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Water Resources as Determinants for Foreign Direct Investments in Land - A Gravity Analysis of Foreign Land Acquisitions 期刊论文
ECOLOGICAL ECONOMICS, 2020, 170
作者:  Hirsch, Cornelius;  Krisztin, Tamas;  See, Linda
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/02
FDI  Foreign Land Acquisition  Bilateral Trade Agreements  Water Resources  Precipitation  Yield Gap  Gravity model  PPML  ZIP  
CRISPR screen in regulatory T cells reveals modulators of Foxp3 期刊论文
NATURE, 2020
作者:  Xu, Daqian;  Wang, Zheng;  Xia, Yan;  Shao, Fei;  Xia, Weiya;  Wei, Yongkun;  Li, Xinjian;  Qian, Xu;  Lee, Jong-Ho;  Du, Linyong;  Zheng, Yanhua;  Lv, Guishuai;  Leu, Jia-shiun;  Wang, Hongyang;  Xing, Dongming;  Liang, Tingbo;  Hung, Mien-Chie;  Lu, Zhimin
收藏  |  浏览/下载:49/0  |  提交时间:2020/07/03

Regulatory T (T-reg) cells are required to control immune responses and maintain homeostasis, but are a significant barrier to antitumour immunity(1). Conversely, T-reg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of proinflammatory properties(2), can promote autoimmunity and/or facilitate more effective tumour immunity(3,4). A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective T-reg therapies for autoimmune disease and cancer. The availability of new functional genetic tools has enabled the possibility of systematic dissection of the gene regulatory programs that modulate Foxp3 expression. Here we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse T-reg cells and applied this technology to perform a targeted loss-of-function screen of around 500 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We identified several modulators of Foxp3 expression, including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin-modifying complex, was revealed to be a positive regulator that stabilized Foxp3 expression  whereas the screen suggested that Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. T-reg-specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient T-reg cells could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in T-reg cells. These results reveal previously unknown modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for T-reg immunotherapies for cancer and autoimmune disease.


A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.


  
Massively parallel coherent laser ranging using a soliton microcomb 期刊论文
NATURE, 2020, 581 (7807) : 164-+
作者:  Casanova, Emmanuelle;  Knowles, Timothy D. J.;  Bayliss, Alex;  Dunne, Julie;  Baranski, Marek Z.;  Denaire, Anthony;  Lefranc, Philippe;  di Lernia, Savino;  Roffet-Salque, Melanie;  Smyth, Jessica;  Barclay, Alistair;  Gillard, Toby;  Classen, Erich;  Coles, Bryony;  Ilett, Michael;  Jeunesse, Christian;  Krueger, Marta;  Marciniak, Arkadiusz;  Minnitt, Steve;  Rotunno, Rocco;  van de Velde, Pieter;  van Wijk, Ivo;  Cotton, Jonathan;  Daykin, Andy;  Evershed, Richard P.
收藏  |  浏览/下载:63/0  |  提交时间:2020/07/03

Coherent ranging, also known as frequency-modulated continuous-wave (FMCW) laser-based light detection and ranging (lidar)(1) is used for long-range three-dimensional distance and velocimetry in autonomous driving(2,3). FMCW lidar maps distance to frequency(4,5) using frequency-chirped waveforms and simultaneously measures the Doppler shift of the reflected laser light, similar to sonar or radar(6,7) and coherent detection prevents interference from sunlight and other lidar systems. However, coherent ranging has a lower acquisition speed and requires precisely chirped(8) and highly coherent(5) laser sources, hindering widespread use of the lidar system and impeding parallelization, compared to modern time-of-flight ranging systems that use arrays of individual lasers. Here we demonstrate a massively parallel coherent lidar scheme using an ultra-low-loss photonic chip-based soliton microcomb(9). By fast chirping of the pump laser in the soliton existence range(10) of a microcomb with amplitudes of up to several gigahertz and a sweep rate of up to ten megahertz, a rapid frequency change occurs in the underlying carrier waveform of the soliton pulse stream, but the pulse-to-pulse repetition rate of the soliton pulse stream is retained. As a result, the chirp from a single narrow-linewidth pump laser is transferred to all spectral comb teeth of the soliton at once, thus enabling parallelism in the FMCW lidar. Using this approach we generate 30 distinct channels, demonstrating both parallel distance and velocity measurements at an equivalent rate of three megapixels per second, with the potential to improve sampling rates beyond 150 megapixels per second and to increase the image refresh rate of the FMCW lidar by up to two orders of magnitude without deterioration of eye safety. This approach, when combined with photonic phase arrays(11) based on nanophotonic gratings(12), provides a technological basis for compact, massively parallel and ultrahigh-frame-rate coherent lidar systems.


  
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:42/0  |  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.


  
Heterogeneities in energy technological learning: Evidence from the US electricity industry 期刊论文
ENERGY POLICY, 2019, 132: 1034-1049
作者:  Shittu, Ekundayo;  Kamdem, Bruno G.;  Weigelt, Carmen
收藏  |  浏览/下载:28/0  |  提交时间:2019/11/27
Technological learning  Policy  Knowledge acquisition  Electricity industry  
Phosphatase activity and nitrogen fixation reflect species differences, not nutrient trading or nutrient balance, across tropical rainforest trees 期刊论文
ECOLOGY LETTERS, 2018, 21 (10) : 1486-1495
作者:  Batterman, Sarah A.;  Hall, Jefferson S.;  Turner, Benjamin L.;  Hedin, Lars O.;  Walter, J. Kimiko LaHaela;  Sheldon, Pete;  van Breugel, Michiel
收藏  |  浏览/下载:23/0  |  提交时间:2019/04/09
Biodiversity  biogeochemical niche  biogeochemistry  nitrogen  nutrient acquisition  nutrient limitation  nutrient strategy  phosphorus  tropical carbon sink  
Effects of free air carbon dioxide enrichment (FACE) on nitrogen assimilation and growth of winter wheat under nitrate and ammonium fertilization 期刊论文
GLOBAL CHANGE BIOLOGY, 2018, 24 (1) : E40-E54
作者:  Dier, Markus;  Meinen, Rieke;  Erbs, Martin;  Kollhorst, Lena;  Baillie, Christin-Kirsty;  Kaufholdt, David;  Kuecke, Martin;  Weigel, Hans-Joachim;  Zoerb, Christian;  Haensch, Robert;  Manderscheid, Remy
收藏  |  浏览/下载:16/0  |  提交时间:2019/04/09
ammonium fertilization  climate change  free air CO2 enrichment  N acquisition  nitrate assimilation  nitrate fertilization  nitrate reductase  Triticum aestivum  
The Myth of U.S. Energy Independence and the Realities of Burden Sharing 科技报告
来源:Center for Strategic and International Studies (CSIS). 出版年: 2016
作者:  Anthony H. Cordesman
收藏  |  浏览/下载:24/0  |  提交时间:2019/04/05
Africa  Burke Chair in Strategy  Counterterrorism and Homeland Security  Defense Budget  Defense Industry  Acquisition  and Innovation  Defense Strategy and Capabilities  Defense and Security  Energy and Geopolitics  Energy and Security  Energy and Sustainability  Geopolitics and International Security  Iran  MENA Stability Reports and Studies  Middle East  Military and Security Issues  Politics  Economics  and Society  Saudi Arabia  the GCC  and the Gulf  Terrorism and Counterinsurgency  U.S. Strategic and Defense Efforts  
Defense Resource Planning Under Uncertainty: An Application of Robust Decision Making to Munitions Mix Planning 科技报告
来源:Rand Corporation. 出版年: 2016
作者:  Robert J. Lempert;  Drake Warren;  Ryan Henry;  Robert W. Button;  Jonathan Klenk;  Kate Giglio
收藏  |  浏览/下载:14/0  |  提交时间:2019/04/05
Military Budgets and Defense Spending  Military Equipment  Military Acquisition and Procurement  Military Strategy  Robust Decision Making  
Contestability Frameworks: An International Horizon Scan 科技报告
来源:Rand Corporation. 出版年: 2016
作者:  Cynthia R. Cook;  Emma Westerman;  Megan McKernan;  Badreddine Ahtchi;  Gordon T. Lee;  Jenny Oberholtzer;  Douglas Shontz;  Jerry M. Sollinger
收藏  |  浏览/下载:14/0  |  提交时间:2019/04/05
Military Budgets and Defense Spending  Australia  Military Acquisition and Procurement  Business Strategies  Robust Decision Making