Equation-free Dynamic Renormalization of a KPZ-type Equation

In the context of equation-free computation, we devise and implement a procedure for using short-time direct simulations of a KPZ type equation to calculate the self-similar solution for its ensemble averaged correlation function. The method involves "lifting" from candidate pair-correlation functions to consistent realization ensembles, short bursts of KPZ-type evolution, and appropriate rescaling of the resulting averaged pair correlation functions. Both the self-similar shapes and their similarity exponents are obtained at a computational cost significantly reduced to that required to reach saturation in such systems

Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia.

Long-term memory (LTM) is believed to be stored in the brain as changes in synaptic connections. Here, we show that LTM storage and synaptic change can be dissociated. Cocultures of Aplysia sensory and motor neurons were trained with spaced pulses of serotonin, which induces long-term facilitation. Serotonin (5HT) triggered growth of new presynaptic varicosities, a synaptic mechanism of long-term sensitization. Following 5HT training, two antimnemonic treatments-reconsolidation blockade and inhibition of PKM--caused the number of presynaptic varicosities to revert to the original, pretraining value. Surprisingly, the final synaptic structure was not achieved by targeted retraction of the 5HT-induced varicosities but, rather, by an apparently arbitrary retraction of both 5HT-induced and original synapses. In addition, we find evidence that the LTM for sensitization persists covertly after its apparent elimination by the same antimnemonic treatments that erase learning-related synaptic growth. These results challenge the idea that stable synapses store long-term memories

Longitudinal Data Methods for Evaluating Genome-by-Epigenome Interactions in Families

Background: Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data. Results: Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score. Conclusions: Comparison of all modeling approaches indicated a need for bias correction in marginal models and similar power for each method, with quadratic inference functions providing a minor decrement in power compared to generalized estimating equations and linear mixed-effects models

Event-driven simulations of a plastic, spiking neural network

We consider a fully-connected network of leaky integrate-and-fire neurons with spike-timing-dependent plasticity. The plasticity is controlled by a parameter representing the expected weight of a synapse between neurons that are firing randomly with the same mean frequency. For low values of the plasticity parameter, the activities of the system are dominated by noise, while large values of the plasticity parameter lead to self-sustaining activity in the network. We perform event-driven simulations on finite-size networks with up to 128 neurons to find the stationary synaptic weight conformations for different values of the plasticity parameter. In both the low and high activity regimes, the synaptic weights are narrowly distributed around the plasticity parameter value consistent with the predictions of mean-field theory. However, the distribution broadens in the transition region between the two regimes, representing emergent network structures. Using a pseudophysical approach for visualization, we show that the emergent structures are of "path" or "hub" type, observed at different values of the plasticity parameter in the transition region.Comment: 9 pages, 6 figure

Enantioselective Organocatalytic Amine Conjugate Addition

The first enantioselective organocatalytic amine conjugate addition has been successfully developed. The application of LUMO-lowering iminium catalysis has enabled the highly chemo- and enantioselective 1,4-addition of a rationally designed N-silyloxycarbamate nucleophile (HOMO-raised) to α,β-unsaturated aldehydes. Imidazolidinone 2•pTSA was found to catalyze the addition of various orthogonally N-protected silyloxycarbamate nucleophiles to a range of α,β-unsaturated aldehydes, affording synthetically useful β-amino aldehyde intermediates. The synthetic utility of the protocol was demonstrated in the rapid synthesis of enantioenriched β-amino acids in one operation and 1,3-amino alcohol derivatives in three operations

Millimeter-wave diode-grid phase shifters

Monolithic diode grids have been fabricated on 2-cm square gallium-arsenide wafers with 1600 Schottky-barrier varactor diodes. Shorted diodes are detected with a liquid-crystal technique, and the bad diodes are removed with an ultrasonic probe. A small-aperture reflectometer that uses wavefront division interference was developed to measure the reflection coefficient of the grids. A Phase shift of 70° with a 7-dB loss was obtained at 93 GHz when the bias on the diode grid was changed from -3 V to 1 V. A simple transmission-line grid model, together with the measured low-frequency parameters for the diodes, was shown to predict the measured performance over the entire capacitive bias range of the diodes, as well as over the complete reactive tuning range provided by a reflector behind the grid, and over a wide range of frequencies form 33 GHz to 141 GHz. This shows that the transmission-line model and the measured low-frequency diode parameters can be used to design an electronic beam-steering array and to predict its performance. An electronic beam-steering array made of a pair of grids using state-of-the-art diodes with 5-Ω series resistances would have a loss of 1.4 dB at 90 GHz

Millimeter-Wave Diode-Grid Frequency Doubler

Monolithic diode grid were fabricated on 2-cm^2 gallium-arsenide wafers in a proof-of-principle test of a quasi-optical varactor millimeter-wave frequency multiplier array concept. An equivalent circuit model based on a transmission-line analysis of plane wave illumination was applied to predict the array performance. The doubler experiments were performed under far-field illumination conditions. A second-harmonic conversion efficiency of 9.5% and output powers of 0.5 W were achieved at 66 GHz when the diode grid was pumped with a pulsed source at 33 GHz. This grid had 760 Schottky-barrier varactor diodes. The average series resistance was 27 Ω, the minimum capacitance was 18 fF at a reverse breakdown voltage of -3 V. The measurements indicate that the diode grid is a feasible device for generating watt-level powers at millimeter frequencies and that substantial improvement is possible by improving the diode breakdown voltage

A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.

Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening