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The Orinoco Low-Level Jet: An Investigation of Its Mechanisms of Formation Using the WRF Model 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (13)
作者:  Jimenez-Sanchez, Giovanni;  Markowski, Paul M.;  Young, George S.;  Stensrud, David J.
收藏  |  浏览/下载:11/0  |  提交时间:2020/08/18
Orinoco low-level jet  forcing mechanisms  dynamical downscaling  momentum balance analysis  LLJs near the equator may originate from processes other than the inertial oscillation  LLJs near the equator may originate from processes other than topographic thermal forcing  
Southern Ocean carbon sink enhanced by sea-ice feedbacks at the Antarctic Cold Reversal 期刊论文
NATURE GEOSCIENCE, 2020, 13 (7) : 489-+
作者:  Fogwill, C. J.;  Turney, C. S. M.;  Menviel, L.;  Baker, A.;  Weber, M. E.;  Ellis, B.;  Thomas, Z. A.;  Golledge, N. R.;  Etheridge, D.;  Rubino, M.;  Thornton, D. P.;  van Ommen, T. D.;  Moy, A. D.;  Curran, M. A. J.;  Davies, S.;  Bird, M., I;  Munksgaard, N. C.;  Rootes, C. M.;  Millman, H.;  Vohra, J.;  Rivera, A.;  Mackintosh, A.;  Pike, J.;  Hall, I. R.;  Bagshaw, E. A.;  Rainsley, E.;  Bronk-Ramsey, C.;  Montenari, M.;  Cage, A. G.;  Harris, M. R. P.;  Jones, R.;  Power, A.;  Love, J.;  Young, J.;  Weyrich, L. S.;  Cooper, A.
收藏  |  浏览/下载:14/0  |  提交时间:2020/06/29
A Long-Lived Sharp Disruption on the Lower Clouds of Venus 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (11)
作者:  Peralta, J.;  Navarro, T.;  Vun, C. W.;  Sanchez-Lavega, A.;  McGouldrick, K.;  Horinouchi, T.;  Imamura, T.;  Hueso, R.;  Boyd, J. P.;  Schubert, G.;  Kouyama, T.;  Satoh, T.;  Iwagami, N.;  Young, E. F.;  Bullock, M. A.;  Machado, P.;  Lee, Y. J.;  Limaye, S. S.;  Nakamura, M.;  Tellmann, S.;  Wesley, A.;  Miles, P.
收藏  |  浏览/下载:17/0  |  提交时间:2020/08/18
International evaluation of an AI system for breast cancer screening 期刊论文
NATURE, 2020, 577 (7788) : 89-+
作者:  McKinney, Scott Mayer;  Sieniek, Marcin;  Godbole, Varun;  Godwin, Jonathan;  Antropova, Natasha;  Ashrafian, Hutan;  Back, Trevor;  Chesus, Mary;  Corrado, Greg C.;  Darzi, Ara;  Etemadi, Mozziyar;  Garcia-Vicente, Florencia;  Gilbert, Fiona J.;  Halling-Brown, Mark;  Hassabis, Demis;  Jansen, Sunny;  Karthikesalingam, Alan;  Kelly, Christopher J.;  King, Dominic;  Ledsam, Joseph R.;  Melnick, David;  Mostofi, Hormuz;  Peng, Lily;  Reicher, Joshua Jay;  Romera-Paredes, Bernardino;  Sidebottom, Richard;  Suleyman, Mustafa;  Tse, Daniel;  Young, Kenneth C.;  De Fauw, Jeffrey;  Shetty, Shravya
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful(1). Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives(2). Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7% and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.


  
A Conceptual Model for Anticipating the Impact of Landscape Evolution on Groundwater Recharge in Degrading Permafrost Environments 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (11)
作者:  Young, N. L.;  Lemieux, J. -M.;  Delottier, H.;  Fortier, R.;  Fortier, P.
收藏  |  浏览/下载:7/0  |  提交时间:2020/05/13
hydrogeology  chronosequence  land cover  permafrost  recharge  water table fluctuation  
Topographic Influence on the African Easterly Jet and African Easterly Wave Energetics 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (8)
作者:  Hamilton, H. L.;  Nunez Ocasio, K. M.;  Evans, J. L.;  Young, G. S.;  Fuentes, J. D.
收藏  |  浏览/下载:8/0  |  提交时间:2020/07/02
African Easterly Waves  African Easterly Jet  topographic influences  West African monsoon  idealized numerical modeling  
A Large Ensemble Approach to Quantifying Internal Model Variability Within the WRF Numerical Model 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2020, 125 (7)
作者:  Bassett, R.;  Young, P. J.;  Blair, G. S.;  Samreen, F.;  Simm, W.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/02
ensemble  initial conditions  internal model variability (IMV)  regional climate model (RCM)  uncertainty  Weather Research and Forecasting (WRF)  
A new coronavirus associated with human respiratory disease in China (vol 579, pg 265, 2020) 期刊论文
NATURE, 2020, 580 (7803) : E7-E7
作者:  Jiao, Huipeng;  Wachsmuth, Laurens;  Kumari, Snehlata;  Schwarzer, Robin;  Lin, Juan;  Eren, Remzi Onur;  Fisher, Amanda;  Lane, Rebecca;  Young, George R.;  Kassiotis, George;  Kaiser, William J.;  Pasparakis, Manolis
收藏  |  浏览/下载:29/0  |  提交时间:2020/07/03
APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline 期刊论文
NATURE, 2020, 581 (7806) : 70-+
作者:  Doherty, Tiarnan A. S.;  Winchester, Andrew J.;  Macpherson, Stuart;  Johnstone, Duncan N.;  Pareek, Vivek;  Tennyson, Elizabeth M.;  Kosar, Sofiia;  Kosasih, Felix U.;  Anaya, Miguel;  Abdi-Jalebi, Mojtaba;  Andaji-Garmaroudi, Zahra;  Wong, E. Laine;  Madeo, Julien;  Chiang, Yu-Hsien;  Park, Ji-Sang;  Jung, Young-Kwang;  Petoukhoff, Christopher E.;  Divitini, Giorgio;  Man, Michael K. L.;  Ducati, Caterina;  Walsh, Aron;  Midgley, Paul A.;  Dani, Keshav M.;  Stranks, Samuel D.
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Breakdown of the blood-brain barrier in individuals carrying the epsilon 4 allele of the APOE gene, but not the epsilon 3 allele, increases with and predicts cognitive impairment and is independent of amyloid beta or tau pathology.


Vascular contributions to dementia and Alzheimer'  s disease are increasingly recognized(1-6). Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction(7), including the early clinical stages of Alzheimer'  s disease(5,8-10). The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer'  s disease(11-14), leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes(15-19), which maintain BBB integrity(20-22). It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the epsilon 3/epsilon 4 or epsilon 4/epsilon 4 alleles) are distinguished from those without APOE4 (epsilon 3/epsilon 3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-beta or tau pathology measured in cerebrospinal fluid or by positron emission tomography(23). High baseline levels of the BBB pericyte injury biomarker soluble PDGFR beta(7,8) in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-beta and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway(19) in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer'  s disease pathology, and might be a therapeutic target in APOE4 carriers.


  
Structural basis for catalysis and substrate specificity of human ACAT1 期刊论文
NATURE, 2020, 581 (7808) : 333-+
作者:  Jiao, Huipeng;  Wachsmuth, Laurens;  Kumari, Snehlata;  Schwarzer, Robin;  Lin, Juan;  Eren, Remzi Onur;  Fisher, Amanda;  Lane, Rebecca;  Young, George R.;  Kassiotis, George;  Kaiser, William J.;  Pasparakis, Manolis
收藏  |  浏览/下载:10/0  |  提交时间:2020/07/03

The structure of human ACAT1, which catalyses the transfer of an acyl group from acyl-coenzyme A to cholesterol to form cholesteryl ester, is resolved by cryo-electron microscopy.


As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma(1). ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer'  s disease and cancer(2-7). Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family(8).