Appraisal of cavity hot-wire probes for wall-shear-stress measurements

Flush-mounted cavity hot-wire probes have emerged as an alternative to classical hot-wire probes mounted several diameters above the surface for wall-shear stress measurements. They aim at increasing the frequency response and accuracy by circumventing the well-known issue of heat transfer to the substrate that hot-wire and hot-film probes possess. Their use, however, depends on the assumption that the cavity does not influence the flow field. In this study, we show that this assumption does not hold, and that turbulence statistics are modified by the presence of the cavity with sizes that are practically in use. The mean velocity and fluctuations increase near the cavity while the shear stress decreases in its surroundings, all seemingly stemming from the fact that the no-slip condition is not present anymore and that flow reversal occurs. Overall, the energy spectra and the probability density function of the wall shear stress fluctuations indicate a change of nature of turbulence by the presence of the cavity

Methodologies for Assessing the Acceptability of Oral Formulations among children and older adults: A Systematic Review

This is an open access article distributed under the terms and conditions of the Creative Commons Attribution NonCommercial-NoDerivatives 4.0 International CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Acceptability of medicinal products in children and older populations is pivotal in ensuring adherence and therapeutic outcomes. This review systematically identifies studies reporting on formulation aspects of oral medications that affect their acceptability in these patient groups. Particular emphasis is placed on the evaluation of the methodologies employed in the studies. Sixty-eight studies were included for analysis, with 51 (75%) in children and 17 (25%) in older populations. The studies evaluated a range of oral formulations; however, the methodologies used differ considerably in participants’ characteristics, study settings, tools, acceptability definitions and criteria. It is evident that there is a lack of standardisation in study design as well as the assessment methods used in assessing acceptability of medicines in children and older populations. This review presents a systematic analysis on methods employed for assessing acceptability of oral medicines in children and older adults, to provide insights and recommendations regarding the design of reliable instruments in future studies.Peer reviewe

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper

EFFECT OF THE SEPARATION WALL IN THE MIXING PROPERTIES OF COAXIAL JETS

The velocity and mixing field of two coaxial jet configurations has been experimentally characterized by means of hot- and cold-wire anemometry to investigate the effect of the initial conditions on the flow development, and to determine the leading processes in the ``mixing transition'' of the two streams. Amongst the possible operating conditions, four configurations with different inner and outer jet bulk velocity pairs $(U_i,U_o)$ have been spatially characterized in terms of velocity and mixing field covering a region where $0.5le r_u=U_o/U_ile 3$ with two different separation wall geometries, namely a sharp and a thick separating wall. For high velocity ratios the difference between the two geometries appears small and inside the experimental accuracy. On the other hand, for nearly unitary velocity ratio and with the thick wall configuration, the presence of a strong wake instability increases the interpenetration between the two streams enhancing the mixing process

A note on the effect of the separation wall in the initial mixing of coaxial jets

Experiments are carried out to characterize the mixing field of two coaxial jet configurations, having, respectively, a thick and a sharp inner duct wall. The influence of the separation wall thickness on the initial development of the "mixing transition" of the two streams is analysed as a function of the jet velocity ratio through measurements with hot- and cold-wire anemometry and by using temperature as a passive scalar. To study the mixing at the near-exit region, a new thickness measure based on the mean scalar concentration is introduced. It is shown that the presence of a sufficiently thick wall significantly increases the interpenetration between the two streams, effectively enhancing the mixing process. However, this is observed only for nearly unitary velocity ratios, which correspond to the existence of a regular alternate vortex shedding from the two sides of the inner duct wall. Conversely, for small and large velocity ratios, the difference in mixing between the two geometries greatly decreases and becomes of the order of the experimental accuracy