Temperature fields in a channel partially filled with a porous material under local thermal non-equilibrium condition-an exact solution

This work examines analytically the forced convection in a channel partially filled with a porous material and subjected to constant wall heat flux. The Darcy–Brinkman–Forchheimer model is used to represent the fluid transport through the porous material. The local thermal non-equilibrium, two-equation model is further employed as the solid and fluid heat transport equations. Two fundamental models (models A and B) represent the thermal boundary conditions at the interface between the porous medium and the clear region. The governing equations of the problem are manipulated, and for each interface model, exact solutions, for the solid and fluid temperature fields, are developed. These solutions incorporate the porous material thickness, Biot number, fluid to solid thermal conductivity ratio and Darcy number as parameters. The results can be readily used to validate numerical simulations. They are, further, applicable to the analysis of enhanced heat transfer, using porous materials, in heat exchangers.

Measurement of electromagnetic pulses generated during interactions of high power lasers with solid targets

A target irradiated with a high power laser pulse, blows off a large amount of charge and as a consequence the target itself becomes a generator of electromagnetic pulses (EMP) owing to high return current flowing to the ground through the target holder. The first measurement of the magnetic field induced by the neutralizing current reaching a value of a few kA was performed with the use of an inductive target probe at the PALS Laser Facility (Cikhardt et al. Rev. Sci. Instrum. 85 (2014) 103507). A full description of EMP generation should contain information on the spatial distribution and temporal variation of the electromagnetic field inside and outside of the interaction chamber. For this reason, we consider the interaction chamber as a resonant cavity in which different modes of EMP oscillate for hundreds of nanoseconds, until the EMP is transmitted outside through the glass windows and EM waves are attenuated. Since the experimental determination of the electromagnetic field distribution is limited by the number of employed antennas, a mapping of the electromagnetic field has to be integrated with numerical simulations. Thus, this work reports on a detailed numerical mapping of the electromagnetic field inside the interaction chamber at the PALS Laser Facility (covering a frequency spectrum from 100 MHz to 3 GHz) using the commercial code COMSOL Multiphysics 5.2. Moreover we carried out a comparison of the EMP generated in the parallelepiped-like interaction chamber used in the Vulcan Petawatt Laser Facility at the Rutherford Appleton Laboratory, against that produced in the spherical interaction chamber of PALS.

A phase I pharmacokinetic and pharmacodynamic study of the oral mitogen-activated protein kinase kinase (MEK) inhibitor, WX-554, in patients with advanced solid tumours

Purpose: We performed a multi-centre phase I study to assess the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the orally available small molecule mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, WX-554, and to determine the optimal biological dose for subsequent trials.
Experimental design: Patients with treatment-refractory, advanced solid tumours, with adequate performance status and organ function were recruited to a dose-escalation study in a standard 3 + 3 design. The starting dose was 25 mg orally once weekly with toxicity, PK and PD guided dose-escalation with potential to explore alternative schedules.
Results: Forty-one patients with advanced solid tumours refractory to standard therapies and with adequate organ function were recruited in eight cohorts up to doses of 150 mg once weekly and 75 mg twice weekly. No dose-limiting toxicities were observed during the study, and a maximum tolerated dose (MTD) was not established. The highest dose cohorts demonstrated sustained inhibition of extracellular signal-regulated kinase (ERK) phosphorylation in peripheral blood mononuclear cells following ex-vivo phorbol 12-myristate 13-acetate stimulation. There was a decrease of 70 ± 26% in mean phosphorylated (p)ERK in C1 day 8 tumour biopsies when compared with pre-treatment tumour levels in the 75 mg twice a week cohort. Prolonged stable disease (>6 months) was seen in two patients, one with cervical cancer and one with ampullary carcinoma.
Conclusions: WX-554 was well tolerated, and an optimal biological dose was established for further investigation in either a once or twice weekly regimens. The recommended phase 2 dose is 75 mg twice weekly.