Shock tunnel studies of scramjet phenomena, supplement 6

Reports by the staff of the University of Queensland on various research studies related to the advancement of scramjet technology are presented. These reports document the tests conducted in the reflected shock tunnel T4 and supporting research facilities that have been used to study the injection, mixing, and combustion of hydrogen fuel in generic scramjets at flow conditions typical of hypersonic flight. In addition, topics include the development of instrumentation and measurement technology, such as combustor wall shear and stream composition in pulse facilities, and numerical studies and analyses of the scramjet combustor process and the test facility operation

Scaling of Transport Coefficients of Porous Media under Compaction

Porous sediments in geological systems are exposed to stress by the above-laying mass and consequent compaction, which may be significantly nonuniform across the massif. We derive scaling laws for the compaction of sediments of similar geological origin. With these laws, we evaluate the dependence of the transport properties of a fluid-saturated porous medium (permeability, effective molecular diffusivity, hydrodynamic dispersion, electrical and thermal conductivities) on its porosity. In particular, we demonstrate that the assumption of a uniform geothermal gradient is not adequate for systems with nonuniform compaction and show the importance of the derived scaling laws for mathematical modelling of methane hydrate deposits; these deposits are believed to have potential for impact on global climate change and Glacial-Interglacial cycles.Comment: 6 pages, 2 figure

Methodological approaches to determining the marine radiocarbon reservoir effect

The marine radiocarbon reservoir effect is an offset in 14C age between contemporaneous organisms from the terrestrial environment and organisms that derive their carbon from the marine environment. Quantification of this effect is of crucial importance for correct calibration of the <sup>14</sup>C ages of marine-influenced samples to the calendrical timescale. This is fundamental to the construction of archaeological and palaeoenvironmental chronologies when such samples are employed in <sup>14</sup>C analysis. Quantitative measurements of temporal variations in regional marine reservoir ages also have the potential to be used as a measure of process changes within Earth surface systems, due to their link with climatic and oceanic changes. The various approaches to quantification of the marine radiocarbon reservoir effect are assessed, focusing particularly on the North Atlantic Ocean. Currently, the global average marine reservoir age of surface waters, R(t), is c. 400 radiocarbon years; however, regional values deviate from this as a function of climate and oceanic circulation systems. These local deviations from R(t) are expressed as +R values. Hence, polar waters exhibit greater reservoir ages (δR = c. +400 to +800 <sup>14</sup>C y) than equatorial waters (δR = c. 0 <sup>14</sup>C y). Observed temporal variations in δR appear to reflect climatic and oceanographic changes. We assess three approaches to quantification of marine reservoir effects using known age samples (from museum collections), tephra isochrones (present onshore/offshore) and paired marine/terrestrial samples (from the same context in, for example, archaeological sites). The strengths and limitations of these approaches are evaluated using examples from the North Atlantic region. It is proposed that, with a suitable protocol, accelerator mass spectrometry (AMS) measurements on paired, short-lived, single entity marine and terrestrial samples from archaeological deposits is the most promising approach to constraining changes over at least the last 5 ky BP

ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1

Organometallic iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis

Platinum complexes related to cisplatin, cis-[PtCl2(NH3)2], are successful anticancer drugs; however, other transition metal complexes offer potential for combating cisplatin resistance, decreasing side effects, and widening the spectrum of activity. Organometallic half-sandwich iridium (IrIII) complexes [Ir(Cpx)(XY)Cl]+/0 (Cpx = biphenyltetramethylcyclopentadienyl and XY = phenanthroline (1), bipyridine (2), or phenylpyridine (3)) all hydrolyze rapidly, forming monofunctional G adducts on DNA with additional intercalation of the phenyl substituents on the Cpx ring. In comparison, highly potent complex 4 (Cpx = phenyltetramethylcyclopentadienyl and XY = N,N-dimethylphenylazopyridine) does not hydrolyze. All show higher potency toward A2780 human ovarian cancer cells compared to cisplatin, with 1, 3, and 4 also demonstrating higher potency in the National Cancer Institute (NCI) NCI-60 cell-line screen. Use of the NCI COMPARE algorithm (which predicts mechanisms of action (MoAs) for emerging anticancer compounds by correlating NCI-60 patterns of sensitivity) shows that the MoA of these IrIII complexes has no correlation to cisplatin (or oxaliplatin), with 3 and 4 emerging as particularly novel compounds. Those findings by COMPARE were experimentally probed by transmission electron microscopy (TEM) of A2780 cells exposed to 1, showing mitochondrial swelling and activation of apoptosis after 24 h. Significant changes in mitochondrial membrane polarization were detected by flow cytometry, and the potency of the complexes was enhanced ca. 5× by co-administration with a low concentration (5 μM) of the γ-glutamyl cysteine synthetase inhibitor L-buthionine sulfoximine (L-BSO). These studies reveal potential polypharmacology of organometallic IrIII complexes, with MoA and cell selectivity governed by structural changes in the chelating ligands

The Mechanism of Methane Gas Migration Through the Gas Hydrate Stability Zone: Insights From Numerical Simulations

Free gas migration through the gas hydrate stability zone (GHSZ) and subsequent gas seepage at the seabed are characteristic features in marine gas hydrate provinces worldwide. The biogenic or thermogenic gas is typically transported along faults from deeper sediment strata to the GHSZ. Several mechanisms have been proposed to explain free gas transport through the GHSZ. While inhibition of hydrate formation by elevated salinities and temperatures have been addressed previously in studies simulating unfocused, area-wide upward advection of gas, which is not adequately supported by field observations, the role of focused gas flow through chimney-like structures has been underappreciated in this context. Our simulations suggest that gas migration through the GHSZ is, fundamentally, a result of methane gas supply in excess of its consumption by hydrate formation. The required high gas flux is driven by local overpressure, built up from gas accumulating below the base of the GHSZ that fractures the overburden when exceeding a critical pressure, thereby creating the chimney-like migration pathway. Initially rapid hydrate formation raises the temperature in the chimney structure, thereby facilitating further gas transport through the GHSZ. As a consequence, high hydrate saturations form preferentially close to the seafloor, where temperatures drop to bottom water values, producing a prominent subsurface salinity peak. Over time, hydrates form at a lower rate throughout the chimney structure, while initial temperature elevation and salinity peak dissipate. Thus, our simulations suggest that the near-surface salinity peak and elevated temperatures are a result of transient high-flux gas migration through the GHSZ

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

DNA resection in eukaryotes: deciding how to fix the break

DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation

Three-component force measurements on a large scramjet in a shock tunnel

A stress-wave force balance for measurement of thrust, lift, and pitching moment on a large scramjet model (40 kg in mass, 1.165 in in length) in a reflected shock tunnel has been designed, calibrated, and tested. Transient finite element analysis was used to model the performance of the balance. This modeling indicates that good decoupling of signals and low sensitivity of the balance to the distribution of. the load can be achieved with a three-bar balance. The balance was constructed and calibrated by applying a series of point loads to the model. A good comparison between finite element analysis and experimental results was obtained with finite element analysis aiding in the interpretation of some experimental results. Force measurements were made in a shock tunnel both with and without fuel injection, and measurements were compared with predictions using simple models of the scramjet and combustion. Results indicate that the balance is capable of resolving lift, thrust, and pitching moments with and without combustion. However vibrations associated with tunnel operation interfered with the signals indicating the importance of vibration isolation for accurate measurements