Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

Biology and ecology of the world’s largest invertebrate, the colossal squid (Mesonychoteuthis hamiltoni): a short review

The colossal squid Mesonychoteuthis hamiltoni (Robson 1925) is the largest (heaviest) living invertebrate and although it is preyed upon by many top predators, its basic biology and ecology remain one of the ocean’s great mysteries. The present study aims to review the current biological knowledge on this squid. It is considered to be endemic in the Southern Ocean (SO) with a circumpolar distribution spreading from the Antarctic continent up to the Sub-Antarctic Front. Small juveniles (<40 mm mantle length) are mainly found from the surface to 500 m, and the late juvenile stages are assumed to undergo ontogenetic descent to depths reaching 2000 m. Thus, this giant spends most of its life in the meso- and bathypelagic realms, where it can reach a total length of 6 m. The maximum weight recorded so far was 495 kg. M. hamiltoni is presently reported from the diets of 17 different predator species, comprising penguins and other seabirds, fishes and marine mammals, and may feed on various prey types, including myctophids, Patagonian toothfish, sleeper sharks and other squid. Stable isotopic analysis places the colossal squid as one of the top predators in the SO. It is assumed that this squid is not capable of high-speed predator–prey interactions, but it is rather an ambush predator. Its eyes, the largest on the planet, seem to have evolved to detect very large predators (e.g., sperm whales) rather than to detect prey at long distances. The study of this unique invertebrate giant constitutes a valuable source of insight into the biophysical principles behind body-size evolution

Separation of track- and shower-like energy deposits in ProtoDUNE-SP using a convolutional neural network

Liquid argon time projection chamber detector technology provides high spatial and calorimetric resolutions on the charged particles traversing liquid argon. As a result, the technology has been used in a number of recent neutrino experiments, and is the technology of choice for the Deep Underground Neutrino Experiment (DUNE). In order to perform high precision measurements of neutrinos in the detector, final state particles need to be effectively identified, and their energy accurately reconstructed. This article proposes an algorithm based on a convolutional neural network to perform the classification of energy deposits and reconstructed particles as track-like or arising from electromagnetic cascades. Results from testing the algorithm on data from ProtoDUNE-SP, a prototype of the DUNE far detector, are presented. The network identifies track- and shower-like particles, as well as Michel electrons, with high efficiency. The performance of the algorithm is consistent between data and simulation

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, U.S.A. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of 7 × 6 × 7.2 m3. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

Erratum to: Comparison of the Z/γ* + jets to γ + jets cross sections in pp collisions at √s = 8

Erratum to: JHEP10(2015)128. ArXiv ePrint: 1505.06520. The online version of the original article can be found at http://dx.doi.org/10.1007/JHEP10(2015)128

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3σ (5σ) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3σ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Alcohol badly affects eye movements linked to steering, providing for automatic in-car detection of drink driving

Driving is a classic example of visually guided behavior in which the eyes move before some other action. When approaching a bend in the road, a driver looks across to the inside of the curve before turning the steering wheel. Eye and steering movements are tightly linked, with the eyes leading, which allows the parts of the brain that move the eyes to assist the parts of the brain that control the hands on the wheel. We show here that this optimal relationship deteriorates with levels of breath alcohol well within the current UK legal limit for driving. The eyes move later, and coordination reduces. These changes lead to bad performance and can be detected by an automated in-car system, which warns the driver is no longer fit to drive

Aerogel Processing

International audienceOne of the problems largely commented in the sol-gel science is how to make large bodies, because gels tend to crack during drying. The drying stresses are attributed to capillary phenomena and differential strain which result from a pressure gradient in the pore liquid. By the supercritical drying (SCD), the capillary stresses are eliminated and monolithic aerogel can be obtained. This chapter focuses on silica aerogel, the most studied aerogel. It presents an overview of the supercritical drying techniques, but also some of the remarkable aerogel properties (optical, mechanical, thermal and acoustical, etc.) with respect to its peculiar microstructure. The chapter briefly presents other kinds of aerogels (oxides and chalcogenideaerogels, composite aerogels, organic aerogels, etc.) and a panel of potential applications