Reasoning about Uncertain Information and Conflict Resolution through Trust Revision

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Single-molecule force spectroscopy quantification of adhesive forces in cucurbit[8]uril host-guest ternary complexes.

Cucurbit[8]uril (CB[8]) heteroternary complexes display certain characteristics making them well-suited for molecular level adhesives. In particular, the ability to control adhesion through careful choice of host-guest binding pairs enables specific, fully reversible adhesion. Understanding the effect of the environment on the adhesive system is also critical when developing new molecular level adhesives. Here we explore the binding forces involved in the methyl viologen · CB[8] · napthol heteroternary complex using single-molecule force spectroscopy (SMFS) under a variety of conditions. From SMFS, the interaction of a single ternary complex was found to be in the region of 140 pN. Additionally, a number of surface interactions could be readily differentiated using the SMFS technique allowing for a deeper understanding of the dynamic heteroternary CB[8] system on the single-molecule scale.This work was supported in part by the Engineering and Physical Sciences Research Council (EPSRC), the Walters-Kundert Charitable Trust and an ERC Starting Investigator grant (ASPiRe, 240629). ZWK, ERJ, YL thank the Royal Society of Chemistry for a grant allowing travel to Tsinghua University to carry out this research. YY would like to acknowledge financial support from the Young Scientists of the National Science Foundation of China (21304052). YL thanks the Chinese Overseas Scholarship Trust for financial support. JdB thanks the Marie Curie Actions program for financial support. PEW thanks the Atomic Weapons and Energy Commission and the Melville Laboratory for Polymer Synthesis for financial support

Transfer of noncoding DNA drives regulatory rewiring in bacteria

Understanding the mechanisms that generate variation is a common pursuit unifying the life sciences. Bacteria represent an especially striking puzzle, because closely related strains possess radically different metabolic and ecological capabilities. Differences in protein repertoire arising from gene transfer are currently considered the primary mechanism underlying phenotypic plasticity in bacteria. Although bacterial coding plasticity has been extensively studied in previous decades, little is known about the role that regulatory plasticity plays in bacterial evolution. Here, we show that bacterial genes can rapidly shift between multiple regulatory modes by acquiring functionally divergent nonhomologous promoter regions. Through analysis of 270,000 regulatory regions across 247 genomes, we demonstrate that regulatory “switching” to nonhomologous alternatives is ubiquitous, occurring across the bacterial domain. Using comparative transcriptomics, we show that at least 16% of the expression divergence between Escherichia coli strains can be explained by this regulatory switching. Further, using an oligonucleotide regulatory library, we establish that switching affects bacterial promoter architecture. We provide evidence that regulatory switching can occur through horizontal regulatory transfer, which allows regulatory regions to move across strains, and even genera, independently from the genes they regulate. Finally, by experimentally characterizing the fitness effect of a regulatory transfer on a pathogenic E. coli strain, we demonstrate that regulatory switching elicits important phenotypic consequences. Taken together, our findings expose previously unappreciated regulatory plasticity in bacteria and provide a gateway for understanding bacterial phenotypic variation and adaptation.National Science Foundation (U.S.) (Grant DEB-0936234

2003 Manifesto on the California Electricity Crisis

The authors, an ad-hocgroup of professionals with experience in regulatory and energy economics, share a common concern with the continuing turmoil facing the electricity industry ("the industry") in California. Most ofthe authorsendorsed the first California Electricity Manifesto issued on January 25, 2001. Almost two years have passed since that first Manifesto. While wholesale electric prices have moderated and California no longer faces the risk of blackouts, in many ways the industry is in worse shape now than it was at the start of 2001. As a result, the group of signatories continues to have a deep concern with the conflicting policy directions being pursued for the industry at both the State and Federal levels of government and the impact the uncertainties associated with these conflicting policies will have, long term, on the economy of California. Theauthorshave once again convened under the auspices of the Institute of Management, Innovation and Organization at the University of California, Berkeley, to put forward ourtheir ideas on a basic set of necessary policies to move the industry forward for the benefit of all Californians and the nation. The authors point out that theydo not pretend to be "representative." They do bring, however, a very diverse range of backgrounds and expertise.Technology and Industry, Regulatory Reform

Graphene transistors are insensitive to pH changes in solution

We observe very small gate-voltage shifts in the transfer characteristic of as-prepared graphene field-effect transistors (GFETs) when the pH of the buffer is changed. This observation is in strong contrast to Si-based ion-sensitive FETs. The low gate-shift of a GFET can be further reduced if the graphene surface is covered with a hydrophobic fluorobenzene layer. If a thin Al-oxide layer is applied instead, the opposite happens. This suggests that clean graphene does not sense the chemical potential of protons. A GFET can therefore be used as a reference electrode in an aqueous electrolyte. Our finding sheds light on the large variety of pH-induced gate shifts that have been published for GFETs in the recent literature

Performance Testing of a Large-Format Reflection Grating Prototype for a Suborbital Rocket Payload

The soft X-ray grating spectrometer on board the Off-plane Grating Rocket Experiment (OGRE) hopes to achieve the highest resolution soft X-ray spectrum of an astrophysical object when it is launched via suborbital rocket. Paramount to the success of the spectrometer are the performance of the $>250$ reflection gratings populating its reflection grating assembly. To test current grating fabrication capabilities, a grating prototype for the payload was fabricated via electron-beam lithography at The Pennsylvania State University's Materials Research Institute and was subsequently tested for performance at Max Planck Institute for Extraterrestrial Physics' PANTER X-ray Test Facility. Bayesian modeling of the resulting data via Markov chain Monte Carlo (MCMC) sampling indicated that the grating achieved the OGRE single-grating resolution requirement of $R_{g}(\lambda/\Delta\lambda)>4500$ at the 94% confidence level. The resulting $R_g$ posterior probability distribution suggests that this confidence level is likely a conservative estimate though, since only a finite $R_g$ parameter space was sampled and the model could not constrain the upper bound of $R_g$ to less than infinity. Raytrace simulations of the system found that the observed data can be reproduced with a grating performing at $R_g=\infty$. It is therefore postulated that the behavior of the obtained $R_g$ posterior probability distribution can be explained by a finite measurement limit of the system and not a finite limit on $R_g$. Implications of these results and improvements to the test setup are discussed.Comment: 25 pages, 16 figures, preprint of an article accepted for publication in the Journal of Astronomical Instrumentation \copyright 2020 [copyright World Scientific Publishing Company] [https://www.worldscientific.com/worldscinet/jai

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes