Perspective on post-menopausal osteoporosis: establishing an interdisciplinary understanding of the sequence of events from the molecular level to whole bone fractures

Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within various disciplines has significantly advanced the state of knowledge, fundamental findings are not widely understood between different disciplines. For that reason, this paper presents noteworthy experimental findings from discrete disciplines focusing on post-menopausal osteoporosis. These studies have established that, in addition to bone loss, significant changes in bone micro-architecture, tissue composition and micro-damage occur. Cellular processes and molecular signalling pathways governing pathological bone resorption have been identified to a certain extent. Ongoing studies endeavour to determine how such changes are initiated at the onset of oestrogen deficiency. It emerges that, because of the discrete nature of previous research studies, the sequence of events that lead to bone fracture is not fully understood. In this paper, two sequences of multi-scale changes are proposed and the experimental challenges that need to be overcome to fully define this sequence are outlined. Future studies must comprehensively characterize the time sequence of molecular-, cellular- and tissue-level changes to attain a coherent understanding of the events that ultimately lead to bone fracture and inform the future development of treatments for post-menopausal osteoporosis.     

Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film

Objective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis.

Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy.

Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption.

Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation.

Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.     

基于超声导波反演参数定征皮质骨骨质状况研究

骨质疏松发生时,人体皮质骨层的孔隙度将增大。为研究皮质骨参数（厚度、横波速度、纵波速度）与骨质疏松症的关系,文章利用有限元方法对不同孔隙度（0∶3%∶27%）的单层皮质骨进行仿真,以3个周期的高斯包络正弦波作为激励,将采集到的超声导波信号先后经过二维傅里叶变换和Burg算法处理后得到频散数据,与基于FloquetBloch理论建立的理论频散曲线数据库进行匹配反演,得到皮质骨厚度、横波速度、纵波速度参数。结果显示皮质骨厚度反演准确,皮质骨孔隙度与横波速度和纵波速度呈负相关,横波速度敏感度为19.0%,纵波速度敏感度为5.5%。横波速度敏感度更高,临床诊断潜力更大。并对6组牛胫骨进行了离体实验,结果显示,反演得到的皮质骨厚度与其实际测量值的平均相对误差为4.0%,且实验频散曲线与理论频散曲线相吻合,验证了文中算法在真实皮质骨参数反演上的可行性和准确性。文中的研究在骨质疏松超声检测中具有应用潜力。     

Characterisation of nano-structured titanium and aluminium nitride coatings by indentation, transmission electron microscopy and electron energy loss spectroscopy

Titanium and aluminium nitride Ti_1 − xAl_xN films deposited by radiofrequency magnetron reactive sputtering onto steel substrate are examined by transmission electron microscopy over all the range of composition (x = 0, 0.5, 0.68, 0.86, 1). The deposition parameters are optimised in order to grow nitride films with low stress over all the composition range. Transmission electron microscopy cross-section images of Vickers indentation prints performed on that set of coatings show the evolution of their damage behaviour as increasing x Al content. Cubic Ti-rich nitrides consist of small grains clustered in rather large columns sliding along each other during indentation. Hexagonal Al-rich films grow in thinner columns which can be bent under the Vickers tip. Indentation tests carried out on TiN and AlN films are simulated using finite element modelling. Particular aspects of shear stresses and displacements in the coating/substrate are investigated. The growth mode and the nanostructure of two typical films, TiN and Ti_0.14Al_0.86N, are studied in detail by combining transmission electron microscopy cross-sections and plan views. Electron energy loss spectrum taken across Ti_0.14Al_0.86N film suggests that a part of nitrogen atoms is in cubic-like local environment though the lattice symmetry of Al-rich coatings is hexagonal. The poorly crystallised domains containing Ti and N atoms in cubic-like environment are obviously located in grain boundaries and afford protection of the coating against cracking.     

Coupling multiscale X-ray physics and micromechanics for bone tissue composition and elasticity determination from micro-CT data,by example of femora from OVX and sham rats

Due to its high resolution, micro-CT (Computed Tomograph) scanning is the key to assess bone quality of sham and OVX (ovariectomized) rats. Combination of basic X-ray physics, such as the energy- and chemistry-dependence of attenuation coefficients, with results from ashing tests on rat bones, delivers mineral, organic, and water volume fractions within the voxels. Additional use of a microelastic model for bone provides voxel-specific elastic properties. The new method delivers realistic bone mass densities, and reveals that OVX protocols may indeed induce some bone mass loss, while the average composition of the bone tissue remains largely unaltered.     

Dynamical modelling of haematopoiesis: an integrated view over the system in homeostasis and under perturbation

A very high number of different types of blood cells must be generated daily through a process called haematopoiesis in order to meet the physiological requirements of the organism. All blood cells originate from a population of relatively few haematopoietic stem cells residing in the bone marrow, which give rise to specific progenitors through different lineages. Steady-state dynamics are governed by cell division and commitment rates as well as by population sizes, while feedback components guarantee the restoration of steady-state conditions. In this study, all parameters governing these processes were estimated in a computational model to describe the haematopoietic hierarchy in adult mice. The model consisted of ordinary differential equations and included negative feedback regulation. A combination of literature data, a novel divide et impera approach for steady-state calculations and stochastic optimization allowed one to reduce possible configurations of the system. The model was able to recapitulate the fundamental steady-state features of haematopoiesis and simulate the re-establishment of steady-state conditions after haemorrhage and bone marrow transplantation. This computational approach to the haematopoietic system is novel and provides insight into the dynamics and the nature of possible solutions, with potential applications in both fundamental and clinical research.     

Reduction of alternating current loss in a high-TC superconducting transmission cable by means of helical pitch adjustment

We have reported that the alternating current (ac) losses in a 66 kV_rms 3-core high-T_C superconducting (HTS) transmission cable fabricated by Tokyo Electric Power Company and Sumitomo Electric Industries Ltd. are calculated correctly by using an electric-circuit model. According to the calculated results, the circumferential field losses are dominant in the total ac losses in compared with the self-field losses and the axial-field losses. The helical pitches of each layer in the HTS cable are designed to obtain almost same layer currents, which gives the minimum self-field losses. We think that the optimum helical pitches giving the minimum total losses are different from the helical pitches designed by the companies and calculate the optimum values in the condition of the same helical direction of each layer in the cable. As a result, for example, it is found that the ac loss of 2.1 W m⁻¹ cc⁻¹ at transporting 1 kA_rms can be reduced to 1.8 W m⁻¹ cc⁻¹ (about 14% reductions) after redesigning the cable with the optimum helical pitches. The optimum helical pitches are obtained for each given transport current. After redesigning, the distribution of layer currents is not uniform and the circumferential fields are reduced.     

燃煤发电厂储煤场自燃热损失的评估

煤炭周转不合理导致了自燃在燃煤发电厂露天储煤场频频发生,降低了入炉煤的发热量,增加了灰分,直接影响锅炉机组运行的安全性和经济性.为了掌握不同存煤阶段煤堆热损失的变化规律,本文以煤场某典型煤种为研究对象,开展了煤场温度监测试验,并在试验的基础上建立自燃热损失评估的数学模型.研究结果表明,存煤初期煤堆热损失以线性函数规律增加,入场存放30d后煤堆热损失以幂指数函数增长的趋势急剧增加,因此应在30～40d内完成入场煤的周转,实现合理存煤、用煤,减少入炉前发热量的损失,为开发燃煤发电厂储煤场自燃热损失评估系统、降低发电成本提供奠定了基础.     

Evaluation of cortical bone by peripheral quantitative computed tomography in continuous ambulatory peritoneal dialysis patients

Several studies have suggested an increased prevalence of osteopenia in dialysis. Peripheral quantitative computed tomography (pQCT) is a new technique that allows the noninvasive evaluation of trabecular and cortical bone separately. The aim of the study was: (1) to evaluate cortical bone by pQCT in continuous ambulatory peritoneal dialysis (CAPD) patients and compare the data with that obtained in healthy controls; and (2) to correlate cortical bone parameters with bone mineral density (BMD) of the lumbar spine and femoral neck and total bone mineral content (TBMC). Cortical bone parameters were obtained in 22 CAPD patients and 27 healthy individuals at the distal radius using a Stratec XCT 960 pQCT machine. In the dialysis patients, we also determined BMD and TBMC by bone densitometry. Dialysis patients, compared with controls, showed a significant reduction in volumetric cortical BMD (VcBMD) (p = 0.04) and cortical thickness (cThk) (p < 0.0001) with a significant increase in radial total cross-sectional area (TA) (p = 0.006), endosteal circumference (p < 0.0001), and buckling ratio (p < 0.0001). In CAPD patients, total time on dialysis correlated negatively with radial total BMD (p < 0.01) and VcBMD (p < 0.01). Age correlated positively with TA (p < 0.01), endosteal (p < 0.01), and periosteal circumferences (p < 0.01). Serum intact parathyroid hormone (PTH) levels correlated positively with endosteal (p = 0.04) and periosteal perimeter (p = 0.01). Total alkaline phosphatase correlated negatively with VcBMD (p < 0.01), and positively with endosteal perimeter (p = 0.02). Total bone mineral content correlated significantly with radial cortical content (p < 0.001), cross-sectional cortical area (cA; p < 0.001), and cThk (p < 0.01) but not with total radial BMD, VcBMD, or buckling ratio. No correlations were found between radial cortical parameters and BMD measured at the lumbar spine or femoral neck. We conclude that dialysis patients show cortical osteopenia with marked cortical thinning partially mediated by PTH action on bone. Total bone mineral content correlated with various radial cortical parameters (content, area, and thickness) but not with others. No correlations were found between cortical bone parameters measured at the peripheral skeleton with areal bone density measured at the axial skeleton. These findings suggest that pQCT may be a new tool in the assessment of bone fragility in dialysis patients.     

快速测定工业沉淀碳酸钙中的铁和锰

采用测定盐酸不溶物后的溶液代替单独称样、溶样、过滤、洗涤、定容后的滤液测定铁和锰。本方法可以快速准确测定铁、锰,工作效率大大提高。     

Visualizing Plasmon Coupling in Closely Spaced Chains of Ag Nanoparticles by Electron Energy‐Loss Spectroscopy

Anisotropic plasmon coupling in closely spaced chains of Ag nanoparticles is visualized using electron energy‐loss spectroscopy in a scanning transmission electron microscope. For dimers as the simplest chain, mapping the plasmon excitations with nanometer spatial resolution and an energy resolution of 0.27 eV intuitively identifies two coupling plasmons. The in‐phase mode redshifts from the ultraviolet region as the interparticle spacing is reduced, reaching the visible range at 2.7 eV. Calculations based on the discrete‐dipole approximation confirm its optical activeness, where the longitudinal direction is constructed as the path for light transportation. Two coupling paths are then observed in an inflexed four‐particle chain.     

纳米Ni0.5Zn0.5Fe2O4铁氧体的制备及电磁损耗特性研究

采用NH4 HCO3与FeCl3·6H2O、Zn(NO3)2·6H2O、Ni(NO3)2·6H2O进行室温固相反应制得Fe(OH)3、Zn3(OH)4CO3·H2O、Ni3(OH)4CO3·4H2O混合前驱物,先经微波加热,再热分解制得纳米粉体.利用激光粒度分析仪、XRD、SEM和TEM对分解产物进行了表征,获得了形貌为球形、颗粒分布均匀、平均粒度为62nm、尖晶石结构的纳米Ni0.5Zn0.5Fe2O4复合铁氧体粉体.经测试样品的相对介电常数和相对磁导率后,发现该纳米铁氧体粉体在100～1800MHz内具有良好的电损耗和磁损耗性能.     

泵内压降和水力损失耦合诱导泵内液氮空化研究

为了研究泵内压降和水力损失耦合诱导泵内液氮空化,采用Zwart空化模型和RNG k-ε湍流模型,并使用CEL语言将饱和蒸气压随温度变化函数关系式导入CFX软件中进行求解,对不同流量下低温泵的空化特性曲线进行分析。研究结果表明,低温泵内压力、温度和空泡体积分数分布与空化的发展程度有关,由于水力损失的作用,小流量工况下,泵内会出现涡状流,从而对叶轮内空化产生影响。     

垂直螺翼式水表下整流器压损特性的数值模拟

应用三维设计软件SolidWorks构建了WS-80型号的垂直螺翼式水表下整流器三维模型,将单个下整流器装配在直管道中建立数值计算模型,并在Gambit中划分网格和指定边界条件;采用有限体积法对控制方程进行离散,通过Simple C算法和Realizablek-ε湍流模型对上述模型中的内流场进行数值模拟,给出了该整流器某一截面上的流场静压力等值线图和速度等值线图,进而得到了下整流器造成的压力损失;分析了下整流器导流体上不开小孔、开小孔和导流体开小孔的基础上在导流体前端开槽这三种情况下,下整流器进出口截面上的压力损失.发现导流体上开小孔在大流量下对于降低压力损失具有明显的作用,并且导流体前端开槽对降低压损也有一定作用,研究结果对垂直螺翼式水表的结构优化设计具有重要指导意义.     

Changes in physicochemical and biological properties of porcine bone derived hydroxyapatite induced by the incorporation of fluoride

Abstract

As the main inorganic component of xenogenic bone graft material, bone-derived biological apatite (BAp) has been widely used in implant dentistry, oral and maxillofacial surgery and orthopedics. However, BAp produced via calcination of animal bones still suffers from some drawbacks, such as insufficient mechanical strength and inadequate degradation rate, which impede its application. Fluoride is known to play important roles in both physiological and pathological processes of human hard tissues for its double effects on bones and teeth. In order to understand the effects of fluoride on the properties of BAp, as well as the mechanism behind them, porcine bone derived hydroxyapatite (PHAp) was prepared via thermal treatment, which was then fluoride incorporated at a series concentrations of sodium fluoride, and noted as 0.25-FPHAp, 0.50-FPHAp, and 0.75-FPHAp respectively. The physicochemical characteristics of the materials, including crystal morphology, crystallinity, functional groups, elemental composition, compressive strength, porosity and solubility, were then determined. The biological properties, such as protein adsorption and cell attachment, were also evaluated. It was found that the spheroid-like crystals of PHAp were changed into rod-like after fluoride substitution, resulting in a fluoride concentration-dependent increase in compressive strength, as well as a decreased porosity and solubility of the apatite. However, even though the addition of fluoride was demonstrated to enhance protein adsorption and cell attachment of the materials, the most favorable results were intriguingly achieved in FPHAp with the least fluoride content. Collectively, low level of fluoride incorporation is proposed promising for the modification of clinically used BAp based bone substitute materials, because of its being able to maintain a good balance between physicochemical and biological properties of the apatite.     

Decrease of dielectric loss in giant dielectric constant CaCu3 Ti4 O12 ceramics by adding CaTiO3

CaCu₃ Ti₄ O₁₂–x CaTiO₃ ceramics (x=0,0.1,0.2,0.3,0.4 and 0.5) was studied by X-ray diffraction, scanning electron microscope and dielectric measurements. It was indicated that some CaTiO₃ entered the boundaries of CaCu₃ Ti₄ O₁₂ grains and/or subgrains. Dielectric measurement showed that the addition of CaTiO₃ lowered the dielectric loss remarkably, especially at low frequencies, while the giant dielectric constant still remained. At room temperature, the dissipation factor of the x=0.5 sample was decreased to 0.02 over the frequency range from 50 to 2000 Hz, and the dielectric constant was kept to be 4000. We explain this phenomenon in terms of internal barrier layer capacitance model by using the impedance spectroscopy analysis.     

Quantification of evolving moisture profiles in concrete samples subjected to temperature gradient by means of rapid neutron tomography: Influence of boundary conditions,hygro-thermal loading history and spalling mitigation additives

Concrete has a tendency to spall, that is, to eject layers when subjected to high temperatures. This is an erratic phenomenon, and our understanding of the underlying physical process is still limited. A driving process is moisture transfer, whose experimental investigation has so far mostly been limited to macroscopic or point-wise observations, limiting both our understanding and the validation of the proposed models. In this paper, a non-contact technique, neutron imaging, is used to extract a the full-field distribution of moisture in 3D and in real time, while the concrete is heated at high temperatures. This reveals a number of processes often underestimated or ignored in the traditional experimental approaches reported in the literature. Notably, the effect on the evolving moisture profiles of varying heating rates for multiple insulation techniques as well the strong influence of the addition of spalling-mitigating additives is presented. The first ever example of neutron tomography of a spalled sample is also reported, and some preliminary analyses of the effect that moisture clog formation and heating rates have on it are revealed.     

PVD法渗Si制备6.5%Si高硅钢过程组织结构与性能演化研究

基于物理气相沉积(PVD)之直流磁控溅射镀膜技术在低硅钢薄板双面共沉积富Si膜,然后高温真空扩散处理使Si渗入低硅钢基体,提高基体含Si量。以沉积Fe5Si3膜+1 180℃×1h扩散为1回合增Si处理,研究了多回合循环增Si处理过程硅钢基体组织结构与性能的演化机理。采用光学显微镜对样品进行了金相分析,采用扫描电镜(SEM)观察了样品的微观组织形貌,并用能谱分析仪(EDS)进行成分分析。用X射线衍射仪(XRD)和透射电镜(TEM)表征了样品的结构特征。经过4回合循环增Si处理可将0.35mm厚低硅钢基体含Si量由3%提高到6.5%,且沿厚度方向Si浓度分布均匀。相比于初始态低硅钢基片,PVD法制成6.5%Si高硅钢中高频铁损值降低40%~50%。