GSTDTAP

浏览/检索结果: 共15条,第1-10条 帮助

已选(0)清除 条数/页:   排序方式:
Resolving the Differences in the Simulated and Reconstructed Temperature Response to Volcanism 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2020, 47 (8)
作者:  Zhu, Feng;  Emile-Geay, Julien;  Hakim, Gregory J.;  King, Jonathan;  Anchukaitis, Kevin J.
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/02
volcanic eruptions  temperature response  simulation-reconstruction comparison  Last Millennium Reanalysis  paleoclimate data assimilation  Superposed Epoch Analysis  
Mechanisms and therapeutic implications of hypermutation in gliomas 期刊论文
NATURE, 2020, 580 (7804) : 517-+
作者:  Feng, Kaibo;  Quevedo, Raundi E.;  Kohrt, Jeffrey T.;  Oderinde, Martins S.;  Reilly, Usa;  White, M. Christina
收藏  |  浏览/下载:27/0  |  提交时间:2020/07/03

A high tumour mutational burden (hypermutation) is observed in some gliomas(1-5)  however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide. Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade. Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations. These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer.


Temozolomide therapy seems to lead to mismatch repair deficiency and hypermutation in gliomas, but not to an increase in response to immunotherapy.


  
B cells are associated with survival and immunotherapy response in sarcoma 期刊论文
NATURE, 2020, 577 (7791) : 556-+
作者:  Willis, J. P.;  Canning, R. E. A.;  Noordeh, E. S.;  Allen, S. W.;  King, A. L.;  Mantz, A.;  Morris, R. G.;  Stanford, S. A.;  Brammer, G.
收藏  |  浏览/下载:15/0  |  提交时间:2020/07/03

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes(1,2). The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely(3,4). To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8(+) T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.


Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.


  
An orbital water-ice cycle on comet 67P from colour changes 期刊论文
NATURE, 2020, 578 (7793) : 49-+
作者:  Oh, Myoung Hwan;  Cho, Min Gee;  Chung, Dong Young;  Park, Inchul;  Kwon, Youngwook Paul;  Ophus, Colin;  Kim, Dokyoon;  Kim, Min Gyu;  Jeong, Beomgyun;  Gu, X. Wendy;  Jo, Jinwoung;  Yoo, Ji Mun;  Hong, Jaeyoung;  McMains, Sara;  Kang, Kisuk;  Sung, Yung-Eun;  Alivisatos, A. Paul;  Hyeon, Taeghwan
收藏  |  浏览/下载:52/0  |  提交时间:2020/07/03

Solar heating of a cometary surface provides the energy necessary to sustain gaseous activity, through which dust is removed(1,2). In this dynamical environment, both the coma(3,4) and the nucleus(5,6) evolve during the orbit, changing their physical and compositional properties. The environment around an active nucleus is populated by dust grains with complex and variegated shapes(7), lifted and diffused by gases freed from the sublimation of surface ices(8,9). The visible colour of dust particles is highly variable: carbonaceous organic material-rich grains(10) appear red while magnesium silicate-rich(11,12) and water-ice-rich(13,14) grains appear blue, with some dependence on grain size distribution, viewing geometry, activity level and comet family type. We know that local colour changes are associated with grain size variations, such as in the bluer jets made of submicrometre grains on comet Hale-Bopp(15) or in the fragmented grains in the coma(16) of C/1999 S4 (LINEAR). Apart from grain size, composition also influences the coma'  s colour response, because transparent volatiles can introduce a substantial blueing in scattered light, as observed in the dust particles ejected after the collision of the Deep Impact probe with comet 9P/Tempel 1(17). Here we report observations of two opposite seasonal colour cycles in the coma and on the surface of comet 67P/Churyumov-Gerasimenko through its perihelion passage(18). Spectral analysis indicates an enrichment of submicrometre grains made of organic material and amorphous carbon in the coma, causing reddening during the passage. At the same time, the progressive removal of dust from the nucleus causes the exposure of more pristine and bluish icy layers on the surface. Far from the Sun, we find that the abundance of water ice on the nucleus is reduced owing to redeposition of dust and dehydration of the surface layer while the coma becomes less red.


  
Rapid Geodetic Analysis of Subduction Zone Earthquakes Leveraging a 3-D Elastic Green's Function Library 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2019, 46 (5) : 2475-2483
作者:  Tung, S.;  Fielding, E. J.;  Bekaert, D. P. S.;  Masterlark, T.
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/26
subduction earthquake  rapid response  geodetic analysis  Green'  s function  finite element model  Mexico megathrust  
FACE facts hold for multiple generations; Evidence from natural CO2 springs 期刊论文
GLOBAL CHANGE BIOLOGY, 2019, 25 (1) : 1-11
作者:  Saban, Jasmine M.;  Chapman, Mark A.;  Taylor, Gail
收藏  |  浏览/下载:3/0  |  提交时间:2019/04/09
atmospheric CO2  climate change  meta-analysis  natural CO2 spring  plant adaptation  plant response  plasticity  
Demand Response Potential: Available when Needed? 期刊论文
ENERGY POLICY, 2018, 115: 181-198
作者:  Mueller, Theresa;  Moest, Dominik
收藏  |  浏览/下载:0/0  |  提交时间:2019/04/09
Demand Response  Demand Response Potential  Renewable Energy Sources  Energy System Analysis  Load Shedding  Load Shifting  
Orbital-scale nonlinear response of East Asian summer monsoon to its potential driving forces in the late Quaternary 期刊论文
CLIMATE DYNAMICS, 2018, 50: 2183-2197
作者:  Yi, Liang;  Shi, Zhengguo;  Tan, Liangcheng;  Deng, Chenglong
收藏  |  浏览/下载:5/0  |  提交时间:2019/04/09
East Asian summer monsoon (EASM)  Nonlinear response  Statistical analysis  Orbital timescale  The late Quaternary  
Global-scale impacts of nitrogen deposition on tree carbon sequestration in tropical, temperate, and boreal forests: A meta-analysis 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (2) : E416-E431
作者:  Schulte-Uebbing, Lena;  de Vries, Wim
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
C-N response  fertilization experiments  forest carbon sink  meta-analysis  nitrogen deposition  woody biomass  
Understanding spatial and temporal Douglas-fir fertilizer response in the Pacific Northwest using boosted regression trees and linear discriminant analysis 期刊论文
FOREST ECOLOGY AND MANAGEMENT, 2017, 406
作者:  Littke, K. M.;  Cross, J.;  Harrison, R. B.;  Zabowski, D.;  Turnblom, E.
收藏  |  浏览/下载:1/0  |  提交时间:2019/04/09
Douglas-fir  Fertilizer response  Boosted regression trees  Linear discriminant analysis  Climate  Elevation