氚气标准源的研制

高性能芯片级原子气室的制备是现阶段芯片级量子传感仪器研制急需解决的关键技术之一。为解决目前芯片级原子气室研制领域存在的碱金属定量填充难、气密性差等问题，开展了高气密性芯片级原子气室制备方法研究，利用微电子机械系统（MEMS）技术实现了芯片级原子气室的批量制备。采用深硅刻蚀技术制备硅气室腔，利用RbN₃的光分解实现碱金属单质的制备及定量填充，采用阳极键合技术对原子气室进行两次硅片/玻璃键合封装，成功获得了以N₂为缓冲气体的Rb碱金属原子气室。对所制备的原子气室进行键合强度、气密性、吸收光谱测试，结果表明原子气室的玻璃/硅片/玻璃键合强度均较高，其中B组原子气室的漏气率平均值为2.2×10^-9 Pa?m³?s^-1，其气密性为目前行业内领先水平。最后从制备工艺上分析了两组原子气室的性能差异原因，为推动量子传感仪器的芯片级集成技术发展奠定重要基础。     

汞离子微波钟及其研究进展

汞离子微波钟是下一代星载原子钟、地面守时原子钟的有力候选者。文章介绍了本团队在汞离子微波钟的离子囚禁、缓冲气体冷却、微波综合器、汞光谱灯等关键技术取得的突破和进展，在此基础上，研制出了小型化汞离子钟整机，其频率稳定度达到了2.3 × 10^-15/10⁵ s，同时开展了分区式线形阱汞离子微波钟的技术研究，实现了离子的高效梭动及系统的闭环锁定，测得频率稳定度3.45 × 10^-13/τ^1/2（τ = 10 ～ 10 000 s），为汞离子微波钟技术的应用奠定了重要基础。     

基于移动光晶格布洛赫振荡的原子干涉重力仪

针对目前传统的原子干涉重力仪—马赫-曾德尔型原子重力仪存在体积较大，影响设备便携性的问题，北京大学实现了国内首个基于移动光晶格的布洛赫振荡原理的小型化原子干涉重力仪。本实验系统的采样率达到0.9 Hz，能够满足长期实时测量的需求，且实验系统中原子的竖直位移约为3 cm，灵敏度达到4.6 × 10² μGal·Hz^-1/2，在2 800 s积分时间内，分辨率可以达到6.50.7?μGal。实验成果为原子干涉重力仪的小型化与实用化指明了未来的发展方向。     

基于冷原子重力仪的轨道移动绝对重力测量

绝对重力测量在铁路路基探测等领域发挥着重要作用，但大多数室外移动重力仪结构复杂或精度一般，可使用的范围有限。研制了一套轨道移动绝对重力测量系统，实现了高集成的系统结构设计、自动化的测试流程，开展了实验室及轨道环境下的绝对重力测量，测量结果可靠。首先，在实验室环境下重力测量灵敏度达到了440 μGal?Hz-1/2，测量300 s的误差小于30 μGal。其次，在炎热、嘈杂的室外轨道移动条件下，绝对重力测量不确定度优于15 μGal，与相对重力仪（LG-1）的测量偏差优于40 μGal。最后，轨道环境下的重力测量灵敏度达到707.9 μGal?Hz-1/2。所提出的轨道移动绝对重力测量系统可以在室外条件下进行快速重力测量，为铁路路基探测提供了新的仪器与解决方案。     

拉曼抑制光频梳微腔的设计与仿真

为了解决回音壁模式下的微腔在产生光频梳时受拉曼效应的影响，尤其在重频GHz时难以产生平滑的光梳谱的问题。首先，设计并调节波导和微环的耦合长度；然后，优化耦合角度，调整微环与波导之间的匹配模式，降低在长波段的耦合Q值，增加拉曼产生的阈值，抑制拉曼效应。通过仿真分析得出，相较于一般的直波导微环耦合结构，设计的弯曲波导微环在短波长处拉曼阈值增加了3倍，且在短波长处产生的光频梳功率提高了20 dB。为回音壁模式微腔结构的设计提供了一定的参考价值。     

滑块摇杆机构对小腿三头肌康复的作用研究

以小腿三头肌的康复训练为应用背景,研究了滑块摇杆机构对小腿三头肌的康复作用。推导了滑块摇杆康复机构的矢量方程,建立了其数学模型,并利用MATLAB软件进行了滑块摇杆康复机构的运动仿真。结果显示：通过控制机构滑块的位移、速度和加速度可以间接地控制末端执行器的运动,从而形成能满足患者不同需求的康复模式;为保证滑块摇杆康复机构在使用过程中的安全性,滑块位移的变化区间应为200~700 mm。开展了滑块摇杆康复机构对小腿三头肌的按摩实验。结果显示,使用滑块摇杆康复机构后,小腿三头肌的表面肌电信号明显改变,使用前后小腿三头肌的肌电值有显著性差异（p1=0.037<0.05）,使用过程中肌电值的峰值有显著性差异（p2=0.018<0.05）,说明该机构对小腿三头肌有显著、有效的康复性刺激。研究结果可为滑块摇杆机构在康复医疗中的应用提供理论参考。     

汽油发动机双回路冷却系统的研究

汽油发动机双回路冷却系统由于其快速暖机以及减磨的优点，已逐渐被业界认可，但国内对其工程设计及应用尚属于起步阶段，缺乏相应完善的设计理论和方法。为了满足轻型汽车污染物排放限值（中国第六阶段）的要求以某1.5 T直列四缸汽油发动机为研究对象，对机体、缸盖双回路冷却系统进行了研究。首先，在按经典公式计算的基础上，通过燃气侧对机体、缸盖散热量的计算，初步确定了机体、缸盖双回路冷却介质的流量分配比例。其次，通过一维流动传热和基于CFD （computational fluid dynamics， 计算流体动力学）的三维联合仿真，确定了最终冷却回路的流量分配。在此基础上，通过一维瞬态流动传热模型仿真对比了单回路和双回路冷却系统在暖机阶段的性能。结果表明：双回路冷却系统中机体的温度比单回路高10 ℃，缸盖的温度比单回路低9.6 ℃，双回路冷却可以显著加快发动机的暖机过程，使发动机在冷启动期间的磨损减小。最后，进行了流量分配验证试验和暖机对比试验，结果表明：在暖机过程中，与单回路冷却系统相比，双回路冷却系统可以使机体温度上升更快，活塞与缸套摩擦减小；在此阶段，怠速工况下油耗降低20.2%，HC（碳氢化合物）排放量降低7.58%，常用工况点（2 000 r ? min-1，200 kPa）下油耗降低8.5%，HC排放量降低10.03%。研究结果可为发动机冷却系统的设计优化提供参考。     

Y形旋转超声波马达的设计与动态特性分析

为了探索和丰富旋转超声波马达的结构,使其满足响应精准且速度快以及控制简便的要求,设计了Y形旋转超声波马达,并对其结构及动态特性进行了分析。Y形旋转超声波马达将3组压电陶瓷片的横向振动复合成驱动足端面对转子的微幅驱动,通过摩擦耦合在惯性作用下推动转子顺时针或逆时针旋转。运用Workbench软件中的Design Exporation组件对Y形旋转超声波马达定子组件的结构尺寸进行了优化设计,提升了定子组件的性能。构建优化后Y形旋转超声波马达定子组件的有限元仿真模型,并通过模态分析获得了定子组件工作所需的固有振型,通过谐响应分析获得了定子组件的幅频特性曲线,通过瞬态分析获得了1个激励周期内定子组件的振动模态,验证了Y形旋转超声波马达的驱动机理。结果表明,Y形旋转超声波马达压电陶瓷片表面施加电压的最佳频率为20 739 Hz,对应的驱动足端面的振幅为6.95 μm。Y形旋转超声波马达结构简单且具有对称性,能效利用率高,对拓宽超声波马达的应用领域有重要参考价值。     

基于滚筒载荷的采煤机滑靴振动分析及实验验证

为了研究采煤机滑靴的振动特性,对采煤机整机进行动力学建模分析。首先,根据采煤机部件的功能,将采煤机划分成前、后滚筒,前、后摇臂,机身,前、后导向滑靴和前、后平滑靴等9个部分;然后,基于拉格朗日法构建了采煤机三向耦合动力学模型;接着,对所构建的动力学模型的坐标耦合问题进行分析,并采用Wilson-θ算法对动力学模型进行仿真求解;最后,通过采煤机振动实验获取了滑靴的三向振动加速度,并与仿真结果进行对比。结果表明：通过仿真与实验获得的滑靴振动加速度的中位数均集中在平衡位置“0 m/s²”处,但仿真结果的四分位数全距大于实验结果,即仿真结果相对发散,而实验结果更为聚集;仿真结果与实验结果的相关系数均大于0.3,呈实相关,其中部分数据的相关系数大于0.5,呈显著相关;在仿真结果与实验结果的P值直方图中,各组数据的P值均大于0.05,说明在95%置信区间内,仿真结果与实验结果无显著差异,表明仿真结果可以近似代替实验结果,具有一定的准确性和实用性。研究结果可为采煤机滑靴的故障诊断、结构优化以及疲劳寿命分析提供理论依据。     

自适应消声系统的设计与性能研究

为了有效控制低频宽带噪声,结构简单的声衬被广泛应用。传统声衬只能消除固定频率的噪声,即当环境噪声频率发生改变时,传统声衬消声性能明显下降。为此,提出了一种自适应消声系统,利用压电声衬工作原理,通过LabVIEW串口通信技术传输与控制数据程序,驱动压电声衬使它能根据噪声频率的变化自适应控制信号;通过调节电源输出电压,改变压电声衬共振腔体积,从而及时有效地调节压电声衬消声频率,拓宽压电声衬的消声频带。分析结果表明,压电声衬共振腔体积减小时,消声频带向低频方向偏移,反之向高频方向偏移;当输出电压为-100~200 V时,自适应消声系统可在噪声频率为1 364~1 420 Hz的环境中一直保持最佳的消声效果,实现了自适应消噪。研究结果表明,对声衬施加直流电源可以对其消声频率进行调节,使其消声频带随着噪声频率的变化而偏移,拓宽其消声频带。设计的消声系统可以实现噪声的自适应控制,可为声衬的主动控制及优化提供参考。     

基于HITEMP数据库的分子吸收光谱高精度快速建模方法

为解决高温环境下分子吸收光谱精确计算的时间复杂性,满足宽光谱测量领域对理论吸收光谱计算的需求,本研究利用Python语言以逐线计算为基础,结合线型函数的简化、线翼截止准则和谱线数据库的优化,建立了基于高温分子吸收参数数据库(High-Temperature molecular spectroscopic absorption parameters data-base,HITEMP)的分子吸收光谱精确快速计算模型。以Hartmann-Tran线型函数作为吸收光谱标准线型编写部分相关二次速度依赖硬碰撞函数(partially-Correlated quadratic-Speed-Dependent Hard-Collision Profile,p Cq SDHC),结合复概率函数(Complex Probability Function,CPF)简化模型实现了线型函数的精确快速计算,相较于理论计算模型计算速度提高了20倍。按照光谱计算残差在10^-5量级确定了固定波数截断结合谱线半宽等倍数截断的线翼截止准则。以阈值线强度10^-25 cm^-...     

Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: optimization and in vivo studies

Background: Multiple sclerosis (MS) is one of the most severe autoimmune disorder of the central nervous system (CNS).

Objective: The present research work was aimed to formulate and investigate teriflunomide (TFM)-loaded intranasal (i.n.) nanostructured lipid carriers (NLC) for the treatment of multiple sclerosis (MS).

Methods: The TFM-loaded NLC (TFM-NLC) nanoparticles were prepared by melt emulsification ultrasonication method using biodegradable and biocompatible polymers. The Box–Behnken statistical design was applied to optimize the formulation. The optimized NLC formulation was subjected to evaluate for particle size, entrapment efficiency (%), in vitro and ex vivo permeation. The safety and efficacy of optimized formulations were demonstrated using pharmacodynamic, subacute toxicity and hepatotoxicity data.

Results: Experimental data demonstrated that optimized NLC formulation (F17) showed significant size (99.82?±?1.36?nm), zeta potential (?22.29?±?1.8?mV) and % entrapment efficiency (83.39?±?1.24%). Alternatively, ex vivo permeation of TFM mucoadhesive NLC (TFM-MNLC) and TFM-NLC was observed 830?±?7.6 and 651?±?9.8?µg/cm², respectively. Whereas, TFM-MNLC shows around 2.0-folds more J_ss than the TFM-NLC. Finally, TFM-MNLC (i.n.) formulation produced the rapid remyelination in cuprizone-treated animals and decreases the number of entries in open compartment of EPM when compared with negative control and TFM-NLC (oral) animals. Simultaneously, the nanoformulation did not reflect any gross changes in hepatic biomarkers and subacute toxicity when compared with control.

Conclusions: Hence it can be inferred that the nose-to-brain delivery of TFM-MNLC can be considered as effective and safe delivery for brain disorders.     

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement

Objective: Indinavir (IDV), an antiretroviral protease inhibitor used in treatment of HIV infection, has limited entry into brain due to efflux by the P-glycoprotein presented in blood–brain barrier. The aim of present study was to develop lactoferrin-treated nanoemulsion containing indinavir (Lf-IDV-NEs) for delivery to brain.

Methods: Indinavir-loaded nanoemulsions (IDV-NEs) were prepared by high-speed homogenization method, and then lactoferrin was coupled to IDV-NEs by water soluble EDC method.

Results: The hydrodynamic diameters, polydispersity index, and zeta potential of IDV-NEs were 112?±?3.5?nm, 0.20?±?0.02, and ?33.2?±?2.6?mV, respectively. From in vivo studies in animal model of rats, the AUC_0–4?h of brain concentration–time profile of IDV-NEs and Lf-IDV-NEs were 1.6 and 4.1 times higher than free drug, respectively. The brain uptake clearance of IDV-NEs and Lf-IDV-NEs were, interestingly, 393- and 420-times higher than the free drug.

Conclusions: It can be concluded that applying both lactoferrin-treated and non-treated nanoemulsions clearly leads to significant brain penetration enhancement of indinavir, an effect which is more pronounced in the case of Lf-IDV-NEs with the higher drug residence time in brain.     

Study on the transdermal penetration mechanism of ibuprofen nanoemulsions

Objective: The purpose of this study was to research the mechanism of percutaneous penetration of Ibuprofen (IBU) nanoemulsion.

Method: Transdermal penetration mechanism of IBU nanoemulsion was investigated by using Fourier transform infra-red spectral analysis (FTIR), differential scanning calorimeter thermogram (DSC), and activation energy (Ea) measurement. The in vivo skin penetration test of rats was carried out using Rhodamine B nanoemulsion to simulate the process of drug penetration into the skin, and the frozen section of the skin was observed by confocal laser scanning microscopy (CLSM).

Result: FTIR spectra and DSC thermogram of rat skin treated with IBU nanoemulsion showed that infiltration occurred due to disruption of the stratum corneum (SC) protein–lipid structure and increasing of fluidity, hydration, and disruption of the lipid bilayer structure of the SC. The significant reduce in Ea (1.255?kcal/mol) for IBU permeating rat skin suggested crucial disruption of the SC lipid bilayers (P?<?0.05), which is speculated that nanoemulsion may create new pathways to promote drug penetration. CLSM revealed that Rhodamine B penetrated into the SC in a shorter period of time and it accumulated around the sebaceous glands.

Conclusion: The study of skin penetration mechanism indicated that nanoemulsion can be perfectly well used as the transdermal penetration of poorly soluble drugs.     

Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid–phospholipid complex

Objective: To prepare and characterize an optimized phospholipid complex of Ursolic acid (UA) to overcome the poor pharmacokinetic properties and to investigate the impact of the complex on hepatoprotective activity and bioavailability in animal model.

Significance: UA is a potential phytoconstituent obtained from several plant sources, which has been explored for its diverse pharmacological activities including hepatoprotection. Its major limitation is poor absorption, rapid elimination, and hence low bioavailability after administration.

Methods: Response surface methodology was adopted to formulate an optimized (UA) complex. The complex was characterized by differential thermal analysis (DTA), Fourier transform-Infrared Spectroscopy, Powder X ray Diffraction, molecular docking, etc. The physico-chemical profile (solubility, oil/water partition coefficient) and in vitro dissolution profile was estimated. The formulation was then used to study hepatoprotective activity and bioavailability in animal models.

Results: Results showed that the phospholipid complex of UA has enhanced the hepatoprotective potential as compared to pure UA at the same dose level. The complex restored the levels of serum hepatic marker enzymes with respect to untreated group and increased the relative bioavailability of UA in rat plasma by 8.49-fold in comparison with pure compound at the same dose level. It enhanced the elimination half-life (t_{1/2 el}) from 0.69 ± 1.76 to 8.28 ± 1.98 h.

Conclusion: Complexation of UA with phospholipid markedly enhanced the hepatoprotective potential of UA by improving its bioavailability and pharmacokinetic parameters.

Novelty statement

The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.

Novelty statement

The present article deals with rational optimization of the formulation parameters for phospholipid complex of ursolic acid by Response Surface Methodology analysis, characterizing the formulation by in silico approach apart from conventional instrumental techniques, and evaluating the in vitro dissolution, pharmacokinetics, and hepatoprotective activity of the complex in animals.     

Formulation development and in vitro evaluation of gentamicin sulfate-loaded PLGA nanoparticles based film for the treatment of surgical site infection by Box–Behnken design

Objective: Gentamicin sulfate (GS)–loaded poly lactic-co-glycolic acid (PLGA) polymeric nanoparticles (PNPs) were developed and incorporated in film for the treatment of surgical site infection (SSI).

Method: PNPs were prepared by double emulsification solvent removal technique using ethyl acetate solution containing PLGA and polyvinyl alcohol (PVA) as an emulsifier. The emulsion was re-emulsified using Gum Kondagogu (GKK). PNPs loaded film was prepared with 5% w/v solution of pullulan in PNPs using solvent casting technique. Design of Experiment (DoE) study using Box–Behnken design was performed for the optimization of PNPs. Drug release study was carried out for PNPs at phosphate buffer saline (PBS) pH 6.4 and simulated wound fluid (SWF) pH 7.4.

Result: PNPs were found to have average particle size 280?±?12.04?nm, polydispersity index (PDI) 0.15?±?0.01 and zeta potential – 4.9?±?0.84?mV. Scanning electron microscopy (SEM) showed spherical nature of PNPs along with particle size of 160?±?35.30?nm confirmed with transmission electron microscopy (TEM). PNPs were found to be effective against Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA). Optimized batch of film showed in vitro disintegration time below 8?min with tensile strength (TS) 0.06?±?0.03 N/cm² and percentage elongation (% E) 70.95?±?4.29. X-ray diffraction study (XRD) confirmed amorphous nature of GS, PLGA, pullulan, GKK and film.

Conclusion: PNPs showed controlled release of GS after an initial burst release. Developed film can be an effective approach for management of SSI and control of antibiotic induced drug resistance.