Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address thes...Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.展开更多
AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups ...AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups to assess pupillary responses under varying light intensities(100,250,500 lx)and pharmacological interventions(1%atropine,1%cyclopentolate,1%tropicamide,or 2%pilocarpine).Baseline pupil size and eccentricity were recorded using a non-contact Python-based imaging system integrating edge detection and pixel-to-distance conversion.Direct illumination effects were measured at sequential time points,followed by drug administration and longitudinal tracking of pupillary changes.The protocol was repeated at 12wk of age for developmental comparisons.Postexperiment,enucleated eyes were analyzed to evaluate in vitro vs in vivo differences.RESULTS:Significant age-dependent differences in pupil dynamics were observed.Both 2-and 12-week-old guinea pigs exhibited marked pupil constriction under direct illumination(P<0.001),with decreased eccentricity post-constriction(P<0.001).Indirect illumination caused inconsistent pupil size changes(2-week:P=0.68;12-week:P=0.49).Pharmacologically,atropine,cyclopentolate,and tropicamide induced pupil dilation(P<0.001),whereas pilocarpine caused constriction(P<0.001).All drug groups showed reduced eccentricity(P<0.001).In vivo/in vitro comparisons revealed significant structural differences.CONCLUSION:This study investigates pupillary responses in developing guinea pigs,revealing a direct pupillary light reflex(PLR)with light intensity-dependent responses,while indirect PLR was undetectable.The differential effects of muscarinic modulators on pupillary responses underscore the critical role of cholinergic signaling in ocular accommodation,with age-related variations in sensitivity.Additionally,a novel non-contact measurement methodology achieved a precision of 0.01 mm for pupillary quantification,enhancing accuracy in ocular studies.展开更多
Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a thi...This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a third-order active RC loop filter, internal quantizer operating at 160 MHz and three DAC circuits. A multi-bit quantizer is used to increase resolution and multi-bit non-return-to-zero (NRZ) DACs are adopted to reduce clock jitter sensitivity. The NRZ DAC circuits with quantizer excess loop delay compensation are set to be half the sampling period of the quantizer for increasing modulator stability. A dynamic element matching (DEM) technique is applied to multi-bit ΣΔ modulators to improve the nonlinearity of the internal DAC. This approach translates the harmonic distortion components of a nonideal DAC in the feedback loop of a ΣΔ modulator to high-frequency components. Capacitor tuning is utilized to overcome loop coefficient shifts due to process variations. The DWA technique is used for reducing DAC noise due to component mismatches. The prototype is implemented in TSMC 0.18 um CMOS process. Experimental results show that the ΣΔ modulator achieves 54-dB dynamic range, 51-dB SNR, and 48-dB SNDR over a 10-MHz signal bandwidth with an oversampling ratio (OSR) of 8, while dissipating 19.8 mW from a 1.2-V supply. Including pads, the chip area is 1.156 mm2.展开更多
An approach to identification of linear continuous-time system is studied with modulating functions. Based on wavelet analysis theory, the multi-resolution modulating functions are designed, and the corresponding filt...An approach to identification of linear continuous-time system is studied with modulating functions. Based on wavelet analysis theory, the multi-resolution modulating functions are designed, and the corresponding filters have been analyzed. Using linear modulating filters, we can obtain an identification model that is parameterized directly in continuous-time model parameters. By applying the results from discrete-time model identification to the obtained identification model, a continuous-time estimation method is developed. Considering the accuracy of parameter estimates, an instrumental variable (Ⅳ) method is proposed, and the design of modulating integral filter is discussed. The relationship between the accuracy of identification and the parameter of modulating filter is investigated, and some points about designing Gaussian wavelet modulating function are outlined. Finally, a simulation study is also included to verify the theoretical results.展开更多
Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of ...Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.展开更多
Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodu...Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.展开更多
Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental...Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.展开更多
An efficient unbiased estimation method is proposed for the direct identification of linear continuous-time system with noisy input and output measurements.Using the Gaussian modulating filters,by numerical integratio...An efficient unbiased estimation method is proposed for the direct identification of linear continuous-time system with noisy input and output measurements.Using the Gaussian modulating filters,by numerical integration,an equivalent discrete identification model which is parameterized with continuous-time model parameters is developed,and the parameters can be estimated by the least-squares (LS) algorithm.Even with white noises in input and output measurement data,the LS estimate is biased,and the bias is determined by the variances of noises.According to the asymptotic analysis,the relationship between bias and noise variances is derived.One equation relating to the measurement noise variances is derived through the analysis of the LS errors.Increasing the degree of denominator of the system transfer function by one,an extended model is constructed.By comparing the true value and LS estimates of the parameters between original and extended model,another equation with input and output noise variances is formulated.So,the noise variances are resolved by the set of equations,the LS bias is eliminated and the unbiased estimates of system parameters are obtained.A simulation example by comparing the standard LS with bias eliminating LS algorithm indicates that the proposed algorithm is an efficient method with noisy input and output measurements.展开更多
The satellite orbital pursuit game focuses on studying spacecraft maneuvering strategies in space.Traditional numerical methods often face real-time inadequacies and adaptability limitations when dealing with highly n...The satellite orbital pursuit game focuses on studying spacecraft maneuvering strategies in space.Traditional numerical methods often face real-time inadequacies and adaptability limitations when dealing with highly nonlinear problems.With the advancement of Deep Reinforcement Learning(DRL)technology,continuous-time orbital control capabilities have significantly improved.Despite this,the existing DRL technologies still need adjustments in action delay and discretization structure to better adapt to practical application scenarios.Combining continuous learning and model planning demonstrates the adaptability of these methods in continuous-time decision problems.Additionally,to more effectively handle action delay issues,a new scheduled action execution technique has been developed.This technique optimizes action execution timing through real-time policy adjustments,thus adapting to the dynamic changes in the orbital environment.A Hierarchical Reinforcement Learning(HRL)strategy was also adopted to simplify the decision-making process for long-distance pursuit tasks by setting phased subgoals to gradually approach the target.The effectiveness of the proposed strategy in practical satellite pursuit scenarios has been verified through simulations of two different tasks.展开更多
As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are in...As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are increasingly recognized as core requirements for next-generation intelligent computing center designs^([1, 2]). For short-range optical interconnections of intra-chip and inter-chip—typically covering tens of meters or less—microring resonant modulators (MRM) are emerging as an ideal solution.展开更多
Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of...Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of sensory stimuli,and it is this valence that serves as the foundational motivation for our subsequent actions.Simply put,all motivational actions fall into two categories:pleasure-seeking behavior guided by positive emotional valence,and pain-avoiding behavior driven by negative emotional valence[1].The ability to shift from one emotional valence to another is an important characteristic of affective states,while the instability of emotional states underlies many psychiatric disorders,highlighting the clinical importance of managing and understanding these fluctuations.This ability to adapt emotional responses can be attained by modulating the gain across distinct neural pathways,thus enabling the nuanced and smooth assignment of valence through the strengthening or weakening of circuit activity[1,2].展开更多
With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most i...With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most important component of high-precision ADC,is widely used in high-quality audio,high-precision instrument measurement,and other fields due to its advantages of high precision,strong noise resistance,and low hardware cost.This article designs a discrete structure third-order four-bit high-precision Sigma-Delta modulator through modeling,with an oversampling rate set to 512.Under ideal conditions,the simulation results show that the SDNR reaches 152.7db and the ENOB is 25.24bits.After introducing non-ideal noise,the system performance has decreased.The simulation results show that the SDNR is as high as 124.5db and the ENOB is 20.39bits.This indicates that the design can achieve high-precision conversion and provide assistance for further research in the future.展开更多
Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,...Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,a femtosecond laser Bessel beam is proposed to process micro-FZP,which is modulated from a Gaussian beam to a Bessel annular beam.The processing time for FZP with an outer diameter of 60μm is reduced from 30 min to 1.5 min on an important semiconductor material gallium arsenide(GaAs),which significantly improves the processing efficiency.In the modulation process,a central ablation hole that has an adverse effect on the diffraction performance is produced,and the adverse effect is eliminated by superimposing the blazed grating hologram.Meanwhile,the FZP machined by spatial light modulator(SLM)has good morphology and higher diffraction efficiency,which provides a strong guarantee for the application of micro-FZP in computed tomography and solar photovoltaic cells.展开更多
Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis ind...Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.展开更多
In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial le...In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial level of dithering noise into the input signal,strategically aimed at mitigating the spurious frequencies commonly encountered in such converters.Validation of our design is performed through simulations using a high-level simulator specialized in mixed-signal circuit analysis.The results underscore the enhanced performance of our circuit,especially in reducing spurious frequencies,highlighting its efficiency and effectiveness.The final circuit exhibits an effective number of bits of 13.展开更多
Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturat...Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.展开更多
While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance re...While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance remains underexplored in field investigations.To evaluate the practical applicability of this emerging technique in adverse shallow sea channels,a field experiment was conducted using three communication modes:orthogonal frequency division multiplexing(OFDM),M-ary frequency-shift keying(MFSK),and direct sequence spread spectrum(DSSS)for reinforcement learning-driven adaptive modulation.Specifically,a Q-learning method is used to select the optimal modulation mode according to the channel quality quantified by signal-to-noise ratio,multipath spread length,and Doppler frequency offset.Experimental results demonstrate that the reinforcement learning-based adaptive modulation scheme outperformed fixed threshold detection in terms of total throughput and average bit error rate,surpassing conventional adaptive modulation strategies.展开更多
Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian cloc...Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.展开更多
The functional properties of glasses are governed by their formation history and the complex relaxation processes they undergo.However,under extreme conditions,glass behaviors are still elusive.In this study,we employ...The functional properties of glasses are governed by their formation history and the complex relaxation processes they undergo.However,under extreme conditions,glass behaviors are still elusive.In this study,we employ simulations with varied protocols to evaluate the effectiveness of different descriptors in predicting mechanical properties across both low-and high-pressure regimes.Our findings demonstrate that conventional structural and configurational descriptors fail to correlate with the mechanical response following pressure release,whereas the activation energy descriptor exhibits robust linearity with shear modulus after correcting for pressure effects.Notably,the soft mode parameter emerges as an ideal and computationally efficient alternative for capturing this mechanical behavior.These findings provide critical insights into the influence of pressure on glassy properties,integrating the distinct features of compressed glasses into a unified theoretical framework.展开更多
基金supported by the Zhongyuan University of Technology Discipline Backbone Teacher Support Program Project(No.GG202417)the Key Research and Development Program of Henan under Grant 251111212000.
文摘Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.
文摘AIM:To investigate the effects of different light intensities and various mydriatic and miotic drugs on pupil accommodation in guinea pigs.METHODS:Forty-two-week-old guinea pigs were randomly divided into four groups to assess pupillary responses under varying light intensities(100,250,500 lx)and pharmacological interventions(1%atropine,1%cyclopentolate,1%tropicamide,or 2%pilocarpine).Baseline pupil size and eccentricity were recorded using a non-contact Python-based imaging system integrating edge detection and pixel-to-distance conversion.Direct illumination effects were measured at sequential time points,followed by drug administration and longitudinal tracking of pupillary changes.The protocol was repeated at 12wk of age for developmental comparisons.Postexperiment,enucleated eyes were analyzed to evaluate in vitro vs in vivo differences.RESULTS:Significant age-dependent differences in pupil dynamics were observed.Both 2-and 12-week-old guinea pigs exhibited marked pupil constriction under direct illumination(P<0.001),with decreased eccentricity post-constriction(P<0.001).Indirect illumination caused inconsistent pupil size changes(2-week:P=0.68;12-week:P=0.49).Pharmacologically,atropine,cyclopentolate,and tropicamide induced pupil dilation(P<0.001),whereas pilocarpine caused constriction(P<0.001).All drug groups showed reduced eccentricity(P<0.001).In vivo/in vitro comparisons revealed significant structural differences.CONCLUSION:This study investigates pupillary responses in developing guinea pigs,revealing a direct pupillary light reflex(PLR)with light intensity-dependent responses,while indirect PLR was undetectable.The differential effects of muscarinic modulators on pupillary responses underscore the critical role of cholinergic signaling in ocular accommodation,with age-related variations in sensitivity.Additionally,a novel non-contact measurement methodology achieved a precision of 0.01 mm for pupillary quantification,enhancing accuracy in ocular studies.
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
文摘This paper presents the design and experimental results of a continuous-time (CT) sigma-delta (ΣΔ) modulator with data-weighted average (DWA) technology for WiMAX applications. The proposed modulator comprises a third-order active RC loop filter, internal quantizer operating at 160 MHz and three DAC circuits. A multi-bit quantizer is used to increase resolution and multi-bit non-return-to-zero (NRZ) DACs are adopted to reduce clock jitter sensitivity. The NRZ DAC circuits with quantizer excess loop delay compensation are set to be half the sampling period of the quantizer for increasing modulator stability. A dynamic element matching (DEM) technique is applied to multi-bit ΣΔ modulators to improve the nonlinearity of the internal DAC. This approach translates the harmonic distortion components of a nonideal DAC in the feedback loop of a ΣΔ modulator to high-frequency components. Capacitor tuning is utilized to overcome loop coefficient shifts due to process variations. The DWA technique is used for reducing DAC noise due to component mismatches. The prototype is implemented in TSMC 0.18 um CMOS process. Experimental results show that the ΣΔ modulator achieves 54-dB dynamic range, 51-dB SNR, and 48-dB SNDR over a 10-MHz signal bandwidth with an oversampling ratio (OSR) of 8, while dissipating 19.8 mW from a 1.2-V supply. Including pads, the chip area is 1.156 mm2.
基金This project was supported by China Postdoctoral Science Foundation (2003034466)Scientific Research Fund of Hunan Provincial Education Department (02B032).
文摘An approach to identification of linear continuous-time system is studied with modulating functions. Based on wavelet analysis theory, the multi-resolution modulating functions are designed, and the corresponding filters have been analyzed. Using linear modulating filters, we can obtain an identification model that is parameterized directly in continuous-time model parameters. By applying the results from discrete-time model identification to the obtained identification model, a continuous-time estimation method is developed. Considering the accuracy of parameter estimates, an instrumental variable (Ⅳ) method is proposed, and the design of modulating integral filter is discussed. The relationship between the accuracy of identification and the parameter of modulating filter is investigated, and some points about designing Gaussian wavelet modulating function are outlined. Finally, a simulation study is also included to verify the theoretical results.
基金Scientific Research Training Program for Young Talents of Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(F.W.),NIH/NIDCR grants DE029012 and DE029465Department of Defense Grant PR190899(R.T.F.)Michigan Musculoskeletal Health Core Center(NIH/NIAMS P30 AR069620)。
文摘Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.
文摘Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.
基金Project(50875028) supported by the National Natural Science Foundation of China
文摘An efficient unbiased estimation method is proposed for the direct identification of linear continuous-time system with noisy input and output measurements.Using the Gaussian modulating filters,by numerical integration,an equivalent discrete identification model which is parameterized with continuous-time model parameters is developed,and the parameters can be estimated by the least-squares (LS) algorithm.Even with white noises in input and output measurement data,the LS estimate is biased,and the bias is determined by the variances of noises.According to the asymptotic analysis,the relationship between bias and noise variances is derived.One equation relating to the measurement noise variances is derived through the analysis of the LS errors.Increasing the degree of denominator of the system transfer function by one,an extended model is constructed.By comparing the true value and LS estimates of the parameters between original and extended model,another equation with input and output noise variances is formulated.So,the noise variances are resolved by the set of equations,the LS bias is eliminated and the unbiased estimates of system parameters are obtained.A simulation example by comparing the standard LS with bias eliminating LS algorithm indicates that the proposed algorithm is an efficient method with noisy input and output measurements.
基金supported by the National Natural Science Foundation of China(No.12202281)the Shanghai Natural Science Foundation,China(No.23ZR1461800)the Research Initiation Fund of Northwestern Polytechnical University,China(No.G2024KY05103)。
文摘The satellite orbital pursuit game focuses on studying spacecraft maneuvering strategies in space.Traditional numerical methods often face real-time inadequacies and adaptability limitations when dealing with highly nonlinear problems.With the advancement of Deep Reinforcement Learning(DRL)technology,continuous-time orbital control capabilities have significantly improved.Despite this,the existing DRL technologies still need adjustments in action delay and discretization structure to better adapt to practical application scenarios.Combining continuous learning and model planning demonstrates the adaptability of these methods in continuous-time decision problems.Additionally,to more effectively handle action delay issues,a new scheduled action execution technique has been developed.This technique optimizes action execution timing through real-time policy adjustments,thus adapting to the dynamic changes in the orbital environment.A Hierarchical Reinforcement Learning(HRL)strategy was also adopted to simplify the decision-making process for long-distance pursuit tasks by setting phased subgoals to gradually approach the target.The effectiveness of the proposed strategy in practical satellite pursuit scenarios has been verified through simulations of two different tasks.
基金supported by the National Natural Science Foundation of China (Grant Nos. 61925505 and 62405070)"Pioneer" and "Leading Goose" R&D Program of Zhejiang Province (Grant No. 2024C01112)National Key Research and Development Program of China (Grant No. 2023YFB2807100)。
文摘As the demand for computing power in data centers continues to grow, balancing data transmitting speed and energy efficiency has emerged as a critical challenge. Highbandwidth, low-power interconnection schemes are increasingly recognized as core requirements for next-generation intelligent computing center designs^([1, 2]). For short-range optical interconnections of intra-chip and inter-chip—typically covering tens of meters or less—microring resonant modulators (MRM) are emerging as an ideal solution.
基金supported by grants from the Key-Area Research and Development Program of Guangdong province(2019B030335001)the National Natural Science Foundation of China(32200815)the China Postdoctoral Science Foundation(2022M721218).
文摘Based on previous experience,learning to avoid or seek certain specific stimuli again in the future is crucial for survival.Our brains are wired to assign a particular valence-either positive or negativeas a result of sensory stimuli,and it is this valence that serves as the foundational motivation for our subsequent actions.Simply put,all motivational actions fall into two categories:pleasure-seeking behavior guided by positive emotional valence,and pain-avoiding behavior driven by negative emotional valence[1].The ability to shift from one emotional valence to another is an important characteristic of affective states,while the instability of emotional states underlies many psychiatric disorders,highlighting the clinical importance of managing and understanding these fluctuations.This ability to adapt emotional responses can be attained by modulating the gain across distinct neural pathways,thus enabling the nuanced and smooth assignment of valence through the strengthening or weakening of circuit activity[1,2].
文摘With the continuous improvement of signal processing accuracy requirements in modern electronic systems,the demand for high-precision analog-to-digital converters(ADCs)is increasing.Sigma-Delta modulator,as the most important component of high-precision ADC,is widely used in high-quality audio,high-precision instrument measurement,and other fields due to its advantages of high precision,strong noise resistance,and low hardware cost.This article designs a discrete structure third-order four-bit high-precision Sigma-Delta modulator through modeling,with an oversampling rate set to 512.Under ideal conditions,the simulation results show that the SDNR reaches 152.7db and the ENOB is 25.24bits.After introducing non-ideal noise,the system performance has decreased.The simulation results show that the SDNR is as high as 124.5db and the ENOB is 20.39bits.This indicates that the design can achieve high-precision conversion and provide assistance for further research in the future.
基金Projects(51875584,51875585,51975590)supported by the National Natural Science Foundation of China。
文摘Femtosecond laser processing is an important machining method for micro-optical components such as Fresnel zone plate(FZP).However,the low processing efficiency of the femtosecond laser restricts its application.Here,a femtosecond laser Bessel beam is proposed to process micro-FZP,which is modulated from a Gaussian beam to a Bessel annular beam.The processing time for FZP with an outer diameter of 60μm is reduced from 30 min to 1.5 min on an important semiconductor material gallium arsenide(GaAs),which significantly improves the processing efficiency.In the modulation process,a central ablation hole that has an adverse effect on the diffraction performance is produced,and the adverse effect is eliminated by superimposing the blazed grating hologram.Meanwhile,the FZP machined by spatial light modulator(SLM)has good morphology and higher diffraction efficiency,which provides a strong guarantee for the application of micro-FZP in computed tomography and solar photovoltaic cells.
文摘Objectives:The phytochemical investigation of traditional herbal medicines holds significant promise for modern drug discovery,particularly in cancer therapy.This study aimed to evaluate the cytotoxicity,apoptosis induction,and immune-modulatory activities of extracts from three herbal medicines with historical use in traditional medicine—Acanthopanax sessiliflorus,Phragmites communis,and Pinus densiflora,as well as their combined extract(GMAS 01/COM),on human lung cancer cells(A549)and normal cell lines,including murine macrophages(RAW 264.7)and human keratinocytes(HaCaT).Methods:Plant extracts were prepared using aqueous extraction,sonication,and rotary evaporation.The total phenolic and flavonoid contents were quantified using the Folin-Ciocalteu and AlCl3 colorimetric methods,respectively.Antioxidant potential was evaluated via 2,2-Diphenyl-1-picrylhydrazyl(DPPH)scavenging and reducing power assays.Cytotoxicity was assessed using an MTT assay,while reactive oxygen species(ROS)generation was quantified using a 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA)assay.Anticancer properties,including colony formation inhibition and migration suppression,were examined using colony formation and wound healing assays.The expression of apoptotic and inflammatory mediators was analysed through qPCR.Results:GMAS 01 selectively induced apoptosis in A549 cells without cytotoxic effects on RAW264.7 and HaCaT cells.Mechanistically,it elevated intracellular ROS and activated the intrinsic mitochondrial apoptotic pathway,evidenced by p53 upregulation,increased Bax,and decreased Bcl-2 expression.GMAS 01 also significantly inhibited colony formation and migration in A549 cells.In RAW264.7 cells,it reduced nitric oxide(NO)production and downregulated iNOS,COX-2,IL-6,and IL-8,indicating strong immunomodulatory activity.Conclusion:GMAS 01 exhibits potent antioxidant,anti-inflammatory,and anticancer effects,likely mediated through ROS-induced mitochondrial apoptosis.However,mechanistic interpretations are limited by the absence of protein-level validation and pathway inhibition studies.Upcoming studies should aim to verify the underlying mechanisms and evaluate their potential for real-world application.
文摘In this paper,we present a novel first-order digitalΣΔconverter tailored for digital-to-analog applications,focusing on achieving both high yield and reduced silicon estate.Our approach incorporates a substantial level of dithering noise into the input signal,strategically aimed at mitigating the spurious frequencies commonly encountered in such converters.Validation of our design is performed through simulations using a high-level simulator specialized in mixed-signal circuit analysis.The results underscore the enhanced performance of our circuit,especially in reducing spurious frequencies,highlighting its efficiency and effectiveness.The final circuit exhibits an effective number of bits of 13.
文摘Vitamin D,beyond its classical role in calcium homeostasis,has emerged as a key regulator of immune function and epithelial barrier integrity.Its deficiency during early childhood—a critical period for immune maturation—has been increasingly implicated in the development of atopic diseases.While extensively studied in asthma,its role in non-respiratory allergic conditions such as atopic dermatitis(AD)and allergic rhinitis(AR)remains comparatively underexplored.This minireview synthesizes current mechanistic and clinical evidence on vitamin D in pediatric AD and AR.In AD,vitamin D promotes epidermal barrier function through upregulation of filaggrin and ceramide synthesis,and enhances antimicrobial defense via induction of antimicrobial peptides.Observational studies consistently report lower serum 25-hydroxyvitamin D in affected children,particularly those with allergic sensitization.Select randomized controlled trials suggest clinical improvement with supplementation,especially at doses>2000 IU/day in deficient individuals.In AR,epidemiological data indicate stronger inverse associations with seasonal(pollen-induced)disease.Proposed mechanisms include modulation of dendritic cells,regulatory T cells,T helper 2 cytokines,and mucosal barrier integrity.The shared immunopathogenesis of AD and AR underscores vitamin D’s relevance.Although promising,clinical evidence remains heterogeneous.Future research should prioritize phenotype-stratified trials to clarify optimal dosing,timing,and individual response determinants,including genetics and microbiome composition.
基金funding from the National Key Research and Development Program of China(No.2018YFE0110000)the National Natural Science Foundation of China(No.11274259,No.11574258)the Science and Technology Commission Foundation of Shanghai(21DZ1205500)in support of the present research.
文摘While reinforcement learning-based underwater acoustic adaptive modulation shows promise for enabling environment-adaptive communication as supported by extensive simulation-based research,its practical performance remains underexplored in field investigations.To evaluate the practical applicability of this emerging technique in adverse shallow sea channels,a field experiment was conducted using three communication modes:orthogonal frequency division multiplexing(OFDM),M-ary frequency-shift keying(MFSK),and direct sequence spread spectrum(DSSS)for reinforcement learning-driven adaptive modulation.Specifically,a Q-learning method is used to select the optimal modulation mode according to the channel quality quantified by signal-to-noise ratio,multipath spread length,and Doppler frequency offset.Experimental results demonstrate that the reinforcement learning-based adaptive modulation scheme outperformed fixed threshold detection in terms of total throughput and average bit error rate,surpassing conventional adaptive modulation strategies.
基金supported in part by grants from the National Key R&D Program of China(2021YFC2400400/04 to L.L.C.)the National Natural Science Foundation of China for Key Program Projects(82030070 to L.L.C.)+2 种基金the National Natural Science Foundation of China for Distinguished Young Scholars(22025102 to Q.W.)the National Natural Science Foundation of China(82271036 to Y.F.W.,22277033 to J.Z.,22177034 to L.K.M.)the Young Elite Scientist Sponsorship Program by CAST(2022QNRC001 to Y.F.W.)。
文摘Circadian rhythm disorders are associated with dysfunction in inflammatory diseases,and targeted regulation of the circadian rhythm could serve as an intervention strategy.RORα/γ,as core components of circadian clock genes,positively modulate the key circadian molecule BMAL1.In this study,Gala-SR,a potent small-molecule compound designed to effectively regulate circadian rhythms,was synthesized through a monosaccharide modification prodrug strategy via a hydrolysable conjugation of galactose onto SR1078,an unique synthetic agonist of RORα/γ.Compared with SR1078,Gala-SR exhibited significantly greater aqueous solubility,cytocompatibility,pharmacokinetic characteristics and efficacy in the targeted activation of RORα.Importantly,Gala-SR ameliorated rhythm disorders by enhancing amplitude of the circadian rhythm both in vitro and in vivo.In circadian rhythm disordered mice with periodontitis,Gala-SR restored local circadian rhythm and mitigated inflammation in periodontal tissue in a circadian clock-dependent manner,and alleviated alveolar bone loss.Our study demonstrates that Gala-SR exhibits great promise in restoration of circadian rhythm and could potentially serve as a targeted therapeutic intervention for treating inflammatory diseases arising from disruptions in circadian rhythm.This work provides a feasible paradigm for the development and translational application of small molecule modulators targeting circadian rhythms.
基金supported by the National Natural Science Foundation of China (Grant Nos.T2325004 and 52161160330)the National Natural Science Foundation of China (Grants No.12504233)+2 种基金Advanced MaterialsNational Science and Technology Major Project (Grant No.2024ZD0606900)the Talent Hub for “AI+New Materials” Basic Researchthe Key Research and Development Program of Ningbo (Grant No.2025Z088)。
文摘The functional properties of glasses are governed by their formation history and the complex relaxation processes they undergo.However,under extreme conditions,glass behaviors are still elusive.In this study,we employ simulations with varied protocols to evaluate the effectiveness of different descriptors in predicting mechanical properties across both low-and high-pressure regimes.Our findings demonstrate that conventional structural and configurational descriptors fail to correlate with the mechanical response following pressure release,whereas the activation energy descriptor exhibits robust linearity with shear modulus after correcting for pressure effects.Notably,the soft mode parameter emerges as an ideal and computationally efficient alternative for capturing this mechanical behavior.These findings provide critical insights into the influence of pressure on glassy properties,integrating the distinct features of compressed glasses into a unified theoretical framework.
