch

Abstract Background The regulatory network underlying the yeast galactose-use pathway has emerged as a model system for the study of regulatory network evolution. Evidence has recently been provided for adaptive evolution in this network following a whole genome duplication event. An ancestral gene encoding a bi-functional galactokinase and co-inducer protein molecule has become subfunctionalized as paralogous genes (GAL1 and GAL3) in Saccharomyces cerevisiae, with most fitness gains being attributable to changes in cis- regulatory elements. However, the quantitative functional implications of the evolutionary changes in this regulatory network remain unexplored. Results We develop a modeling framework to examine the evolution of the GAL regulatory network. This enables us to translate molecular changes in the regulatory network to changes in quantitative network function. We computationally reconstruct an inferred ancestral version of the network and trace the evolutionary paths in the lineage leading to S. cerevisiae. We explore the evolutionary landscape of possible regulatory networks and find that the operation of intermediate networks leading to S. cerevisiae differs substantially depending on the order in which evolutionary changes accumulate; in particular, we systematically explore evolutionary paths and find that some network features cannot be optimized simultaneously. Conclusions We find that a computational modeling approach can be used to analyze the evolution of a well-studied regulatory network. Our results are consistent with several experimental studies of the evolutionary of the GAL regulatory network, including increased fitness in Saccharomyces due to duplication and adaptive regulatory divergence. The conceptual and computational tools that we have developed may be applicable in further studies of regulatory network evolution

Iridium Catalyzed Carbocyclizations: Efficient (5+2) Cycloadditions of Vinylcyclopropanes and Alkynes.

Third-row transition metal catalysts remain a largely untapped resource in cycloaddition reactions for the formation of medium-sized rings. Herein, we report the first examples of iridium-catalyzed inter- and intramolecular vinylcyclopropane (VCP)-alkyne (5+2) cycloadditions. DFT modeling suggests that catalysis by iridium(I) proceeds through a mechanism similar to that previously reported for rhodium(I)-catalyzed VCP-alkyne cycloadditions, but a smaller free energy span for iridium enables substantially faster catalysis under favorable conditions. The system is characterized by up to quantitative yields and is amenable to an array of disubstituted alkynes and vinylcyclopropanes

Numerical simulation of travelling wave induced electrothermal fluid flow

Many microdevices for manipulating particles and cells use electric fields to produce a motive force on the particles. The movement of particles in non-uniform electric fields is called dielectrophoresis, and the usual method of applying this effect is to pass the particle suspension over a microelectrode structure. If the suspension has a noticeable conductivity, one important side effect is that the electric field drives a substantial conduction current through the fluid, causing localized Joule-heating. The resulting thermal gradient produces local conductivity and permittivity changes in the fluid. dielectrophoretic forces acting upon these pockets of fluid will then produce motion of both the fluid and the particles. This paper presents a numerical solution of the electrical force and the resulting electrothermal driven fluid flow on a travelling wave structure. This common electrode geometry consists of interdigitated electrodes laid down in a long array, with the phase of the applied potential shifted by 90° on each subsequent electrode. The resulting travelling electric field was simulated and the thermal field and electrical body force on the fluid calculated, for devices constructed from two typical materials: silicon and glass. The electrothermal fluid flow in the electrolyte over the electrode array was then numerically simulated. The model predicts that the thermal field depends on the conductivity and applied voltage, but more importantly on the geometry of the system and the material used in the construction of the device. The velocity of the fluid flow depends critically on the same parameters, with slight differences in the thermal field for glass and silicon leading to diametrically opposite flow direction with respect to the travelling field for the two materials. In addition, the imposition of slight external temperature gradients is shown to have a large effect on the fluid flow in the device, under certain conditions leading to a reversal of the fluid flow direction

Tonotopic organization in human auditory cortex revealed by progressions of frequency sensitivity

organization in human auditory cortex revealed by progression