Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributi...Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributions[1–3].The potential for shared genetic risk across related diseases has motivated us to examine the contributions of rare variants in canonical and non-canonical diseaseassociated genes in a group of MNDs to understand the gap in heritability.To this end,we have leveraged a wellcharacterized cohort from the CReATe(Clinical Research in amyotrophic lateral sclerosis and Related Disorders for Therapeutic Development)Consortium’s Phenotype-Genotype-Biomarker(PGB1)study.展开更多
The 2025 U.S.National Security Strategy,published on December 4,reaffirms America’s decades-spanning policy of pursuing global domination,emphasizing"burden sharing"in recognition of both the multipolar wo...The 2025 U.S.National Security Strategy,published on December 4,reaffirms America’s decades-spanning policy of pursuing global domination,emphasizing"burden sharing"in recognition of both the multipolar world’s growing capabilities and the growing limitations of the U.S.itself.Despite the obvious intentions,the paper expresses,many have mistakenly interpreted it as signaling U.S.展开更多
Climate financing is a key issue in current negotiations on climate protection. This study establishes a climate financing model based on a mechanism in which donor countries set up funds for climate financing and rec...Climate financing is a key issue in current negotiations on climate protection. This study establishes a climate financing model based on a mechanism in which donor countries set up funds for climate financing and recipient countries use the funds exclusively for carbon emission reduction. The burden-sharing principles are based on GDP, historical emissions, and consumption- based emissions. Using this model, we develop and analyze a series of scenario simulations, including a financing program negotiated at the Cancun Climate Change Conference （2010） and several subsequent programs. Results show that sustained climate financing can help to combat global climate change. However, the Cancun Agreements are projected to result in a reduction of only 0.0I^C in global warming by 2100 compared to the scenario without climate financing. Longer-term climate financing programs should be established to achieve more significant benefits. Our model and simulations also show that climate financing has economic benefits for develop- ing countries. Developed countries will suffer a slight GDP loss in the early stages of climate financing, but the long- term economic growth and the eventual benefits of climate mitigation will compensate for this slight loss. Different burden-sharing principles have very similar effects on global temperature change and economic growth of recipient countries, but they do result in differences in GDP changes for Japan and the FSU. The GDP-based principle results in a larger share of financial burden for Japan, while the historical emissions-based principle results in a larger share of financial burden for the FSU. A larger burden share leads to a greater GDP loss.展开更多
基金The CReATe Consortium(U54 NS092091)is part of the NIH RDCRN,an initiative of the Office of Rare Diseases Research(ORDR),National Center for Advancing Translational Sciences(NCATS)CReATe is funded through a collaboration between NCATS and the National Institute of Neurologic Disorders and Stroke(NINDS)+1 种基金Supplemental support for the study included St.Jude Children’s Research Hospital American Lebanese Syrian Associated Charities(ALSAC)for genomics sequencing,and the ALS Association(grants 17-LGCA-331 and 16-TACL-242)for additional biorepository and sequencing supportThe analysis team is partly funded by National Cancer Institute grant P30 CA021765.MN is supported by the Wellcome Trust(226519/Z/22/Z).
文摘Main text Emerging evidence suggests an intricate genetic architecture in motor neuron diseases(MNDs),involving not only monogenic causes but also,to varying extents,risk alleles and oligogenic or polygenic contributions[1–3].The potential for shared genetic risk across related diseases has motivated us to examine the contributions of rare variants in canonical and non-canonical diseaseassociated genes in a group of MNDs to understand the gap in heritability.To this end,we have leveraged a wellcharacterized cohort from the CReATe(Clinical Research in amyotrophic lateral sclerosis and Related Disorders for Therapeutic Development)Consortium’s Phenotype-Genotype-Biomarker(PGB1)study.
文摘The 2025 U.S.National Security Strategy,published on December 4,reaffirms America’s decades-spanning policy of pursuing global domination,emphasizing"burden sharing"in recognition of both the multipolar world’s growing capabilities and the growing limitations of the U.S.itself.Despite the obvious intentions,the paper expresses,many have mistakenly interpreted it as signaling U.S.
基金This work was supported by the National Basic Research Program of China （No. 2012CB955800）, the National Social Science Foundation of China （Grant No. 14CGJ025） and the CAS Strategic Priority Research Program （Grant No. XDA05150900）.
文摘Climate financing is a key issue in current negotiations on climate protection. This study establishes a climate financing model based on a mechanism in which donor countries set up funds for climate financing and recipient countries use the funds exclusively for carbon emission reduction. The burden-sharing principles are based on GDP, historical emissions, and consumption- based emissions. Using this model, we develop and analyze a series of scenario simulations, including a financing program negotiated at the Cancun Climate Change Conference （2010） and several subsequent programs. Results show that sustained climate financing can help to combat global climate change. However, the Cancun Agreements are projected to result in a reduction of only 0.0I^C in global warming by 2100 compared to the scenario without climate financing. Longer-term climate financing programs should be established to achieve more significant benefits. Our model and simulations also show that climate financing has economic benefits for develop- ing countries. Developed countries will suffer a slight GDP loss in the early stages of climate financing, but the long- term economic growth and the eventual benefits of climate mitigation will compensate for this slight loss. Different burden-sharing principles have very similar effects on global temperature change and economic growth of recipient countries, but they do result in differences in GDP changes for Japan and the FSU. The GDP-based principle results in a larger share of financial burden for Japan, while the historical emissions-based principle results in a larger share of financial burden for the FSU. A larger burden share leads to a greater GDP loss.
