Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties. In this study, a rapid and validated ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTof-MS) method was developed to investigate the metabolism of scoparone in rat for the first time. The new method reduced the sample handling and analytical time by three- to six-fold, and the detection limit by five- to 1000-fold, compared to published methods. Far more metabolites were detected and identified compared to published data, which were preliminarily identified as scopoletin, isoscopoletin, isofraxidin, and fraxidin, respectively, when subjected to tandem mass spectrometry analyses. It is found that the metabolic trajectory of scoparone in rat focused on phase I metabolism which is obviously different from published results, and revealed a wide range of pharmacological properties of scoparone partly attributed to the bioactivities of its metabolites.

Development and validation of a ultra performance LC-ESI/MS method for analysis of metabolic phenotypes of healthy men in day and night urine samples

Ultra-performance LC coupled to quadrupole TOF/MS (UPLC-QTOF/MS) in positive and negative ESI was developed and validated to analyze metabolite profiles for urine from healthy men during the day and at night. Data analysis using principal components analysis (PCA) revealed differences between metabolic phenotypes of urine in healthy men during the day and at night. Positive ions with mass-to-charge ratio (m/z) 310.24 (5.35 min), 286.24 (4.74 min) and 310.24 (5.63 min) were elevated in the urine from healthy men at night compared to that during the day. Negative ions elevated in day urine samples of healthy men included m/z 167.02 (0.66 min), 263.12 (2.55 min) and 191.03 (0.73 min), whilst ions m/z 212.01 (4.77 min) were at a lower concentration in urine of healthy men during the day compared to that at night. The ions m/z 212.01 (4.77 min), 191.03 (0.73 min) and 310.24 (5.35 min) preliminarily correspond to indoxyl sulfate, citric acid and N-acetylneuraminic acid, providing further support for an involvement of phenotypic difference in urine of healthy men in day and night samples, which may be associated with notably different activities of gut microbiota, velocity of tricarboxylic acid cycle and activity of sialic acid biosynthesis in healthy men as regulated by circadian rhythm of the mammalian bioclock.

Timing, origin and emplacement dynamics of mass flows offshore of SE Montserrat in the last 110 ka : implications for landslide and tsunami hazards, eruption history, and volcanic island evolution

Mass flows on volcanic islands generated by volcanic lava dome collapse and by larger-volume flank collapse can be highly dangerous locally and may generate tsunamis that threaten a wider area. It is therefore important to understand their frequency, emplacement dynamics, and relationship to volcanic eruption cycles. The best record of mass flow on volcanic islands may be found offshore, where most material is deposited and where intervening hemipelagic sediment aids dating. Here we analyze what is arguably the most comprehensive sediment core data set collected offshore from a volcanic island. The cores are located southeast of Montserrat, on which the Soufriere Hills volcano has been erupting since 1995. The cores provide a record of mass flow events during the last 110 thousand years. Older mass flow deposits differ significantly from those generated by the repeated lava dome collapses observed since 1995. The oldest mass flow deposit originated through collapse of the basaltic South Soufriere Hills at 103-110 ka, some 20-30 ka after eruptions formed this volcanic center. A ∼1.8 km3 blocky debris avalanche deposit that extends from a chute in the island shelf records a particularly deep-seated failure. It likely formed from a collapse of almost equal amounts of volcanic edifice and coeval carbonate shelf, emplacing a mixed bioclastic-andesitic turbidite in a complex series of stages. This study illustrates how volcanic island growth and collapse involved extensive, large-volume submarine mass flows with highly variable composition. Runout turbidites indicate that mass flows are emplaced either in multiple stages or as single events.

Optical data encryption using time-dependent dynamics of refractive index changes in LiNbO3

We present a method for optical encryption of information, based on the time-dependent dynamics of writing and erasure of refractive index changes in a bulk lithium niobate medium. Information is written into the photorefractive crystal with a spatially amplitude modulated laser beam which when overexposed significantly degrades the stored data making it unrecognizable. We show that the degradation can be reversed and that a one-to-one relationship exists between the degradation and recovery rates. It is shown that this simple relationship can be used to determine the erasure time required for decrypting the scrambled index patterns. In addition, this method could be used as a straightforward general technique for determining characteristic writing and erasure rates in photorefractive media.

Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula: Liuwei Dihuang Wan

Liuwei Dihuang Wan (LWD), a classic Chinese medicinal formulae, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. It has attracted increasingly much attention as one of the most popular and valuable herbal medicines. However, the systematic analysis of the chemical constituents of LDW is difficult and thus has not been well established. In this paper, a rapid, sensitive and reliable ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) method with automated MetaboLynx analysis in positive and negative ion mode was established to characterize the chemical constituents of LDW. The analysis was performed on a Waters UPLCTM HSS T3 using a gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. Under the optimized conditions, a total of 50 peaks were tentatively characterized by comparing the retention time and MS data. It is concluded that a rapid and robust platform based on UPLC-ESI-Q-TOF-MS has been successfully developed for globally identifying multiple-constituents of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of the chemical constituents of LDW. This article is protected by copyright. All rights reserved.

Experiential learning as a constraint-led process: an ecological dynamics perspective

In this paper we present key ideas for an ecological dynamics approach to learning that reveal the importance of learner–environment interactions to frame outdoor experiential learning.We propose that ecological dynamics provides a useful framework for understanding the interacting constraints of the learning process and for designing learning opportunities in outdoor experiential learning.

Numerical characterization of the mechanical properties of metal nanowires

Nanowires (NWs) have attracted appealing and broad application owing to their remarkable mechanical, optical, electrical, thermal and other properties. To unlock the revolutionary characteristics of NWs, a considerable body of experimental and theoretical work has been conducted. However, due to the extremely small dimensions of NWs, the application and manipulation of the in situ experiments involve inherent complexities and huge challenges. For the same reason, the presence of defects appears as one of the most dominant factors in determining their properties. Hence, based on the experiments' deficiency and the necessity of investigating different defects' influence, the numerical simulation or modelling becomes increasingly important in the area of characterizing the properties of NWs. It has been noted that, despite the number of numerical studies of NWs, significant work still lies ahead in terms of problem formulation, interpretation of results, identification and delineation of deformation mechanisms, and constitutive characterization of behaviour. Therefore, the primary aim of this study was to characterize both perfect and defected metal NWs. Large-scale molecular dynamics (MD) simulations were utilized to assess the mechanical properties and deformation mechanisms of different NWs under diverse loading conditions including tension, compression, bending, vibration and torsion. The target samples include different FCC metal NWs (e.g., Cu, Ag, Au NWs), which were either in a perfect crystal structure or constructed with different defects (e.g. pre-existing surface/internal defects, grain/twin boundaries). It has been found from the tensile deformation that Young's modulus was insensitive to different styles of pre-existing defects, whereas the yield strength showed considerable reduction. The deformation mechanisms were found to be greatly influenced by the presence of defects, i.e., different defects acted in the role of dislocation sources, and many affluent deformation mechanisms had been triggered. Similar conclusions were also obtained from the compressive deformation, i.e., Young's modulus was insensitive to different defects, but the critical stress showed evident reduction. Results from the bending deformation revealed that the current modified beam models with the considerations of surface effect, or both surface effect and axial extension effect were still experiencing certain inaccuracy, especially for the NW with ultra small cross-sectional size. Additionally, the flexural rigidity of the NW was found to be insensitive to different pre-existing defects, while the yield strength showed an evident decrease. For the resonance study, the first-order natural frequency of the NW with pre-existing surface defects was almost the same as that from the perfect NW, whereas a lower first-order natural frequency and a significantly degraded quality factor was observed for NWs with grain boundaries. Most importantly, the <110> FCC NWs were found to exhibit a novel beat phenomenon driven by a single actuation, which was resulted from the asymmetry in the lattice spacing in the (110) plane of the NW cross-section, and expected to exert crucial impacts on the in situ nanomechanical measurements. In particular, <110> Ag NWs with rhombic, truncated rhombic, and triangular cross-sections were found to naturally possess two first-mode natural frequencies, which were envisioned with applications in NEMS that could operate in a non-planar regime. The torsion results revealed that the torsional rigidity of the NW was insensitive to the presence of pre-existing defects and twin boundaries, but received evident reduction due to grain boundaries. Meanwhile, the critical angle decreased considerably for defected NWs. This study has provided a comprehensive and deep investigation on the mechanical properties and deformation mechanisms of perfect and defected NWs, which will greatly extend and enhance the existing knowledge and understanding of the properties/performance of NWs, and eventually benefit the realization of their full potential applications. All delineated MD models and theoretical analysis techniques that were established for the target NWs in this research are also applicable to future studies on other kinds of NWs. It has been suggested that MD simulation is an effective and excellent tool, not only for the characterization of the properties of NWs, but also for the prediction of novel or unexpected properties.

An ecological dynamics approach to skill acquisition : implications for development of talent in sport.

This paper proposes how ecological dynamics, a theory focusing on the performer-environment relationship, provides a basis for understanding skill acquisition in sport. From this perspective, learners are conceptualized as complex, neurobiological systems in which inherent self-organisation tendencies support the emergence of adaptive behaviours under a range of interacting task and environmental constraints. Intentions, perceptions and actions are viewed as intertwined processes which underpin functional movement solutions assembled by each learner during skill acquisition. These ideas suggest that skill acquisition programmes need to sample information from the performance environment to guide behaviour in practice tasks. Skill acquisition task protocols should allow performers to use movement variability to explore and create opportunities for action, rather than constraining them to passively receiving information. This conceptualisation also needs to characterize the design of talent evaluation tests, which need to faithfully represent the perception-action relationships in the performance environment. Since the dynamic nature of changing task constraints in sports cannot be predicted over longer timescales, an implication is that talent programmes should focus on developing performance expertise in each individual, rather than over-relying on identification of expert performers at specific points in time.

Control of infrastructure inspection aircraft vertical dynamics in the presence of thermal disturbances

The low-altitude aircraft inspection of powerlines, or other linear infrastructure networks, is emerging as an important application requiring specialised control technologies. Despite some recent advances in automated control related to this application, control of the underactuated aircraft vertical dynamics has not been completely achieved, especially in the presence of thermal disturbances. Rejection of thermal disturbances represents a key challenge to the control of inspection aircraft due to the underactuated nature of the dynamics and specified speed, altitude, and pitch constraints. This paper proposes a new vertical controller consisting of a backstepping elevator controller with feedforward-feedback throttle controller. The performance of our proposed approach is evaluated against two existing candidate controllers.

Simulating land cover changes and their impacts on land surface temperature in Dhaka, Bangladesh

Despite research that has been conducted elsewhere, little is known, to-date, about land cover dynamics and their impacts on land surface temperature (LST) in fast growing mega cities of developing countries. Landsat satellite images of 1989, 1999, and 2009 of Dhaka Metropolitan (DMP) area were used for analysis. This study first identified patterns of land cover changes between the periods and investigated their impacts on LST; second, applied artificial neural network to simulate land cover changes for 2019 and 2029; and finally, estimated their impacts on LST in respective periods. Simulation results show that if the current trend continues, 56% and 87% of the DMP area will likely to experience temperatures in the range of greater than or equal to 30°C in 2019 and 2029, respectively. The findings possess a major challenge for urban planners working in similar contexts. However, the technique presented in this paper would help them to quantify the impacts of different scenarios (e.g., vegetation loss to accommodate urban growth) on LST and consequently to devise appropriate policy measures.

Acquisition of expertise in cricket fast bowling : perceptions of expert players and coaches

Objectives: Experiential knowledge of elite athletes and coaches was investigated to reveal insights on expertise acquisition in cricket fast bowling. Design: Twenty-one past or present elite cricket fast bowlers and coaches of national or international level were interviewed using an in-depth, open-ended, semi-structured approach. Methods: Participants were asked about specific factors which they believed were markers of fast bowling expertise potential. Of specific interest was the relative importance of each potential component of fast bowling expertise and how components interacted or developed over time. Results: The importance of intrinsic motivation early in development was highlighted, along with physical, psychological and technical attributes. Results supported a multiplicative and interactive complex systems model of talent development in fast bowling, in which component weightings were varied due to individual differences in potential experts. Dropout rates in potential experts were attributed to misconceived current talent identification programmes and coaching practices, early maturation and physical attributes, injuries and lack of key psychological attributes and skills. Conclusions: Data are consistent with a dynamical systems model of expertise acquisition in fast bowling, with numerous trajectories available for talent development. Further work is needed to relate experiential and theoretical knowledge on expertise in other sports.

City relative price dynamics in Australia : are structural breaks important?

This paper examines the dynamic behaviour of relative prices across seven Australian cities by applying panel unit root test procedures with structural breaks to quarterly consumer price index data for 1972 Q1–2011 Q4. We find overwhelming evidence of convergence in city relative prices. Three common structural breaks are endogenously determined at 1985, 1995, and 2007. Further, correcting for two potential biases, namely Nickell bias and time aggregation bias, we obtain half-life estimates of 2.3–3.8 quarters that are much shorter than those reported by previous research. Thus, we conclude that both structural breaks and bias corrections are important to obtain shorter half-life estimates.

Structural dynamics education in the new millennium

Structural Dynamics is the study of the response of structures to dynamic or time varying loads. This topic has emerged to be one of importance to all structural engineers due to three important issues with structural engineering in the new millennium. These are: (1) vibration and problems in slender structures that have emerged due to new material technology and aesthetic requirements, (ii) ageing structures such as bridges whoese health needs to be monitored and appropriate retrofitting carried out to prevent failure and (iii) increased vulnerability of structures to random loads such as seismic, impact and blast loads. Knowledge of structural dynamics is necessary to address these issues and their consequences. During the past two decades, research in structural dynamics has generated considerable amount of new information to address these issues. This new knowledge is not readily made available to practicing engineers and very little or none of it enters the classrooms. There is no universal emphasis on including structural dynamics and their recently generated new knowledge into the civil/structural curriculum. This paper argues for the need to include structural dynamics into the syllabus of all civil engineering courses especially those having a first or second major in structural engineering. This will enable our future structural engineers to design and maintain safe and efficient structures.

Correlating flow induced shear stress and chondrocytes activity in micro-porous scaffold using computational fluid dynamics and rapid prototyping

Flow induced shear stress plays an important role in regulating cell growth and distribution in scaffolds. This study sought to correlate wall shear stress and chondrocytes activity for engineering design of micro-porous osteochondral grafts based on the hypothesis that it is possible to capture and discriminate between the transmitted force and cell response at the inner irregularities. Unlike common tissue engineering therapies with perfusion bioreactors in which flow-mediated stress is the controlling parameter, this work assigned the associated stress as a function of porosity to influence in vitro proliferation of chondrocytes. D-optimality criterion was used to accommodate three pore characteristics for appraisal in a mixed level fractional design of experiment (DOE); namely, pore size (4 levels), distribution pattern (2 levels) and density (3 levels). Micro-porous scaffolds (n=12) were fabricated according to the DOE using rapid prototyping of an acrylic-based bio-photopolymer. Computational fluid dynamics (CFD) models were created correspondingly and used on an idealized boundary condition with a Newtonian fluid domain to simulate the dynamic microenvironment inside the pores. In vitro condition was reproduced for the 3D printed constructs seeded by high pellet densities of human chondrocytes and cultured for 72 hours. The results showed that cell proliferation was significantly different in the constructs (p<0.05). Inlet fluid velocity of 3×10-2mms-1 and average shear stress of 5.65×10-2 Pa corresponded with increased cell proliferation for scaffolds with smaller pores in hexagonal pattern and lower densities. Although the analytical solution of a Poiseuille flow inside the pores was found insufficient for the description of the flow profile probably due to the outside flow induced turbulence, it showed that the shear stress would increase with cell growth and decrease with pore size. This correlation demonstrated the basis for determining the relation between the induced stress and chondrocyte activity to optimize microfabrication of engineered cartilaginous constructs.

Locally weighted learning model predictive control for nonlinear and time varying dynamics

This paper proposes an online learning control system that uses the strategy of Model Predictive Control (MPC) in a model based locally weighted learning framework. The new approach, named Locally Weighted Learning Model Predictive Control (LWL-MPC), is proposed as a solution to learn to control robotic systems with nonlinear and time varying dynamics. This paper demonstrates the capability of LWL-MPC to perform online learning while controlling the joint trajectories of a low cost, three degree of freedom elastic joint robot. The learning performance is investigated in both an initial learning phase, and when the system dynamics change due to a heavy object added to the tool point. The experiment on the real elastic joint robot is presented and LWL-MPC is shown to successfully learn to control the system with and without the object. The results highlight the capability of the learning control system to accommodate the lack of mechanical consistency and linearity in a low cost robot arm.