Development of a multimodal imaging probe for detecting aggressive prostate cancer

This thesis reports on the synthesis, development and validation of a novel, non-toxic dual modal bio-imaging probe that targets a conformational molecular switch and relocalisation of cell surface Endo180 into endosomes that occurs during the early stages of aggressive prostate cancer.InP/ZnS quantum dots were synthesised using a successive heating methodology following the introduction of a cooling phase between the addition of ‘shelling’ precursors. Photoluminescent quantum yields following the synthesis of InP/ZnS (2) quantum dots are reported at 85.30% in hexane and 57% in water (following phase transfer).An OI/MR dual-modal imaging probe was successfully synthesised following the surface modification of InP/ZnS (2) – TGA with Ln(III) DOTA chelate derivative (Ln = Gd, Eu and Tb). Up to 190 Gd(III) chelates were added to the surface of InP/ZnS (2) – TGA resulting in a combined r1 value of 1609.94 mM-1s-1 (InP/ZnS (2) – Gd.5a) when InP/ZnS (2) is synthesised with InI3. High values of photoluminescent quantum yield were achieved of up to 19.9% (InP/ZnS (2) – Gd.5.b) with no shift in emission properties observed following surface functionalisation when compared to InP/ZnS (2) – TGA.A targeted dual modal OI/MR imaging probe for the early detection of aggressive prostate cancer has been developed, via a two-step surface modification of InP/ZnS (2) – TGA with Endo180 conformational specific antibodies (A5.158, 39.10) and Gd(III) chelate (Gd.5a).Work presented in chapter 2 has formed part of the publication, Clarke, M. T.; Viscomi, N.; Chamberlain, T. W.; Hondow, N.; Adawi, A. M.; Sturge, J.; Erwin, S. C.; Bouillard, J.-S. G.; Tamang, S.; Stasiuk, G. J. Near Unity Quantum Yield in InP Based Quantum Dots through Thermal Diffusion. Commun. Chem. 2019, 2

Aboriginal youth, hip hop and the politics of identification

This paper explores the identity work taking place around contemporary subcultural hip hop amongst Australian indigenous youth in two disadvantaged urban locations. Previous work on Aboriginal hip hop has been attentive to the interface between tradition and modernity. However, existing scholarship has lacked a deeper ethnographic understanding of the dynamics between youth and parent cultures, and the tensions between the two generations. This article is based on research with young hip hop enthusiasts, community activists and educators. It deals with the cultural politics of identification and sees hip hop practice as associated with a process in which Aboriginality is crystallized as a principal affiliation and as offering an account for experiences of social marginalization. Far from being an outlet for expressing a prior or essential Aboriginality, hip hop as cultural practice is associated with the production of particular identifications

The Importance of Exploring Neptune’s Aurora and Ionosphere

Whitepaper #261 submitted to the Planetary Science and Astrobiology Decadal Survey 2023-2032. Topics: atmospheric/exospheric evolution; giant planets systems Neptune’s aurorae are some of the least well understood within the entire solar system. Observing them with in-situ space missions will greatly improve our understanding of the aurorae and their atmospheric and magnetospheric context, and will provide a new understanding of all Ice Giant aurorae, both within the solar system and around other stars

X-ray Spectroscopy of Cooling Clusters

We review the X-ray spectra of the cores of clusters of galaxies. Recent high resolution X-ray spectroscopic observations have demonstrated a severe deficit of emission at the lowest X-ray temperatures as compared to that expected from simple radiative cooling models. The same observations have provided compelling evidence that the gas in the cores is cooling below half the maximum temperature. We review these results, discuss physical models of cooling clusters, and describe the X-ray instrumentation and analysis techniques used to make these observations. We discuss several viable mechanisms designed to cancel or distort the expected process of X-ray cluster cooling.Comment: To appear in Physics Reports, 71 pages, 20 figure

The freshwater system west of the Antarctic Peninsula : spatial and temporal changes

Author Posting. © American Meteorological Society, 2013. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 26 (2013): 1669–1684, doi:10.1175/JCLI-D-12-00246.1.Climate change west of the Antarctic Peninsula is the most rapid of anywhere in the Southern Hemisphere, with associated changes in the rates and distributions of freshwater inputs to the ocean. Here, results from the first comprehensive survey of oxygen isotopes in seawater in this region are used to quantify spatial patterns of meteoric water (glacial discharge and precipitation) separately from sea ice melt. High levels of meteoric water are found close to the coast, due to orographic effects on precipitation and strong glacial discharge. Concentrations decrease offshore, driving significant southward geostrophic flows (up to ~30 cm s−1). These produce high meteoric water concentrations at the southern end of the sampling grid, where collapse of the Wilkins Ice Shelf may also have contributed. Sea ice melt concentrations are lower than meteoric water and patchier because of the mobile nature of the sea ice itself. Nonetheless, net sea ice production in the northern part of the sampling grid is inferred; combined with net sea ice melt in the south, this indicates an overall southward ice motion. The survey is contextualized temporally using a decade-long series of isotope data from a coastal Antarctic Peninsula site. This shows a temporal decline in meteoric water in the upper ocean, contrary to expectations based on increasing precipitation and accelerating deglaciation. This is driven by the increasing occurrence of deeper winter mixed layers and has potential implications for concentrations of trace metals supplied to the euphotic zone by glacial discharge. As the regional freshwater system evolves, the continuing isotope monitoring described here will elucidate the ongoing impacts on climate and the ecosystem.The Palmer LTER participants acknowledge Award 0823101 from the Organisms and Ecosystems program in NSF OPP2013-09-0

Comparative metagenomics reveals the distinctive adaptive features of the Spongia officinalis endosymbiotic consortium

Current knowledge of sponge microbiome functioning derives mostly from comparative analyses with bacterioplankton communities. We employed a metagenomics-centered approach to unveil the distinct features of the Spongia officinalis endosymbiotic consortium in the context of its two primary environmental vicinities. Microbial metagenomic DNA samples (n = 10) from sponges, seawater, and sediments were subjected to Hiseq Illumina sequencing (c. 15 million 100 bp reads per sample). Totals of 10,272 InterPro (IPR) predicted protein entries and 784 rRNA gene operational taxonomic units (OTUs, 97% cut-off) were uncovered from all metagenomes. Despite the large divergence in microbial community assembly between the surveyed biotopes, the S. officinalis symbiotic community shared slightly greater similarity (p < 0.05), in terms of both taxonomy and function, to sediment than to seawater communities. The vast majority of the dominant S. officinalis symbionts (i.e., OTUs), representing several, so-far uncultivable lineages in diverse bacterial phyla, displayed higher residual abundances in sediments than in seawater. CRISPR-Cas proteins and restriction endonucleases presented much higher frequencies (accompanied by lower viral abundances) in sponges than in the environment. However, several genomic features sharply enriched in the sponge specimens, including eukaryotic-like repeat motifs (ankyrins, tetratricopeptides, WD-40, and leucine-rich repeats), and genes encoding for plasmids, sulfatases, polyketide synthases, type IV secretion proteins, and terpene/terpenoid synthases presented, to varying degrees, higher frequencies in sediments than in seawater. In contrast, much higher abundances of motility and chemotaxis genes were found in sediments and seawater than in sponges. Higher cell and surface densities, sponge cell shedding and particle uptake, and putative chemical signaling processes favoring symbiont persistence in particulate matrices all may act as mechanisms underlying the observed degrees of taxonomic connectivity and functional convergence between sponges and sediments. The reduced frequency of motility and chemotaxis genes in the sponge microbiome reinforces the notion of a prevalent mutualistic mode of living inside the host. This study highlights the S. officinalis "endosymbiome" as a distinct consortium of uncultured prokaryotes displaying a likely "sit-and-wait" strategy to nutrient foraging coupled to sophisticated anti-viral defenses, unique natural product biosynthesis, nutrient utilization and detoxification capacities, and both microbe-microbe and host-microbe gene transfer amenability.Portuguese Foundation for Science and Technology (FCT) [PTDC/BIA-MIC/3865/2012, PTDC/MAR-BIO/1547/2014]; Education, Audiovisual and Culture Executive Agency (European Commission, Erasmus Mundus Programme) [EMA2 lot7/SALA1206422]info:eu-repo/semantics/publishedVersio

Cancellous bone and theropod dinosaur locomotion. Part I—an examination of cancellous bone architecture in the hindlimb bones of theropods

This paper is the first of a three-part series that investigates the architecture of cancellous (‘spongy’) bone in the main hindlimb bones of theropod dinosaurs, and uses cancellous bone architectural patterns to infer locomotor biomechanics in extinct non-avian species. Cancellous bone is widely known to be highly sensitive to its mechanical environment, and has previously been used to infer locomotor biomechanics in extinct tetrapod vertebrates, especially primates. Despite great promise, cancellous bone architecture has remained little utilized for investigating locomotion in many other extinct vertebrate groups, such as dinosaurs. Documentation and quantification of architectural patterns across a whole bone, and across multiple bones, can provide much information on cancellous bone architectural patterns and variation across species. Additionally, this also lends itself to analysis of the musculoskeletal biomechanical factors involved in a direct, mechanistic fashion. On this premise, computed tomographic and image analysis techniques were used to describe and analyse the three-dimensional architecture of cancellous bone in the main hindlimb bones of theropod dinosaurs for the first time. A comprehensive survey across many extant and extinct species is produced, identifying several patterns of similarity and contrast between groups. For instance, more stemward non-avian theropods (e.g. ceratosaurs and tyrannosaurids) exhibit cancellous bone architectures more comparable to that present in humans, whereas species more closely related to birds (e.g. paravians) exhibit architectural patterns bearing greater similarity to those of extant birds. Many of the observed patterns may be linked to particular aspects of locomotor biomechanics, such as the degree of hip or knee flexion during stance and gait. A further important observation is the abundance of markedly oblique trabeculae in the diaphyses of the femur and tibia of birds, which in large species produces spiralling patterns along the endosteal surface. Not only do these observations provide new insight into theropod anatomy and behaviour, they also provide the foundation for mechanistic testing of locomotor hypotheses via musculoskeletal biomechanical modelling

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers