Solubility parameter based screening methods for early stage formulation development of itraconazole amorphous solid dispersions

Objectives: This article uses conventional and newly extended solubility parameter (δ) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz). Methods: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction. Key findings: The rank order of itz miscibility with polymers using both conventional and novel δ-based approaches was 17PF > VA64 > Soluplus > EPO, and the application of the Flory–Huggins lattice model to itz–excipient binary systems corroborated the findings. The solid-state characterisation analyses of the formulations manufactured by melt extrusion correlated well with pre-formulation screening. Long-term storage studies showed that the physical stability of 17PF/vitamin E TPGS–itz was poor compared with Soluplus and VA64 formulations, and for EPO/itz systems variation in stability may be observed depending on the preparation method. Conclusion: Results have demonstrated that although δ-based screening may be useful in predicting the initial state of amorphous solid dispersions, assessment of the physical behaviour of the formulations at relevant temperatures may be more appropriate for the successful development of commercially acceptable amorphous drug products.

Co-tape casting fabrication, field assistant sintering and evaluation of a coke resistant La0.2Sr0.7TiO3-Ni/YSZ functional gradient anode supported solid oxide fuel cell

The ability to directly utilize hydrocarbons and other renewable liquid fuels is one of the most important issues affecting the large scale deployment of solid oxide fuel cells (SOFCs). Herein we designed La_0.2Sr_0.7TiO₃-Ni/YSZ functional gradient anode (FGA) supported SOFCs, prepared with a co-tape casting method and sintered using the field assisted sintering technique (FAST). Through SEM observations, it was confirmed that the FGA structure was achieved and well maintained after the FAST process. Distortion and delamination which usually results after conventional sintering was successfully avoided. The La_0.2Sr_0.7TiO₃-Ni/YSZ FGA supported SOFCs showed a maximum power density of 600mWcm^-2 at 750°C, and was stable for 70h in CH₄. No carbon deposition was detected using Raman spectroscopy. These results confirm the potential coke resistance of La_0.2Sr_0.7TiO₃-Ni/YSZ FGA supported SOFCs.

Copper- and arsenate-induced oxidative stress in Holcus lanatus L. clones with differential sensitivity

The biochemical responses of Holcus lanatus L. to copper and arsenate exposure were investigated in arsenate-tolerant and -non-tolerant plants from uncontaminated and arsenic/copper-contaminated sites. Increases in lipid peroxidation, superoxide dismutase (SOD) activity and phytochelatin (PC) production were correlated with increasing copper and arsenate exposure. In addition, significant differences in biochemical responses were observed between arsenate-tolerant and -non-tolerant plants. Copper and arsenate exposure led to the production of reactive oxygen species, resulting in significant lipid peroxidation in non-tolerant plants. However, SOD activity was suppressed upon metal exposure, possibly due to interference with metallo-enzymes. It was concluded that in non-tolerant plants, rapid arsenate influx resulted in PC production, glutathione depletion and lipid peroxidation. This process would also occur in tolerant plants, but by decreasing the rate of influx, they were able to maintain their constitutive functions, detoxify the metals though PC production and quench reactive oxygen species by SOD activity.

Experimental and Numerical Benchmarking of an Improved Impeller Meanline Modelling Method for Automotive Turbocharger Centrifugal Compressors

After the development of a new single-zone meanline modelling technique, benchmarking of the technique and the modelling methods used during its development are presented. The new meanline model had been developed using the results of three automotive turbocharger centrifugal compressors, and single passage CFD models based on their geometry.

The target of the current study was to test the new meanline modelling method on two new centrifugal compressor stages, again from the automotive turbocharger variety. Furthermore the single passage CFD modelling method used in the previous study would be again employed here and also benchmarked.

The benchmarking was twofold; firstly test the overall performance prediction accuracy of the single-zone meanline model. Secondly, test the detailed performance estimation of the CFD model using detailed interstage static pressure tappings.

The final component of this study exposed the weaknesses in the current modelling methods used (explicitly during this study). The non-axisymmetric flow field at the leading and trailing edges for the two compressors was measured and is presented here for the complete compressor map, highlighting the distortion relative to the tongue.

Modifications of Surface Properties of Beta Ti by Laser Surface Treatment

β -type Ti-alloy is a promising biomedical implant material as it has a low Young’s modulus but is also known to have inferior surface hardness. Various surface treatments can be applied to enhance the surface hardness. Physical vapour deposition (PVD) and chemical vapour deposition (CVD) are two examples of this but these techniques have limitations such as poor interfacial adhesion and high distortion. Laser surface treatment is a relatively new surface modification method to enhance the surface hardness but its application is still not accepted by the industry. The major problem of this process involves surface melting which results in higher surface roughness after the laser surface treatment. This paper will report the results achieved by a 100 W CW fiber laser for laser surface treatment without the surface being melted. Laser processing parameters were carefully selected so that the surface could be treated without surface melting and thus the surface finish of the component could be maintained. The surface and microstructural characteristics of the treated samples were examined using X-ray diffractometry (XRD), optical microscopy (OM), 3-D surface profile & contact angle measurements and nano-indentation test.

Passive Intermodulation in Distributed Circuits with Cascaded Discrete Nonlinearities

The principle aspects of passive intermodulation (PIM) characterisation in distributed printed circuits with cascaded lumped nonlinearities are presented. Mechanisms of PIM generations have been investigated experimentally and modelled using the formalism of X-parameters. The devised equivalent circuit models are applied to the analysis of microstrip lines with distributed and cascaded lumped sources of nonlinearity. The dynamic measurements have revealed that PIM generation rates in straight and meandered microstrip lines differ and significantly deviate from those expected for the respective discrete sources of nonlinearity. The obtained results indicate that multiple physical sources of nonlinearity contribute to PIM generation in printed circuits. Finally, it is demonstrated that the electrical discontinuities can have significant effect on the overall PIM response of the distributed passive circuits and cause PIM product leakage and parasitic coupling between isolated circuit elements.

On Passive Intermodulation Test of Analog and Digital Systems

This paper presents initial results of evaluating suitability of the conventional two-tone CW passive intermodulation (PIM) test for characterization of modulated signal distortion by passive nonlinearities in base station antennas and RF front-end. A comprehensive analysis of analog and digitally modulated waveforms in the transmission lines with weak distributed nonlinearity has been performed using the harmonic balance analysis and X-parameters in Advanced Design System (ADS) simulator. The nonlinear distortion metrics used in the conventional two-tone CW PIM test have been compared with the respective spectral metrics applied to the modulated waveforms, such as adjacent channel power ratio (ACPR) and error vector magnitude (EVM). It is shown that the results of two-tone CW PIM tests are consistent with the metrics used for assessment of signal integrity of both analog and digitally modulated waveforms.

Reframing EU Public Health Governance:From Risk to Citizenship and Participation

Risk is the dominant frame for the European Union’s growing albeit often overlooked public health governance. The starting point for this chapter is the distortion of public health priorities by and within this frame. I argue that existing efforts to identify, underline and tackle the distortions can be strengthened by reframing governance as a matter of citizenship so as to develop citizen participation in decision making.

The Rossiter-McLaughlin effect reloaded: Probing the 3D spin-orbit geometry, differential stellar rotation, and the spatially-resolved stellar spectrum of star-planet systems

When a planet transits its host star, it blocks regions of the stellar surface from view; this causes a distortion of the spectral lines and a change in the line-of-sight (LOS) velocities, known as the Rossiter-McLaughlin (RM) effect. Since the LOS velocities depend, in part, on the stellar rotation, the RM waveform is sensitive to the star-planet alignment (which provides information on the system’s dynamical history). We present a new RM modelling technique that directly measures the spatially-resolved stellar spectrum behind the planet. This is done by scaling the continuum flux of the (HARPS) spectra by the transit light curve, and then subtracting the infrom the out-of-transit spectra to isolate the starlight behind the planet. This technique does not assume any shape for the intrinsic local profiles. In it, we also allow for differential stellar rotation and centre-to-limb variations in the convective blueshift. We apply this technique to HD 189733 and compare to 3D magnetohydrodynamic (MHD) simulations. We reject rigid body rotation with high confidence (>99% probability), which allows us to determine the occulted stellar latitudes and measure the stellar inclination. In turn, we determine both the sky-projected (λ ≈ −0.4 ± 0.2◦) and true 3D obliquity (ψ ≈ 7+12 −4 ◦ ). We also find good agreement with the MHD simulations, with no significant centre-to-limb variations detectable in the local profiles. Hence, this technique provides a new powerful tool that can probe stellar photospheres, differential rotation, determine 3D obliquities, and remove sky-projection biases in planet migration theories. This technique can be implemented with existing instrumentation, but will become even more powerful with the next generation of high-precision radial velocity spectrographs.

Numerical considerations for the implementation of a comprehensive composite damage model

A comprehensive continuum damage mechanics model [1] had been developed to capture the detailed
behaviour of a composite structure under a crushing load. This paper explores some of the difficulties
encountered in the implementation of this model and their mitigation. The use of reduced integration
element and a strain softening model both negatively affect the accuracy and stability of the
simulation. Damage localisation effects demanded an accurate measure of characteristic length. A
robust algorithm for determining the characteristic length was implemented. Testing showed that this
algorithm produced marked improvements over the use of the default characteristic length provided
by Abaqus. Zero-energy or hourglass modes, in reduced integration elements, led to reduced
resistance to bending. This was compounded by the strain softening model, which led to the formation
of elements with little resistance to deformation that could invert if left unchecked. It was shown,
through benchmark testing, that by deleting elements with excess distortions and controlling the mesh
using inbuilt distortion/hourglass controls, these issues can be alleviated. These techniques
contributed significantly to the viability and usability of the damage model.

Modifications of Surface Properties of Beta Ti by Laser Gas Diffusion Nitriding

Beta-type Ti-alloy is a promising biomedical implant material as it has a low Young’s modulus and is also known to have inferior surface hardness. Various surface treatments can be applied to enhance the surface hardness. Physical vapor deposition and chemical vapor deposition are two examples of this but these techniques have limitations such as poor interfacial adhesion and high distortion. Laser surface treatment is a relatively new surface modification method to enhance the surface hardness but its application is still not accepted by the industry. The major problem of this process involves surface melting which results in higher surface roughness after the laser surface treatment. This paper will report the results achieved by a 100 W continuous wave (CW) fiber laser for laser surface treatment without the surface being melted. Laser processing parameters were carefully selected so that the surface could be treated without surface melting and thus the surface finish of the component could be maintained. The surface and microstructural characteristics of the treated samples were examined using x-ray diffractometry, optical microscopy, three-dimensional surface profile and contact angle measurements, and nanoindentation test.

Passive Intermodulation of Analog and Digital Signals on Transmission Lines with Distributed Nonlinearities: Modelling and Characterization

Passive intermodulation (PIM) often limits the performance of communication systems with analog and digitally-modulated signals and especially of systems supporting multiple carriers. Since the origins of the apparently multiple physical sources of nonlinearity causing PIM are not fully understood, the behavioral models are frequently used to describe the process of PIM generation. In this paper a polynomial model of memoryless nonlinearity is deduced from PIM measurements of a microstrip line with distributed nonlinearity with two-tone CW signals. The analytical model of nonlinearity is incorporated in Keysight Technology’s ADS simulator to evaluate the metrics of signal fidelity in the receive band for analog and digitally-modulated signals. PIM-induced distortion and cross-band interference with modulated signals are compared to those with two-tone CW signals. It is shown that conventional metrics can be applied to quantify the effect of distributed nonlinearities on signal fidelity. It is found that the two-tone CW test provides a worst-case estimate of cross-band interference for two-carrier modulated signals whereas with a three-carrier signal PIM interference in the receive band is noticeably overestimated. The simulated constellation diagrams for QPSK signals demonstrate that PIM interference exhibits the distinctive signatures of correlated distortion and this indicates that there are opportunities for mitigating PIM interference and that PIM interference cannot be treated as noise. One of the interesting results is that PIM distortion on a transmission line results in asymmetrical regrowth of output PIM interference for modulated signals.