Purpose The present study examined the effects of a reciprocal,slow velocity forearm flexion and extension task on fatigue-induced changes in isokinetic torque,agonist and antagonist muscle activation,and coactivation...Purpose The present study examined the effects of a reciprocal,slow velocity forearm flexion and extension task on fatigue-induced changes in isokinetic torque,agonist and antagonist muscle activation,and coactivation ratios at slow and moderate velocities.Methods Nine women(mean±SD:age=21.0±1.7 years;body mass=68.1±8.2 kg;height=167.4±7.2 cm)completed pre-testing for forearm flexion and extension isokinetic peak torque at 60 and 180°/s,a fatiguing task of 50 maximal,recip-rocal,isokinetic muscle actions at 60°/s,and post-testing.The amplitude(AMP)of the electromyographic(EMG)signals from the biceps and triceps were simultaneously recorded.Torque and EMG AMP were normalized to the corresponding values from the pre-testing peak torque movements.Repeated measures ANOVAs and pairwise comparisons were used to identify mean changes in torque,EMG AMP,and coactivation ratios.Results The torque analyses indicated significant decreases from pre-to post-testing for forearm flexion(14.1%±5.0%;P<0.001)and extension(25.4%±12.2%;P<0.001)at 60°.At 180°/s there was a significant decrease,collapsed across the forearm movements(24.7%±11.7%;P<0.001).For EMG AMP and coactivation ratios,there were no changes(P>0.05)from pre-to post-testing for either velocity or movement.Conclusions The torque responses were velocity-specific,with greater fatigability exhibited for forearm extension versus flexion at 60°/s,but no differences at 180°/s.The parallel EMG AMP responses between the agonist and antagonist muscles for both velocities supported the lack of fatigue-induced changes in coactivation ratios.Thus,our results demonstrated that fatigue-induced decreases in torque were not attributable to increases in antagonist activation or coactivation.展开更多
The production of CH_(3)COOH from CO_(2)and CH_(4) has stimulated much interest due to the high energy density of C2 species.Various kinds of catalysts have been developed while the high dissociation barrier of CH_(4)...The production of CH_(3)COOH from CO_(2)and CH_(4) has stimulated much interest due to the high energy density of C2 species.Various kinds of catalysts have been developed while the high dissociation barrier of CH_(4) and low selectivity still hinders the efficiency of the reaction.We have herein proposed a novel catalyst with single metals loaded on 2D BC_(3)N_(2) substrate(M@2D-BC_(3)N_(2))based on density functional theory.Among numerous candidates,Pt@2D-BC_(3)N_(2) possesses the most favorable reactivity with an ultralow barrier of CH_(4) splitting(0.26 e V),which is due to the efficient capture ability of CH_(4) on Pt site.Besides,the selectivity for CH_(3)COOH is also very high,which mainly stems from the unique electronic properties of molecules and substrate:The degenerated states,including s,px,pyand pz,in CO_(2)reflects the existence of delocalizedπbonds between C and O.This can interact with states of Pt(s),Pt(pz),Pt(dxz),Pt(dyz),and Pt(z2)in Pt@2D-BC_(3)N_(2).The kinetics model also proves that our system can promote CH_(3)COOH production via simply increasing the temperature or the coverage of CH_(4) and CO_(2).Our results provide a reasonable illustration in clarifying mechanism and propose promising candidates with high reactivity for further study.展开更多
Synthetic gene activators consisting of nucleasedead Cas9(dCas9)for single-guide RNA(sgRNA)-directed promoter binding and a transcriptional activation domain(TAD)represent new tools for gene activation from endogenous...Synthetic gene activators consisting of nucleasedead Cas9(dCas9)for single-guide RNA(sgRNA)-directed promoter binding and a transcriptional activation domain(TAD)represent new tools for gene activation from endogenous genomic locus in basic and applied plant research.However,multiplex gene coactivation by d Cas9-TADs has not been demonstrated in whole plants.There is also room to optimize the performance of these tools.Here,we report that our previously developed gene activator,dCas9-TV,could simultaneously upregulate OsGW7 and OsER1 in rice by up to 3,738 fold,with one sg RNA targeting to each promoter.The gene coactivation could persist to at least the fourth generation.Astonishingly,thepolycistronictRNA-sgRNAexpression under the maize ubiquitin promoter,a Pol II promoter,could cause enormous activation of these genes by up to>40,000-fold in rice.Moreover,the yeast GCN4 coiled coil-mediated dCas9-TV dimerization appeared to be promising for enhancing gene activation.Finally,we successfully introduced a self-amplification loop for dCas9-TV expression in Arabidopsis to promote the transcriptional upregulation of AtFLS2,a previously characterized dCas9-TV-refractory gene with considerable basal expression.Collectively,this work illustrates the robustness of dCas9-TV in multigene coactivation and provides broadly useful strategies for boosting transcriptional activation efficacy of dCas9-TADs in plants.展开更多
Unmanned Aerial Vehicles(UAVs)are useful in dangerous and dynamic tasks such as search-and-rescue,forest surveillance,and anti-terrorist operations.These tasks can be solved better through the collaboration of multipl...Unmanned Aerial Vehicles(UAVs)are useful in dangerous and dynamic tasks such as search-and-rescue,forest surveillance,and anti-terrorist operations.These tasks can be solved better through the collaboration of multiple UAVs under human supervision.However,it is still difficult for human to monitor,understand,predict and control the behaviors of the UAVs due to the task complexity as well as the black-box machine learning and planning algorithms being used.In this paper,the coactive design method is adopted to analyze the cognitive capabilities required for the tasks and design the interdependencies among the heterogeneous teammates of UAVs or human for coherent collaboration.Then,an agent-based task planner is proposed to automatically decompose a complex task into a sequence of explainable subtasks under constrains of resources,execution time,social rules and costs.Besides,a deep reinforcement learning approach is designed for the UAVs to learn optimal policies of a flocking behavior and a path planner that are easy for the human operator to understand and control.Finally,a mixed-initiative action selection mechanism is used to evaluate the learned policies as well as the human’s decisions.Experimental results demonstrate the effectiveness of the proposed methods.展开更多
In this investigation, an approach using Coac-tive Neuro-Fuzzy Inference System (CANFIS) as diagnosis system for breast cancer has been proposed on Wisconsin Breast Cancer Data (WBCD). It is occasionally difficult to ...In this investigation, an approach using Coac-tive Neuro-Fuzzy Inference System (CANFIS) as diagnosis system for breast cancer has been proposed on Wisconsin Breast Cancer Data (WBCD). It is occasionally difficult to attain the ultimate diagnosis even for medical experts due to the complexity and non-linearity of the rela-tionships between the large measured factors, which can be possibly resolved with a human like decision-making process using Artificial Intelligence (AI) algorithms. CANFIS is an AI algorithm which has the advantages of both fuzzy inference system and neural networks and can deal with ambiguous data and learn from the past data by itself. The Multi Layer Percep-tron Neural Network (MLPNN), Probabilistic Neural Network (PNN) Principal Component Analysis (PCA), Support Vector Machine (SVM) and Self Organizing Map (SOM) were also tested and benchmarked for their展开更多
Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during th...Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during the recovery sleep remains unclear. In the current study, we performed sleep deprivation experiments on ten adult rats, and recorded the local field potentials from default mode network(DMN) regions during sleep before and after sleep deprivation. The DMN dynamics was assessed with the configurations of coactive micropatterns(CAMPs) using our previously proposed CAMP method. Our analysis revealed that the effects of sleep deprivation on DMN dynamics in the slow-wave sleep(SWS) state and the rapid eye-movement sleep(REM)state were disparate. Dynamic configurations of DMN activity in the SWS state were significantly impaired after sleep deprivation, with increased occurrence of low-activity CAMP and reorganized transition structure across three CAMPs. Moreover,enhanced functional connectivity and improved efficiencies in all CAMP networks were observed during the SWS state in the recovery sleep. However, there were no significant alterations in either DMN dynamics or CAMP network structures in the REM sleep state after sleep deprivation. Our results described the alterations of DMN dynamics in different sleep states after sleep deprivation, and illustrated the differential effects of sleep deprivation on two sleep states. These findings demonstrated the underlying neural mechanisms of the effects of sleep deprivation on DMN activity during sleep and increased our understanding of the physiological roles of the DMN in maintain sleep homeostasis after sleep deprivation.展开更多
Objective:Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback,which can result in alterations of gene expression and luteinizing hormone(LH)surge dysfunctio...Objective:Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback,which can result in alterations of gene expression and luteinizing hormone(LH)surge dysfunction.We hypothesize that age-related changes in E2-responsive gene expression are due to altered histone acetylation by histone deacetylases(HDACs)or estrogen receptor-alpha(ERα)coactivators with histone acetyltransferase(HAT)activity.Methods:In the present study,young and middle-aged female rats were ovariectomized(OVX)and treated with E2 or oil once per day for 2 days.At the time of the expected LH surge,the anterior and posterior hypothalami were dissected,and gene expression of 11 HDACs and 4 ERαcoactivators with HAT activity was measured using real-time polymerase chain reaction.Results:In the anterior hypothalamus,age affected the gene expression of 3 HDACs(Hdac3,Hdac5,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp).E2 treatment significantly decreased mRNA levels of 4 HDACs(Hdac4,Hdac5,Hdac10,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp)in young females(3-4 months).However,none of the genes responded to E2 in the middle-aged females(9-11 months),except Hdac10.In the posterior hypothalamus,age influenced Hdac5 and Src1 mRNA expression.E2 treatment increased Hdac4 and Crebbp mRNA levels in the young but not middle-aged females.Conclusions:These data suggest that E2 regulates HDACs and ERαcoactivators with HAT activity in an age-and E2-dependent manner,which may contribute to the age-related gene expression changes on the day of LH surge in female reproductive aging.展开更多
The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orches...The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are expressed throughout postembryonic development with little change in their expression levels. These results support the view that these coactivators participate in gene regulation by TR during metamorphosis.展开更多
Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontr...Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontrolled proliferation.The needs for particular transcription programs for cancer growth could be cancer-type-selective.The dependencies of certain transcription regulators could be exploited for therapeutic benefits.Anaplastic thyroid cancer(ATC)is an extremely aggressive human cancer for which new treatment modalities are urgently needed.Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis.Despite this genetic complexity,mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival.The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies.However,an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses,which would provide an opportunity to target transcriptional regulators for treatment of ATC.Here,we review the current understanding of how genetic alterations in cancer distorted the transcription program,leading to acquisition of transcriptional addiction.We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC.展开更多
We propose a unified approach for systems integration and behavior regulation expressing the autonomy of Systems of Systems. For this, we precise the notion of autonomyas a transposition of the living organisms case a...We propose a unified approach for systems integration and behavior regulation expressing the autonomy of Systems of Systems. For this, we precise the notion of autonomyas a transposition of the living organisms case and we develop the notion of artificial tendencies and behavioral intentions. We present a multi-agent model allowing theimplementation with a new multi-scale control.展开更多
文摘Purpose The present study examined the effects of a reciprocal,slow velocity forearm flexion and extension task on fatigue-induced changes in isokinetic torque,agonist and antagonist muscle activation,and coactivation ratios at slow and moderate velocities.Methods Nine women(mean±SD:age=21.0±1.7 years;body mass=68.1±8.2 kg;height=167.4±7.2 cm)completed pre-testing for forearm flexion and extension isokinetic peak torque at 60 and 180°/s,a fatiguing task of 50 maximal,recip-rocal,isokinetic muscle actions at 60°/s,and post-testing.The amplitude(AMP)of the electromyographic(EMG)signals from the biceps and triceps were simultaneously recorded.Torque and EMG AMP were normalized to the corresponding values from the pre-testing peak torque movements.Repeated measures ANOVAs and pairwise comparisons were used to identify mean changes in torque,EMG AMP,and coactivation ratios.Results The torque analyses indicated significant decreases from pre-to post-testing for forearm flexion(14.1%±5.0%;P<0.001)and extension(25.4%±12.2%;P<0.001)at 60°.At 180°/s there was a significant decrease,collapsed across the forearm movements(24.7%±11.7%;P<0.001).For EMG AMP and coactivation ratios,there were no changes(P>0.05)from pre-to post-testing for either velocity or movement.Conclusions The torque responses were velocity-specific,with greater fatigability exhibited for forearm extension versus flexion at 60°/s,but no differences at 180°/s.The parallel EMG AMP responses between the agonist and antagonist muscles for both velocities supported the lack of fatigue-induced changes in coactivation ratios.Thus,our results demonstrated that fatigue-induced decreases in torque were not attributable to increases in antagonist activation or coactivation.
基金funded by the National Natural Science Foundation of China(No.21603109)the Henan Joint Fund of the National Natural Science Foundation of China(No.U1404216)+1 种基金the Special Fund of Tianshui Normal University,China(No.CXJ202008)the Scientific Research Program Funded by Shaanxi Provincial Education Department(No.20JK0676)。
文摘The production of CH_(3)COOH from CO_(2)and CH_(4) has stimulated much interest due to the high energy density of C2 species.Various kinds of catalysts have been developed while the high dissociation barrier of CH_(4) and low selectivity still hinders the efficiency of the reaction.We have herein proposed a novel catalyst with single metals loaded on 2D BC_(3)N_(2) substrate(M@2D-BC_(3)N_(2))based on density functional theory.Among numerous candidates,Pt@2D-BC_(3)N_(2) possesses the most favorable reactivity with an ultralow barrier of CH_(4) splitting(0.26 e V),which is due to the efficient capture ability of CH_(4) on Pt site.Besides,the selectivity for CH_(3)COOH is also very high,which mainly stems from the unique electronic properties of molecules and substrate:The degenerated states,including s,px,pyand pz,in CO_(2)reflects the existence of delocalizedπbonds between C and O.This can interact with states of Pt(s),Pt(pz),Pt(dxz),Pt(dyz),and Pt(z2)in Pt@2D-BC_(3)N_(2).The kinetics model also proves that our system can promote CH_(3)COOH production via simply increasing the temperature or the coverage of CH_(4) and CO_(2).Our results provide a reasonable illustration in clarifying mechanism and propose promising candidates with high reactivity for further study.
基金supported by a grant from the National Transgenic Science and Technology Major Program of China(2019ZX08010003-001-009)。
文摘Synthetic gene activators consisting of nucleasedead Cas9(dCas9)for single-guide RNA(sgRNA)-directed promoter binding and a transcriptional activation domain(TAD)represent new tools for gene activation from endogenous genomic locus in basic and applied plant research.However,multiplex gene coactivation by d Cas9-TADs has not been demonstrated in whole plants.There is also room to optimize the performance of these tools.Here,we report that our previously developed gene activator,dCas9-TV,could simultaneously upregulate OsGW7 and OsER1 in rice by up to 3,738 fold,with one sg RNA targeting to each promoter.The gene coactivation could persist to at least the fourth generation.Astonishingly,thepolycistronictRNA-sgRNAexpression under the maize ubiquitin promoter,a Pol II promoter,could cause enormous activation of these genes by up to>40,000-fold in rice.Moreover,the yeast GCN4 coiled coil-mediated dCas9-TV dimerization appeared to be promising for enhancing gene activation.Finally,we successfully introduced a self-amplification loop for dCas9-TV expression in Arabidopsis to promote the transcriptional upregulation of AtFLS2,a previously characterized dCas9-TV-refractory gene with considerable basal expression.Collectively,this work illustrates the robustness of dCas9-TV in multigene coactivation and provides broadly useful strategies for boosting transcriptional activation efficacy of dCas9-TADs in plants.
基金co-supported by the National Natural Science Foundation of China(Nos.61906203,61876187)the National Key Laboratory of Science and Technology on UAV,Northwestern Polytechnical University,China(No.614230110080817)。
文摘Unmanned Aerial Vehicles(UAVs)are useful in dangerous and dynamic tasks such as search-and-rescue,forest surveillance,and anti-terrorist operations.These tasks can be solved better through the collaboration of multiple UAVs under human supervision.However,it is still difficult for human to monitor,understand,predict and control the behaviors of the UAVs due to the task complexity as well as the black-box machine learning and planning algorithms being used.In this paper,the coactive design method is adopted to analyze the cognitive capabilities required for the tasks and design the interdependencies among the heterogeneous teammates of UAVs or human for coherent collaboration.Then,an agent-based task planner is proposed to automatically decompose a complex task into a sequence of explainable subtasks under constrains of resources,execution time,social rules and costs.Besides,a deep reinforcement learning approach is designed for the UAVs to learn optimal policies of a flocking behavior and a path planner that are easy for the human operator to understand and control.Finally,a mixed-initiative action selection mechanism is used to evaluate the learned policies as well as the human’s decisions.Experimental results demonstrate the effectiveness of the proposed methods.
文摘In this investigation, an approach using Coac-tive Neuro-Fuzzy Inference System (CANFIS) as diagnosis system for breast cancer has been proposed on Wisconsin Breast Cancer Data (WBCD). It is occasionally difficult to attain the ultimate diagnosis even for medical experts due to the complexity and non-linearity of the rela-tionships between the large measured factors, which can be possibly resolved with a human like decision-making process using Artificial Intelligence (AI) algorithms. CANFIS is an AI algorithm which has the advantages of both fuzzy inference system and neural networks and can deal with ambiguous data and learn from the past data by itself. The Multi Layer Percep-tron Neural Network (MLPNN), Probabilistic Neural Network (PNN) Principal Component Analysis (PCA), Support Vector Machine (SVM) and Self Organizing Map (SOM) were also tested and benchmarked for their
基金supported by the MOST 2030 Brain Project (Grant No.2022ZD0208500)the National Natural Science Foundation of China(Grant Nos. 31771149, 81861128001, and 61933003)partly supported by the CAMS Innovation Fund for Medical Sciences (CIFMS)(Grant No.2019-I2M-5-039)。
文摘Sleep deprivation causes disturbances of the neural activity, leading to the impairment of brain functions. However, the exact mechanism of sleep deprivation and how it affects the dynamics of brain activity during the recovery sleep remains unclear. In the current study, we performed sleep deprivation experiments on ten adult rats, and recorded the local field potentials from default mode network(DMN) regions during sleep before and after sleep deprivation. The DMN dynamics was assessed with the configurations of coactive micropatterns(CAMPs) using our previously proposed CAMP method. Our analysis revealed that the effects of sleep deprivation on DMN dynamics in the slow-wave sleep(SWS) state and the rapid eye-movement sleep(REM)state were disparate. Dynamic configurations of DMN activity in the SWS state were significantly impaired after sleep deprivation, with increased occurrence of low-activity CAMP and reorganized transition structure across three CAMPs. Moreover,enhanced functional connectivity and improved efficiencies in all CAMP networks were observed during the SWS state in the recovery sleep. However, there were no significant alterations in either DMN dynamics or CAMP network structures in the REM sleep state after sleep deprivation. Our results described the alterations of DMN dynamics in different sleep states after sleep deprivation, and illustrated the differential effects of sleep deprivation on two sleep states. These findings demonstrated the underlying neural mechanisms of the effects of sleep deprivation on DMN activity during sleep and increased our understanding of the physiological roles of the DMN in maintain sleep homeostasis after sleep deprivation.
基金funded by Shanghai Science and Technology Committee(17ZR1403300).
文摘Objective:Female reproductive aging is characterized by reduced responsiveness of the hypothalamus to E2-positive feedback,which can result in alterations of gene expression and luteinizing hormone(LH)surge dysfunction.We hypothesize that age-related changes in E2-responsive gene expression are due to altered histone acetylation by histone deacetylases(HDACs)or estrogen receptor-alpha(ERα)coactivators with histone acetyltransferase(HAT)activity.Methods:In the present study,young and middle-aged female rats were ovariectomized(OVX)and treated with E2 or oil once per day for 2 days.At the time of the expected LH surge,the anterior and posterior hypothalami were dissected,and gene expression of 11 HDACs and 4 ERαcoactivators with HAT activity was measured using real-time polymerase chain reaction.Results:In the anterior hypothalamus,age affected the gene expression of 3 HDACs(Hdac3,Hdac5,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp).E2 treatment significantly decreased mRNA levels of 4 HDACs(Hdac4,Hdac5,Hdac10,and Hdac11)and 2 ERαcoactivators(Src2 and Crebbp)in young females(3-4 months).However,none of the genes responded to E2 in the middle-aged females(9-11 months),except Hdac10.In the posterior hypothalamus,age influenced Hdac5 and Src1 mRNA expression.E2 treatment increased Hdac4 and Crebbp mRNA levels in the young but not middle-aged females.Conclusions:These data suggest that E2 regulates HDACs and ERαcoactivators with HAT activity in an age-and E2-dependent manner,which may contribute to the age-related gene expression changes on the day of LH surge in female reproductive aging.
文摘The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are expressed throughout postembryonic development with little change in their expression levels. These results support the view that these coactivators participate in gene regulation by TR during metamorphosis.
基金supported by the Intramural Research Program of the Center for Cancer ResearchNational Cancer Institute,National Institutes of Health(ZIA BC 011191).
文摘Dysregulation of genes perpetuates cancer progression.During carcinogenesis,cancer cells acquire dependency of aberrant transcriptional programs(known as“transcription addiction”)to meet the high demands for uncontrolled proliferation.The needs for particular transcription programs for cancer growth could be cancer-type-selective.The dependencies of certain transcription regulators could be exploited for therapeutic benefits.Anaplastic thyroid cancer(ATC)is an extremely aggressive human cancer for which new treatment modalities are urgently needed.Its resistance to conventional treatments and the lack of therapeutic options for improving survival might have been attributed to extensive genetic heterogeneity due to subsequent evolving genetic alterations and clonal selections during carcinogenesis.Despite this genetic complexity,mounting evidence has revealed a characteristic transcriptional addiction of ATC cells resulting in evolving diverse oncogenic signaling for cancer cell survival.The transcriptional addiction has presented a huge challenge for effective targeting as shown by the failure of previous targeted therapies.However,an emerging notion is that many different oncogenic signaling pathways activated by multiple upstream driver mutations might ultimately converge on the transcriptional responses,which would provide an opportunity to target transcriptional regulators for treatment of ATC.Here,we review the current understanding of how genetic alterations in cancer distorted the transcription program,leading to acquisition of transcriptional addiction.We also highlight recent findings from studies aiming to exploit the opportunity for targeting transcription regulators as potential therapeutics for ATC.
文摘We propose a unified approach for systems integration and behavior regulation expressing the autonomy of Systems of Systems. For this, we precise the notion of autonomyas a transposition of the living organisms case and we develop the notion of artificial tendencies and behavioral intentions. We present a multi-agent model allowing theimplementation with a new multi-scale control.
