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Multispecific drugs herald a new era of biopharmaceutical innovation 期刊论文
NATURE, 2020, 580 (7803) : 329-338
作者:  Gallego, Laura D.;  Schneider, Maren;  Mittal, Chitvan;  Romanauska, Anete;  Carrillo, Ricardo M. Gudino;  Schubert, Tobias;  Pugh, B. Franklin;  Koehler, Alwin
收藏  |  浏览/下载:32/0  |  提交时间:2020/07/03

The modern biopharmaceutical industry traces its roots to the dawn of the twentieth century, coincident with marketing of aspirin-a signature event in the history of modern drug development. Although the archetypal discovery process did not change markedly in the first seven decades of the industry, the past fifty years have seen two successive waves of transformative innovation in the development of drug molecules: the rise of '  rational drug discovery'  methodology in the 1970s, followed by the invention of recombinant protein-based therapeutic agents in the 1980s. An incipient fourth wave is the advent of multispecific drugs. The successful development of prospectively designed multispecific drugs has the potential to reconfigure our ideas of how target-based therapeutic molecules can work, and what it is possible to achieve with them. Here I review the two major classes of multispecific drugs: those that enrich a therapeutic agent at a particular site of action and those that link a therapeutic target to a biological effector. The latter class-being freed from the constraint of having to directly modulate the target upon binding-may enable access to components of the proteome that currently cannot be targeted by drugs.


  
Video-based AI for beat-to-beat assessment of cardiac function 期刊论文
NATURE, 2020, 580 (7802) : 252-+
作者:  Pleguezuelos-Manzano, Cayetano;  Puschhof, Jens;  Huber, Axel Rosendahl;  van Hoeck, Arne;  Wood, Henry M.;  Nomburg, Jason;  Gurjao, Carino;  Manders, Freek;  Dalmasso, Guillaume;  Stege, Paul B.;  Paganelli, Fernanda L.;  Geurts, Maarten H.;  Beumer, Joep;  Mizutani, Tomohiro;  Miao, Yi;  van der Linden, Reinier;  van der Elst, Stefan;  Garcia, K. Christopher;  Top, Janetta;  Willems, Rob J. L.;  Giannakis, Marios;  Bonnet, Richard;  Quirke, Phil;  Meyerson, Matthew;  Cuppen, Edwin;  van Boxtel, Ruben;  Clevers, Hans
收藏  |  浏览/下载:117/0  |  提交时间:2020/07/03

A video-based deep learning algorithm-EchoNet-Dynamic-accurately identifies subtle changes in ejection fraction and classifies heart failure with reduced ejection fraction using information from multiple cardiac cycles.


Accurate assessment of cardiac function is crucial for the diagnosis of cardiovascular disease(1), screening for cardiotoxicity(2) and decisions regarding the clinical management of patients with a critical illness(3). However, human assessment of cardiac function focuses on a limited sampling of cardiac cycles and has considerable inter-observer variability despite years of training(4,5). Here, to overcome this challenge, we present a video-based deep learning algorithm-EchoNet-Dynamic-that surpasses the performance of human experts in the critical tasks of segmenting the left ventricle, estimating ejection fraction and assessing cardiomyopathy. Trained on echocardiogram videos, our model accurately segments the left ventricle with a Dice similarity coefficient of 0.92, predicts ejection fraction with a mean absolute error of 4.1% and reliably classifies heart failure with reduced ejection fraction (area under the curve of 0.97). In an external dataset from another healthcare system, EchoNet-Dynamic predicts the ejection fraction with a mean absolute error of 6.0% and classifies heart failure with reduced ejection fraction with an area under the curve of 0.96. Prospective evaluation with repeated human measurements confirms that the model has variance that is comparable to or less than that of human experts. By leveraging information across multiple cardiac cycles, our model can rapidly identify subtle changes in ejection fraction, is more reproducible than human evaluation and lays the foundation for precise diagnosis of cardiovascular disease in real time. As a resource to promote further innovation, we also make publicly available a large dataset of 10,030 annotated echocardiogram videos.


  
Grand challenges in the science of wind energy 期刊论文
SCIENCE, 2019, 366 (6464) : 443-+
作者:  Veers, Paul;  Dykes, Katherine;  Lantz, Eric;  Barth, Stephan;  Bottasso, Carlo L.;  Carlson, Ola;  Clifton, Andrew;  Green, Johney;  Green, Peter;  Holttinen, Hannele;  Laird, Daniel;  Lehtomaki, Ville;  Lundquist, Julie K.;  Manwell, James;  Marquis, Melinda;  Meneveau, Charles;  Moriarty, Patrick;  Munduate, Xabier;  Muskulus, Michael;  Naughton, Jonathan;  Pao, Lucy;  Paquette, Joshua;  Peinke, Joachim;  Robertson, Amy;  Sanz Rodrigo, Javier;  Sempreviva, Anna Maria;  Smith, J. Charles;  Tuohy, Aidan;  Wiser, Ryan
收藏  |  浏览/下载:18/0  |  提交时间:2019/11/27
Negative emissions and international climate goals-learning from and about mitigation scenarios 期刊论文
CLIMATIC CHANGE, 2019
作者:  Hilaire, Jerome;  Minx, Jan C.;  Callaghan, Max W.;  Edmonds, Jae;  Luderer, Gunnar;  Nemet, Gregory F.;  Rogelj, Joeri;  Zamora, Maria del Mar
收藏  |  浏览/下载:13/0  |  提交时间:2019/11/27
Negative emission  Carbon dioxide removal  Systematic evidence synthesis  Integrated assessment model  1  5 degrees C  2 degrees C  
Mapping the landscape of climate services 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2019, 14 (9)
作者:  Larosa, Francesca;  Mysiak, Jaroslav
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/27
climate innovation  climate services  bibliometrics  network science  climate adaptation  
Do government subsidies promote firm-level innovation? Evidence from the Korean renewable energy technology industry 期刊论文
ENERGY POLICY, 2019, 132: 1333-1344
作者:  Sung, Bongsuk
收藏  |  浏览/下载:0/0  |  提交时间:2019/11/27
Government subsidy  Firm-level innovation  Renewable energy technology industry  Korea  
Regulatory mechanism design of GHG emissions in the electric power industry in China 期刊论文
ENERGY POLICY, 2019, 131: 187-201
作者:  Feng, Tian-tian;  Gong, Xiao-lei;  Guo, Yu-hua;  Yang, Yi-sheng;  Dong, Jun
收藏  |  浏览/下载:11/0  |  提交时间:2019/11/27
Electric power industry  Greenhouse gas emission  Regulatory mechanism  
The discourses of power - governmental approaches to business models in the renewable energy transition 期刊论文
ENERGY POLICY, 2019, 130: 41-59
作者:  Bryant, Scott T.;  Straker, Karla;  Wrigley, Cara
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/27
Energy strategy discourses  Government energy policy  Energy utility  Variable renewable energy (VRE)  Business models  Content analysis  
Government-funded research increasingly fuels innovation 期刊论文
SCIENCE, 2019, 364 (6446) : 1139-+
作者:  Fleming, L.;  Greene, H.;  Li, G.;  Marx, M.;  Yao, D.
收藏  |  浏览/下载:1/0  |  提交时间:2019/11/27
Geographical proximity and renewable energy diffusion: An empirical approach 期刊论文
ENERGY POLICY, 2019, 129: 422-435
作者:  Fadly, Dalia;  Fontes, Francisco
收藏  |  浏览/下载:8/0  |  提交时间:2019/11/26
Renewable energy  Trade  Geography  Policy adoption  Technology diffusion  Panel fixed effects