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Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity(More)
High-throughput recording of signals embedded within inaccessible micro-environments is a technological challenge. The ideal recording device would be a nanoscale machine capable of quantitatively transducing a wide range of variables into a molecular recording medium suitable for long-term storage and facile readout in the form of digital data. We have(More)
We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. This analysis suggests potential cost-effective strategies for dense connectivity mapping at the scale of whole mammalian brains.
We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing,(More)
To record from a given neuron, a recording technology must be able to separate the activity of that neuron from the activity of its neighbors. Here, we develop a Fisher information based framework to determine the conditions under which this is feasible for a given technology. This framework combines measurable point spread functions with measurable noise(More)
A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a "molecular ticker tape", in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying(More)
Current high-resolution imaging techniques require an intact sample that preserves spatial relationships. We here present a novel approach, "puzzle imaging," that allows imaging a spatially scrambled sample. This technique takes many spatially disordered samples, and then pieces them back together using local properties embedded within the sample. We show(More)
DNA polymerase (pol) processivity, i.e., the bases a polymerase extends before falling off the DNA, and activity are important for copying difficult DNA sequences, including simple repeats. Y-family pols would be appealing for copying difficult DNA and incorporating non-natural dNTPs, due to their low fidelity and loose active site, but are limited by poor(More)
Population growth and globally increasing standards of living have put a significant strain on the energy-food-water nexus. Limited water availability particularly affects agriculture, as it accounts for over 70% of global freshwater withdrawals (Aquastat). This study outlines the fundamental nature of plant water consumption and suggests a >50% reduction(More)
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