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Changes of crop failure risks in the United States associated with large-scale climate oscillations in the Atlantic and Pacific Oceans 期刊论文
ENVIRONMENTAL RESEARCH LETTERS, 2020, 15 (6)
作者:  Schillerberg, Tayler A.;  Tian, Di
收藏  |  浏览/下载:11/0  |  提交时间:2020/08/18
climate oscillation  crop failure  Bayesian analysis  maize  winter wheat  the United States  
Preparation of cyclohexene isotopologues and stereoisotopomers from benzene 期刊论文
NATURE, 2020, 581 (7808) : 288-+
作者:  Shimazaki, Yuya;  Schwartz, Ido;  Watanabe, Kenji;  Taniguchi, Takashi;  Kroner, Martin;  Imamoglu, Atac
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine(1). Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules(1). Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington'  s disease(2), was recently approved by the United States'  Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial(1,3,4). The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound(5), improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug(6,7), these processes are often unselective and the stereoisotopic purity can be difficult to measure(7,8). Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.


Cyclohexene isotopologues and stereoisotopomers with varying degrees of deuteration are formed by binding a tungsten complex to benzene, which facilitates the selective incorporation of deuterium into any position on the ring.


  
Integrating genomic features for non-invasive early lung cancer detection 期刊论文
NATURE, 2020, 580 (7802) : 245-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.


Radiologic screening of high-risk adults reduces lung-cancer-related mortality(1,2)  however, a small minority of eligible individuals undergo such screening in the United States(3,4). The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)(5), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed '  lung cancer likelihood in plasma'  (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


  
Psychiatry under the shadow of white supremacy 期刊论文
NATURE, 2020, 580 (7804) : 449-450
作者:  Mallapaty, Smriti
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

From the start, racism has shaped the care of people with mental illness in the United States. By Mical Raz.


From the start, racism has shaped the care of people with mental illness in the United States. By Mical Raz.


  
Premature mortality related to United States cross-state air pollution 期刊论文
NATURE, 2020, 578 (7794) : 261-+
作者:  Helmink, Beth A.;  Reddy, Sangeetha M.;  Gao, Jianjun;  Zhang, Shaojun;  Basar, Rafet;  Thakur, Rohit;  Yizhak, Keren;  Sade-Feldman, Moshe;  Blando, Jorge;  Han, Guangchun;  Gopalakrishnan, Vancheswaran;  Xi, Yuanxin;  Zhao, Hao;  Amaria, Rodabe N.;  Tawbi, Hussein A.;  Cogdill, Alex P.;  Liu, Wenbin;  LeBleu, Valerie S.;  Kugeratski, Fernanda G.;  Patel, Sapna;  Davies, Michael A.;  Hwu, Patrick;  Lee, Jeffrey E.;  Gershenwald, Jeffrey E.;  Lucci, Anthony;  Arora, Reetakshi;  Woodman, Scott;  Keung, Emily Z.;  Gaudreau, Pierre-Olivier;  Reuben, Alexandre;  Spencer, Christine N.;  Burton, Elizabeth M.;  Haydu, Lauren E.;  Lazar, Alexander J.;  Zapassodi, Roberta;  Hudgens, Courtney W.;  Ledesma, Deborah A.;  Ong, SuFey;  Bailey, Michael;  Warren, Sarah;  Rao, Disha;  Krijgsman, Oscar;  Rozeman, Elisa A.;  Peeper, Daniel;  Blank, Christian U.;  Schumacher, Ton N.;  Butterfield, Lisa H.;  Zelazowska, Monika A.;  McBride, Kevin M.;  Kalluri, Raghu;  Allison, James;  Petitprez, Florent;  Fridman, Wolf Herman;  Sautes-Fridman, Catherine;  Hacohen, Nir;  Rezvani, Katayoun;  Sharma, Padmanee;  Tetzlaff, Michael T.;  Wang, Linghua;  Wargo, Jennifer A.
收藏  |  浏览/下载:37/0  |  提交时间:2020/05/13

Outdoor air pollution adversely affects human health and is estimated to be responsible for five to ten per cent of the total annual premature mortality in the contiguous United States(1-3). Combustion emissions from a variety of sources, such as power generation or road traffic, make a large contribution to harmful air pollutants such as ozone and fine particulate matter (PM2.5)(4). Efforts to mitigate air pollution have focused mainly on the relationship between local emission sources and local air quality(2). Air quality can also be affected by distant emission sources, however, including emissions from neighbouring federal states(5,6). This cross-state exchange of pollution poses additional regulatory challenges. Here we quantify the exchange of air pollution among the contiguous United States, and assess its impact on premature mortality that is linked to increased human exposure to PM2.5 and ozone from seven emission sectors for 2005 to 2018. On average, we find that 41 to 53 per cent of air-quality-related premature mortality resulting from a state'  s emissions occurs outside that state. We also find variations in the cross-state contributions of different emission sectors and chemical species to premature mortality, and changes in these variations over time. Emissions from electric power generation have the greatest cross-state impacts as a fraction of their total impacts, whereas commercial/residential emissions have the smallest. However, reductions in emissions from electric power generation since 2005 have meant that, by 2018, cross-state premature mortality associated with the commercial/residential sector was twice that associated with power generation. In terms of the chemical species emitted, nitrogen oxides and sulfur dioxide emissions caused the most cross-state premature deaths in 2005, but by 2018 primary PM2.5 emissions led to cross-state premature deaths equal to three times those associated with sulfur dioxide emissions. These reported shifts in emission sectors and emission species that contribute to premature mortality may help to guide improvements to air quality in the contiguous United States.


  
How poorer countries are scrambling to prevent a coronavirus disaster 期刊论文
NATURE, 2020, 580 (7802) : 173-174
作者:  Prasad, Vinay
收藏  |  浏览/下载:3/0  |  提交时间:2020/07/03

Snapshots from four nations struggling to limit deaths faster than the United States and other wealthy countries.


Snapshots from four nations struggling to limit deaths faster than the United States and other wealthy countries.


  
THE SCIENTIST BATTLING THE ADDICTION CRISIS 期刊论文
NATURE, 2020, 580 (7802) : 178-181
作者:  Jones, Nicola
收藏  |  浏览/下载:1/0  |  提交时间:2020/07/03

Nora Volkow leads the world'  s biggest funder of addiction research at a time when the United States is grappling with a devastating surge in drug use.


Nora Volkow leads the world'  s biggest funder of addiction research at a time when the United States is grappling with a devastating surge in drug use.


  
When climate change is not blamed: the politics of disaster attribution in international perspective 期刊论文
CLIMATIC CHANGE, 2019
作者:  Lahsen, Myanna;  Couto, Gabriela de Azevedo;  Lorenzoni, Irene
收藏  |  浏览/下载:15/0  |  提交时间:2020/02/17
climate change  disasters  extreme events  attribution politics  global South  Brazil  United States  framing  
Seasonal Variations and Long-Term Trend of Dust Particle Number Concentration Over the Northeastern United States 期刊论文
JOURNAL OF GEOPHYSICAL RESEARCH-ATMOSPHERES, 2019
作者:  Zhang, Yanda;  Luo, Gan;  Yu, Fangqun
收藏  |  浏览/下载:5/0  |  提交时间:2020/02/17
dust number concentration  dust seasonal variation  dust long-term trenddust vertical properties  Northeastern United States  
Declining US regional and continental trends in intra-annual and interannual extreme temperature swings 期刊论文
INTERNATIONAL JOURNAL OF CLIMATOLOGY, 2019
作者:  DeGaetano, Arthur T.;  Lim, Li-Sha
收藏  |  浏览/下载:7/0  |  提交时间:2020/02/17
intra-annual variability  temperature extremes  time series  United States