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.

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.

The Impact of Model Based Offset Scaling Technique on the Amplitude Variation with Offset Responses from 3D Seismic Data Acquired from the Tano Basin, Offshore Ghana

Amplitudes have been found to be a function of incident angle and offset. Hence data required to test for amplitude variation with angle or offset needs to have its amplitudes for all offsets preserved and not stacked. Amplitude Variation with Offset (AVO)/Amplitude Variation with Angle (AVA) is necessary to account for information in the offset/angle parameter (mode converted S-wave and P-wave velocities). Since amplitudes are a function of the converted S- and P-waves, it is important to investigate the dependence of amplitudes on the elastic (P- and S-waves) parameters from the seismic data. By modelling these effects for different reservoir fluids via fluid substitution, various AVO geobody classes present along the well and in the entire seismic cube can be observed. AVO analysis was performed on one test well (Well_1) and 3D pre-stack angle gathers from the Tano Basin. The analysis involves creating a synthetic model to infer the effect of offset scaling techniques on amplitude responses in the Tano basin as compared to the effect of unscaled seismic data. The spectral balance process was performed to match the amplitude spectra of all angle stacks to that of the mid (26°) stack on the test lines. The process had an effect primarily on the far (34° - 40°) stacks. The frequency content of these stacks slightly increased to match that of the near and mid stacks. In offset scaling process, the root mean square (RMS) amplitude comparison between the synthetic and seismic suggests that the amplitude of the far traces should be reduced relative to the nears by up to 16%. However, the exact scaler values depend on the time window considered. This suggests that the amplitude scaling with offset delivered from seismic processing is only approximately correct and needs to be checked with well synthetics and adjusted accordingly prior to use for AVO studies. The AVO attribute volumes generated were better at resolving anomalies on spectrally balanced and offset scaled data than data delivered from conventional processing. A typical class II AVO anomaly is seen along the test well from the cross-plot analysis and AVO attribute cube which indicates an oil filled reservoir.

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.

The Effect of Lateral Offset Distance on the Aerodynamics and Fuel Economy of Vehicle Queues

The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take advantage of these developments.Here we consider the case of many vehicles forming a queue,i.e.,vehicles traveling at a predetermined speed and distance apart.While the majority of existing studies on this subject have focused on the influence of the longitudinal vehicle spacing,vehicle speed,and the number of vehicles on aerodynamic drag and fuel economy,this study considers the lateral offset distance of the vehicle queue.The group fuel consumption savings rate is calculated and analyzed.As also demonstrated by experimental results,some aerodynamic benefits exist.Moreover,the fuel consumption saving rate of the vehicle queue decreases as the lateral offset distance increases.

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. .

CLOCK inhibits the proliferation of porcine ovarian granulosa cells by targeting ASB9

Background Clock circadian regulator(CLOCK)is a core factor of the mammalian biological clock system in regulat-ing female fertility and ovarian physiology.However,CLOCK’s specific function and molecular mechanism in porcine granulosa cells(GCs)remain unclear.In this study,we focused on CLOCK’s effects on GC proliferation.Results CLOCK significantly inhibited cell proliferation in porcine GCs.CLOCK decreased the expression of cell cycle-related genes,including CCNB1,CCNE1,and CDK4 at the mRNA and protein levels.CDKN1A levels were upregulated by CLOCK.ASB9 is a newly-identified target of CLOCK that inhibits GC proliferation;CLOCK binds to the E-box element in the ASB9 promoter.Conclusions These findings suggest that CLOCK inhibits the proliferation of porcine ovarian GCs by increasing ASB9 level.

基于PI闭环反馈的EtherCAT分布式时钟漂移补偿优化

接入工业总线的设备的增加会导致高延迟等同步性问题。基于EtherCAT对分布式时钟同步算法进行研究与分析,针对其在漂移补偿过程中存在补偿精度低的问题,提出了一种基于闭环反馈控制思想的动态漂移补偿算法。算法先利用定点数改进本地时钟,再利用PI控制调节漂移补偿值。最后搭建了测试平台,包括基于SOEM实现的主站与基于STM32+FPGA架构实现的从站,优化前后的算法分别在FPGA中实现。测试结果表明:定点数改进的本地时钟分辨率可以达到2^(-20) ns, PI闭环反馈优化后的漂移补偿算法可以将同步误差降低到25 ns之内,明显提高从站之间的同步性能。

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.

Major roles of the circadian clock in cancer

Circadian rhythms are natural rhythms that widely exist in all creatures,and regulate the processes and physiological functions of various biochemical reactions.The circadian clock is critical for cancer occurrence and progression.Its function is regulated by metabolic activities,and the expression and transcription of various genes.This review summarizes the composition of the circadian clock;the biological basis for its function;its relationship with,and mechanisms in,cancer;its various functions in different cancers;the effects of anti-tumor treatment;and potential therapeutic targets.Research in this area is expected to advance understanding of circadian locomotor output cycles kaput(CLOCK)and brain and muscle ARNT-like protein 1(BMAL1)in tumor diseases,and contribute to the development of new anti-tumor treatment strategies.

A combined magnetic field stabilization system for improving the stability of 40Ca^(+) optical clock

Future applications of portable40Ca^(+)optical clocks require reliable magnetic field stabilization to improve frequency stability, which can be achieved by implementing an active and passive magnetic field noise suppression system. On the one hand, we have optimized the magnetic shielding performance of the portable optical clock by reducing its apertures and optimizing its geometry;on the other hand, we have introduced an active magnetic field noise suppression system to further suppress the magnetic field noise experienced by the ions. These efforts reduced the ambient magnetic field noise by about 10000 times, significantly reduced the linewidth of the clock transition spectrum, improved the stability of the portable40Ca+optical clock, and created the conditions for using portable optical clocks in non-laboratory magnetic field environments. This active magnetic field suppression scheme has the advantages of simple installation and wide applicability.

Assessment of the ballistic response of honeycomb sandwich structures subjected to offset and normal impact

In the present study,experimental and numerical investigations were carried out to examine the behavior of sandwich panels with honeycomb cores.The high velocity impact tests were carried out using a compressed air gun.A sharp conical nosed projectile was impacted normally and with some offset distance(20 mm and 40 mm).The deformation,failure mode and energy dissipation characteristics were obtained for both kinds of loading.Moreover,the explicit solver was run in Abaqus to create the finite element model.The numerically obtained test results were compared with the experimental to check the accuracy of the modelling.The numerical result was further employed to obtain strain energy dissipation in each element by externally running user-defined code in Abaqus.Furthermore,the influence of inscribe circle diameter and cell wall and face sheet thickness on the energy dissipation,deformation and failure mode was examined.The result found that ballistic resistance and deformation were higher against offset impact compared to the normal impact loading.Sandwich panel impacted at 40 mm offset distance required 3 m/s and 1.9 m/s more velocity than 0 and 20 mm offset distance.Also,increasing the face sheet and wall thickness had a positive impact on the ballistic resistance in terms of a higher ballistic limit and energy absorption.However,inscribe circle diameter had a negative influence on the ballistic resistance.Also,the geometrical parameters of the sandwich structure had a significant influence on the energy dissipation in the different deformation directions.The energy dissipation in plastic work was highest for circumferential direction,regardless of impact condition followed by tangential,radial and axial directions.

Theoretical calculations on Landé g-factors and quadratic Zeeman shift coefficients of nsnp ^(3)P_(0)^(o) clock states in Mg and Cd optical lattice clocks

The study of magnetic field effects on the clock transition of Mg and Cd optical lattice clocks is scarce.In this work,the hyperfine-induced Landég-factors and quadratic Zeeman shift coefficients of the nsnp ^(3)P_(0)^(o) clock states for ^(111,113)Cd and ^(25)Mg were calculated by using the multi-configuration Dirac–Hartree–Fock theory.To obtain accurate values of these parameters,the impact of electron correlations and furthermore the Breit interaction and quantum electrodynamical effects on the Zeeman and hyperfine interaction matrix elements,and energy separations were investigated in detail.We also estimated the contributions from perturbing states to the Landég-factors and quadratic Zeeman shift coefficients concerned so as to truncate the summation over the perturbing states without loss of accuracy.Our calculations provide important data for estimating the first-and second-order Zeeman shifts of the clock transition for the Cd and Mg optical lattice clocks.

Sympathetic electromagnetically induced transparency ground state cooling of a~(40)Ca^(+)–~(27)Al^(+)pair in an~(27)Al^(+)clock

We report on electromagnetically induced transparency cooling of ^(40)Ca^(+)to sympathetically cool the threedimensional secular modes of motion in a ^(40)Ca^(+)–^(27)Al^(+)two-ion pair near the ground state.We observe simultaneous ground state cooling across all radial modes and axial modes of a ^(40)Ca^(+)–^(27)Al^(+)ion pair,occupying a broader cooling range in frequency space over 3 MHz.The cooling time is observed to be less than 1 ms.The mean phonon number and heating rates of all motional modes are measured.This study is not only an important step for reducing the secular motion time-dilation shift uncertainty and uptime ratio of ^(27)Al^(+)optical clock,but also essential for high-fidelity quantum simulations and quantum information processors using trapped ions.

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.

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.