Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only ...Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.展开更多
As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus ...As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.展开更多
Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed...Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.展开更多
Bardet-Biedl syndrome（BBS） is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of c...Bardet-Biedl syndrome（BBS） is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of cilia. Leucine zipper transcription factor-like 1（LZTFL1）has been identified as a BBS protein（BBS17）, because patients with mutations in this gene exhibit the common BBS phenotypes. In this study, we generated a knockout mouse model to investigate the effects of LZTFL1 depletion. Lztfl1 knockout mice were born with low birth weight, reached similar weight to those of wild-type mice at 10 weeks of age, and later gained more weight than their wild-type counterparts. LZTFL1 was localized to the primary cilium of kidney cells, and the absence of LZTFL1 increased the ciliary localization of BBS9. Moreover, in the retinas of Lztfl1 knockout mice, the photoreceptor outer segment was shortened, the distal axoneme of photoreceptor connecting cilium was significantly enlarged, and rhodopsin was targeted to the outer nuclear layer. TUNEL assay showed that many of these abnormal photoreceptor cells in Lztfl1 knockout mice underwent apoptosis. Interestingly, the absence of LZTFL1 caused an abnormal increase of the adaptor protein complex 1（AP1） in some photoreceptor cells. Based on these data, we conclude that LZTFL1 is a cilium protein and regulates animal weight and photoreceptor connecting cilium function probably by controlling microtubule assembly and protein trafficking in cilia.展开更多
We introduce novel methods to determine optimum detection thresholds for the Progressive Multi-Channel Correlation (PMCC) algorithm used by the International Data Centre (IDC) to perform infrasound and seismic station...We introduce novel methods to determine optimum detection thresholds for the Progressive Multi-Channel Correlation (PMCC) algorithm used by the International Data Centre (IDC) to perform infrasound and seismic station-level nuclear-event detection. Receiver Operating Characteristic (ROC) curve analysis is used with real ground truth data to determine the trade-off between the probability of detection (PD) and the false alarm rate (FAR) at various detection thresholds. Further, statistical detection theory via maximum a posteriori and Bayes cost approaches is used to determine station-level optimum “family” size thresholds before detections should be considered for network-level processing. These threshold-determining methods are extensible for family-characterizing statistics other than “size,” such as a family’s collective F-statistic or signal-to-noise ratio (SNR). Therefore, the reliability of analysts’ decisions as to whether families should be preserved for network-level processing can only benefit from access to multiple, independent, optimum decision thresholds based upon size, F-statistic, SNR, etc.展开更多
In a recent publication it was shown that homonuclear scalar couplings in directly detected protein NMR spectra can be“decoupled”using deep neural networks,including cases where existing methods fail[1].The work har...In a recent publication it was shown that homonuclear scalar couplings in directly detected protein NMR spectra can be“decoupled”using deep neural networks,including cases where existing methods fail[1].The work harkens back to the introduction of maximum entropy and non-uniform sampling,and it elegantly illustrates how new approaches can be devised in the conceptualization of NMR experiments,freeing researchers from conventional thinking and approaches.The work opens up a new era in biomolecular NMR spectroscopy,where experimental design is tailored towards processing with deep neural networks.(https://doi.org/10.1021/jacs.1c04010).展开更多
Lane change prediction is critical for crash avoidance but challenging as it requires the understanding of the instantaneous driving environment.With cutting-edge artificial intelligence and sensing technologies,auton...Lane change prediction is critical for crash avoidance but challenging as it requires the understanding of the instantaneous driving environment.With cutting-edge artificial intelligence and sensing technologies,autonomous vehicles(AVs)are expected to have exceptional perception systems to capture instantaneously their driving environments for predicting lane changes.By exploring the Waymo open motion dataset,this study proposes a framework to explore autonomous driving data and investigate lane change behaviors.In the framework,this study develops a Long Short-Term Memory(LSTM)model to predict lane changing behaviors.The concept of Vehicle Operating Space(VOS)is introduced to quantify a vehicle's instantaneous driving environment as an important indicator used to predict vehicle lane changes.To examine the robustness of the model,a series of sensitivity analysis are conducted by varying the feature selection,prediction horizon,and training data balancing ratios.The test results show that including VOS into modeling can speed up the loss decay in the training process and lead to higher accuracy and recall for predicting lane-change behaviors.This study offers an example along with a methodological framework for transportation researchers to use emerging autonomous driving data to investigate driving behaviors and traffic environments.展开更多
Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of t...Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(P<0.01), less time in bed(P<0.05), more sleep disruption(P<0.01), and poorer daytime functioning and alertness(P<0.05). Evening types were less likely to consider sleep important for performance(P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.展开更多
For the past twenty years,chemokines have emerged as a family of critical mediators of cell migration during immune surveillance,development,inflammation and cancer progression.Chemokines bind to seven transmembrane G...For the past twenty years,chemokines have emerged as a family of critical mediators of cell migration during immune surveillance,development,inflammation and cancer progression.Chemokines bind to seven transmembrane G protein-coupled receptors(GPCRs)that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation.Although chemokines have evolved to benefit the host,inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases.Therefore,understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets.This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis,inflammation,immune responses and cancer.展开更多
The empirical rules for the prediction of solid solution formation proposed so far in the literature usually have very compromised predictability.Some rules with seemingly good predictability were,however,tested using...The empirical rules for the prediction of solid solution formation proposed so far in the literature usually have very compromised predictability.Some rules with seemingly good predictability were,however,tested using small data sets.Based on an unprecedented large dataset containing 1252 multicomponent alloys,machine-learning methods showed that the formation of solid solutions can be very accurately predicted(93%).The machine-learning results help identify the most important features,such as molar volume,bulk modulus,and melting temperature.展开更多
In this research,a Graphical Processing Unit(GPU)accelerated Discrete Element Method(DEM)code was developed and coupled with the Computational Fluid Dynamic(CFD)software MFiX to simulate granular and multiphase flows ...In this research,a Graphical Processing Unit(GPU)accelerated Discrete Element Method(DEM)code was developed and coupled with the Computational Fluid Dynamic(CFD)software MFiX to simulate granular and multiphase flows with heat transfers and chemical reactions.The Fortran-based CFD solver was coupled with the CUDA/C++based DEM solver through inter-process pipes.The speedup to the CPU version of MFiX-DEM is about 130-243 folds in the simulation of particle packings.In fluidized bed simulations,the DEM computation time is reduced from 91%to 17%with a speedup of 78 folds.The simulation of Geldart A particle fluidization revealed a similar level of importance of both fluid and particle coarse-graining.The filtered drag derived from the two-fluid model is suitable for Euler-Lagrangian simulations with both fluid and particle coarse-graining.It overcorrects the influence of sub-grid structures if used for simulations with only fluid coarse-graining.展开更多
High-granularity vehicle trajectory data can help researchers develop traffic simulation models,understand traffic flow characteristics,and thus propose insightful strategies for road traffic management.This paper pro...High-granularity vehicle trajectory data can help researchers develop traffic simulation models,understand traffic flow characteristics,and thus propose insightful strategies for road traffic management.This paper proposes a novel vehicle trajectory extraction method that can extract high-granularity vehicle trajectories from aerial videos.The proposed method includes video calibration,vehicle detection and tracking,lane marking identification,and vehicle motion characteristics calculation.In particular,the authors propose a Monte-Carlo-based lane marking identification approach to identify each vehicle's lane.This is a challenging problem for vehicle trajectory extraction,especially when the aerial videos are taken from a high altitude.The authors applied the proposed method to extract vehicle trajectories from several high-resolution aerial videos recorded from helicopters.The extracted dataset is named by the High-Granularity Highway Simulation(HIGH-SIM)vehicle trajectory dataset.To demonstrate the effectiveness of the proposed method and understand the quality of the HIGHSIM dataset,we compared the HIGH-SIM dataset with a well-known dataset,the NGSIM US-101 dataset,regarding the accuracy and consistency aspects.The comparison results showed that the HIGH-SIM dataset has more reasonable speed and acceleration distributions than the NGSIM US-101 dataset.Also,the internal and platoon consistencies of the HIGH-SIM dataset give lower errors compared to the NGSIM US-101 dataset.To benefit future research,the authors have published the HIGH-SIM dataset online for public use.展开更多
Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB...Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SSIP modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies （ADA）, whereas mice immunized with SSIP, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.展开更多
This article presents the development and validation of the Superquadric Discrete Element Method(SuperDEM)for non-spherical particle simulation using a superquadric particle method in open-source CFD suite MFiX.A supe...This article presents the development and validation of the Superquadric Discrete Element Method(SuperDEM)for non-spherical particle simulation using a superquadric particle method in open-source CFD suite MFiX.A superquadric particle-particle contact algorithm with accelerating and stabilizing strategy was developed.A superquadric particle-arbitrary wall contact algorithm was developed,which enables the simulation in complex geometry.The solver was validated by comparing with experimental data generated in this study or available in the literature.Tests include cylinder contacting with a wall,static packing of M&M chocolate candies in a cylindrical container,static packing of cylinders in a cylindrical container,dynamic angle of repose of cylinders in a rotating drum,and discharging of chocolate candies from a hopper.Besides,MPI parallelization of the solver was implemented and the parallel performance of the solver using MPI was assessed through large-scale simulations of 1 million,10 million,and 100 million particles on up to 6800 cores,which demonstrates that the SuperDEM solver has great potential for industrial-scale systems simulation.展开更多
Polysiloxane coatings on yttria stabilized zirconia(YSZ)microspheres of 500μm were simulated in a spout fluidized bed coater using Multiphase Flow with Interface Exchange-Discrete Element Modelling(MFiX-DEM).Two diff...Polysiloxane coatings on yttria stabilized zirconia(YSZ)microspheres of 500μm were simulated in a spout fluidized bed coater using Multiphase Flow with Interface Exchange-Discrete Element Modelling(MFiX-DEM).Two different coater configurations were developed to study the influence of gas velocity and its distribution on particle dynamics.The presence of the Wurster tube not only enhances the dis-tribution but also increases the overall residence time of the particles.Investigations were also carried out with different Wurster tube positions(normal,10%and 20%lowered from its initial position).Among these,20%lowered Wurster tube position demonstrated the most effective coating process.The effects of gas inlet pressure on the average gas velocity and the distribution of particles were analyzed.More than 97%of the particles can be retained.The derived results,including average gas velocity,particle retention percentage,and distribution of particles with gas velocity,are being used to guide the experimental work in obtaining defect-free coatings for YSZ microspheres.展开更多
An unknown in coupled Eulerian-Lagrangian models for particle flow,such as CFD-DEM,which has received fairly little attention in the literature to date is the size of the filter width in the transfer kernel.This work ...An unknown in coupled Eulerian-Lagrangian models for particle flow,such as CFD-DEM,which has received fairly little attention in the literature to date is the size of the filter width in the transfer kernel.This work provides a preliminary glimpse at how this parameter can influence the solution in cold-flow,unbounded fluidization.Comparison to previously published direct numerical simulation data is used to suggest an appropriate range for this parameter.展开更多
A phase-field model is proposed to simulate coherency loss coupled with microstructure evolution.A special field variable is employed to describe the degree of coherency loss of each particle and its evolution is gove...A phase-field model is proposed to simulate coherency loss coupled with microstructure evolution.A special field variable is employed to describe the degree of coherency loss of each particle and its evolution is governed by a Ginzburg-Landau type kinetic equation.For the sake of computational efficiency,a flood-fill algorithm is introduced that can drastically reduce the required number of field variables,which allows the model to efficiently simulate a large number of particles sufficient for characterizing their statistical features during Ostwald ripening.The model can incorporate size dependence of coherency loss,metastability of coherent particles,and effectively incorporate the underlying mechanisms of coherency loss by introducing a so-called differential energy criterion.The model is applied to simulate coarsening of Al3Sc precipitates in aluminum alloy and comprehensively compared with experiments.Our results clearly show how the particle size distribution is changed during coherency loss and affects the coarsening rate.展开更多
Modeling of ductile fracture in polycrystalline structures is challenging,since it requires integrated modeling of cracks,crystal plasticity,and grains.Here we extend the typical phase-field framework to the situation...Modeling of ductile fracture in polycrystalline structures is challenging,since it requires integrated modeling of cracks,crystal plasticity,and grains.Here we extend the typical phase-field framework to the situations with constraints on the order parameters,and formulate two types of phase-field models on ductile fracture.The Type-Ⅰ model incorporates three sets of order parameters,which describe the distributions of cracks,plastic strain,and grains,respectively.Crystal plasticity is employed within grain interiors accommodated by J_(2)plasticity at grain boundaries.The applications of the Type-Ⅰ model to single crystals and bicrystals demonstrate the influences of grain orientations and grain boundaries on crack growth.In the Type-Ⅱ model,J_(2)plasticity is assumed for the whole system and grain structures are neglected.Taking advantage of the efficiency of the fast Fourier transform,our Type-Ⅱ model is employed to study low cycle fatigue.Crack closure and striation-like patterning of plastic strain are observed in the simulations.Crack growth rate is analyzed as a function of the J-integral,and the simulated fatigue life as a function of plastic strain agrees with the Coffin–Manson relation without a priori assumption.展开更多
文摘Hepatitis B-associated hepatocellular carcinoma (HBV-HCC) remains an intractable high-mortality solidtumor cancer that accounted for 42% of global HCC cases in 2019. Despite some developments in systemic therapy,only a small subset of late-stage HCC patients responds positively to recently developed therapeutic innovations.MicroRNAs (miRNAs) act as an ancillary epigenetic system that can regulate genome expression in all cancerpathways including HCC. The molecular mechanisms of miRNA regulation in cancer pathogenesis offered researchersa new approach that was widely hoped would translate into miRNA-based drugs and diagnostics. Thirty years on,miRNA-based diagnostic and therapeutic agents for HCC remain a work-in-progress (WIP) and no current miRNAHCC clinical trial has progressed to Phase 4. The question remains why this is the case after 30 years and what is theway forward. The major findings and contribution of this paper are that it illustrates the complexity of the HBVmiRNA interactome in HBV-HCC in all cellular processes, as well as the ancillary role of miRNA in the epigeneticand immune systems. This is combined with a review of the outcomes and problems of clinical trials, to explain whymiRNA therapeutics and diagnostics have not progressed to approved drugs or serum-based diagnostic tests. The wayforward suggests a radical rethink might be so that involves the incorporation of AI, bioinformatics, andnanotechnology to solve the problem.
基金funded by the External Cooperation Program of Chinese Academy of Sciences (Grant No. 153211KYSB20160001)the National Key Research and Development Program of China (Grant No. 2016YFC1202902)+1 种基金the Key Program of Chinese Academy of Sciences (Grant No. ZDRW-ZS2016-4)funded by FNLCR Contract HHSN261200800001E
文摘As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.
文摘Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.
基金funded in whole or in part with federal funds from the National Cancer Institute,National Institutes of Health,under contract(HHSN261200800001E)supported by the National Institute of Allergy and Infectious Diseases
文摘Bardet-Biedl syndrome（BBS） is a heterogeneous disease characterized by deficiencies in various organs that are caused by defects in genes involved in the genesis, structural maintenance, and protein trafficking of cilia. Leucine zipper transcription factor-like 1（LZTFL1）has been identified as a BBS protein（BBS17）, because patients with mutations in this gene exhibit the common BBS phenotypes. In this study, we generated a knockout mouse model to investigate the effects of LZTFL1 depletion. Lztfl1 knockout mice were born with low birth weight, reached similar weight to those of wild-type mice at 10 weeks of age, and later gained more weight than their wild-type counterparts. LZTFL1 was localized to the primary cilium of kidney cells, and the absence of LZTFL1 increased the ciliary localization of BBS9. Moreover, in the retinas of Lztfl1 knockout mice, the photoreceptor outer segment was shortened, the distal axoneme of photoreceptor connecting cilium was significantly enlarged, and rhodopsin was targeted to the outer nuclear layer. TUNEL assay showed that many of these abnormal photoreceptor cells in Lztfl1 knockout mice underwent apoptosis. Interestingly, the absence of LZTFL1 caused an abnormal increase of the adaptor protein complex 1（AP1） in some photoreceptor cells. Based on these data, we conclude that LZTFL1 is a cilium protein and regulates animal weight and photoreceptor connecting cilium function probably by controlling microtubule assembly and protein trafficking in cilia.
文摘We introduce novel methods to determine optimum detection thresholds for the Progressive Multi-Channel Correlation (PMCC) algorithm used by the International Data Centre (IDC) to perform infrasound and seismic station-level nuclear-event detection. Receiver Operating Characteristic (ROC) curve analysis is used with real ground truth data to determine the trade-off between the probability of detection (PD) and the false alarm rate (FAR) at various detection thresholds. Further, statistical detection theory via maximum a posteriori and Bayes cost approaches is used to determine station-level optimum “family” size thresholds before detections should be considered for network-level processing. These threshold-determining methods are extensible for family-characterizing statistics other than “size,” such as a family’s collective F-statistic or signal-to-noise ratio (SNR). Therefore, the reliability of analysts’ decisions as to whether families should be preserved for network-level processing can only benefit from access to multiple, independent, optimum decision thresholds based upon size, F-statistic, SNR, etc.
基金the Intramural Research Program of the National Cancer Institute,National Institutes of Health,and this work falls under Project ZIA BC 011132。
文摘In a recent publication it was shown that homonuclear scalar couplings in directly detected protein NMR spectra can be“decoupled”using deep neural networks,including cases where existing methods fail[1].The work harkens back to the introduction of maximum entropy and non-uniform sampling,and it elegantly illustrates how new approaches can be devised in the conceptualization of NMR experiments,freeing researchers from conventional thinking and approaches.The work opens up a new era in biomolecular NMR spectroscopy,where experimental design is tailored towards processing with deep neural networks.(https://doi.org/10.1021/jacs.1c04010).
文摘Lane change prediction is critical for crash avoidance but challenging as it requires the understanding of the instantaneous driving environment.With cutting-edge artificial intelligence and sensing technologies,autonomous vehicles(AVs)are expected to have exceptional perception systems to capture instantaneously their driving environments for predicting lane changes.By exploring the Waymo open motion dataset,this study proposes a framework to explore autonomous driving data and investigate lane change behaviors.In the framework,this study develops a Long Short-Term Memory(LSTM)model to predict lane changing behaviors.The concept of Vehicle Operating Space(VOS)is introduced to quantify a vehicle's instantaneous driving environment as an important indicator used to predict vehicle lane changes.To examine the robustness of the model,a series of sensitivity analysis are conducted by varying the feature selection,prediction horizon,and training data balancing ratios.The test results show that including VOS into modeling can speed up the loss decay in the training process and lead to higher accuracy and recall for predicting lane-change behaviors.This study offers an example along with a methodological framework for transportation researchers to use emerging autonomous driving data to investigate driving behaviors and traffic environments.
基金supported by the Department of Defense Congressionally Directed Medical Research Programs,Joint Program Committee-5 Early Assessment and Intervention Working Group(N1634)。
文摘Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype(“morningness”or “eveningness”) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness,and symptoms of depression, anxiety, and post-traumatic stress disorder(PTSD) in US service members(n=298).Although predominantly young males(who skew toward eveningness in civilian populations), these Sailors skewed toward morningness(35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD(P<0.01), less time in bed(P<0.05), more sleep disruption(P<0.01), and poorer daytime functioning and alertness(P<0.05). Evening types were less likely to consider sleep important for performance(P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.
基金This project was funded in part by federal funds from the National Cancer Institute,National Institutes of Health,under Contract No.HHSN261200800001Ewas supported in part by the Intramural Research Program of the NCI,NIH.
文摘For the past twenty years,chemokines have emerged as a family of critical mediators of cell migration during immune surveillance,development,inflammation and cancer progression.Chemokines bind to seven transmembrane G protein-coupled receptors(GPCRs)that are expressed by a wide variety of cell types and cause conformational changes in trimeric G proteins that trigger the intracellular signaling pathways necessary for cell movement and activation.Although chemokines have evolved to benefit the host,inappropriate regulation or utilization of these small proteins may contribute to or even cause diseases.Therefore,understanding the role of chemokines and their GPCRs in the complex physiological and diseased microenvironment is important for the identification of novel therapeutic targets.This review introduces the functional array and signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as their roles in homeostasis,inflammation,immune responses and cancer.
基金Research performed by Leidos Research Support Team staff was conducted under the RSS contract 89243318CFE000003This research was supported in part by an appointment to the U.S.Department of Energy(DOE)Postgraduate Research Program at the National Energy Technology Laboratory(NETL)administered by the Oak Ridge Institute for Science and EducationThis research used resources of Oak Ridge National Laboratory’s Compute and Data Environment for Science(CADES)and the Oak Ridge Leadership Computing Facility,which is supported by the Office of Science of the U.S.Department of Energy under Contract No.DE-AC05-00OR22725.
文摘The empirical rules for the prediction of solid solution formation proposed so far in the literature usually have very compromised predictability.Some rules with seemingly good predictability were,however,tested using small data sets.Based on an unprecedented large dataset containing 1252 multicomponent alloys,machine-learning methods showed that the formation of solid solutions can be very accurately predicted(93%).The machine-learning results help identify the most important features,such as molar volume,bulk modulus,and melting temperature.
文摘In this research,a Graphical Processing Unit(GPU)accelerated Discrete Element Method(DEM)code was developed and coupled with the Computational Fluid Dynamic(CFD)software MFiX to simulate granular and multiphase flows with heat transfers and chemical reactions.The Fortran-based CFD solver was coupled with the CUDA/C++based DEM solver through inter-process pipes.The speedup to the CPU version of MFiX-DEM is about 130-243 folds in the simulation of particle packings.In fluidized bed simulations,the DEM computation time is reduced from 91%to 17%with a speedup of 78 folds.The simulation of Geldart A particle fluidization revealed a similar level of importance of both fluid and particle coarse-graining.The filtered drag derived from the two-fluid model is suitable for Euler-Lagrangian simulations with both fluid and particle coarse-graining.It overcorrects the influence of sub-grid structures if used for simulations with only fluid coarse-graining.
基金supported in part by the United States National Science Foundation Grant#1932452 and Federal Highway Administration Grant#DTFH6116D00030.
文摘High-granularity vehicle trajectory data can help researchers develop traffic simulation models,understand traffic flow characteristics,and thus propose insightful strategies for road traffic management.This paper proposes a novel vehicle trajectory extraction method that can extract high-granularity vehicle trajectories from aerial videos.The proposed method includes video calibration,vehicle detection and tracking,lane marking identification,and vehicle motion characteristics calculation.In particular,the authors propose a Monte-Carlo-based lane marking identification approach to identify each vehicle's lane.This is a challenging problem for vehicle trajectory extraction,especially when the aerial videos are taken from a high altitude.The authors applied the proposed method to extract vehicle trajectories from several high-resolution aerial videos recorded from helicopters.The extracted dataset is named by the High-Granularity Highway Simulation(HIGH-SIM)vehicle trajectory dataset.To demonstrate the effectiveness of the proposed method and understand the quality of the HIGHSIM dataset,we compared the HIGH-SIM dataset with a well-known dataset,the NGSIM US-101 dataset,regarding the accuracy and consistency aspects.The comparison results showed that the HIGH-SIM dataset has more reasonable speed and acceleration distributions than the NGSIM US-101 dataset.Also,the internal and platoon consistencies of the HIGH-SIM dataset give lower errors compared to the NGSIM US-101 dataset.To benefit future research,the authors have published the HIGH-SIM dataset online for public use.
文摘Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SSIP modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies （ADA）, whereas mice immunized with SSIP, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.
文摘This article presents the development and validation of the Superquadric Discrete Element Method(SuperDEM)for non-spherical particle simulation using a superquadric particle method in open-source CFD suite MFiX.A superquadric particle-particle contact algorithm with accelerating and stabilizing strategy was developed.A superquadric particle-arbitrary wall contact algorithm was developed,which enables the simulation in complex geometry.The solver was validated by comparing with experimental data generated in this study or available in the literature.Tests include cylinder contacting with a wall,static packing of M&M chocolate candies in a cylindrical container,static packing of cylinders in a cylindrical container,dynamic angle of repose of cylinders in a rotating drum,and discharging of chocolate candies from a hopper.Besides,MPI parallelization of the solver was implemented and the parallel performance of the solver using MPI was assessed through large-scale simulations of 1 million,10 million,and 100 million particles on up to 6800 cores,which demonstrates that the SuperDEM solver has great potential for industrial-scale systems simulation.
基金supported by the Office of Nuclear Energy of Department of Energy(grant No.DE-NE0008807).
文摘Polysiloxane coatings on yttria stabilized zirconia(YSZ)microspheres of 500μm were simulated in a spout fluidized bed coater using Multiphase Flow with Interface Exchange-Discrete Element Modelling(MFiX-DEM).Two different coater configurations were developed to study the influence of gas velocity and its distribution on particle dynamics.The presence of the Wurster tube not only enhances the dis-tribution but also increases the overall residence time of the particles.Investigations were also carried out with different Wurster tube positions(normal,10%and 20%lowered from its initial position).Among these,20%lowered Wurster tube position demonstrated the most effective coating process.The effects of gas inlet pressure on the average gas velocity and the distribution of particles were analyzed.More than 97%of the particles can be retained.The derived results,including average gas velocity,particle retention percentage,and distribution of particles with gas velocity,are being used to guide the experimental work in obtaining defect-free coatings for YSZ microspheres.
文摘An unknown in coupled Eulerian-Lagrangian models for particle flow,such as CFD-DEM,which has received fairly little attention in the literature to date is the size of the filter width in the transfer kernel.This work provides a preliminary glimpse at how this parameter can influence the solution in cold-flow,unbounded fluidization.Comparison to previously published direct numerical simulation data is used to suggest an appropriate range for this parameter.
基金This technical effort was performed in support of the Cross-Cutting Technologies Program of the National Energy Technology Laboratory(NETL)under the RSS contract 89243318CFE000003The research was executed through NETL Research&Innovation Center’s project coordinated by David E.Alman and was specifically under the advanced alloy development FWP led by Drs.David Alman and Jeffrey A.Hawk and in part through the XMAT project.This work partially used the Extreme Science and Engineering Discovery Environment(XSEDE),which is supported by National Science Foundation grant number ACI-1548562.
文摘A phase-field model is proposed to simulate coherency loss coupled with microstructure evolution.A special field variable is employed to describe the degree of coherency loss of each particle and its evolution is governed by a Ginzburg-Landau type kinetic equation.For the sake of computational efficiency,a flood-fill algorithm is introduced that can drastically reduce the required number of field variables,which allows the model to efficiently simulate a large number of particles sufficient for characterizing their statistical features during Ostwald ripening.The model can incorporate size dependence of coherency loss,metastability of coherent particles,and effectively incorporate the underlying mechanisms of coherency loss by introducing a so-called differential energy criterion.The model is applied to simulate coarsening of Al3Sc precipitates in aluminum alloy and comprehensively compared with experiments.Our results clearly show how the particle size distribution is changed during coherency loss and affects the coarsening rate.
文摘Modeling of ductile fracture in polycrystalline structures is challenging,since it requires integrated modeling of cracks,crystal plasticity,and grains.Here we extend the typical phase-field framework to the situations with constraints on the order parameters,and formulate two types of phase-field models on ductile fracture.The Type-Ⅰ model incorporates three sets of order parameters,which describe the distributions of cracks,plastic strain,and grains,respectively.Crystal plasticity is employed within grain interiors accommodated by J_(2)plasticity at grain boundaries.The applications of the Type-Ⅰ model to single crystals and bicrystals demonstrate the influences of grain orientations and grain boundaries on crack growth.In the Type-Ⅱ model,J_(2)plasticity is assumed for the whole system and grain structures are neglected.Taking advantage of the efficiency of the fast Fourier transform,our Type-Ⅱ model is employed to study low cycle fatigue.Crack closure and striation-like patterning of plastic strain are observed in the simulations.Crack growth rate is analyzed as a function of the J-integral,and the simulated fatigue life as a function of plastic strain agrees with the Coffin–Manson relation without a priori assumption.
