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Li, Feng

Publications and source records attributed to Li, Feng.

At least 19 records

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse DNA-encoded chemical libraries (DECLs) against the kinase domain of ALK2. Off-DNA synthesis of DECL hits and biochemical validation revealed nanomolar potent ALK2 inhibitors. Further structure-activity relationship studies yielded center for drug discovery (CDD)-2789, a potent [NanoBRET (NB) cell IC50: 0.54 μM] and metabolically stable analog with good pharmacological profile. Crystal structures of ALK2 bound with CDD-2281, CDD-2282, or CDD-2789 show that these inhibitors bind the active site through Van der Waals interactions and solvent-mediated hydrogen bonds. CDD-2789 exhibits high selectivity toward ALK2/ALK1 in KINOMEscan analysis and NB K192 assay. In cell-based studies, ALK2 inhibitors effectively attenuated activin A and BMP-induced Phosphorylated SMAD1/5 activation in fibroblasts from individuals with FOP in a dose-dependent manner. Thus, CDD-2789 is a valuable tool compound for further investigation of the biological functions of ALK2 and ALK1 and the therapeutic potential of specific inhibition of ALK2.

Jimmidi, Ravikumar

Overview of the recent experimental research on the J-TEXT tokamak

The J-TEXT capability is enhanced compared to two years ago with several upgrades of its diagnostics and the increase of electron cyclotron resonance heating (ECRH) power to 1 MW. With the application of electron cyclotron wave (ECW), the ECW assisted plasma startup is achieved; the tearing mode is suppressed; the toroidal injection of 300 kW ECW drives around 24 kA current; fast electrons are generated with toroidal injected ECW and the runaway current conversion efficiency increases with ECRH power. The mode coupling between 2/1 and 3/1 modes are extensively studied. The coupled 2/1 and 3/1 modes usually lead to major disruption. Their coupling can be either suppressed or avoided by external resonant magnetic perturbation fields and hence avoids the major disruption. It is also found that the 2/1 threshold of external field is significantly reduced by a pre-excited 3/1 mode, which can be either a locked island or an external kink mode. The disruption control is studied by developing prediction methods capable of cross tokamak application and by new mitigation methods, such as the biased electrode or electromagnetic pellet injector. The high-density operation and related disruptions are studied from various aspects. Approaching the density limit, the collapse of the edge shear layer is observed and such collapse can be prevented by applying edge biasing, leading to an increased density limit. The density limit is also observed to increase, if the plasma is operated in the poloidal divertor configuration or the plasma purity is increased by increasing the pre-filled gas pressure or ECRH power during the start-up phase.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY

Recent Antarctic Sea Ice Extent Variability and Its Relation to Atmospheric Circulation in Reanalyses and Seasonal Forecasts

Sea ice is considered an important indicator of climate change. Interest has focused on the trend towards reduced sea ice cover in the Arctic Ocean, particularly during summer months. In the Southern Hemisphere, sea ice has also received attention due to a trend towards increasing cover, in opposition to the Northern Hemisphere and to climate model projections. This all changed in the austral spring 2016, when the Southern Ocean sea ice cover dropped dramatically, and has remained consistently at below average values up to the present. Here I review some of the issues and perceived causes of the 2016 sea ice reduction. Several studies have suggested a change in surface winds, which would allow warmer waters to move upwards in the water column and towards the surface. Results from the GMAO (Global Modeling and Assimilation Office) ocean data assimilation system are consistent with this hypothesis, and indicate a significant warming of subsurface waters occurred in the winter of 2016, and has remained in place.

Polar

Effects of Greenhouse Gas Increase and Stratospheric Ozone Depletion on Stratospheric Mean Age of Air in 1960-2010

The relative impacts of greenhouse gas (GHG) increase and stratospheric ozone depletion on stratospheric mean age of air in the 1960-2010 period are quantified using the Goddard Earth Observing System Chemistry-Climate Model. The experiment compares controlled simulations using a coupled atmosphere-ocean version of the Goddard Earth Observing System Chemistry-Climate Model, in which either GHGs or ozone depleting substances, or both factors evolve over time. The model results show that GHGs and ozone-depleting substances have about equal contributions to the simulated mean age decrease, but GHG increases account for about two thirds of the enhanced strength of the lower stratospheric residual circulation. It is also found that both the acceleration of the diabatic circulation and the decrease of the mean age difference between downwelling and upwelling regions are mainly caused by GHG forcing. The results show that ozone depletion causes an increase in the mean age of air in the Antarctic summer lower stratosphere through two processes: (1) a seasonal delay in the Antarctic polar vortex breakup that inhibits young midlatitude air from mixing with the older air inside the vortex, and (2) enhanced Antarctic downwelling that brings older air from middle and upper stratosphere into the lower stratosphere.

stratospheric ozone depletion

Early Action on HFCs Mitigates Future Atmospheric Change

As countries take action to mitigate global warming, both by ratifying the UNFCCC Paris Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases (GHGs), the distinct structure of their atmospheric impacts, and how the timing of potential GHG regulations would affect future changes in atmospheric temperature and ozone. Chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid-21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19K at 80hPa. Three HFC mitigation scenarios demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90 of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

Kigali Amendment

Early Action on Hfcs Mitigates Future Atmospheric Change

As countries take action to mitigate global warming, both by ratifying theUNFCCCParis Agreement and enacting the Kigali Amendment to the Montreal Protocol to manage hydrofluorocarbons (HFCs), it is important to consider the relative importance of the pertinent greenhouse gases and the distinct structure of their atmospheric impacts, and how the timing of potential greenhouse gas regulations would affect future changes in atmospheric temperature and ozone. HFCs should be explicitly considered in upcoming climate and ozone assessments, since chemistry-climate model simulations demonstrate that HFCs could contribute substantially to anthropogenic climate change by the mid- 21st century, particularly in the upper troposphere and lower stratosphere i.e., global average warming up to 0.19 Kat 80 hPa. The HFCmitigation scenarios described in this study demonstrate the benefits of taking early action in avoiding future atmospheric change: more than 90% of the climate change impacts of HFCs can be avoided if emissions stop by 2030.

HFC

Impact of Stratospheric Ozone Zonal Asymmetries on the Tropospheric Circulation

The depletion and recovery of Antarctic ozone plays a major role in changes of Southern Hemisphere (SH) tropospheric climate. Recent studies indicate that the lack of polar ozone asymmetries in chemistry climate models (CCM) leads to a weaker and warmer Antarctic vortex, and smaller trends in the tropospheric mid-latitude jet and the surface pressure. However, the tropospheric response to ozone asymmetries is not well understood. In this study we report on a series of integrations of the Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) to further examine the effect of zonal asymmetries on the state of the stratosphere and troposphere. Integrations with the full, interactive stratospheric chemistry are compared against identical simulations using the same CCM except that (1) the monthly mean zonal mean stratospheric ozone from first simulation is prescribed and (2) ozone is relaxed to the monthly mean zonal mean ozone on a three day time scale. To analyze the tropospheric response to ozone asymmetries, we examine trends and quantify the differences in temperatures, zonal wind and surface pressure among the integrations.

Chemistry-Climate Modeling

The Effects of Interactive Stratospheric Chemistry on Antarctic and Southern Ocean Climate Change in an AOGCM

Stratospheric ozone depletion has played a dominant role in driving Antarctic climate change in the last decades. In order to capture the stratospheric ozone forcing, many coupled atmosphere-ocean general circulation models (AOGCMs) prescribe the Antarctic ozone hole using monthly and zonally averaged ozone field. However, the prescribed ozone hole has a high ozone bias and lacks zonal asymmetry. The impacts of these biases on model simulations, particularly on Southern Ocean and the Antarctic sea ice, are not well understood. The purpose of this study is to determine the effects of using interactive stratospheric chemistry instead of prescribed ozone on Antarctic and Southern Ocean climate change in an AOGCM. We compare two sets of ensemble simulations for the 1960-2010 period using different versions of the Goddard Earth Observing System 5 - AOGCM: one with interactive stratospheric chemistry, and the other with prescribed monthly and zonally averaged ozone and 6 other stratospheric radiative species calculated from the interactive chemistry simulations. Consistent with previous studies using prescribed sea surface temperatures and sea ice concentrations, the interactive chemistry runs simulate a deeper Antarctic ozone hole and consistently larger changes in surface pressure and winds than the prescribed ozone runs. The use of a coupled atmosphere-ocean model in this study enables us to determine the impact of these surface changes on Southern Ocean circulation and Antarctic sea ice. The larger surface wind trends in the interactive chemistry case lead to larger Southern Ocean circulation trends with stronger changes in northerly and westerly surface flow near the Antarctica continent and stronger upwelling near 60S. Using interactive chemistry also simulates a larger decrease of sea ice concentrations. Our results highlight the importance of using interactive chemistry in order to correctly capture the influences of stratospheric ozone depletion on climate change over Antarctic and the Southern Ocean.

Antarctic climate change

Air Mass Origin in the Arctic and its Response to Future Warming

We present the first climatology of air mass origin in the Arctic in terms of rigorously defined air mass fractions that partition air according to where it last contacted the planetary boundary layer (PBL). Results from a present-day climate integration of the GEOSCCM general circulation model reveal that the Arctic lower troposphere below 700 mb is dominated year round by air whose last PBL contact occurred poleward of 60degN, (Arctic air, or air of Arctic origin). By comparison, approx. 63% of the Arctic troposphere above 700 mb originates in the NH midlatitude PBL, (midlatitude air). Although seasonal changes in the total fraction of midlatitude air are small, there are dramatic changes in where that air last contacted the PBL, especially above 700 mb. Specifically, during winter air in the Arctic originates preferentially over the oceans, approx. 26% in the East Pacific, and approx. 20% in the Atlantic PBL. By comparison, during summer air in the Arctic last contacted the midlatitude PBL primarily over land, overwhelmingly so in Asia (approx. 40 %) and, to a lesser extent, in North America (approx. 24%). Seasonal changes in air-mass origin are interpreted in terms of seasonal variations in the large-scale ventilation of the midlatitude boundary layer and lower troposphere, namely changes in the midlatitude tropospheric jet and associated transient eddies during winter and large scale convective motions over midlatitudes during summer.

tropospheric transport

Seasonal Ventilation of the Stratosphere: Robust Diagnostics from One-Way Flux Distributions

We present an analysis of the seasonally varying ventilation of the stratosphere using one-way flux distributions. Robust transport diagnostics are computed using GEOSCCM subject to fixed present-day climate forcings. From the one-way flux, we determine the mass of the stratosphere that is in transit since entry through the tropical tropopause to its exit back into the troposphere, partitioned according to stratospheric residence time and exit location. The seasonalities of all diagnostics are quantified with respect to the month of year (a) when air enters the stratosphere, (b) when the mass of the stratosphere is partitioned, and (c) when air exits back into the troposphere. We find that the return flux, within 3 months since entry, depends strongly on when entry occurred: (34 +/- 10)% more of the air entering the stratosphere in July leaves poleward of 45 deg N compared to air that enters in January. The month of year when the air mass is partitioned is also found to be important: The stratosphere contains about six times more air of tropical origin during late summer and early fall that will leave poleward of 45 deg within 6 months since entering the stratosphere compared to during late winter to late spring. When the entire mass of the air that entered the stratosphere at the tropics regardless of its residence time is considered, we find that (51 +/- 1)% and (39 +/- 2)% will leave poleward of 10 deg in the Northern Hemisphere (NH) and Southern Hemisphere (SH), respectively.

Stratosphere-Troposphere Exchange

Impacts of Atmosphere-Ocean Coupling on Southern Hemisphere Climate Change

Climate in the Southern Hemisphere (SH) has undergone significant changes in recent decades. These changes are closely linked to the shift of the Southern Annular Mode (SAM) towards its positive polarity, which is driven primarily by Antarctic ozone depletion. There is growing evidence that Antarctic ozone depletion has significant impacts on Southern Ocean circulation change. However, it is poorly understood whether and how ocean feedback might impact the SAM and climate change in the SH atmosphere. This outstanding science question is investigated using the Goddard Earth Observing System Coupled Atmosphere-Ocean-Chemistry Climate Model(GEOS-AOCCM).We perform ensemble simulations of the recent past (1960-2010) with and without the interactive ocean. For simulations without the interactive ocean, we use sea surface temperatures and sea ice concentrations produced by the interactive ocean simulations. The differences between these two ensemble simulations quantify the effects of atmosphere-ocean coupling. We will investigate the impacts of atmosphere-ocean coupling on stratospheric processes such as Antarctic ozone depletion and Antarctic polar vortex breakup. We will address whether ocean feedback affects Rossby wave generation in the troposphere and wave propagation into the stratosphere. Another focuson this study is to assess how ocean feedback might affect the tropospheric SAM response to Antarctic ozone depletion

Chemistry-Climate Modeling

A Systematic Approach for Real-Time Operator Functional State Assessment

A task overload condition often leads to high stress for an operator, causing performance degradation and possibly disastrous consequences. Just as dangerous, with automated flight systems, an operator may experience a task underload condition (during the en-route flight phase, for example), becoming easily bored and finding it difficult to maintain sustained attention. When an unexpected event occurs, either internal or external to the automated system, the disengaged operator may neglect, misunderstand, or respond slowly/inappropriately to the situation. In this paper, we discuss an approach for Operator Functional State (OFS) monitoring in a typical aviation environment. A systematic ground truth finding procedure has been designed based on subjective evaluations, performance measures, and strong physiological indicators. The derived OFS ground truth is continuous in time compared to a very sparse estimation of OFS based on an expert review or subjective evaluations. It can capture the variations of OFS during a mission to better guide through the training process of the OFS assessment model. Furthermore, an OFS assessment model framework based on advanced machine learning techniques was designed and the systematic approach was then verified and validated with experimental data collected in a high fidelity Boeing 737 simulator. Preliminary results show highly accurate engagement/disengagement detection making it suitable for real-time applications to assess pilot engagement.

Zhang, Guangfan

Engagement Assessment Using EEG Signals

In this paper, we present methods to analyze and improve an EEG-based engagement assessment approach, consisting of data preprocessing, feature extraction and engagement state classification. During data preprocessing, spikes, baseline drift and saturation caused by recording devices in EEG signals are identified and eliminated, and a wavelet based method is utilized to remove ocular and muscular artifacts in the EEG recordings. In feature extraction, power spectrum densities with 1 Hz bin are calculated as features, and these features are analyzed using the Fisher score and the one way ANOVA method. In the classification step, a committee classifier is trained based on the extracted features to assess engagement status. Finally, experiment results showed that there exist significant differences in the extracted features among different subjects, and we have implemented a feature normalization procedure to mitigate the differences and significantly improved the engagement assessment performance.

Li, Feng

Long-Term Changes in Stratospheric Age Spectra in the 21st Century in the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM)

In this study we investigate the long-term variations in the stratospheric age spectra using simulations of the 21st century with the Goddard Earth Observing System Chemistry- Climate Model (GEOSCCM). Our purposes are to characterize the long-term changes in the age spectra and identify processes that cause the decrease of the mean age in a warming climate. Changes in the age spectra in the 21st century simulations are characterized by decreases in the modal age, the mean age, the spectral width, and the tail decay timescale. Our analyses show that the decrease in the mean age is caused by two processes: the acceleration of the residual circulation that increases the young air masses in the stratosphere, and the weakening of the recirculation that leads to the decrease of tail of the age spectra and the decrease of the old air masses. The weakening of the stratospheric recirculation is also strongly correlated with the increase of the residual circulation. One important result of this study is that the decrease of the tail of the age spectra makes an important contribution to the decrease of the main age. Long-term changes in the stratospheric isentropic mixing are investigated. Mixing increases in the subtropical lower stratosphere, but its impact on the age spectra is outweighed by the increase of the residual circulation. The impacts of the long-term changes in the age spectra on long-lived chemical traces are also investigated. 37 2

Li, Feng

Imbalanced Learning for Functional State Assessment

This paper presents results of several imbalanced learning techniques applied to operator functional state assessment where the data is highly imbalanced, i.e., some function states (majority classes) have much more training samples than other states (minority classes). Conventional machine learning techniques usually tend to classify all data samples into majority classes and perform poorly for minority classes. In this study, we implemented five imbalanced learning techniques, including random undersampling, random over-sampling, synthetic minority over-sampling technique (SMOTE), borderline-SMOTE and adaptive synthetic sampling (ADASYN) to solve this problem. Experimental results on a benchmark driving lest dataset show thai accuracies for minority classes could be improved dramatically with a cost of slight performance degradations for majority classes,

Li, Feng

Seasonal Variations of Stratospheric Age Spectra in GEOSCCM

There are many pathways for an air parcel to travel from the troposphere to the stratosphere, each of which takes different time. The distribution of all the possible transient times, i.e. the stratospheric age spectrum, contains important information on transport characteristics. However, it is computationally very expensive to compute seasonally varying age spectra, and previous studies have focused mainly on the annual mean properties of the age spectra. To date our knowledge of the seasonality of the stratospheric age spectra is very limited. In this study we investigate the seasonal variations of the stratospheric age spectra in the Goddard Earth Observing System Chemistry Climate Model (GEOSCCM). We introduce a method to significantly reduce the computational cost for calculating seasonally dependent age spectra. Our simulations show that stratospheric age spectra in GEOSCCM have strong seasonal cycles and the seasonal cycles change with latitude and height. In the lower stratosphere extratropics, the average transit times and the most probable transit times in the winter/early spring spectra are more than twice as old as those in the summer/early fall spectra. But the seasonal cycle in the subtropical lower stratosphere is nearly out of phase with that in the extratropics. In the middle and upper stratosphere, significant seasonal variations occur in the sUbtropics. The spectral shapes also show dramatic seasonal change, especially at high latitudes. These seasonal variations reflect the seasonal evolution of the slow Brewer-Dobson circulation (with timescale of years) and the fast isentropic mixing (with timescale of days to months).

Li, Feng

Narrowing of the Upwelling Branch of the Brewer-Dobson Circulation and Hadley Cell in Chemistry-Climate Model Simulations of the 21st Century

Changes in the width of the upwelling branch of the Brewer-Dobson circulation and Hadley cell in the 21st Century are investigated using simulations from a coupled chemistry-climate model. In these model simulations the tropical upwelling region narrows in the troposphere and lower stratosphere. The narrowing of the Brewer-Dobson circulation is caused by an equatorward shift of Rossby wave critical latitudes and Eliassen-Palm flux convergence in the subtropical lower stratosphere. In the troposphere, the model projects an expansion of the Hadley cell's poleward boundary, but a narrowing of the Hadley cell's rising branch. Model results suggest that eddy forcing may also play a part in the narrowing of the rising branch of the Hadley cell.

Li, Feng

Narrowing of the Upwelling Branch of the Brewer-Dobson Circulation and Hadley Cell in Chemistry-Climate Model Simulations of the 21st Century

Changes in the width of the upwelling branch of the Brewer-Dobson circulation and Hadley cell in the 21st Century are investigated using simulations from a coupled chemistry-climate model. In these model simulations the tropical upwelling region narrows in the troposphere and lower stratosphere. The narrowing of the Brewer-Dobson circulation is caused by an equatorward shift of Rossby wave critical latitudes and Eliassen-Palm flux convergence in the subtropical lower stratosphere. In the troposphere, the model projects an expansion of the Hadley cell's poleward boundary, but a narrowing of the Hadley rising branch. Model results suggest that the narrowing of the Hadley cell ascent is also eddy-driven.

Li, Feng