亲子关系与CLOCK基因rs1801260多态性对学前儿童亲社会行为的交互影响:性别的调节作用

研究探讨了亲子关系与CLOCK基因rs1801260多态性对学前儿童亲社会行为的交互影响及性别的调节作用。以694名学前儿童(M_(年龄)=5.06岁,SD=0.87)及其父母为测试对象,收集儿童的唾液样本进行基因分型,由儿童父母填写亲子关系和儿童亲社会行为量表。研究结果发现,亲子亲密与亲子冲突对亲社会行为的主效应显著。亲子冲突、CLOCK基因rs1801260多态性和性别三重交互影响儿童的亲社会行为,即与携带C等位基因的男孩相比,携带TT基因型的男孩在低亲子冲突下会表现出更多的亲社会行为,在高亲子冲突下则表现出更少的亲社会行为。但亲子冲突与CLOCK基因rs1801260多态性对女孩亲社会行为的交互作用不显著。研究结果为深入理解学前儿童亲社会行为形成的基因-环境交互作用机制提供了证据。

A frequency servo SoC with output power stabilization loop technology for miniaturized atomic clocks

A frequency servo system-on-chip(FS-SoC)featuring output power stabilization technology is introduced in this study for high-precision and miniaturized cesium(Cs)atomic clocks.The proposed power stabilization loop(PSL)technique,incorporating an off-chip power detector(PD),ensures that the output power of the FS-SoC remains stable,mitigating the impact of power fluctuations on the atomic clock's stability.Additionally,a one-pulse-per-second(1PPS)is employed to syn-chronize the clock with GPS.Fabricated using 65 nm CMOS technology,the measured phase noise of the FS-SoC stands at-69.5 dBc/Hz@100 Hz offset and-83.9 dBc/Hz@1 kHz offset,accompanied by a power dissipation of 19.7 mW.The Cs atomic clock employing the proposed FS-SoC and PSL obtains an Allan deviation of 1.7×10^(-11) with 1-s averaging time.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

Piperine regulates the circadian rhythms of hepatic clock gene expressions and gut microbiota in high-fat diet-induced obese rats

The interplay between the host circadian clock and microbiota has significant influences on host metabolism processes,and circadian desynchrony triggered by high-fat diet(HFD)is closely related to metabolic disorders.In this study,the modulatory effects of piperine(PIP)on lipid metabolism homeostasis,gut microbiota community and circadian rhythm of hepatic clock gene expressions in obese rats were investigated.The Sprague-Dawley(SD)rats were fed with normal diet(ND),HFD and HFD supplemented with PIP,respectively.After 9 weeks,rats were sacrificed with tissue and fecal samples collected for circadian analysis.Results showed that chronic PIP administration ameliorated the obesity-induced alterations in lipid metabolism and dysregulation of hepatic clock gene expressions in obese rats.The gut microbial communities studied through 16S rRNA sequencing showed that PIP ameliorated the imbalanced nicrobiota and recovered the circadian rhythm of Lactobacillaceae,Desulfovibrionaceae,Paraprevotellaceae,and Lachnospiraceae.The fecal metabolic profiles indicated that 3-dehydroshikimate,cytidine and lithocholyltaurine were altered,which were involved in the amino acid and fatty acid metabolism process.These findings could provide theoretical basis for PIP to work as functional food to alleviate the lipid metabolism disorder,circadian rhythm misalignment,and gut microbiota dysbiosis with wide applications in the food and pharmaceutic industries.

MEMS Huygens Clock Based on Synchronized Micromechanical Resonators

With the continuous miniaturization of electronic devices,microelectromechanical system(MEMS)oscillators that can be combined with integrated circuits have attracted increasing attention.This study reports a MEMS Huygens clock based on the synchronization principle,comprising two synchronized MEMS oscillators and a frequency compensation system.The MEMS Huygens clock improved shorttime stability,improving the Allan deviation by a factor of 3.73 from 19.3 to 5.17 ppb at 1 s.A frequency compensation system based on the MEMS oscillator’s temperature-frequency characteristics was developed to compensate for the frequency shift of the MEMS Huygens clock by controlling the resonator current.This effectively improved the long-term stability of the oscillator,with the Allan deviation improving by 1.6343105 times to 30.9 ppt at 6000 s.The power consumption for compensating both oscillators simultaneously is only 2.85 mW·℃^(-1).Our comprehensive solution scheme provides a novel and precise engineering solution for achieving high-precision MEMS oscillators and extends synchronization applications in MEMS.

A redundant subspace weighting procedure for clock ensemble

A redundant-subspace-weighting(RSW)-based approach is proposed to enhance the frequency stability on a time scale of a clock ensemble.In this method,multiple overlapping subspaces are constructed in the clock ensemble,and the weight of each clock in this ensemble is defined by using the spatial covariance matrix.The superimposition average of covariances in different subspaces reduces the correlations between clocks in the same laboratory to some extent.After optimizing the parameters of this weighting procedure,the frequency stabilities of virtual clock ensembles are significantly improved in most cases.

Flowering-time regulation by the circadian clock:From Arabidopsis to crops

Precise timing of flowering in plants is critical for their growth and reproductive processes.One factor controlling flowering time is the cycle of light and darkness within a day,known as the photoperiod.Plants are classified into long-day,short-day,and day-neutral plants based on light requirements for floral initiation.Although the molecular mechanisms that govern this differentiation remain incompletely understood,studies have consistently shown that the circadian clock plays a central role in regulating photoperiod response across diverse plant species.However,there is a scarcity of reviews describing the regulatory network linking the circadian clock with photoperiodic flowering.This review summarizes that regulatory network,focusing on the distinct roles of clock genes in long-day and short-day plants.We also discuss the strategies of clock gene mutations contributing to geographic variation in longday and short-day crops.

A Yb optical clock with a lattice power enhancement cavity

We construct a power enhancement cavity to form an optical lattice in an ytterbium optical clock.It is demonstrated that the intra-cavity lattice power can be increased by about 45 times,and the trap depth can be as large as 1400Er when laser light with a power of only 0.6 W incident to the lattice cavity.Such high trap depths are the key to accurate evaluation of the lattice-induced light shift with an uncertainty down to~1×10-18.By probing the ytterbium atoms trapped in the power-enhanced optical lattice,we obtain a 4.3 Hz-linewidth Rabi spectrum,which is then used to feedback to the clock laser for the close loop operation of the optical lattice clock.We evaluate the density shift of the Yb optical lattice clock based on interleaving measurements,which is-0.46(62)mHz.This result is smaller compared to the density shift of our first Yb optical clock without lattice power enhancement cavity mainly due to a larger lattice diameter of 344μm.

Physics package based on intracavity laser cooling ^(87)Rb atoms for space cold atom microwave clock

This article proposes a new physics package to enhance the frequency stability of the space cold atom clock with the advantages of a microgravity environment. Clock working processes, including atom cooling, atomic state preparation,microwave interrogation, and transition probability detection, are integrated into the cylindrical microwave cavity to achieve a high-performance and compact physics package for the space cold atom clock. We present the detailed design and ground-test results of the cold atom clock physics package in this article, which demonstrates a frequency stability of 1.2×10^(-12) τ^(-1/2) with a Ramsey linewidth of 12.5 Hz, and a better performance is predicted with a 1 Hz or a narrower Ramsey linewidth in microgravity environment. The miniaturized cold atom clock based on intracavity cooling has great potential for achieving space high-precision time-frequency reference in the future.

A novel small-animal locomotor activity recording device for biological clock research

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian rhythm.This study demonstrated how to construct a simple and intelligent running-wheel recording system.The running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's cover.Then,the RJ25 adaptor relayed the running signal to the main control board.Finally,the main control board was connected to the USB port of the computer with the USB connection.Data were collected using the online-accessible,self-created software Magturning.Through Magturning,generated data were saved and exported in real time.Afterward,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light conditions.In conclusion,this new device can record circadian activity of rodents.Our device is appropriate for interdisciplinary investigations related to biological clock research.

Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

Proposal for a realtime Einstein-synchronization-defined satellite virtual clock

Realization of high performance satellite onboard clock is vital for various positioning, navigation, and timing applications. For further improvement of the synchronization-based satellite time and frequency references, we propose a geosynchronous(GEO) satellite virtual clock concept based on ground–satellite synchronization and present a beacon transponder structure for its implementation(scheduled for launch in 2025), which does not require atomic clocks to be mounted on the satellite. Its high performance relies only on minor modifications to the existing transponder structure of GEO satellites. We carefully model the carrier phase link and analyze the factors causing link asymmetry within the special relativity. Considering that performance of such synchronization-based satellite clocks is primarily limited by the link's random phase noise, which cannot be adequately modeled, we design a closed-loop experiment based on commercial GEO satellites for pre-evaluation. This experiment aims at extracting the zero-means random part of the ground-satellite Ku-band carrier phase via a feedback loop. Ultimately, we obtain a 1σ value of 0.633 ps(two-way link), following the Gaussian distribution. From this result, we conclude that the proposed real-time Einstein-synchronization-defined satellite virtual clock can achieve picosecond-level replication of onboard time and frequency.

A proposal for detecting weak electromagnetic waves around 2.6μm wavelength with Sr optical clock

Infrared signal detection is widely used in many fields.Due to the detection principle,however,the accuracy and range of detection are limited.Thanks to the ultra stability of the^(87)Sr optical lattice clock,external infrared electromagnetic wave disturbances can be responded to.Utilizing the ac Stark shift of the clock transition,we propose a new method to detect infrared signals.According to our calculations,the theoretical detection accuracy in the vicinity of its resonance band of 2.6μm can reach the order of 10-14W,while the minimum detectable signal of common detectors is on the order of 10^(-10)W.

Einstein’s Concept of Clock Synchronization Conflicts with the Second Relativity Postulate

Einstein defined clock synchronization whenever photon pulses with timetags traverse a fixed distance between two clocks with equal time spans ineither direction. Using the second relativity postulate, he found clocksmounted on a rod uniformly moving parallel with the rod’s length cannot besynchronized, but clocks attached to a stationary rod can. He dismissed thisdiscrepancy by claiming simultaneity and clock synchronization were not commonbetween inertial frames, but this paper proves with both Galilean and Lorentztransformations that simultaneity and clock synchronization are preservedbetween inertial frames. His derivation means moving clocks can never besynchronized in a “resting” inertial frame. Ultraprecise atomic clocks intimekeeping labs daily contradict his results. No algebraic error occurred inEinstein’s derivations. The two cases of clocksattached to a rod reveal three major conflicts with the currentsecond postulate. The net velocity between a photon source and detector plusthe “universal” velocity c is mathematically equivalent toEinstein’s clock synchronization method. As the ultraprecise timekeepingcommunity daily synchronizes atomic clocks on the moving Earth withultraprecise time uncertainty well below Einstein’s lowest limit ofsynchronization, the theoretical resolution of the apparent conflict isaccomplished by expanding the second relativity postulate to incorporate thenet velocity between the photon source and detector with the emitted velocity c as components of the total velocity c. This means the magnitudeof the total photon velocity can exceed the speed limit (299792458 m/s) set by the standard velocity c. .

Human tracking in camera network with non-overlapping FOVs

An adaptive human tracking method across spatially separated surveillance cameras with non-overlapping fields of views （FOVs） is proposed. The method relies on the two cues of the human appearance model and spatio-temporal information between cameras. For the human appearance model, an HSV color histogram is extracted from different human body parts （head, torso, and legs）, then a weighted algorithm is used to compute the similarity distance of two people. Finally, a similarity sorting algorithm with two thresholds is exploited to find the correspondence. The spatio- temporal information is established in the learning phase and is updated incrementally according to the latest correspondence. The experimental results prove that the proposed human tracking method is effective without requiring camera calibration and it becomes more accurate over time as new observations are accumulated.

Adaptive topology learning of camera network across non-overlapping views

An adaptive topology learning approach is proposed to learn the topology of a practical camera network in an unsupervised way. The nodes are modeled by the Gaussian mixture model. The connectivity between nodes is judged by their cross-correlation function, which is also used to calculate their transition time distribution. The mutual information of the connected node pair is employed for transition probability calculation. A false link eliminating approach is proposed, along with a topology updating strategy to improve the learned topology. A real monitoring system with five disjoint cameras is built for experiments. Comparative results with traditional methods show that the proposed method is more accurate in topology learning and is more robust to environmental changes.

大负荷运动后骨骼肌核心时钟基因Bmal1/Clock、Cry1/Per1的节律性振荡变化趋势

目的:探讨大负荷运动对骨骼肌核心时钟基因节律性表达的影响。方法:将208只8周龄SD大鼠随机分为对照(control,C)组与运动(Exercise,E)组,E组予以一次大负荷运动训练。每6 h取各组比目鱼肌,采用透射电镜观察骨骼肌纤维超微结构,通过实时荧光定量PCR实验测定骨骼肌核心时钟基因Bmal1、Clock、Cry1、Per1表达量,并使用余弦分析软件circacompare(R package)获取拟合余弦曲线参数,分析其节律性振荡的变化趋势。结果:1)C组Bmal1、Clock、Cry1、Per1 mRNA在72 h内呈现3个完整近日节律周期;E组Bmal1 mRNA、Cry1和Per1mRNA在0~24 h、Clock mRNA在0~72 h近日节律消失。2)与C组相比,E组Bmal1 mRNA在0、6、12和18 h显著升高,Clock mRNA在0 h时显著升高;Cry1、Per1 mRNA在0、12 h显著降低。3)C组各时相肌纤维超微结构正常,E组0、24和48 h均出现不同程度肌小节结构破坏、线粒体肿胀及聚集等改变,72 h有所缓解。结论:一次大负荷运动可诱发骨骼肌核心时钟基因Bmal1/Clock、Cry1/Per1节律振荡紊乱,其变化趋势与肌纤维超微结构损伤时相基本一致。

An Improved Hybrid Genetic Algorithm for Chemical Plant Layout Optimization with Novel Non-overlapping and Toxic Gas Dispersion Constraints

New approaches for facility distribution in chemical plants are proposed including an improved non-overlapping constraint based on projection relationships of facilities and a novel toxic gas dispersion constraint. In consideration of the large number of variables in the plant layout model, our new method can significantly reduce the number of variables with their own projection relationships. Also, as toxic gas dispersion is a usual incident in a chemical plant, a simple approach to describe the gas leakage is proposed, which can clearly represent the constraints of potential emission source and sitting facilities. For solving the plant layout model, an improved genetic algorithm (GA) based on infeasible solution fix technique is proposed, which improves the globe search ability of GA. The case study and experiment show that a better layout plan can be obtained with our method, and the safety factors such as gas dispersion and minimum distances can be well handled in the solution.

A novel non-overlapping approach to accurately represent 2D arbitrary particles for DEM modelling

Mechanical behaviors of granular materials are complicated and greatly influenced by the particle shape.Current,some composite approaches have been proposed for realistic particle shape modelling within discrete element method(DEM),while they cannot give a good representation to the shape and mass properties of a real particle.In this work,a novel algorithm is developed to model an arbitrary particle using a cluster of non-overlapping disks.The algorithm mainly consists of two components:boundary filling and domain filling.In the boundary filling,some disks are placed along the boundary for a precise representation of the particle shape,and some more disks are placed in the domain to give an approximation to the mass properties of the particle in the domain filling.Besides,a simple method is proposed to correct the mass properties of a cluster after domain filling and reduce the number of the disks in a cluster for lower computational load.Moreover,it is another great merit of the algorithm that a cluster generated by the algorithm can be used to simulate the particle breakage because of no overlaps between the disks in a cluster.Finally,several examples are used to show the robust performance of the algorithm.A current FORTRAN version of the algorithm is available by contacting the author.

CLOCK氧化还原修饰介导内源性H_(2)O_(2)对小鼠细胞呼吸的调节作用

目的探究生物钟核心转录因子昼夜节律运动输出周期蛋白(CLOCK)介导内源性过氧化氢(H_(2)O_(2))对细胞呼吸的调节作用和机制。方法利用Seahorse细胞能量代谢分析仪检测Clock^(C195S)小鼠胚胎成纤维细胞(MEFs)和成体成纤维细胞(MAFs)细胞氧耗能力和糖酵解能力;通过q-PCR检测细胞呼吸关键代谢酶基因表达水平;MEFs进行抗氧化剂Trolox处理后,用Amplex■ Red试剂盒检测内源性H_(2)O_(2)的含量,并通过生物素碘乙酰胺(BIAM)探针标记检测CLOCK蛋白氧化还原修饰的改变,进一步检测处理后的细胞氧耗能力和细胞呼吸关键代谢酶基因表达水平。结果Clock^(C195S)细胞氧耗能力和糖酵解能力下降,烟酰胺腺嘌呤二核苷酸(NAD)合成关键酶烟酰胺单核苷酸腺苷转移酶(NMNAT2)表达降低(P<0.05),NAD含量下降;Trolox处理导致细胞内源性H_(2)O_(2)含量降低,Clock wt MEFs氧耗能力降低而Clock^(C195S) MEFs变化无统计学意义。结论CLOCK蛋白可以通过195位点半胱氨酸氧化还原修饰介导内源性H_(2)O_(2)对细胞呼吸的调节作用。