Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the ...evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 630 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal. We find that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.
The geographical shift of global anthropogenic aerosols from the developed countries to the Asian continent since the 1980s could potentially perturb the regional and global climate due to ...aerosol‐cloud‐radiation interactions. We use an atmospheric general circulation model with different aerosol scenarios to investigate the radiative and microphysical effects of anthropogenic aerosols from different regions on the radiation budget, precipitation, and large‐scale circulations. An experiment contrasting anthropogenic aerosol scenarios in 1970 and 2010 shows that the altered cloud reflectivity and solar extinction by aerosols results in regional surface temperature cooling in East and South Asia, and warming in the US and Europe, respectively. These aerosol‐induced temperature changes are consistent with the relative temperature trends from 1980 to 2010 over different regions in the reanalysis data. A reduced meridional streamfunction and zonal winds over the tropics as well as a poleward shift of the jet stream suggest weakened and expanded tropical circulations, which are induced by the redistributed aerosols through a relaxing of the meridional temperature gradient. Consequently, precipitation is suppressed in the deep tropics and enhanced in the subtropics. Our assessments of the aerosol effects over the different regions suggest that the increasing Asian pollution accounts for the weakening of the tropics circulation, while the decreasing pollution in Europe and US tends to shift the circulation systems southward. Moreover, the aerosol indirect forcing is predominant over the total aerosol forcing in magnitude, while aerosol radiative and microphysical effects jointly shape the meridional energy distributions and modulate the circulation systems.
Key Points
The emission shift contributes to the “dimming” in Asia and “brightening” in the US and Europe
Atmospheric meridional circulations are weakened by the redistributed aerosols
Aerosol effects from different regions contribute distinctively to the circulation modification
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy ...in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8
T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.
Multiple distributed controllers have been used in software-defined networks (SDNs) to improve scalability and reliability, where each controller manages one static partition of the network. In this ...paper, we show that dynamic mapping between switches and controllers can improve efficiency in managing traffic load variations. In particular, we propose balanced controller (BalCon) and BalConPlus, two SDN switch migration schemes to achieve load balance among SDN controllers with small migration cost. BalCon is suitable for the scenarios where the network does not require a serial processing of switch requests. For other scenarios, BalConPlus is more suitable, as it is immune to the switch migration blackout and does not cause any service disruption. Simulations demonstrate that BalCon and BalConPlus significantly reduce the load imbalance among SDN controllers by migrating only a small number of switches with low computation overhead. We also build a prototype testbed based on the open-source SDN framework RYU to verify the practicality and effectiveness of BalCon and BalConPlus. Experiment confirms the results of the simulations. It also shows that BalConPlus is immune to switch migration blackout, an adverse effect in the baseline BalCon.
Software-Defined Networking (SDN) is a new network technology that decouples the control plane logic from the data plane and uses a programmable software controller to manage network operation and ...the state of network components. In an SDN network, a logically centralized controller uses a global network view to conduct management and operation of the network. The centralized control of the SDN network presents a tremendous opportunity for network operators to refactor the control plane and to improve the performance of applications. For the application of load balancing, the logically centralized controller conducts Real-time Least loaded Server selection (RLS) for multiple domains, where new flows pass by for the first time. The function of RLS is to enable the new flows to be forwarded to the least loaded server in the entire network. However, in a large-scale SDN network, the logically centralized controller usually consists of multiple distributed controllers. Existing multiple controller state synchronization schemes are based on Periodic Synchronization (PS), which can cause undesirable situations. For example, frequent synchronizations may result in high synchronization overhead of controllers. State desynchronization among controllers during the interval between two consecutive synchronizations could lead to forwarding loops and black holes. In this paper, we propose a new type of controller state synchronization scheme, Load Variance-based Synchronization (LVS), to improve the load-balancing performance in the multi-controller multi-domain SDN network. Compared with PS-based schemes, LVS-based schemes conduct effective state synchronizations among controllers only when the load of a specific server or domain exceeds a certain threshold, which significantly reduces the synchronization overhead of controllers. The results of simulations show that LVS achieves loop-free forwarding and good load-balancing performance with much less synchronization overhead, as compared with existing schemes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Amid growing rates of burnout, physicians report increasing electronic health record (EHR) usage alongside decreasing clinical facetime with patients. There exists a pressing need to improve ...physician-computer-patient interactions by streamlining EHR workflow. To identify interventions to improve EHR design and usage, we systematically characterize EHR activity among internal medicine residents at a tertiary academic hospital across various inpatient rotations and roles from June 2013 to November 2016. Logged EHR timestamps were extracted from Stanford Hospital's EHR system (Epic) and cross-referenced against resident rotation schedules. We tracked the quantity of EHR logs across 24-hour cycles to reveal daily usage patterns. In addition, we decomposed daily EHR time into time spent on specific EHR actions (e.g. chart review, note entry and review, results review).In examining 24-hour usage cycles from general medicine day and night team rotations, we identified a prominent trend in which night team activity promptly ceased at the shift's end, while day team activity tended to linger post-shift. Across all rotations and roles, residents spent on average 5.38 hours (standard deviation = 2.07) using the EHR. PGY1 (post-graduate year one) interns and PGY2+ residents spent on average 2.4 and 4.1 times the number of EHR hours on information review (chart, note, and results review) as information entry (note and order entry).Analysis of EHR event log data can enable medical educators and programs to develop more targeted interventions to improve physician-computer-patient interactions, centered on specific EHR actions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atmospheric aerosols affect weather and global general circulation by modifying cloud and precipitation processes, but the magnitude of cloud adjustment by aerosols remains poorly quantified and ...represents the largest uncertainty in estimated forcing of climate change. Here we assess the effects of anthropogenic aerosols on the Pacific storm track, using a multiscale global aerosol–climate model (GCM). Simulations of two aerosol scenarios corresponding to the present day and preindustrial conditions reveal long-range transport of anthropogenic aerosols across the north Pacific and large resulting changes in the aerosol optical depth, cloud droplet number concentration, and cloud and ice water paths. Shortwave and longwave cloud radiative forcing at the top of atmosphere are changed by −2.5 and +1.3 W m ⁻², respectively, by emission changes from preindustrial to present day, and an increased cloud top height indicates invigorated midlatitude cyclones. The overall increased precipitation and poleward heat transport reflect intensification of the Pacific storm track by anthropogenic aerosols. Hence, this work provides, for the first time to the authors’ knowledge, a global perspective of the effects of Asian pollution outflows from GCMs. Furthermore, our results suggest that the multiscale modeling framework is essential in producing the aerosol invigoration effect of deep convective clouds on a global scale.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Formic acid (HCO
2
H) is an important potential hydrogen storage material, which, in the presence of appropriate catalysts can be selectively dehydrogenated to give H
2
and CO
2
. In this work, well ...defined N^C cyclometallated iridium(
iii
) complexes based on 2-aryl imidazoline ligands are found to be excellent catalysts for the decomposition of HCO
2
H-NEt
3
mixtures to give H
2
and CO
2
under mild conditions with high turnover frequencies (up to 147 000 h
−1
at 40 °C) and essentially no CO formation. The modular structures of these catalysts have allowed for the construction of structure-activity relationships for the complexes, leading to the rational optimisation of the catalyst structure with respect to both the rate of H
2
production and catalyst lifetime. In particular, the presence of the remote γ-NH unit in the ligand is shown to be essential for catalytic activity, without which no reaction occurs. Mechanistic studies suggest that the dehydrogenation is rate-limited by the step of hydride protonation, which is made feasible by the γ-NH unit
via
an unusual form of long-range metal-ligand bifunctional catalysis involving formic acid-assisted proton hopping.
Bifunctional cyclometallated iridium complexes bearing a γ-NH group catalyse the rapid dehydrogenation of formic acid under mild conditions.
Severe acute respiratory syndrome (SARS) emerged in 2002 to 2003 in southern China. The origin of its etiological agent, the SARS coronavirus (SARS-CoV), remains elusive. Here we report that species ...of bats are a natural host of coronaviruses closely related to those responsible for the SARS outbreak. These viruses, termed SARS-like coronaviruses (SL-CoVs), display greater genetic variation than SARS-CoV isolated from humans or from civets. The human and civet isolates of SARS-CoV nestle phylogenetically within the spectrum of SL-CoVs, indicating that the virus responsible for the SARS outbreak was a member of this coronavirus group.
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