A graphical method for practical and informative identifiability analyses of physiological models: A case study of insulin kinetics and sensitivity

peer reviewedBackground: Derivative based a-priori structural identifiability analyses of mathematical models can offer valuable insight into the identifiability of model parameters. However, these analyses are only capable of a binary confirmation of the mathematical distinction of parameters and a positive outcome can begin to lose relevance when measurement error is introduced. This article presents an integral based method that allows the observation of the identifiability of models with two-parameters in the presence of assay error. Methods: The method measures the distinction of the integral formulations of the parameter coefficients at the proposed sampling times. It can thus predict the susceptibility of the parameters to the effects of measurement error. The method is tested in-silico with Monte Carlo analyses of a number of insulin sensitivity test applications. Results: The method successfully captured the analogous nature of identifiability observed in Monte Carlo analyses of a number of cases including protocol alterations, parameter changes and differences in participant behaviour. However, due to the numerical nature of the analyses, prediction was not perfect in all cases. Conclusions: Thus although the current method has valuable and significant capabilities in terms of study or test protocol design, additional developments would further strengthen the predictive capability of the method. Finally, the method captures the experimental reality that sampling error and timing can negate assumed parameter identifiability and that identifiability is a continuous rather than discrete phenomenon

Apportionment of primary and secondary organic aerosols in Southern California during the 2005 Study of Organic Aerosols in Riverside (SOAR-1)

Ambient sampling was conducted in Riverside, California during the 2005 Study of Organic Aerosols in Riverside to characterize the composition and sources of organic aerosol using a variety of state-of-the-art instrumentation and source apportionment techniques. The secondary organic aerosol (SOA) mass is estimated by elemental carbon and carbon monoxide tracer methods, water soluble organic carbon content, chemical mass balance of organic molecular markers, and positive matrix factorization of high-resolution aerosol mass spectrometer data. Estimates obtained from each of these methods indicate that the organic fraction in ambient aerosol is overwhelmingly secondary in nature during a period of several weeks with moderate ozone concentrations and that SOA is the single largest component of PM1 aerosol in Riverside. Average SOA/OA contributions of 70−90% were observed during midday periods, whereas minimum SOA contributions of ~45% were observed during peak morning traffic periods. These results are contrary to previous estimates of SOA throughout the Los Angeles Basin which reported that, other than during severe photochemical smog episodes, SOA was lower than primary OA. Possible reasons for these differences are discussed

Inhibition of activin/nodal signalling is necessary for pancreatic differentiation of human pluripotent stem cells

Peer reviewedPublisher PD

Design and fabrication of diffractive atom chips for laser cooling and trapping

It has recently been shown that optical reflection gratings fabricated directly into an atom chip provide a simple and effective way to trap and cool substantial clouds of atoms [1,2]. In this article we describe how the gratings are designed and micro-fabricated and we characterise their optical properties, which determine their effectiveness as a cold atom source. We use simple scalar diffraction theory to understand how the morphology of the gratings determines the power in the diffracted beams

Effects of crystal habit on the sticking propensity of ibuprofen — A case study

This study demonstrates the effect of active pharmaceutical ingredient (API) particle habit on the sticking propensity of ibuprofen. Four diverse crystal habits with similar physico chemical properties are reported and the sticking propensity was found to increase with shape regularity. The surface energy of the extreme habits were shown to be different where particles that were more regular in shape exhibited surface energies of 9 mJ/m2 higher than those that were needle-like in habit. Computational and experimental data reveals that the increase in surface energy of the regular shaped particles can be attributed to the increase in the specific (polar) component, which is due to greater presence of faces which contain the carboxylic acid functionality at the surface. The increase in the specific energy component is shown to correlate with the sticking propensity of ibuprofen. It is proposed that investigation of the chemical causality of sticking, for this API and others, using the techniques demonstrated in this paper will be of increasing importanc

Competing Ultrafast Energy Relaxation Pathways in Photoexcited Graphene

For most optoelectronic applications of graphene a thorough understanding of the processes that govern energy relaxation of photoexcited carriers is essential. The ultrafast energy relaxation in graphene occurs through two competing pathways: carrier-carrier scattering -- creating an elevated carrier temperature -- and optical phonon emission. At present, it is not clear what determines the dominating relaxation pathway. Here we reach a unifying picture of the ultrafast energy relaxation by investigating the terahertz photoconductivity, while varying the Fermi energy, photon energy, and fluence over a wide range. We find that sufficiently low fluence ($\lesssim$ 4 $\mu$J/cm$^2$) in conjunction with sufficiently high Fermi energy ($\gtrsim$ 0.1 eV) gives rise to energy relaxation that is dominated by carrier-carrier scattering, which leads to efficient carrier heating. Upon increasing the fluence or decreasing the Fermi energy, the carrier heating efficiency decreases, presumably due to energy relaxation that becomes increasingly dominated by phonon emission. Carrier heating through carrier-carrier scattering accounts for the negative photoconductivity for doped graphene observed at terahertz frequencies. We present a simple model that reproduces the data for a wide range of Fermi levels and excitation energies, and allows us to qualitatively assess how the branching ratio between the two distinct relaxation pathways depends on excitation fluence and Fermi energy.Comment: Nano Letters 201

Physical modeling of unsteady turbulence in breaking tidal bores

A tidal bore is an unsteady flow motion generated by the rapid water level rise at the river mouth during the early flood tide under macrotidal and appropriate bathymetric conditions. This paper presents a study that physically investigates the turbulent properties of tidal bores. Results from some experimental measurements of free-surface fluctuations and turbulent velocities conducted on smooth and rough beds are reported. The free-surface measurements were conducted with Froude numbers of 1-1.7. Both undular and breaking bores were observed. Using an ensemble-averaging technique, the free-surface fluctuations of breaking tidal bores are characterized. Immediately before the roller, the free-surface curves gradually upwards. The passage of the bore roller is associated with some large water elevation fluctuations; the largest free-surface fluctuations are observed during the first half of the bore roller. The turbulent velocity measurements were performed at several vertical elevations during and shortly after the passage of breaking bores. Both the instantaneous and ensemble-averaged velocity data highlight a strong flow deceleration at all elevations during the bore passage. Close to the bed, the longitudinal velocity component becomes negative immediately after the roller passage, implying the existence of a transient recirculation. The height and duration of the transient are a function of the bed roughness, with a higher and longer recirculation region above the rough bed. The vertical velocity data presented some positive, upward motion beneath the front with increasing maximum vertical velocity with increasing distance from the bed. The transverse velocity data show some large fluctuations with nonzero ensemble average after the roller passage that highlight some intense secondary motion advected behind the bore front. DOI: 10.1061/(ASCE)HY.1943-7900.0000542. (C) 2012 American Society of Civil Engineers