PET imaging of tumours with a 64Cu labeled macrobicyclic cage amine ligand tethered to Tyr3-octreotate

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.

The effects of land use on leaf-litter processing by macro-invertebrates in an Australian temperate coastal stream

Replacement of riparian vegetation by pasture has occurred worldwide and is predicted to have strong effects on macroinvertebrate community structure and function in streams, but this has rarely been examined. In this study, leaf processing and macroinvertebrate community structure were examined in a single stream using experimental leaf-packs and surveys of natural leaf-packs. Two sites in each of three land use categories were selected to represent reaches in forest, pasture and forest-pasture boundary regions. In two experiments using tethered leaf-packs, no differences were found in mean leaf breakdown between land use types. However, shredding invertebrates were absent from the pasture sites, so leaf breakdown in pasture resulted from chemical, physical and microbial processes only. Amounts of fine particulate organic matter in experimental leaf-packs were higher in pasture reaches than the forest and boundary reaches but did not influence leaf breakdown. Macroinvertebrate species richness did not differ between land uses. A predictive model developed for species richness and total abundance enabled direct comparison of assemblages on experimental packs to natural leaf-packs. In the forest reach and at the forest-pasture boundary, macroinvertebrate species richness and total abundance increased proportionally with the number of leaves within a pack, but this relationship was not observed in the pasture reach. Pasture land use on Skenes Creek was therefore associated with weakened relationships between allochthonous inputs and macroinvertebrate communities, but this did not alter leaf breakdown.

RF communication between surface and underwater robotic swarms

In order for underwater robots to communicate with land and air based robots on an equal basis, high speed communications is required. If the robots are not to be tethered then wireless communications is the only possibility. Sonar communications is too slow. Unfortunately radio waves are rapidly attenuated under water due to phenomena such as skin depth. These experiments attempt to extend the range of underwater radio communications.

A constructivist approach to the teaching & learning of astronomy

Astronomy is one of the recurrent contemporary issues in the mass media where news related to comets, new stars, satellites, space tests, etc., frequently appear. Through this media presence students develop an interest in learning about aspects of astronomy. However, the information students gain from various sources, both inside and outside the classroom, doesn't often increase their knowledge about the most basic and common aspects of astronomy (Martinez Pena & Gil Quilez, 2001). Studies that have explored students' and teachers' understandings of astronomical concepts (Kalkan et al, 2007; Trumper, 2001) have found many alternative conceptions relating to basic astronomical processes such as day and night, the seasons, gravity and the relative distances between celestial objects.

Solid state NMR characterization of lithium conducting ceramics

⁷Li solid state NMR has been used to characterize lithium aluminium titanium phosphate and lithium lanthanum titanate ceramics. Both materials have high ionic mobilities at room temperature and this is reflected in their static ⁷Li powder patterns. In the case of the phosphate based ceramic, a narrow Lorentzian peak is observed above 300 K, which narrows further with increasing temperature. The accompanying quadrupolar structure, with C_Q (quadrupolar coupling constant) ~ 40 kHz, suggests that the lithium ions are hopping rapidly between equivalent, high electric field gradient sites. The ²⁷Al and ³¹P magic angle spinning (MAS) spectra reveal an asymmetric phosphorus peak and two distinct aluminium resonances. The room temperature powder pattern of Li_0.33La_0.57TiO₃ shows a dipolar broadened peak which narrows quite suddenly at 310 K revealing quadrupolar satellites with C_Q ~ 900 Hz. A second lithium site is also observed in this material, as indicated by a further, weaker quadrupolar structure (C_Q ~ 40 kHz).

The zwitterion 1-butylimidazolium-3- (n-butanesulfonate)

The mol­ecule of the title compound, C₁₁H₂₀N₂O₃S, contains a positively charged imidazolium head group and a negatively charged sulfonate tethered together by a four-carbon chain. There is weak intermolecular hydrogen bonding within the structure between the sulfonate O atoms and the H atoms of the imidazolium ring. The sulfonate group causes a twisting of the butyl chain and a decrease in the dihedral angle between the second and third carbon chain compared to the unsubstituted butyl group.

‘Inspired and assisted’, or ‘berated and destroyed’? Research leadership, management and performativity in troubled times

Research leadership in Australian universities takes place against a backdrop of policy reforms concerned with measurement and comparison of institutional research performance. In particular, the Excellence in Research in Australian initiative undertaken by the Australian Research Council sets out to evaluate research quality in Australian universities, using a combination of expert review process, and assessment of performance against ‘quality indicators’. Benchmarking exercises of this sort continue to shape institutional policy and practice, with inevitable effects on the ways in which research leadership, mentoring and practice are played out within university faculties and departments. In an exploratory study that interviewed 32 Australian academics in universities in four Australian states, we asked participants, occupying formal or informal research leadership roles, to comment on their perceptions of research leadership as envisioned and enacted in their particular workplaces. We found a pervasive concern amongst participants that coalesced around binaries characterized in metaphoric terms of ‘carrots and whips’. Research leadership was seen by many as managerial in nature, and as such, largely tethered to instrumentalist notions of productivity and performativity, while research cultures were seen as languishing under the demoralizing weight of reward and punishment systems. Here, we consider what is at stake for the future of the academic workforce under such conditions, arguing that new models of visionary research leadership are urgently needed in the ‘troubled times’ of techno-bureaucratic university reforms.

π-Selective stationary phases: (II) Adsorption behaviour of substituted aromatic compounds on n-alkyl-phenyl stationary phases

The frontal analysis method was used to measure the adsorption isotherms of phenol, 4-chlorophenol, p-cresol, 4-methoxyphenol and caffeine on a series of columns packed with home-made alkyl-phenyl bonded silica particles. These ligands consist of a phenyl ring tethered to the silica support via a carbon chain of length ranging from 0 to 4 atoms. The adsorption isotherm models that fit best to the data account for solute–solute interactions that are likely caused by π–π interactions occurring between aromatic compounds and the phenyl group of the ligand. These interactions are the dominant factor responsible for the separation of low molecular weight aromatic compounds on these phenyl-type stationary phases. The saturation capacities depend on whether the spacer of the ligands have an even or an odd number of carbon atoms, with the even alkyl chain lengths having a greater saturation capacity than the odd alkyl chain lengths. The trends in the adsorption equilibrium constant are also significantly different for the even and the odd chain length ligands.

Edge effects in patchy seagrass landscapes : the role of predation in determining fish distribution

Predation is often described as an underlying mechanism to explain edge effects. We assessed the importance of predation in determining edge effects in seagrass using two approaches: a video survey to sample predators at small scales across seagrass edges, and a tethering experiment to determine if predation was an underlying mechanism causing edge effects. Underwater videos were placed at four positions: middle of seagrass patches; edge of seagrass; sand immediately adjacent to seagrass and sand distant from seagrass. Fish abundances and the time fish spent in view were measured. The main predatory fish (Australian salmon, Arripis spp.) spent more time over adjacent sand than other positions, while potential prey species (King George whiting, Sillaginodes punctata (Cuvier), recruits) were more common in the middle of seagrass patches. Other species, including the smooth toadfish, Tetractenos glaber (Freminville), and King George whiting adults, spent more time over sand adjacent to seagrass than distant sand, which may be related to feeding opportunities. King George whiting recruits and pipefish (Stigmatopora spp.) were tethered at each of the four positions. More whiting recruits were preyed upon at outer than inner seagrass patches, and survival time was greater in the middle of shallow seagrass patches than other positions. Relatively few pipefish were preyed upon, but of those that were, survival time was lower over sand adjacent to seagrass than at the seagrass edge or middle. Video footage revealed that salmon were the dominant predators of both tethered King George whiting recruits and pipefish. The distribution of predators and associated rate of predation can explain edge effects for some species (King George whiting) but other mechanisms, or combinations of mechanisms, are determining edge effects for other species (pipefish).

Force amplification response of actin filaments under confined compression

Actin protein is a major component of the cell cytoskeleton, and its ability to respond to external forces and generate propulsive forces through the polymerization of filaments is central to many cellular processes. The mechanisms governing actin's abilities are still not fully understood because of the difficulty in observing these processes at a molecular level. Here, we describe a technique for studying actin–surface interactions by using a surface forces apparatus that is able to directly visualize and quantify the collective forces generated when layers of noninterconnected, end-tethered actin filaments are confined between 2 (mica) surfaces. We also identify a force-response mechanism in which filaments not only stiffen under compression, which increases the bending modulus, but more importantly generates opposing forces that are larger than the compressive force. This elastic stiffening mechanism appears to require the presence of confining surfaces, enabling actin filaments to both sense and respond to compressive forces without additional mediating proteins, providing insight into the potential role compressive forces play in many actin and other motor protein-based phenomena.

Assessing effects of diel period, gear selectivity and predation on patterns of microhabitat use by fish in a mangrove dominated system in SE Australia

The relative value of temperate mangroves to fish, and the processes driving patterns of microhabitat use within this habitat, are unknown. There are 3 quickly identifiable microhabitats within temperate Australian mangroves: (1) forest (the area of mangroves with trees); (2) pneumatophores (the area directly seaward of the forest without trees but with pneumatophores [aerial roots]); and (3) channel (the area directly seaward of the pneumatophores without gross structural attributes such as trees or pneumatophores). Duplicate fyke and gill nets were both initially used to sample fish in the 3 microhabitats described above. Sampling took place across the seaward edge of mangroves on 10 sampling occasions (5 night and 5 day), in a large estuarine system in SE Australia. Fish assemblages (693 fish from 20 species and 15 families) varied significantly (p < 0.05) between the forest and the channel, and between diel periods for each gear (net type), but there was little difference in the assemblage structure of fish between forest–pneumatophore or pneumatophore–channel microhabitats. Juvenile lifestages (61% of all fish) and commercially important taxa (76%) were common. Abundance, biomass and species richness of fish were generally lower in the forest than the other microhabitats, but this pattern varied significantly (p < 0.05) between diel periods, among sampling occasions, and with water depth. Highly quantitative pop nets provided a preliminary assessment of whether differential gear selectivity caused patterns between microhabitats, but less rich fish assemblages were again recorded in forests than in pneumatophores. The importance of predation in structuring fish assemblages across microhabitats was assessed by measuring survival of juvenile fish tethered in 3 predation treatments (predator exclusion, cage control, and uncaged). Survival rates were high across the predator treatments and did not vary among microhabitats. The variation in fish assemblages across microhabitats within mangroves was not consistent with a model of mangrove structure providing a refuge for juvenile fish from predation, but instead could indicate differences in efficiency of gear types among microhabitats and/or other ‘edge effect’-driven processes such as the provision of food and/or shelter.

Azide photochemistry for facile modification of graphitic surfaces : preparation of DNA-coated carbon nanotubes for biosensing

A facile, two-step method for chemically attaching single-stranded DNA to graphitic surfaces, represented here by carbon nanotubes, is reported. In the first step, an azide-containing compound, N-5-azido-nitrobenzoyloxy succinimide (ANB-NOS), is used to form photo-adducts on the graphitic surfaces in a solid-state photochemical reaction, resulting in active ester groups being oriented for the subsequent reactions. In the second step, pre-synthesized DNA strands bearing a terminal amine group are coupled in an aqueous solution with the active esters on the photo-adducts. The versatility of the method is demonstrated by attaching pre-synthesized DNA to surfaces of carbon nanotubes in two platforms—as vertically-aligned multi-walled carbon nanotubes on a solid support and as tangled single-walled carbon nanotubes in mats. The reaction products at various stages were characterized by x-ray photoelectron spectroscopy. Two different assays were used to check that the DNA strands attached to the carbon nanotubes were able to bind their partner strands with complementary base sequences. The first assay, using partner DNA strands tethered to gold nanoparticles, enabled the sites of DNA attachment to the carbon nanotubes to be identified in TEM images. The second assay, using radioactively labelled partner DNA strands, quantified the density of functional DNA strands attached to the carbon nanotubes. The diversity of potential applications for these DNA-modified carbon-nanotube platforms is exemplified here by the successful use of a DNA-modified single-walled carbon-nanotube mat as an electrode for the specific detection of metal ions.