Highlights • First FDA approvals for anti-PD-1 antibodies for patients with metastatic melanoma. • Promising response from ongoing clinical trials with several anti-PD-1/L1 antibodies. • Need to ...define bio-markers to predict response from anti-PD-1/L1 antibody therapy. • Multiple checkpoint inhibitors that are under pre-clinical development. • Future studies will identify ideal combinations of checkpoint inhibitors.
Manmade reservoirs are important components of the terrestrial water balance. Thus, considering the hydro‐climatic effects of reservoirs is important in water cycle studies at a river basin to global ...scales; yet, reservoirs are represented poorly in large‐scale hydrological and climate models. Here we present a high‐resolution (5 km) continental‐scale reservoir storage dynamics and release scheme by enhancing existing schemes and adding critical novel parameterizations to improve reservoir storage and release simulations. The new scheme simulates river‐floodplain‐reservoir storages in an integrated manner considering their spatial and temporal variations. A new calibration scheme is also incorporated to better simulate reservoir dynamics considering cascade‐reservoir effects. Further, since no reservoir bathymetry data are available over large domains, we use a state‐of‐the‐art digital elevation model and reservoir extent data to derive reservoir bed elevation. The new scheme is integrated within the river‐floodplain routing scheme of a continental hydrological model LEAF‐Hydro‐Flood. Results from the simulation of ~1,900 reservoirs within the contiguous United States suggest that the model well captures the observed reservoir storage‐release dynamics. Comparison of our results with those from the existing schemes suggest a significant improvement; importantly, the new scheme reduces the excessive and frequent reservoir overfilling and underfilling. Comparison of results with satellite‐based surface water data shows that the model accurately reproduces the large‐scale patterns of reservoir‐floodplain inundation extents. It is expected that the results of this study will inform the incorporation of reservoirs in hyper‐resolution models to improve simulations of terrestrial water storage and flow and examine reservoir‐atmosphere interactions over large domains.
Key Points
A high‐resolution continental‐scale model is developed for the integrated simulation of river, floodplain, and reservoir storage dynamics
Simulation of reservoir release is improved using an advanced generic reservoir operation rule and an efficient calibration algorithm
First results of river‐floodplain‐reservoirs storage dynamics are presented
The Mekong River Basin (MRB) is undergoing unprecedented changes due to the recent acceleration in large-scale dam construction. While the hydrology of the MRB is well understood and the effects of ...some of the existing dams have been studied, the potential effects of the planned dams on flood pulse dynamics over the entire Lower Mekong remains unexamined. Here, using hydrodynamic model simulations, we show that the effects of flow regulation on downstream river-floodplain dynamics are relatively predictable along the mainstream Mekong, but flow regulations could potentially disrupt the flood dynamics in the Tonle Sap River (TSR) and small distributaries in the Mekong Delta. Results suggest that TSR flow reversal could cease if the Mekong flood pulse is dampened by 50% and delayed by one-month. While flood occurrence in the vicinity of the Tonle Sap Lake and middle reach of the delta could increase due to enhanced low flow, it could decrease by up to five months in other areas due to dampened high flow, particularly during dry years. Further, areas flooded for less than five months and over six months are likely to be impacted significantly by flow regulations, but those flooded for 5-6 months could be impacted the least.
The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic ...aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of β-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.
Excellent electrostatic control offered by gate-all-around (GAA) geometry makes multinanowire (multi-NW) MOSFET a promising candidate for sub-10-nm technology nodes. Unfortunately, the GAA geometry ...is susceptible to the increased self-heating due to poor heat dissipation from the nanowires (NWs) to the substrate. Therefore, an understanding of spatio-temporal temperature rise, AT(x, y, z; t), at the NW level is important for predicting activity-induced variability within an IC, as well as characterization of various reliability issues, such as, NBTI, PBTI, HCI, and TDDB that depend sensitively on self-heating. In this paper, a 3-D electrothermal simulation model is developed to explore and interpret self-heating and heat dissipation in GAA devices. Our results identify complex heat dissipation pathways characterized by multiple time constants. First, the nanowires heat up quickly (τ GAA -NW ~ n Sec ), then heat spreads all over the gate contact pad (τ G-pad ~ 100 nSec), and finally, the heat exits through the heat sink at the bottom of the substrate (τ sub ~ mSec). A systematic thermoreflectance measurement of temperature helps us to identify the time constants, and validates the model. Our results have implications for the design, characterization, circuit-operation, and reliability of high-performance GAA devices.
•A relationship between flooded area and fish catch in the Lower Mekong is presented.•Flow alteration by dams could potentially impact fish catch in the downstream.•Significant land use change ...occurred due to rise in meat production to replace fish.•Virtual water demands tripled in the past 25 years due to the dietary shift.
This study links the changing hydrology in the Lower Mekong River Basin (LMRB) caused by accelerated dam construction to a dietary shift from fish to land-animal meat (meat hereafter) as a primary source of protein. A shift toward a westernized diet in the LMRB countries (i.e., Cambodia, Lao PDR, Thailand, and Vietnam) has been observed in the recent past. However, neither the hydrological changes from dam construction as a cause for the dietary shift nor the effects of increasing shift from fish to meat on virtual water have been adequately studied. Here, we derive a univariate relationship between fish catch and flooded areas by using a hydrodynamic model and yearly fish catch data. We find a strong correlation between catch per capita and yearly flood occurrence in the LMRB. Results suggest that fish catch in the Tonlé Sap Lake region may reduce by ~8% under a scenario of altered flood occurrence caused by potential reduction in peak flow in the main stem Mekong by 50%. The same reduction in peak flow could, however, lead to an increase in catch within a larger LMRB sub-region but such increase would be marginal. Next, based on the historical production and consumption of meat, we find an increase in meat production and consumption per capita over time. Further, analysis of land use change suggests a 2% cropland expansion mainly due to an increase in meat production. Finally, from the virtual water trade (VWT) network we find that the total VWT of the LMRB tripled from 1988 to 2016 due to a significant rise in trade partners.
Visible-light-induced intramolecular C–O bond formation was developed using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT), which allows the regiocontrolled construction of cyclic ethers and ...lactones. The reaction is likely to proceed through the single-electron oxidation of the phenyl group, followed by the formation of a benzylic radical, thus preventing a competing 1,5-hydrogen abstraction pathway. Detailed mechanistic studies suggest that molecular oxygen is used to trap the radical intermediate to form benzyl alcohol, which undergoes cyclization. This new approach serves as a powerful platform by providing efficient access to valuable five- and six-membered cyclic ethers and lactones with a unified protocol.
Numerous studies have examined the changes in streamflow in the Mekong River Basin (MRB) using observations and hydrological modeling; however, there is a lack of integrated modeling studies that ...explicitly simulate the natural and human‐induced changes in flood dynamics over the entire basin. Here we simulate the river‐floodplain‐reservoir inundation dynamics over the MRB for 1979–2016 period using a newly integrated, high‐resolution (~5 km) river hydrodynamics‐reservoir operation model. The framework is based on the river‐floodplain hydrodynamic model CaMa‐Flood in which a new reservoir operation scheme is incorporated by including 86 existing MRB dams. The simulated flood extent is downscaled to a higher resolution (~90 m) to investigate fine‐scale inundation dynamics, and results are validated with ground‐ and satellite‐based observations. It is found that the historical variations in surface water storage have been governed primarily by climate variability; the impacts of dams on river‐floodplain hydrodynamics were marginal until 2009. However, results indicate that the dam impacts increased noticeably in 2010 when the basin‐wide storage capacity doubled due to the construction of new mega dams. Further, results suggest that the future flood dynamics in the MRB would be considerably different than in the past even without climate change and additional dams. However, it is also found that the impacts of dams can largely vary depending on reservoir operation strategies. This study is expected to provide the basis for high‐resolution river‐floodplain‐reservoir modeling for a holistic assessment of the impacts of dams and climate change on the floodpulse‐dependent hydro‐ecological systems in the MRB and other global regions.
Key Points
A high‐resolution model is presented for the integrated simulation of river‐floodplain‐reservoir inundation dynamics
Historical impacts of dams on the Mekong River flood dynamics are found to be marginal compared to that of climate variability
Potential future dam impacts on the Mekong flood dynamics could be largely different than today even under business‐as‐usual conditions
While many groups attribute the greatly accelerated (i.e., excess) HCI degradation in modern transistors to the difference between the peak temperature and the average temperature (ΔT L,Diff = ΔT pk ...L - ΔT avg L ≫ 0) in self-heated FinFETs and other multigate transistors under dc or low-frequency stress, others find no evidence of the ΔT L,Diff -related excess degradation for ICs operating at high frequencies. In this letter, we resolve the puzzle by using a hierarchical electro-thermal device-circuit predictive model for HCI degradation to demonstrate that ΔT L,Diff →0 beyond a technology-specific transition frequency (ω c ), and therefore, excess HCI degradation disappears at ω ≫ ω c . The proposed analytical model directly correlates HCI performance to power pulse trains characterized by frequency (f) and power duty cycle (ξ) of a digital circuit. Self-heating will continue to reduce HCI-lifetime of surround gate transistors due to the increase of average temperature (ΔT avg L ), but the excess degradation caused by ΔT L,Diff will not be a concern for high-speed digital circuits.
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