Prior research has shown that executive function (EF) ability predicts science achievement. Here, we ask whether EF alsopredicts science learning. We focus on the shifting EF, and predict that students with high (vs. low) shifting ability will beable to better learn new science concepts from interleaved (vs. blocked) instruction than students with low shifting ability.We are evaluating this hypothesis in a study where eighth graders learn about different attributes (origin, texture, compo-sition) of different rock types (igneous, sedimentary, metamorphic) in instruction that is either blocked by or interleavedacross rock types. We are measuring shifting using the WCST and local-global tasks. We are collecting post-test and long-term retention measures of learning and transfer. We predict better performance for high (vs. low) shifting individuals andfor interleaved (vs. blocked) instruction, and an overadditive interaction because shifting ability is critical for noticing thediscriminations that interleaved instruction highlights.

Tversky and Kahneman (1973) found that, under time pressure, people massively underestimated the expansion of 8! (correct value 40,320), and this bias was mitigated for participants presented the descending (8x7x6x5x4x3x2x1; Median=2,250) vs. ascending order (1x2x3x4x5x6x7x8; Median=512). In a first-ever replication (N=140), we also found predominant underestimation, but no significant between-subjects descending vs. ascending order effect. However, when participants then estimated the opposite order, we reproduced this order effect within-subjects. Finally, participants received calibration information (the correct value of 6! or 10!) and again estimated both orders of 8!. Participants who received 10! made more accurate estimates for 8! (Median=38,000), which did not differ statistically from the correct value. Participants who received 6! still grossly underestimated (Median=2,678.5), despite 8! being closer to 6! than 10! in linear and log units. Thus, we surprisingly found the classic factorial estimation bias only within-subjects, and provide evidence for how calibration can reduce it.

The traveling salesperson problem (TSP) is an NP-Hard problem that computers find difficult to solve. Humans are surprisingly good at solving the TSP, with solutions within 10% of optimal for problems with up to 100 points, constructed in time linear with the number of points. We propose that humans solve the TSP by initially clustering the points and then connecting them first within and then between clusters. In this study, 67 participants first clustered 40 stimuli and then solved them as TSPs. Strikingly, participants' TSP solutions perfectly followed their clusters for 52% of the stimuli. Further, participants' TSP solutions' were more congruent with their clusters for stimuli with statistically higher levels of clustered structure. This provides strong evidence for the clustering proposal. Random TSP solutions, however, showed no such congruence to cluster structure. These findings suggest that clustering might be a fundamental ability for reasoning about graph-theoretic algorithmic problems.

Transcription of herpesviral late genes is stimulated after the onset of viral DNA replication but otherwise restricted. Late gene expression in gammaherpesviruses requires the coordination of six early viral proteins, termed viral transactivation factors (vTFs). Here, we mapped the organization of this protein complex for Kaposi's sarcoma-associated herpesvirus. Disruption of this complex via point mutation of the interaction interface between the open reading frame 24 (ORF24) and ORF34 vTFs ablated both late gene expression and viral replication.

Human solutions to the Traveling Salesperson Problem (TSP) are surprisingly close to optimal and unexpectedly efficient. We posit that humans solve instances of the TSP by first clustering the points into smaller regions and then solving each cluster as a simpler TSP. Prior research has shown that participants cluster visual stimuli reliably. That is, their clustering and re-clustering of the same stimulus are similar, especially when the stimulus is relatively more clustered. In this study, participants solved the same TSP instances twice. On the second presentation, half of the instances were flipped about the horizontal and vertical axes. Participants solved the TSP reliably, with their two tours of the same instance sharing 77 percent of the same edges on average. In addition, within-participant reliability was higher for more clustered versus more dispersed instances. Our findings are consistent with the proposal that people use clustering strategies to solve the TSP.

Humans efficiently find near-optimal (i.e., near-minimum-length) tours when solving small instances of the TravelingSalesperson Problem (TSP), a problem hard for computers. We hypothesize that this is possible because they use thefollowing strategy: cluster the points, solve the smaller TSPs for each cluster, and then solve the TSP defined by theclusters. This study focused on the antecedent process of human clustering. 42 participants clustered 56 sets of 15 to 40points on two occasions. We found that human clustering is generally reliable (M Fowlkes-Mallows Index = 0.75) forall problem sizes. Reliability was higher for problems that showed statistical evidence of cluster structure versus no suchstructure, and was not affected when the problem was flipped for the second presentation. Thus, humans are sensitive tocluster structure, and clustering is a stable foundation for solving TSP instances. This sets the stage for future research onclustering-based TSP strategies.

The strategy of synergistic application of biological and chemical catalysis is an important approach for efficiently converting renewable biomass into chemicals and fuels. In particular, the method of determining the appropriate intermediate between the two catalytic methods is critical. In this work, we demonstrate p-cymene production through the integration of biosynthesis and heterogenous catalysis and show how a preferred biologically derived precursor could be determined. On the biological side, we performed the limonene and 1,8-cineole production through the mevalonate pathway. Titers of 0.605 g/L and a 1.052 g/L were achieved, respectively. This difference is in agreement with the toxicity of these compounds toward the producing microorganisms, which has implications for subsequent development of the microbial platform. On the heterogeneous catalysis side, we performed the reaction with both biological precursors to allow for direct comparison. Using hydrogenation/dehydrogenation metals on supports with acid sites, both limonene and 1,8-cineole were converted to p-cymene with similar yields under equivalent reaction conditions. Thus, we could determine that the most promising strategy would be to target 1,8-cineole, the higher titer and lower toxicity bio-derived precursor with subsequent catalytic conversion to p-cymene. We further optimized the biological production of 1,8-cineole via fed-batch fermentation and reached the titer of 4.37 g/L which is the highest known 1,8-cineole titer from microbial production. This work provides a valuable paradigm for early stage considerations to determine the best route for the high-efficiency production of a target biobased molecule using an integration of biology and chemistry.

Mapping host-pathogen interactions has proven instrumental for understanding how viruses manipulate host machinery and how numerous cellular processes are regulated. DNA viruses such as herpesviruses have relatively large coding capacity and thus can target an extensive network of cellular proteins. To identify the host proteins hijacked by this pathogen, we systematically affinity tagged and purified all 89 proteins of Kaposi's sarcoma-associated herpesvirus (KSHV) from human cells. Mass spectrometry of this material identified over 500 virus-host interactions. KSHV causes AIDS-associated cancers, and its interaction network is enriched for proteins linked to cancer and overlaps with proteins that are also targeted by HIV-1. We found that the conserved KSHV protein ORF24 binds to RNA polymerase II and brings it to viral late promoters by mimicking and replacing cellular TATA-box-binding protein (TBP). This is required for herpesviral late gene expression, a complex and poorly understood phase of the viral lifecycle.

Reference-free genome phasing is vital for understanding allele inheritance and the impact of single-molecule DNA variation on phenotypes. To achieve thorough phasing across homozygous or repetitive regions of the genome, long-read sequencing technologies are often used to perform phased de novo assembly. As a step toward reducing the cost and complexity of this type of analysis, we describe new methods for accurately phasing Oxford Nanopore Technologies (ONT) sequence data with the Shasta genome assembler and a modular tool for extending phasing to the chromosome scale called GFAse. We test using new variants of ONT PromethION sequencing, including those using proximity ligation, and show that newer, higher accuracy ONT reads substantially improve assembly quality.

ABSTRACT

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to the high rates of transmission by individuals who are asymptomatic at the time of transmission 1, 2 . Frequent, widespread testing of the asymptomatic population for SARS-CoV-2 is essential to suppress viral transmission. Despite increases in testing capacity, multiple challenges remain in deploying traditional reverse transcription and quantitative PCR (RT-qPCR) tests at the scale required for population screening of asymptomatic individuals. We have developed SwabSeq, a high-throughput testing platform for SARS-CoV-2 that uses next-generation sequencing as a readout. SwabSeq employs sample-specific molecular barcodes to enable thousands of samples to be combined and simultaneously analyzed for the presence or absence of SARS-CoV-2 in a single run. Importantly, SwabSeq incorporates an in vitro RNA standard that mimics the viral amplicon, but can be distinguished by sequencing. This standard allows for end-point rather than quantitative PCR, improves quantitation, reduces requirements for automation and sample-to-sample normalization, enables purification-free detection, and gives better ability to call true negatives. After setting up SwabSeq in a high-complexity CLIA laboratory, we performed more than 80,000 tests for COVID-19 in less than two months, confirming in a real world setting that SwabSeq inexpensively delivers highly sensitive and specific results at scale, with a turn-around of less than 24 hours. Our clinical laboratory uses SwabSeq to test both nasal and saliva samples without RNA extraction, while maintaining analytical sensitivity comparable to or better than traditional RT-qPCR tests. Moving forward, SwabSeq can rapidly scale up testing to mitigate devastating spread of novel pathogens.