Contributors: Agip, Ahmed-Noor, Blaza, James N, Fedor, Justin, Hirst, Judy
... Single-particle electron cryomicroscopy (cryo-EM) has led to a revolution in structural work on mammalian respiratory complex I. Complex I (mitochondrial NADH:ubiquinone oxidoreductase), a membrane-bound redox-driven proton pump, is one of the largest and most complicated enzymes in the mammalian cell. Rapid progress, following the first 5-Å resolution data on bovine complex I in 2014, has led to a model for mouse complex I at 3.3-Å resolution that contains 96% of the 8,518 residues and to the identification of different particle classes, some of which are assigned to biochemically defined states. Factors that helped improve resolution, including improvements to biochemistry, cryo-EM grid preparation, data collection strategy, and image processing, are discussed. Together with recent structural data from an ancient relative, membrane-bound hydrogenase, cryo-EM on mammalian complex I has provided new insights into the proton-pumping machinery and a foundation for understanding the enzyme's catalytic mechanism.
Contributors: Smith, CP, Harmon, SA, Barrett, Tristan, Bittencourt, LK, Law, YM, Shebel, H, An, JY, Czarniecki, M, Mehralivand, S, Coskun, M
... Background: The Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) has been in use since 2015; while interreader reproducibility has been studied, there has been a paucity of studies investigating the intrareader reproducibility of PI-RADSv2. Purpose: To evaluate both intra- and interreader reproducibility of PI-RADSv2 in the assessment of intraprostatic lesions using multiparametric magnetic resonance imaging (mpMRI). Study Type: Retrospective. Population/Subjects: In all, 102 consecutive biopsy-naïve patients who underwent prostate MRI and subsequent MR/transrectal ultrasonography (MR/TRUS)-guided biopsy. Field Strength/Sequences: Prostate mpMRI at 3T using endorectal with phased array surface coils (TW MRI, DW MRI with ADC maps and b2000 DW MRI, DCE MRI). Assessment: Previously detected and biopsied lesions were scored by four readers from four different institutions using PI-RADSv2. Readers scored lesions during two readout rounds with a 4-week washout period. Statistical Tests: Kappa (κ) statistics and specific agreement (Po) were calculated to quantify intra- and interreader reproducibility of PI-RADSv2 scoring. Lesion measurement agreement was calculated using the intraclass correlation coefficient (ICC). Results: Overall intrareader reproducibility was moderate to substantial (κ = 0.43–0.67, Po = 0.60–0.77), while overall interreader reproducibility was poor to moderate (κ = 0.24, Po = 46). Readers with more experience showed greater interreader reproducibility than readers with intermediate experience in the whole prostate (P = 0.026) and peripheral zone (P = 0.002). Sequence-specific interreader agreement for all readers was similar to the overall PI-RADSv2 score, with κ = 0.24, 0.24, and 0.23 and Po = 0.47, 0.44, and 0.54 in T2-weighted, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE), respectively. Overall intrareader and interreader ICC for lesion measurement was 0.82 and 0.71, respectively. Data Conclusion: PI-RADSv2 provides moderate intrareader reproducibility, poor interreader reproducibility, and moderate interreader lesion measurement reproducibility. These findings suggest a need for more standardized reader training in prostate MRI. Level of Evidence: 2. Technical Efficacy: Stage 2.
Contributors: Yu, Hans, Juniper, Matthew, Magri, Luca
... Reduced-order models based on level-set methods are widely used tools to qualitatively capture and track the nonlinear dynamics of an interface. The aim of this paper is to develop a physics-informed, data-driven, statistically rigorous learning algorithm for state and parameter estimation with level-set methods. A Bayesian approach based on data assimilation is introduced. Data assimilation is enabled by the ensemble Kalman lter and smoother, which are used in their probabilistic formulations. The level-set data assimilation framework is veri ed in onedimensional and two-dimensional test cases, where state estimation, parameter estimation and uncertainty quanti cation are performed. The statistical performance of the proposed ensemble Kalman lter and smoother is quanti ed by twin experiments. In the twin experiments, the combined state and parameter estimation fully recovers the reference solution, which validates the proposed algorithm. The level-set data assimilation framework is then applied to the prediction of the nonlinear dynamics of a forced premixed ame, which exhibits the formation of sharp cusps and intricate topological changes, such as pinch-o events. The proposed physics-informed statistical learning algorithm opens up new possibilities for making reduced-order models of interfaces quantitatively predictive, any time that reference data is available.
Insights into the structure and dynamics of the upper mantle beneath Bass Strait, southeast Australia, using shear wave splitting
Contributors: Bello, M, Cornwell, DG, Rawlinson, Nicholas, Reading, AM
... © 2019 Elsevier B.V. We investigate the structure of the upper mantle using teleseismic shear wave splitting measurements obtained at 32 broadband seismic stations located in Bass Strait and the surrounding region of southeast Australia. Our dataset includes ∼366 individual splitting measurements from SKS and SKKS phases. The pattern of seismic anisotropy from shear wave splitting analysis beneath the study area is complex and does not always correlate with magnetic lineaments or current N-S absolute plate motion. In the eastern Lachlan Fold Belt, fast shear waves are polarized parallel to the structural trend (∼N25E). Further south, fast shear wave polarization directions trend on average N25–75E from the Western Tasmania Terrane through Bass Strait to southern Victoria, which is consistent with the presence of an exotic Precambrian microcontinent in this region as previously postulated. Stations located on and around the Neogene-Quaternary Newer Volcanics Province in southern Victoria display sizeable delay times (∼2.7 s). These values are among the largest in the world and hence require either an unusually large intrinsic anisotropy frozen within the lithosphere, or a contribution from both the lithospheric and asthenospheric mantle. In the Eastern Tasmania Terrane, nearly all observed fast directions are approximately NW-SE. Although part of our data set strongly favours anisotropy originating from “fabric” frozen in the lithospheric mantle, a contribution from the asthenospheric flow related to the present day plate motion is also required to explain the observed splitting parameters. We suggest that deviation of asthenospheric mantle flow around lithospheric roots could be occurring, and so variations in anisotropy related to mantle flow may be expected. Alternatively, the pattern of fast polarisation orientations observed around Bass Strait may be consistent with radial mantle flow associated with a plume linked to the recently discovered Cosgrove volcanic track. However, it is difficult to characterise the relative contributions to the observed splitting from the lithospheric vs. asthenospheric upper mantle due to poor backazimuthal coverage of the data.
Contributors: Hirst, Judy
... In the mitochondrial inner membrane the respiratory enzymes associate to form supramolecular assemblies known as supercomplexes. The existence of supercomplexes is now widely accepted-but what functional or structural advantages, if any, do they confer?
Contributors: Jaliel, Jialiele, Puddy, RK, Sánchez, R, Jordan, AN, Sothmann, B, Farrer, I, Griffiths, JP, Ritchie, David, Smith, Charles
... We demonstrate experimentally an autonomous nanoscale energy harvester that utilizes the physics of resonant tunneling quantum dots. Gate-defined quantum dots on GaAs/AlGaAs high-electron-mobility transistors are placed on either side of a hot-electron reservoir. The discrete energy levels of the quantum dots are tuned to be aligned with low energy electrons on one side and high energy electrons on the other side of the hot reservoir. The quantum dots thus act as energy filters and allow for the conversion of heat from the cavity into electrical power. Our energy harvester, measured at an estimated base temperature of 75 mK in a He3/He4 dilution refrigerator, can generate a thermal power of 0.13 fW for a temperature difference across each dot of about 67 mK.
Contributors: Rideaux, Reuben, Michael, Elizabeth, Welchman, Andrew E
... Throughout the brain, information from individual sources converges onto higher order neurons. For example, information from the two eyes first converges in binocular neurons in area V1. Some neurons appear tuned to similarities between sources of information, which makes intuitive sense in a system striving to match multiple sensory signals to a single external cause, i.e., establish causal inference. However, there are also neurons that are tuned to dissimilar information. In particular, some binocular neurons respond maximally to a dark feature in one eye and a light feature in the other. Despite compelling neurophysiological and behavioural evidence supporting the existence of these neurons (Cumming & Parker, 1997; Janssen, Vogels, Liu, & Orban, 2003; Katyal, Vergeer, He, He, & Engel, 2018; Kingdom, Jennings, & Georgeson, 2018; Tsao, Conway, & Livingstone, 2003), their function has remained opaque. To determine how neural mechanisms tuned to dissimilarities support perception, here we use electroencephalography to measure human observers’ steady-state visually evoked potentials (SSVEPs) in response to change in depth after prolonged viewing of anticorrelated and correlated random-dot stereograms (RDS). We find that adaptation to anticorrelated RDS results in larger SSVEPs, while adaptation to correlated RDS has no effect. These results are consistent with recent theoretical work suggesting ‘what not’ neurons play a suppressive role in supporting stereopsis (Goncalves & Welchman, 2017); that is, selective adaptation of neurons tuned to binocular mismatches reduces suppression resulting in increased neural excitability.
Contributors: Birrell, Paul, Wernisch, Lorenz, Tom, Brian, Held, Leonhard, Roberts, Gareth O, Pebody, Richard G, Angelis, Daniela De
... A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased, and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter non-identifiability.
Contributors: Hoitzing, Hanne, Gammage, Payam A, Haute, Lindsey Van, Minczuk, Michal, Johnston, Iain G, Jones, Nick S
Contributors: Popa, Daniel, Ali, Syed Zeeshan, Hopper, Richard, Dai, Ying, Udrea, Florin
... We present a novel single-chip thermopile sensor array for mid-infrared room temperature imaging. The array is fabricated on a single complementary metal-oxide-semiconductor (CMOS) dielectric membrane, composed of single-crystal silicon (Si) p+ and n+ elements, and standard CMOS tungsten metal layers for thermopile cold junction heatsinking, significantly reducing the chip size and simplifying its processing. We demonstrate a 16×16 pixel device with 34 V/W responsivity and enhanced optical absorption in the 8-14 μm waveband, with a suitable performance for gesture recognition and people-counting applications. Our simple, low-cost sensor is an attractive on-chip array for a variety of applications in the mid-infrared spectral region.