Blockade of immune
checkpoint PD-1/PD-L1 has been a promising anticancer
strategy; however, clinically available PD-1/PD-L1 small-molecule
inhibitors are lacking. In view of the high potency of compound 2 (BMS-1002), structural fine tuning of the methoxy linkage
together with diverse modification in the solvent interaction region
was conducted. A series of novel derivatives featuring a difluoromethyleneoxy
linkage were designed. Compound 43 was identified as
the most promising PD-1/PD-L1 inhibitor with an IC50 value
of 10.2 nM in the HTRF assay. This compound is capable of promoting
CD8+ T cell activation through inhibiting PD-1/PD-L1 cellular
signaling. Moreover, in the Hepa1-6 syngeneic mouse model, administration
of compound 43 at 1 mg/kg dosage promoted CD8+ T cell activation and delayed the tumor growth with good tolerance.
Notably, the tumor in one mouse of the compound 43-treated
group was completely regressed. These results indicate that compound 43 is a promising candidate worthy of further investigation.
This paper attempts to propose hybrid methodology of compiling water resource extended input-output (IO) table at county level (According to administrative structure of China, a county is subordinate to its province, and provincial level is parallel to state level of other countries). By combining Non-Survey-based RAS-technique for possible iterated results and Partial-Survey-based current situation for actual ongoing resource-consumption, we aimed to depict a more accurate structure for water resource consumption and regional economic impact analysis at a county level in the arid area. Additionally, non-parameter methodology was adopted to interpolate missing data. Since human interventions continually have impacted on the natural environment that would finally lead to over-consumption of natural resources, we introduced water consumption caused by cultivation in the Primary Industry and water usage in other industries into a local input-output matrix of Shandan County in Gansu Province, China. Evidence of empirical analysis shows that the modified IO table can more accurately describe economic structure than weighted provincial average IO table does. Moreover, industrialization is ongoing with economic diversity and continually generating water use demand even though also stimulating imports of light industrial products according to the Partial-Survey reports. It demonstrates that industrialization and increasing household consumption drive a high speed of economic growth but with a high cost of water consumption through the Secondary and Tertiary Industries, even at a far rural area. Hence, water scarcity would be a constraint
OPEN ACCESSSustainability 2014, 6 3302 on sustainable development in regions such as Shandan County when taking economic valuation of natural water consumption into account.
Government subsidy to crop insurance has been advocated as a policy alternative to support growth of agricultural production and farmers' income in China since the country joined the WTO. However, cautions have been raised as the crop insurance program may impact the environment negatively. This study tries to explore farmers' behaviors with regard to agrochemical use with household data applied to a simultaneous equation system consisting of disaggregated input models. It is found that decisions on fertilizer, pesticides, and agro-film applications do have different impacts on crop insurance participation, and are influenced by the latter in different ways. It is also implied that encouraging farmers' participation in crop insurance under current low-premium and low-indemnity terms does not have a significantly negative impact on the environment. Copyright 2007 International Association of Agricultural Economists.
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