Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells : evidence from myeloma-bearing mouse model

The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122(+) cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8(+) T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8alphaalpha and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-gamma and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.

CHURNs : freshness assurance for humans

We present CHURNs, a method for providing freshness and authentication assurances to human users. In computer-to-computer protocols, it has long been accepted that assurances of freshness such as random nonces are required to prevent replay attacks. Typically, no such assurance of freshness is presented to a human in a human-and-computer protocol. A Computer–HUman Recognisable Nonce (CHURN) is a computer-aided random sequence that the human has a measure of control over and input into. Our approach overcomes limitations such as ‘humans cannot do random’ and that humans will follow the easiest path. Our findings show that CHURNs are significantly more random than values produced by unaided humans; that humans may be used as a second source of randomness, and we give measurements as to how much randomness can be gained from humans using our approach; and that our CHURN-generator makes the user feel more in control, thus removing the need for complete trust in devices and underlying protocols. We give an example of how a CHURN may be used to provide assurances of freshness and authentication for humans in a widely used protocol.

The Soldier's Wife (LP)

Audio recording of 10 tracks funded by Legacy, The Australia Council, and Arts Queensland. The recordings explore the untold stories of soldiers' wives through song. It features the vocal and songwriting talents of Jackie Marshall, Bertie Page, Sahara Beck, Emma Bosworth, Roz Pappalardo, and Kristy Apps. Recorded, Mixed, Mastered, and Co-Produced by Phil Graham.

Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium

The rat theta class glutathione S-transferase (GST) 5-5 has been shown to affect the mutagenicity of halogenated alkanes and epoxides. In Salmonella typhimurium TA1535 expressing the rat GST5-5 the number of revertants was increased compared to the control strain by CH2Br2, ethylene dibromide (EDB) and 1,2,3,4-diepoxybutane (BDE); in contrast, mutagenicity of 1,2-epoxy-3-(4'-nitrophenoxy)propane (EPNP) was reduced. S.typhimurium TA1535 cells were transformed with an expression plasmid carrying the cDNA of the human theta ortholog GST1-1 either in sense or antisense orientation, the latter being the control. These transformed bacteria were utilized for mutagenicity assays. Mutagenicity of EDB, BDE, CH2Br2, epibromohydrin and 1,3-dichloroacetone was higher in the S.typhimurium TA1535 expressing GSTT1-1 than in the control strain. The expression of active enzyme did not affect the mutagenicity of 1,2-epoxy-3-butene or propylene oxide, GSTT1-1 expression reduced the mutagenicity of EPNP. Glutathione S-transferase 5-5 and GSTT1-1 modulate genotoxicity of several industrially important chemicals in the same way. Polymorphism of the GSTT1 locus in humans may therefore cause differences in cancer susceptibility between the two phenotypes.

Uninhabited

"A young couple go to a remote and deserted coral island for a camping holiday, only to find that the island is inhabited by a ghost seeking retribution for a past outrage. - Written by Bill Bennett " "Synopsis: Based on actual events…. Harry and Beth want a different kind of holiday. So they charter a boat to drop them off on a remote coral island on the Great Barrier Reef. The island is idyllic – surrounded by a wide reef, covered in palms and full of birds and other wildlife, small and totally deserted. Or is it? The young lovers soon come to believe there is someone else on the island. Things go missing from their camp – and then they discover someone else’s footprints in the sand. What they didn’t realise was that the island has a ghost – a young girl who had died in shocking circumstances some eighty years earlier. The ghost at first plays mischievously with the young couple, but then turns malevolent. And their idyllic island holiday becomes a nightmare."

Interpreting discovered patterns in terms of ontology concepts

Semantic Web offers many possibilities for future Web technologies. Therefore, it is a need to search for ways that can bring the huge amount of unstructured documents from current Web to Semantic Web automatically. One big challenge in searching for such ways is how to understand patterns by both humans and machine. To address this issue, we present an innovative model which interprets patterns to high level concepts. These concepts can explain the patterns' meanings in a human understandable way while improving the information filtering performance. The model is evaluated by comparing it against one state-of-the-art benchmark model using standard Reuters dataset. The results show that the proposed model is successful. The significance of this model is three fold. It gives a way to interpret text mining output, provides a technique to find concepts relevant to the whole set of patterns which is an essential feature to understand the topic, and to some extent overcomes information mismatch and overload problems of existing models. This model will be very useful for knowledge based applications.

Estimating the burden of disease attributable to urban outdoor air pollution in South Africa in 2000

Objectives To quantify the mortality burden attributed to urban outdoor air pollution in South Africa in 2000. Design The study followed comparative risk assessment (CRA) methodology developed by the World Heath Organization (WHO). In most urban areas, annual mean concentrations of particulate matter (PM) with diameters less than 10 μum (PM10) from monitoring network data and PM with diameters less than 2.5 μm (PM2.5) derived using a ratio method were weighted according to population size. PM10 and PM2.5 data from air-quality assessment studies in areas not covered by the network were also included. Population-attributable fractions calculated using risk coefficients presented in the WHO study were weighted by the proportion of the total population (33%) in urban environments, and applied to revised estimates of deaths and years of life lost (YLLs) for South Africa in 2000. Setting South Africa. Subjects Children under 5 years and adults 30 years and older. Outcome measures Mortality and YLLs from lung cancer and cardiopulmonary disease in adults (30 years and older), and from acute respiratory infections (ARIs) in children aged 0 - 4 years. Results Outdoor air pollution in urban areas in South Africa was estimated to cause 3.7% of the national mortality from cardiopulmonary disease and 5.1% of mortality attributable to cancers of the trachea, bronchus and lung in adults aged 30 years and older, and 1.1% of mortality from ARIs in children under 5 years of age. This amounts to 4 637 or 0.9% (95% uncertainty interval 0.3 - 1.5%) of all deaths and about 42 000 YLLs, or 0.4% (95% uncertainty interval 0.1 - 0.7%) of all YLLs in persons in South Africa in 2000. Conclusion Urban air pollution has under-recognised public health impacts in South Africa. Fossil fuel combustion emissions and traffic-related air pollution remain key targets for public health in South Africa.

Correcting flaws in Mitchell’s analysis of EPBC

Efficient error-Propagating Block Chaining (EPBC) is a block cipher mode intended to simultaneously provide both confidentiality and integrity protection for messages. Mitchell’s analysis pointed out a weakness in the EPBC integrity mechanism that can be used in a forgery attack. This paper identifies and corrects a flaw in Mitchell’s analysis of EPBC, and presents other attacks on the EPBC integrity mechanism.

Automated sensory data alignment for environmental and epidermal change monitoring

In this paper we present research adapting a state of the art condition-invariant robotic place recognition algorithm to the role of automated inter- and intra-image alignment of sensor observations of environmental and skin change over time. The approach involves inverting the typical criteria placed upon navigation algorithms in robotics; we exploit rather than attempt to fix the limited camera viewpoint invariance of such algorithms, showing that approximate viewpoint repetition is realistic in a wide range of environments and medical applications. We demonstrate the algorithms automatically aligning challenging visual data from a range of real-world applications: ecological monitoring of environmental change, aerial observation of natural disasters including flooding, tsunamis and bushfires and tracking wound recovery and sun damage over time and present a prototype active guidance system for enforcing viewpoint repetition. We hope to provide an interesting case study for how traditional research criteria in robotics can be inverted to provide useful outcomes in applied situations.

Toward the adaptive generation of bespoke game content

In this chapter, we explore methods for automatically generating game content—and games themselves—adapted to individual players in order to improve their playing experience or achieve a desired effect. This goes beyond notions of mere replayability and involves modeling player needs to maximize their enjoyment, involvement, and interest in the game being played. We identify three main aspects of this process: generation of new content and rule sets, measurement of this content and the player, and adaptation of the game to change player experience. This process forms a feedback loop of constant refinement, as games are continually improved while being played. Framed within this methodology, we present an overview of our recent and ongoing research in this area. This is illustrated by a number of case studies that demonstrate these ideas in action over a variety of game types, including 3D action games, arcade games, platformers, board games, puzzles, and open-world games. We draw together some of the lessons learned from these projects to comment on the difficulties, the benefits, and the potential for personalized gaming via adaptive game design.

CLEIMS: Outcomes of a randomised educational trial of extended immersion in medical simulation

To report the outcomes of a randomised educational trial of a new methodology for extended immersion in medical simulation for senior medical students. Clinical Learning through Extended Immersion in Medical Simulation (CLEIMS) is a new methodology for medical student learning. It involves senior students working in teams of 4-5 through the clinical progress of one or more patients over a week, utilising a range of simulation methodologies (simulated patient assessment, simulated significant other briefing, virtual story continuations, pig-trotter wound repair, online simulated on-call modules, interprofessional simulated ward rounds and high fidelity mannequin-based emergency simulations), to enhance learning in associated workshops and seminars. A randomised educational trial comparing the methodology to seminars and workshops alone began in 2010 and interim results were reported at last year’s conference. Updated results are presented here and final primary endpoint outcomes will be available by the time of the conference.