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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.

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.

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.

Frequent and widespread testing of members of the population who are asymptomatic for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the mitigation of the transmission of the virus. Despite the recent increases in testing capacity, tests based on quantitative polymerase chain reaction (qPCR) assays cannot be easily deployed at the scale required for population-wide screening. Here, we show that next-generation sequencing of pooled samples tagged with sample-specific molecular barcodes enables the testing of thousands of nasal or saliva samples for SARS-CoV-2 RNA in a single run without the need for RNA extraction. The assay, which we named SwabSeq, incorporates a synthetic RNA standard that facilitates end-point quantification and the calling of true negatives, and that reduces the requirements for automation, purification and sample-to-sample normalization. We used SwabSeq to perform 80,000 tests, with an analytical sensitivity and specificity comparable to or better than traditional qPCR tests, in less than two months with turnaround times of less than 24 h. SwabSeq could be rapidly adapted for the detection of other pathogens.

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.

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.

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.

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.

Purpose: To investigate the relationship between nocturnal blood pressure (BP) dip and parapapillary choroidal vessel density (pCVD) in patients with normal-tension glaucoma (NTG) Methods: This study analyzed 267 eyes of 267 untreated NTG patients who underwent 24-hour (h) intraocular pressure (IOP) and ambulatory BP monitoring in the habitual position. Patients were classified into 3 groups [non-dippers (nocturnal BP dip < 10%), dippers (nocturnal BP dip between 10% and 20%, and over-dippers (nocturnal BP dip > 20%)], and pCVDs were measured by using optical coherence tomography angiography (OCTA) images. Logistic regression analyses were performed to identify clinical factors associated with "over-dipper" cases. Linear regression analyses were conducted to determine the correlation between various clinical variables and pCVD. Results: In clinical characteristics, over-dippers exhibited lower pCVD values compared to non-dippers or dippers (P = 0.004). High diurnal intraocular pressure (IOP) fluctuation (P = 0.031), high diurnal mean arterial pressure (MAP) fluctuation (P = 0.001), and low pCVD (P = 0.002) were identified as predictors of being "over-dipper" in multivariable logistic regression analyses. Moreover, peripapillary retinal vessel density (P = 0.040), presence of choroidal microvasculature dropout (P = 0.039), and nocturnal MAP dip % (P = 0.002) showed significant correlations with pCVD according to multivariable linear regression analyses. Conclusion: Over-dippers presented with lower pCVD than non-dippers or dippers as measured by OCTA choroidal images. Low pCVD was a predictor of "over-dipper" cases and associated with a greater percentage of nocturnal MAP dip in NTG patients. 24-h ambulatory BP monitoring may provide further information for detecting low pCVD in NTG patients with nocturnal BP dip. [ABSTRACT FROM AUTHOR]

The concept of a lithiophilic electrode proves inadequate in describing carbon‐based electrode materials due to their substantial mismatch in surface energy with lithium metal. However, their notable capacity for lithium chemisorption can increase active lithium concentration required for nucleation and growth, thereby enhancing the electrochemical performance of lithium metal anodes (LMAs). In this study, we elucidate the effects of the supersaturated electrode which has high active lithium capacity around equilibrium lithium potential on LMAs through an in‐depth electrochemical comparison using two distinct carbon electrode platforms with differing carbon structures but similar two‐dimensional morphologies. In the supersaturated electrode, both the dynamics and thermodynamic states involved in lithium nucleation and growth mechanisms are significantly improved, particularly under continuous current supply conditions. Furthermore, the chemical structures of the solid‐electrolyte‐interface layers (SEIs) are greatly influenced by the elevated surface lithium concentration environment, resulting in the formation of more conductive lithium‐rich SEI layers. The improved dynamics and thermodynamics of surface lithium, coupled with the formation of enhanced SEI layers, contribute to higher power capabilities, enhanced Coulombic efficiencies, and improved cycling performances of LMAs. These results provide new insight into understanding the enhancements in heterogeneous lithium nucleation and growth kinetics on the supersaturated electrode. [ABSTRACT FROM AUTHOR]

This study presents a sustainable approach to extracting hydrogen fluoride (HF) from wastewater using hollow fiber membrane contactors. HF, a widely used yet hazardous chemical, requires efficient separation techniques due to its environmental and health concerns. Our research compared two operational modes, vacuum mode and liquid–liquid extraction mode, revealing the latter as more efficient for HF separation. Notably, this study introduces a novel aspect by employing a data‐driven decision‐making method, Bayesian optimization (BO) for process optimization of the liquid–liquid extraction mode, aiming to maximize HF removal efficiency at low experimental costs. Subsequent validation through a 96‐h experimental run confirms the suitability of the optimized conditions for industrial applications. This study not only demonstrates an efficient HF separation process using hollow fiber membrane contactors but also establishes a new standard for complex industrial process optimization. [ABSTRACT FROM AUTHOR]

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.

Hepatitis B virus (HBV), particularly through the HBx protein, induces oxidative stress during liver infections. This study reveals that HBx increases reactive oxygen species (ROS) via two distinct mechanisms. The first mechanism is p53-independent, likely involving mitochondrial dysfunction, as demonstrated by elevated ROS levels in p53-deficient Hep3B cells and p53-knocked-down HepG2 cells after HBx expression or HBV infection. The increase in ROS persisted even when p53 transcriptional activity was inhibited by pifithrin-α (PFT-α), a p53 inhibitor. The second mechanism is p53-dependent, wherein HBx activates p53, which then amplifies ROS production through a feedback loop involving ROS and p53. The ability of HBx to elevate ROS levels was higher in HepG2 than in Hep3B cells. Knocking down p53 in HepG2 cells lowered ROS levels, while ectopic p53 expression in Hep3B cells raised ROS. HBx-activated p53 downregulated catalase and upregulated manganese-dependent superoxide dismutase, contributing to ROS amplification. The transcriptional activity of p53 was crucial for these effects, as cells with a p53 R175H mutation or those treated with PFT-α generated less ROS. Additionally, HBx variants with Ser-101 increased p53 and ROS levels, whereas variants with Pro-101 did not. These dual mechanisms of HBx-induced ROS generation are likely significant in the pathogenesis of HBV and may contribute to liver diseases, including hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Informal cross-border trade (ICBT) refers to the illegal activities of cross-border commerce conducted by unregistered small-scale traders. We seek to develop insights to understand the ICBT value chain and offer policy recommendations to successfully integrate it into the formal economy. Using a game-theoretic model, we analyze the operations and key market dynamics of ICBT. We analyze the policy implications of three representative UN directives: enhancing marginalized traders' access to formal channels, reducing export tax rates for formal traders, and introducing an alternative simplified trade regime (STR) for informal traders. All three policies result in an increase in government proceeds when the inherent profitability of the formal or STR channels is sufficiently high. Furthermore, social welfare increases when the policies effectively balance wholesale price competition within the formal and informal channels. We apply our model to a case study based on Uganda's agricultural exports over an 11-year horizon. The access enhancement policy is most effective in increasing government proceeds but least effective in improving the welfare of other participants. The tax reduction policy enhances traders' profitability but sacrifices the welfare of farmers and government proceeds substantially. Finally, the STR acknowledgement policy results in the largest increase in profitability of marginalized traders and farmers but comes at the cost of government proceeds. This paper was accepted by Jay Swaminathan, operations management. Funding: This work was supported by the Institute of Management Research, College of Business Administration, Seoul National University. Supplemental Material: The data and online appendix are available at https://doi.org/10.1287/mnsc.2022.02479. [ABSTRACT FROM AUTHOR]

Abundant and economical sodium (Na) metal batteries promise superior energy densities compared to lithium‐ion batteries; however, they face commercialization challenges owing to problematic interfacial reactions leading to dendrite formation during cycling. This paper reports the ultra‐long and rapid operation of Na metal batteries enabled by the introduction of a vinylpyrrolidone (VP)‐based multifunctional interface stabilizer in the electrolyte. The VP electrolyte additive provides benefits such as surface flattening, durable solid electrolyte interphase layer formation, preservation of fresh Na, and acceleration of horizontal crystal growth along the (110) plane. Symmetric Na–Na cells with the stabilizer exhibit notably stable operation for over 5 000 cycles at a high current density of 5 mA cm−2, surpassing previous research. Performance improvement is also demonstrated in a full‐cell configuration with an Na3V2(PO4)2O2F cathode. This approach offers a promising solution for achieving performance levels comparable to lithium‐ion batteries in Na metal battery technology. [ABSTRACT FROM AUTHOR]