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Rachel Myers,1 Megan Grundy,2 Cliff Rowe,1 Christian M Coviello,1 Luca Bau,2 Philippe Erbs,3 Johann Foloppe,3 Jean-Marc Balloul,3 Colin Story,1 Constantin C Coussios,2 Robert Carlisle2 1OxSonics Ltd, The Magdalen Centre, 2BUBBL, IBME, Department of Engineering Science, University of Oxford, Oxford, UK; 3Transgene SA, Illkirch-Graffenstaden, France Abstract: The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US), can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox), cetuximab, adenovirus (Ad) and vaccinia virus (VV), representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a “cavitation test rig” was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene luciferase within the Ad and VV constructs tested here allowed the infectivity of these viruses to be easily quantified. Exposure to cavitation did not impact on the activity of either virus. These data provide compelling evidence that the US parameters used to safely and successfully delivery nanomedicines to tumors in preclinical models do not detrimentally impact on the structure or activity of these nanomedicines. Keywords: nanomedicine, antibody, virus, ultrasound, cavitation

Mid-infrared (mid-IR) diffuse reflectance spectroscopy can be used to effectively analyse soil, but the preparation of soil samples by grinding is time consuming. Soil samples are usually finely ground to a particle size of less than 0.250 mm because the spectrometer's beam aperture is approximately 1-2 mm in diameter. Larger particles can generate specular reflections and spectra that do not adequately represent the soil sample. Grinding soil to small particle sizes enables the diffuse reflectance of light and more representative sample measurements. Here, we report on research that investigates the effect that grinding to different particle sizes have on soil mid-IR spectra. Our aims were to compare the effect of grinding soil to different particle sizes (2.000 mm, 1.000 mm, 0.500 mm, 0.250 mm and 0.106 mm) on the frequencies of mid-IR spectra, and compare the effect of these particle sizes on the accuracy of spectroscopic calibrations to predict organic carbon, sand, silt and clay contents. Using the Commonwealth Scientific and Industrial Research Organisation's (CSIRO) National visible-near infrared database, we selected 227 soil samples from the National Soil Archive for our experiments, and designed an experiment whereby each soil sample was ground in triplicate to the different particle sizes. These ground samples were measured using an FT-IR spectrometer with a spectral range of 4000-600 [cm.sup.-1]. Grinding to particle sizes that are ≤ 2.000 mm reduces subsample variability. Smaller particle sizes produce finer and sharper absorption features, which are related to organic carbon, and clay and sand mineralogies. Generally, better predictions for clay, sand and soil organic carbon contents were achieved using soil that is more finely ground, but there were no statistically significant differences between predictions that use soil ground to 1 mm, 0.5 mm, 0.25 mm. Grinding did not affect predictions of silt content. Recommendations on how much grinding is required for mid-IR analysis should also consider the time, cost and effort needed to prepare the soil samples as well as the purpose of the analysis. Additional keywords: mid infrared, mid-IR diffuse reflectance spectroscopy, FT-IR, particle size, sample preparation, sand, silt, clay, organic carbon. Received 22 January 2015, accepted 4 June 2015, published online 1 October 2015, Introduction Mid-infrared (mid-IR) spectroscopy is an effective soil analytical technique that provides rapid and inexpensive soil information. Research has shown that absorptions in the mid-IR portion of the electromagnetic spectrum [...]

The Australian Soil Resources Information System (ASRIS) database compiles the best publicly available information available across Commonwealth, State, and Territory agencies into a national database of soil profile data, digital soil and land resources maps, and climate, terrain, and lithology datasets. These datasets are described in detail in this paper. Most datasets are thematic grids that cover the intensively used agricultural zones in Australia. Additional keywords: Australia, integrated database, natural resources management, national soil database., Introduction Knowledge about soils and their behaviour is critical for effective management of natural resources at landscape and ecosystem scales to meet the twin goals of sustainable production and environmental [...]

Lipid peroxidation potential increases with age in tissues such as liver and varies among inbred mouse strains, indicating that genetic influences may be important. Quantitative genetic analysis of hepatic lipid peroxidation was performed on two populations of 150 day old mice derived from the C57BL/6J (B) and DBA/2J (D) inbred mouse strains. Malondialdehyde (MDA) was measured as an index of lipid peroxidation potential in liver tissue from 378 BXD F2 mice and from approximately 30 mice from each of 22 BXD recombinant inbred (RI) mouse strains. A wide variation in MDA levels was present, with gender differences apparent in both the F2 population and in the RI strains. Quantitative trait locus (QTL) analysis of the F2 population identified several chromosomal regions with LOD scores greater than 3.0. Similar analysis of the BXD RI data confirmed two of the QTL nominated in the F2 population and further narrowed the chromosomal region.

Blast cell survival in suspension culture is associated with chemoresistance in acute myeloid leukaemia (AML). Autonomous production of IL-1β by AML blasts is linked with a proliferative response, although its role in survival and hence apoptosis-resistance has not been examined in this disease. Cells that secreted more than 193 pg/ml IL-1β were significantly more resistant to spontaneous apoptosis in 48-h culture than those that produced less than 19.7 pg/ml IL-1β (P=0008). Exogenous rhIL-1β significantly enhanced 48-h survival in 25/29 blast cell samples (P=0.0001). IL-1 receptor ligation is known to activate at least three survival pathways: those mediated by PI-3 kinase, IL-1 receptor-associated kinase (IRAK) and ceramidase. In apoptosis-sensitive AML blasts with a strong survival response to rhIL-1β, inhibitors of all three pathways down-modulated an IL-1β-mediated increase in blast survival, but only the inhibition of all three pathways totally eliminated viable blasts. In apoptosis-resistant and apoptosis-sensitive primary AML samples, the three inhibitors all increased apoptosis in vitro after 48k Exogenous rhIL-β1 induced the hyperphosphorylation of Bcl-2. It also increased the activation of NF-κB in 5/15 blast samples. IL-1β-mediated survival pathways may be a factor in apoptosis-resistance in primary AML blasts, and may therefore contribute to chemoresistance. [ABSTRACT FROM AUTHOR]