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1.
PLoS One ; 19(5): e0302882, 2024.
Article in English | MEDLINE | ID: mdl-38718059

ABSTRACT

Winter wheat is one of the most important crops in the world. It is great significance to obtain the planting area of winter wheat timely and accurately for formulating agricultural policies. Due to the limited resolution of single SAR data and the susceptibility of single optical data to weather conditions, it is difficult to accurately obtain the planting area of winter wheat using only SAR or optical data. To solve the problem of low accuracy of winter wheat extraction only using optical or SAR images, a decision tree classification method combining time series SAR backscattering feature and NDVI (Normalized Difference Vegetation Index) was constructed in this paper. By synergy using of SAR and optical data can compensate for their respective shortcomings. First, winter wheat was distinguished from other vegetation by NDVI at the maturity stage, and then it was extracted by SAR backscattering feature. This approach facilitates the semi-automated extraction of winter wheat. Taking Yucheng City of Shandong Province as study area, 9 Sentinel-1 images and one Sentinel-2 image were taken as the data sources, and the spatial distribution of winter wheat in 2022 was obtained. The results indicate that the overall accuracy (OA) and kappa coefficient (Kappa) of the proposed method are 96.10% and 0.94, respectively. Compared with the supervised classification of multi-temporal composite pseudocolor image and single Sentinel-2 image using Support Vector Machine (SVM) classifier, the OA are improved by 10.69% and 5.66%, respectively. Compared with using only SAR feature for decision tree classification, the producer accuracy (PA) and user accuracy (UA) for extracting the winter wheat are improved by 3.08% and 8.25%, respectively. The method proposed in this paper is rapid and accurate, and provide a new technical method for extracting winter wheat.


Subject(s)
Decision Trees , Seasons , Triticum , Triticum/growth & development , China , Crops, Agricultural/growth & development
2.
Adv Sci (Weinh) ; : e2400405, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682479

ABSTRACT

Lithium-ion batteries (LIBs) are currently the predominant energy storage power source. However, the urgent issues of enhancing electrochemical performance, prolonging lifetime, preventing thermal runaway-caused fires, and intelligent application are obstacles to their applications. Herein, bio-inspired electrodes owning spatiotemporal management of self-healing, fast ion transport, fire-extinguishing, thermoresponsive switching, recycling, and flexibility are overviewed comprehensively, showing great promising potentials in practical application due to the significantly enhanced durability and thermal safety of LIBs. Taking advantage of the self-healing core-shell structures, binders, capsules, or liquid metal alloys, these electrodes can maintain the mechanical integrity during the lithiation-delithiation cycling. After the incorporation of fire-extinguishing binders, current collectors, or capsules, flame retardants can be released spatiotemporally during thermal runaway to ensure safety. Thermoresponsive switching electrodes are also constructed though adding thermally responsive components, which can rapidly switch LIB off under abnormal conditions and resume their functions quickly when normal operating conditions return. Finally, the challenges of bio-inspired electrode designs are presented to optimize the spatiotemporal management of LIBs. It is anticipated that the proposed electrodes with spatiotemporal management will not only promote industrial application, but also strengthen the fundamental research of bionics in energy storage.

3.
Sensors (Basel) ; 23(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37960396

ABSTRACT

The main application scenario for wearable sensors involves the generation of data and monitoring metrics. fNIRS (functional near-infrared spectroscopy) allows the nonintrusive monitoring of human visual perception. The quantification of visual perception by fNIRS facilitates applications in engineering-related fields. This study designed a set of experimental procedures to effectively induce visible alterations and to quantify visual perception in conjunction with the acquisition of Hbt (total hemoglobin), Hb (hemoglobin), and HbO2 (oxygenated hemoglobin) data obtained from HfNIRS (high-density functional near-infrared spectroscopy). Volunteers completed the visual task separately in response to different visible changes in the simulated scene. HfNIRS recorded the changes in Hbt, Hb, and HbO2 during the study, the time point of the visual difference, and the time point of the task change. This study consisted of one simulated scene, two visual variations, and four visual tasks. The simulation scene featured a car driving location. The visible change suggested that the brightness and saturation of the car operator interface would change. The visual task represented the completion of the layout, color, design, and information questions answered in response to the visible change. This study collected data from 29 volunteers. The volunteers completed the visual task separately in response to different visual changes in the same simulated scene. HfNIRS recorded the changes in Hbt, Hb, and HbO2 during the study, the time point of the visible difference, and the time point of the task change. The data analysis methods in this study comprised a combination of channel dimensionality reduction, feature extraction, task classification, and score correlation. Channel downscaling: This study used the data of 15 channels in HfNIRS to calculate the mutual information between different channels to set a threshold, and to retain the data of the channels that were higher than those of the mutual information. Feature extraction: The statistics derived from the visual task, including time, mean, median, variance, extreme variance, kurtosis, bias, information entropy, and approximate entropy were computed. Task classification: This study used the KNN (K-Nearest Neighbors) algorithm to classify different visual tasks and to calculate the accuracy, precision, recall, and F1 scores. Scoring correlation: This study matched the visual task scores with the fluctuations of Hbt, Hb, and HbO2 and observed the changes in Hbt, Hb, and HbO2 under different scoring levels. Mutual information was used to downscale the channels, and seven channels were retained for analysis under each visual task. The average accuracy was 96.3% ± 1.99%; the samples that correctly classified the visual task accounted for 96.3% of the total; and the classification accuracy was high. By analyzing the correlation between the scores on different visual tasks and the fluctuations of Hbt, Hb, and HbO2, it was found that the higher the score, the more obvious, significant, and higher the fluctuations of Hbt, Hb, and HbO2. Experiments found that changes in visual perception triggered changes in Hbt, Hb, and HbO2. HfNIRS combined with Hbt, Hb, and HbO2 recorded by machine learning algorithms can effectively quantify visual perception. However, the related research in this paper still needs to be further refined, and the mathematical relationship between HfNIRS and visual perception needs to be further explored to realize the quantitative study of subjective and objective visual perception supported by the mathematical relationship.


Subject(s)
Hemoglobins , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Oxyhemoglobins , Algorithms , Visual Perception
4.
Front Bioeng Biotechnol ; 11: 1153265, 2023.
Article in English | MEDLINE | ID: mdl-37077231

ABSTRACT

Objective: Autonomous vehicles (Avs) have paved the way for the arrangement of swivel seats in vehicles, which could pose a challenge to traditional safety systems. The integration of automated emergency braking (AEB) and pre-pretension (PPT) seatbelts improves protection for a vehicle's occupant. The objective of this study is to explore the control strategies of an integrated safety system for swiveled seating orientations. Methods: Occupant restraints were examined in various seating configurations using a single-seat model with a seat-mounted seatbelt. Seat orientation was set at different angles, from -45° to 45° with 15° increments. A pretension was used on the shoulder belt to represent an active belt force cooperating with AEB. A generic full frontal vehicle pulse of 20 mph was applied to the sled. The occupant's kinematics response under various integrated safety system control strategies was analyzed by extracting a head pre-crash kinematics envelope. The injury values were calculated for various seating directions with or without an integrated safety system at the collision speed of 20 mph. Results: In a lateral movement, the excursions of the dummy head were 100 mm and 70 mm in the global coordinate system for negative and positive seat orientations, respectively. In the axial movement, the head traveled 150 mm and 180 mm in the global coordinate system for positive and negative seating directions, respectively. The 3-point seatbelt did not restrain the occupant symmetrically. The occupant experienced greater y-axis excursion and smaller x-axis excursion in the negative seat position. Various integrated safety system control strategies led to significant differences in head movement in the y direction. The integrated safety system reduced the occupant's potential injury risks in different seating positions. When the AEB and PPT were activated, the absolute HIC15, brain injury criteria (BrIC), neck injury (Nij), and chest deflection were reduced in most seating directions. However, the pre-crash increased the injury risks at some seating positions. Conclusion: The pre-pretension seatbelt could reduce the occupant's forward movement in the rotating seat positions in a pre-crash period. The occupant's pre-crash motion envelope was generated, which could be beneficial to future restraint systems and vehicle interior design. The integrated safety system could reduce injuries in different seating orientations.

5.
Sensors (Basel) ; 22(23)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36502134

ABSTRACT

Big data already covers intelligent vehicles and is driving the autonomous driving industry's transformation. However, the large amounts of driving data generated will result in complex issues and a huge workload for the test and verification processes of an autonomous driving system. Only effective and precise data extraction and recording aimed at the challenges of low efficiency, poor quality, and a long-time limit for traditional data acquisition can substantially reduce the algorithm development cycle. Based on the premise of driver-dominated vehicle movement, the virtual decision-making of autonomous driving systems under the accompanying state was considered as a reference. Based on a dynamic time warping algorithm and forming a data filtering approach under a dynamic time window, an automatic trigger recording control model for human-vehicle difference feature data was suggested. In this method, the data dimension was minimized, and the efficiency of the data mining was improved. The experimental findings showed that the suggested model decreased recorded invalid data by 75.35% on average and saved about 2.65 TB of data storage space per hour. Compared with industrial-grade methods, it saves an average of 307 GB of storage space per hour.


Subject(s)
Algorithms , Intelligence , Humans , Data Mining , Big Data , Time Factors
6.
Adv Sci (Weinh) ; 9(5): e2103796, 2022 02.
Article in English | MEDLINE | ID: mdl-34923778

ABSTRACT

Vigorous development of electric vehicles is one way to achieve global carbon reduction goals. However, fires caused by thermal runaway of the power battery has seriously hindered large-scale development. Adding thermal runaway retardants (TRRs) to electrolytes is an effective way to improve battery safety, but it often reduces electrochemical performance. Therefore, it is difficult to apply in practice. TRR encapsulation is inspired by the core-shell structures such as cells, seeds, eggs, and fruits in nature. In these natural products, the shell isolates the core from the outside, and has to break as needed to expose the core, such as in seed germination, chicken hatching, etc. Similarly, TRR encapsulation avoids direct contact between the TRR and the electrolyte, so it does not affect the electrochemical performance of the battery during normal operation. When lithium-ion battery (LIB) thermal runaway occurs, the capsules release TRRs to slow down and even prevent further thermal runaway. This review aims to summarize the fundamentals of bioinspired TRR capsules and highlight recent key progress in LIBs with TRR capsules to improve LIB safety. It is anticipated that this review will inspire further improvement in battery safety, especially for emerging LIBs with high-electrochemical performance.


Subject(s)
Electric Power Supplies , Lithium , Capsules , Electrolytes , Ions , Lithium/chemistry
7.
iScience ; 24(5): 102401, 2021 May 21.
Article in English | MEDLINE | ID: mdl-33997686

ABSTRACT

Lithium-ion batteries are applied in electric vehicles to mitigate climate change. However, their practical applications are impeded by poor safety performance owing mainly to the cell eruption gas (CEG) fire triangle. Here, we report quantitatively the three fire boundaries corresponding to the CEG fire triangle of four types of mainstream cells with the state of charge (SOC) values ranging from 0% to 143% based on 29 thermal runaway tests conducted in an inert atmosphere in open literature. Controlling the SOC and/or selecting a reasonable cell type can alter the minimum CEG and oxygen concentrations required for ignition, thereby changing the probability of a battery fire. The ignition temperature varies greatly according to the type of ignition source type. Temperature and ignition source type play a leading role in the ignition mode. Breaking any fire boundary will stop the ignition of CEG, thus significantly improving the battery safety performance.

8.
Sensors (Basel) ; 21(3)2021 Jan 25.
Article in English | MEDLINE | ID: mdl-33504010

ABSTRACT

Brain-like intelligent decision-making is a prevailing trend in today's world. However, inspired by bionics and computer science, the linear neural network has become one of the main means to realize human-like decision-making and control. This paper proposes a method for classifying drivers' driving behaviors based on the fuzzy algorithm and establish a brain-inspired decision-making linear neural network. Firstly, different driver experimental data samples were obtained through the driving simulator. Then, an objective fuzzy classification algorithm was designed to distinguish different driving behaviors in terms of experimental data. In addition, a brain-inspired linear neural network was established to realize human-like decision-making and control. Finally, the accuracy of the proposed method was verified by training and testing. This study extracts the driving characteristics of drivers through driving simulator tests, which provides a driving behavior reference for the human-like decision-making of an intelligent vehicle.

9.
Rev Assoc Med Bras (1992) ; 66(5): 637-642, 2020 May.
Article in English | MEDLINE | ID: mdl-32638955

ABSTRACT

Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the "most comfortable" driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.


Subject(s)
Posture , Sitting Position , Automobiles , Ergonomics , Humans , Lumbar Vertebrae
10.
Traffic Inj Prev ; 21(4): 254-258, 2020.
Article in English | MEDLINE | ID: mdl-32310690

ABSTRACT

Objective:The moral and ethical issue is a great challenge to the development of autonomous vehicles. There may be distinctions between the choices made by an observer and a participant. The paper is designed to investigate whether drivers will sacrifice the fewest people to save more people in social dilemma, and whether human drivers would give priority to protecting pedestrians or self-protection in an emergency.Methodology: The experiment was conducted with a total of 50 participants assigned to three groups. Three experimental scenarios were designed and each of them contained a social dilemma. A driving simulator was used in this study to explore the choices of human drivers in social dilemma. In addition, the simulator results were compared with those of questionnaire survey.Result: In study 1, 73% of 22 participants swerved into the right lane to hit only one pedestrian for the safety of other five. In study 2 and 3, more participants chose to hit the barrier to protect the pedestrian.Conclusion: A conclusion can be drawn from the second and third group of experiments that most drivers consider not only their own safety, but the safety of pedestrians. Most of the participants intended to minimize the total amount of harm in social dilemma. The choice of crashing into barriers to protect a pedestrian can also be seen as a way to minimize the total amount of harm.


Subject(s)
Automobile Driving/psychology , Conflict, Psychological , Instinct , Adult , Choice Behavior , Computer Simulation , Female , Humans , Male , Pedestrians , Self Care , Surveys and Questionnaires , Young Adult
11.
Sensors (Basel) ; 20(7)2020 Mar 26.
Article in English | MEDLINE | ID: mdl-32225085

ABSTRACT

Simultaneous localization and mapping have become a basic requirement for most automatic moving robots. However, the LiDAR scan suffers from skewing caused by high-acceleration motion that reduces the precision in the latter mapping or classification process. In this study, we improve the quality of mapping results through a de-skewing LiDAR scan. By integrating high-sampling frequency IMU (inertial measurement unit) measurements and establishing a motion equation for time, we can get the pose of every point in this scan's frame. Then, all points in this scan are corrected and transformed into the frame of the first point. We expand the scope of optimization range from the current scan to a local range of point clouds that not only considers the motion of LiDAR but also takes advantage of the neighboring LiDAR scans. Finally, we validate the performance of our algorithm in indoor and outdoor experiments to compare the mapping results before and after de-skewing. Experimental results show that our method smooths the scan skewing on each channel and improves the mapping accuracy.

12.
Rev Assoc Med Bras (1992) ; 66(5): 637-642, 2020. graf
Article in English | Sec. Est. Saúde SP, LILACS | ID: biblio-1136251

ABSTRACT

SUMMARY Using computer-aided engineering (CAE) in the concept design stage of automobiles has become a hotspot in human factor engineering research. Based on human musculoskeletal biomechanical computational software, a seated human-body musculoskeletal model was built to describe the natural sitting posture of a driver. The interaction between the driver and car in various combinations of seat-pan/back-rest inclination angles was analyzed using an inverse-dynamics approach. In order to find out the "most comfortable" driving posture of the seat-pan/back-rest, the effect of seat-pan/back-rest inclination angles on the muscle activity degree, and the intradiscal L4-L5 compression force were investigated. The results showed that a much larger back-rest inclination angle, approximately 15°, and a slight backward seat-pan, about 7°, may relieve muscle fatigue and provide more comfort while driving. Subsequently, according to the findings above, a preliminary driving-comfort function was constructed.


RESUMO O uso de engenharia assistida por computador (CAE) na fase de projeto do conceito do automóvel tornou-se um ponto de acesso na pesquisa de fatores humanos. Com base no software computacional biomecânico musculoesquelético humano, foi construído um modelo musculoesquelético sentado para descrever a postura sentada natural de um condutor. A interação entre um motorista e um carro em várias combinações de ângulos de inclinação do assento-pan/encosto foi analisada usando uma abordagem dinâmica do verso. A fim de descobrir a postura de condução "mais confortável" do assento-pan/encosto, o efeito dos ângulos de inclinação do assento-pan/dorso sobre o grau de atividade muscular e a força de compressão intradiscal L4-L5 foi investigado. Os resultados mostraram que um ângulo de inclinação para trás muito maior, aproximadamente 15°, e um ligeiro assento-pan para trás, cerca de 7°, pode aliviar a fadiga muscular e levar a dirigir em uma posição confortável. Posteriormente, de acordo com as conclusões acima expostas, foi construída uma função preliminar de conforto ao dirigir.


Subject(s)
Humans , Posture , Sitting Position , Automobiles , Ergonomics , Lumbar Vertebrae
13.
Cell ; 170(3): 577-592.e10, 2017 Jul 27.
Article in English | MEDLINE | ID: mdl-28753431

ABSTRACT

Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.


Subject(s)
Neoplasms/genetics , Neoplasms/pathology , RNA Interference , Cell Line, Tumor , Gene Library , Gene Regulatory Networks , Humans , Multiprotein Complexes/metabolism , Neoplasms/metabolism , Oncogenes , RNA, Small Interfering , Signal Transduction , Transcription Factors/metabolism
14.
Traffic Inj Prev ; 17(4): 423-9, 2016 05 18.
Article in English | MEDLINE | ID: mdl-26375629

ABSTRACT

OBJECTIVE: A driver's instinctive response of the lower extremity in braking movement consists of two parts, including reaction time and braking reaction behavior. It is critical to consider these two components when conducting studies concerning driver's brake movement intention and injury analysis. The purposes of this study were to investigate the driver reaction time to an oncoming collision and muscle activation of lower extremity muscles at the collision moment. The ultimate goal is to provide data that aid in both the optimization of intervention time of an active safety system and the improvement of precise protection performance of a passive safety system. METHOD: A simulated collision scene was constructed in a driving simulator, and 40 young volunteers (20 male and 20 female) were recruited for tests. Vehicle control parameters and electromyography characteristics of eight muscles of the lower extremity were recorded. The driver reaction time was divided into pre-motor time (PMT) and muscle activation time (MAT). Muscle activation level (ACOL) at the collision moment was calculated and analysed. RESULTS: PMT was shortest for the tibialis anterior (TA) muscle (243∼317 ms for male and 278∼438 ms for female). Average MAT of the TA ranged from 28-55 ms. ACOL was large (5∼31% for male and 5∼23% for female) at 50 km/h, but small (<12%) at 100 km/h. ACOL of the gluteus maximus was smallest (<3%) in the 25 and 100 km/h tests. ACOL of RF of men was significantly smaller than that of women at different speeds. CONCLUSIONS: Ankle dorsiflexion is firstly activated at the beginning of the emergency brake motion. Males showed stronger reaction ability than females, as suggested by male's shorter PMT. The detection of driver's brake intention is upwards of 55ms sooner after introducing the electromyography. Muscle activation of the lower extremity is an important factor for 50 km/h collision injury analysis. For higher speed collisions, this might not be a major factor. The activations of certain muscles may be ignored for crash injury analysis at certain speeds, such as gluteus maximus at 25 or 100 km/h. Furthermore, the activation of certain muscles should be differentiated between males and females during injury analysis.


Subject(s)
Accidents, Traffic/statistics & numerical data , Automobile Driving/psychology , Lower Extremity/physiology , Reaction Time/physiology , Adult , Automobile Driving/statistics & numerical data , Computer Simulation , Electromyography , Female , Humans , Male , Muscle, Skeletal/physiology , Young Adult
15.
Biomed Mater Eng ; 26 Suppl 1: S563-73, 2015.
Article in English | MEDLINE | ID: mdl-26406050

ABSTRACT

A driver's response to a front-coming vehicle collision consists of braking reaction time and braking behavior. The purpose was to investigate drivers' responses at different speeds, relative distances, and particularly the behavior on the accelerator at the collision moment. Twelve young men participated in driving simulator tests. Vehicle parameters and electromyograms (EMGs) of the drivers' tibialis anterior muscles were recorded and responses were analyzed. The drivers' braking reaction time windows were divided into pre-motor time, muscle activation time, accelerator release time, and movement time. By comparing the reaction times and collision times, braking behaviors were investigated. It was found that movement times (r = -0.281) decreased with speed. Pre-motor times (r = 0.326) and muscle activation times (r = 0.281) increased with relative distance. At the collision moment, the probability of the driver's lower extremity being on the accelerator, in the air, and on the brake pedal was 7.4%, 18.9%, and 73.7%, respectively. With higher speeds and smaller distances, the lower extremity was more likely to be in the air or even on the accelerator in different muscle activation states. The driver will collide in normal driving postures which muscles are not or not fully activated in very urgent situation.


Subject(s)
Accidents, Traffic , Automobile Driving , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Psychomotor Performance/physiology , Reaction Time/physiology , Adult , Electromyography/methods , Humans , Leg/physiology , Male , Reproducibility of Results , Sensitivity and Specificity
16.
Biomed Mater Eng ; 26 Suppl 1: S619-27, 2015.
Article in English | MEDLINE | ID: mdl-26406056

ABSTRACT

Frontal vehicle collisions can cause injury to a driver's cervical muscles resulting from intense changes in muscle strain and muscle load. This study investigated the influence of collision forces in a sled test environment using a modified Hybrid III 50th percentile dummy equipped with simulated spring-type muscles. Cervical muscle responses including strain and load of the sternocleidomastoid (SCM), splenius capitis (SPL), and trapezius (TRP) were analyzed, and muscle injury was assessed. The SCM, SPL, and TRP suffered average peak muscle strains of 21%, 40%, and 23%, respectively, exceeding the injury threshold. The average peak muscle loads of the SCM, SPL and TRP were 11 N, 25 N, and 25 N, respectively, lower than the ultimate failure load. The SPL endured the largest injury, while the injuries to the SCM and TRP were relatively small. This is a preliminary study to assess the cervical muscle of driver during a frontal vehicle collision. This study provides a foundation for investigating the muscle response and injury in sled test environments, which can lead to the improvement of occupant protections.


Subject(s)
Manikins , Models, Biological , Muscle Contraction , Neck Muscles/injuries , Neck Muscles/physiopathology , Whiplash Injuries/physiopathology , Accidents, Traffic , Computer Simulation , Humans , Stress, Mechanical , Tensile Strength
18.
Elife ; 4: e06535, 2015 Jun 17.
Article in English | MEDLINE | ID: mdl-26083714

ABSTRACT

CDK9 is the kinase subunit of positive transcription elongation factor b (P-TEFb) that enables RNA polymerase (Pol) II's transition from promoter-proximal pausing to productive elongation. Although considerable interest exists in CDK9 as a therapeutic target, little progress has been made due to lack of highly selective inhibitors. Here, we describe the development of i-CDK9 as such an inhibitor that potently suppresses CDK9 phosphorylation of substrates and causes genome-wide Pol II pausing. While most genes experience reduced expression, MYC and other primary response genes increase expression upon sustained i-CDK9 treatment. Essential for this increase, the bromodomain protein BRD4 captures P-TEFb from 7SK snRNP to deliver to target genes and also enhances CDK9's activity and resistance to inhibition. Because the i-CDK9-induced MYC expression and binding to P-TEFb compensate for P-TEFb's loss of activity, only simultaneously inhibiting CDK9 and MYC/BRD4 can efficiently induce growth arrest and apoptosis of cancer cells, suggesting the potential of a combinatorial treatment strategy.


Subject(s)
Cyclin-Dependent Kinase 9/metabolism , Gene Expression Regulation , Nuclear Proteins/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Transcription Factors/metabolism , Cell Cycle Proteins , Cyclin-Dependent Kinase 9/antagonists & inhibitors , Humans , Positive Transcriptional Elongation Factor B/metabolism
19.
J Med Chem ; 57(21): 9124-9, 2014 Nov 13.
Article in English | MEDLINE | ID: mdl-25368984

ABSTRACT

Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.


Subject(s)
Antineoplastic Agents/chemical synthesis , Pyridones/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Mice , Pyridones/pharmacokinetics , Pyridones/pharmacology , Pyrimidines/pharmacokinetics , Pyrimidines/pharmacology , Structure-Activity Relationship
20.
Biomed Mater Eng ; 24(6): 2697-706, 2014.
Article in English | MEDLINE | ID: mdl-25226974

ABSTRACT

In this study a musculoskeletal model of driver steering maneuver was established. The model was driven by the steering angle and steering torque when performing typical steering test. The simulation was calculated using inverse dynamics. Maximum muscle activity and the muscle activity of each muscle were studied afterwards. The key muscles that generated steering torque were scapular portion of deltoid, infraspinatus, latissimus dorsi, subscapularis, triceps long head and triceps lateral head. Muscle co-contraction was analyzed quantitatively and was significantly different from muscle activity. This paper presents a preliminary research on the mechanical properties of upper limb muscles during steering maneuver. The results can serve as references for vehicle design and performance evaluation using the physiological characteristics of drivers.


Subject(s)
Automobile Driving , Models, Biological , Movement/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Postural Balance/physiology , Task Performance and Analysis , Arm/physiology , Computer Simulation , Humans , Torque
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