DNA is an ultra-high-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. To overcome the second barrier, here we encapsulate data-encoding DNA file sequences within impervious silica capsules that are surface-labeled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling efficient and direct selection of sets of files with Boolean logic. We demonstrate random access of image files from an image database using fluorescence sorting with selection sensitivity of 1 in 10 6 files, which thereby enables 1 in 10 6N per N optical channels. Our strategy thereby offers retrieval of random file subsets from exabyte and larger-scale long-term DNA file storage databases, offering a scalable solution for random-access of archival files in massive molecular datasets.

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits.

As an engineering material, DNA is well suited for the construction of biochemical circuits and systems, because it is simple enough that its interactions can be rationally designed using Watson–Crick base pairing rules, yet the design space is remarkably rich. When designing DNA systems, this simplicity permits using functional sections of each strand, called domains, without considering particular nucleotide sequences. However, the actual sequences used may have interactions not predicted at the domain-level abstraction, and new rigorous analysis techniques are needed to determine the extent to which the chosen sequences conform to the system’s domain-level description. We have developed a computational method for verifying sequence-level systems by identifying discrepancies between the domain-level and sequence-level behaviour. This method takes a DNA system, as specified using the domain-level tool Peppercorn, and analyses data from the stochastic sequence-level simulator Multistrand and sequence-level thermodynamic analysis tool NUPACK to estimate important aspects of the system, such as reaction rate constants and secondary structure formation. These techniques, implemented as the Python package KinDA, will allow researchers to predict the kinetic and thermodynamic behaviour of domain-level systems after sequence assignment, as well as to detect violations of the intended behaviour.

It has been observed that the performing for high stakes can, paradoxically, lead to uncharacteristically poor performance. Here we investigate a novel approach to attenuating such ‘choking under pressure’ by instructing participants performing a demanding motor task that rewards successful performance with a monetary gain, to reappraise this incentive as a monetary loss for unsuccessful performance. We show that when participants applied this simple strategy, choking was significantly reduced. This strategy also influenced participants’ neural and physiological activity. When participants reappraised the incentive as a potential monetary loss, the representation of the magnitude of the incentive in the ventral striatum Blood Oxygenation Level Dependent (BOLD) signal was attenuated. In addition, individual differences in the degree of attenuation of the neural response to incentive predicted the effectiveness of the reappraisal strategy in reducing choking. Furthermore, participants’ skin conductance changed in proportion to the magnitude of the incentive being played for, and was exaggerated on high incentive trials on which participants failed. Reappraisal of the incentive abolished this exaggerated skin conductance response. This represents the first experimental association of sympathetic arousal with choking. Taken together, these results suggest that reappraisal of the incentive is indeed a promising intervention for attenuating choking under pressure.

DNA is an ultra-high-density storage medium that could meet exponentially growing 1 worldwide data storage demand. However, accessing arbitrary data subsets within exabyte-2 scale DNA data pools is limited by the finite addressing space for individual DNA-based 3 blocks of data. Here, we form files by encapsulating data-encoding DNA within silica 4 capsules that are surface-labeled with multiple unique barcodes. Barcoding is performed 5 with single-stranded DNA representing file metadata that enables Boolean logic selection on 6 the entire pool of data. We demonstrate encapsulation and Boolean selection of sub-pools of 7 image files using fluorescence-activated sorting, with selection sensitivity of 1 in 10 6 files per 8 channel. Our strategy in principle enables retrieval of targeted data subsets from exabyte-9 and larger-scale data pools, thereby offering a random access file system for massive 10 molecular data sets. 11 12 DNA is the polymer used for storage and transmission of genetic information in biology. In 13 principle, DNA can also be used as a medium for the storage of arbitrary digital information at 14 densities far exceeding existing commercial data storage technologies and at scales well beyond 15 the capacity of current data centers 1 . Ongoing advances in nucleic acid synthesis and sequencing 16 technologies also continue to reduce dramatically the cost of writing and reading DNA, thereby 17rendering DNA-based digital information storage potentially viable economically in the near 18 future 2-5 . As demonstrations of its viability as a general information storage medium, to date 19 books, images, computer programs, audio clips, works of art, and Shakespeare's sonnets have all 20 been stored in DNA using a variety of encoding schemes 6-12 . In each case, digital information was 21 converted to DNA sequences and typically fragmented into 100-200 nucleotide (nt) blocks of data 22