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.

A digital watermarking framework with application to medical image security

Dealing with digital medical images is raising many new security problems with legal and ethical complexities for local archiving and distant medical services. These include image retention and fraud, distrust and invasion of privacy. This project was a significant step forward in developing a complete framework for systematically designing, analyzing, and applying digital watermarking, with a particular focus on medical image security. A formal generic watermarking model, three new attack models, and an efficient watermarking technique for medical images were developed. These outcomes contribute to standardizing future research in formal modeling and complete security and computational analysis of watermarking schemes.

Review and future options for computer modelling in the sugar industry

Computer modelling has been used extensively in some processes in the sugar industry to achieve significant gains. This paper reviews the investigations carried out over approximately the last twenty five years,including the successes but also areas where problems and delays have been encountered. In that time the capability of both hardware and software have increased dramatically. For some processes such as cane cleaning, cane billet preparation, and sugar drying, the application of computer modelling towards improved equipment design and operation has been quite limited. A particular problem has been the large number of particles and particle interactions in these applications, which, if modelled individually, is computationally very intensive. Despite the problems, some attempts have already been made and knowledge gained on tackling these issues. Even if the detailed modelling is wanting, a model can provide some useful insights into the processes. Some options to attack these more intensive problems include the use of commercial software packages, which are usually very robust and allow the addition of user-supplied subroutines to adapt the software to particular problems. Suppliers of such software usually charge a fee per CPU licence, which is often problematic for large problems that require the use of many CPUs. Another option to consider is using open source software that has been developed with the capability to access large parallel resources. Such software has the added advantage of access to the full internal coding. This paper identifies and discusses the detail of software options with the potential capability to achieve improvements in the sugar industry.

A digital airport experience : design-led innovation in support of airport strategy

The digital era is proving to be one of disruption, where new technologies matched with innovative business models can be harnessed to attack even the most established of companies. For businesses with the relative certainty of captive customer bases, such as airports, the ability to digitally diversify offers the opportunity to venture into new modes of operation. For an airport, this opportunity can also be leveraged to sustain superior customer support regardless of a customer’s location in the world. This research paper presents a case study of the development of an Australian Airport Corporation’s mobile application as part of a greater digital strategy initiative using a design-led approach to innovate. An action research method provides the platform for an intensive embedded practice and study of design-led innovation within the major Australian Airport Corporation. The findings reveal design-led innovation to be a crucial in-house idea generation and concept development capability enabling the bridging of distinct corporate domains associated with commercialisation, operations and customer experience. A Digital Innovation Checklist is presented as an output of this research which structures an organizational approach toward digital channel innovation. The practitioner’s checklist is designed to aid in the future development of digital channels within the broader spectrum of strategy by addressing business assumptions.

A gray-box neural network-based model identification and fault estimation scheme for nonlinear dynamic systems

A novel gray-box neural network model (GBNNM), including multi-layer perception (MLP) neural network (NN) and integrators, is proposed for a model identification and fault estimation (MIFE) scheme. With the GBNNM, both the nonlinearity and dynamics of a class of nonlinear dynamic systems can be approximated. Unlike previous NN-based model identification methods, the GBNNM directly inherits system dynamics and separately models system nonlinearities. This model corresponds well with the object system and is easy to build. The GBNNM is embedded online as a normal model reference to obtain the quantitative residual between the object system output and the GBNNM output. This residual can accurately indicate the fault offset value, so it is suitable for differing fault severities. To further estimate the fault parameters (FPs), an improved extended state observer (ESO) using the same NNs (IESONN) from the GBNNM is proposed to avoid requiring the knowledge of ESO nonlinearity. Then, the proposed MIFE scheme is applied for reaction wheels (RW) in a satellite attitude control system (SACS). The scheme using the GBNNM is compared with other NNs in the same fault scenario, and several partial loss of effect (LOE) faults with different severities are considered to validate the effectiveness of the FP estimation and its superiority.

Mechanisms of mono- and poly-ubiquitination : ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine

Ubiquitination involves the attachment of ubiquitin to lysine residues on substrate proteins or itself, which can result in protein monoubiquitination or polyubiquitination. Ubiquitin attachment to different lysine residues can generate diverse substrate-ubiquitin structures, targeting proteins to different fates. The mechanisms of lysine selection are not well understood. Ubiquitination by the largest group of E3 ligases, the RING-family E3 s, is catalyzed through co-operation between the non-catalytic ubiquitin-ligase (E3) and the ubiquitin-conjugating enzyme (E2), where the RING E3 binds the substrate and the E2 catalyzes ubiquitin transfer. Previous studies suggest that ubiquitination sites are selected by E3-mediated positioning of the lysine toward the E2 active site. Ultimately, at a catalytic level, ubiquitination of lysine residues within the substrate or ubiquitin occurs by nucleophilic attack of the lysine residue on the thioester bond linking the E2 catalytic cysteine to ubiquitin. One of the best studied RING E3/ E2 complexes is the Skp1/Cul1/F box protein complex, SCFCdc4, and its cognate E2, Cdc34, which target the CDK inhibitor Sic1 for K48-linked polyubiquitination, leading to its proteasomal degradation. Our recent studies of this model system demonstrated that residues surrounding Sic1 lysines or lysine 48 in ubiquitin are critical for ubiquitination. This sequence-dependence is linked to evolutionarily conserved key residues in the catalytic region of Cdc34 and can determine if Sic1 is mono- or poly-ubiquitinated. Our studies indicate that amino acid determinants in the Cdc34 catalytic region and their compatibility to those surrounding acceptor lysine residues play important roles in lysine selection. This may represent a general mechanism in directing the mode of ubiquitination in E2 s.

Assessment of cone beam CT registration for prostate radiation therapy : fiducial marker and soft tissue methods

Introduction This investigation aimed to assess the consistency and accuracy of radiation therapists (RTs) performing cone beam computed tomography (CBCT) alignment to fiducial markers (FMs) (CBCTFM) and the soft tissue prostate (CBCTST). Methods Six patients receiving prostate radiation therapy underwent daily CBCTs. Manual alignment of CBCTFM and CBCTST was performed by three RTs. Inter-observer agreement was assessed using a modified Bland–Altman analysis for each alignment method. Clinically acceptable 95% limits of agreement with the mean (LoAmean) were defined as ±2.0 mm for CBCTFM and ±3.0 mm for CBCTST. Differences between CBCTST alignment and the observer-averaged CBCTFM (AvCBCTFM) alignment were analysed. Clinically acceptable 95% LoA were defined as ±3.0 mm for the comparison of CBCTST and AvCBCTFM. Results CBCTFM and CBCTST alignments were performed for 185 images. The CBCTFM 95% LoAmean were within ±2.0 mm in all planes. CBCTST 95% LoAmean were within ±3.0 mm in all planes. Comparison of CBCTST with AvCBCTFM resulted in 95% LoA of −4.9 to 2.6, −1.6 to 2.5 and −4.7 to 1.9 mm in the superior–inferior, left–right and anterior–posterior planes, respectively. Conclusions Significant differences were found between soft tissue alignment and the predicted FM position. FMs are useful in reducing inter-observer variability compared with soft tissue alignment. Consideration needs to be given to margin design when using soft tissue matching due to increased inter-observer variability. This study highlights some of the complexities of soft tissue guidance for prostate radiation therapy.

Relationship of lightning ground flashes to rainfall and wet bulb temperature

The close relationship between rain and lightning is well known. However, there are numerous documented observations of heavy rain accompanied by little or no lightning activity (Williams et al, 1992; Jayaratne, 1993). Kuleshov et al (2002) studied thunderstorm distribution and frequency in Australia and concluded that thunderstorm frequency (as expressed by number of thunder-days) in Australia does not, in general, appear to vary in any consistent way with rainfall. However, thunder-days describe occurrence of thunderstorms as heard by an observer, and therefore could be only proxy data to evaluate actual lightning activity (i.e. number of total or cloud-to-ground flashes). Field experiments have demonstrated a strong increase in lightning activity with convective available potential energy (CAPE). It has also been shown that CAPE increases linearly with potential wet bulb temperature, Tw (Williams et al, 1992). In this study, we examine the relationship between lightning ground flash incidence and the two parameters – surface rainfall and surface wet bulb maximum temperature for selected localities around Australia...

The role of radiotherapy patients in provision of student interpersonal skills feedback

Background At Queensland University of Technology, student radiation therapists receive regular feedback from clinical staff relating to clinical interpersonal skills. Although this is of great value, there is anecdotal evidence that students communicate differently with patients when under observation. Purpose The aim of this pilot was to counter this perceived observer effect by allowing patients to provide students with additional feedback. Materials and methods Radiotherapy patients from two departments were provided with anonymous feedback forms relating to aspects of student interpersonal skills. Clinical assessors, mentors and students were also provided with feedback forms, including questions about the role of patient feedback. Patient perceptions of student performance were correlated with staff feedback and assessment scores. Results Results indicated that the feedback was valued by both students and patients. Students reported that the additional dimension focused them on communication, set goals for development and increased motivation. These changes derived from both feedback and study participation, suggesting that the questionnaires could be a useful teaching tool. Patients scored more generously than mentors, although there was agreement in relative grading. Conclusions The anonymous questionnaire is a convenient and valuable method of gathering patient feedback on students. Future iterations will determine the optimum timing for this method of feedback.

Silvicultural management of Hypsipyla species

Existing evidence for successful silvicultural control of Hypsipyla spp. is conflicting and to a large extent anecdotal. Levels of attack have been correlated with factors such as shade, planting density, species mixtures, site characteristics, etc. These factors have often been poorly defined and are usually interdependent. The actual mechanisms that determine whether or not Hypsipyla spp. adversely affects plants we define as host-finding, host suitability, host recovery and natural enemies. These mechanisms can be influenced by the silvicultural techniques applied to a stand. Success of silvicultural techniques can usually be attributed to more than one mechanism and it is difficult to assess which is most the important for minimising the impact of Hypsipyla as these analytical data are lacking. This highlights the need for further research on silvicultural methods for controlling Hypsipyla spp. However, several silvicultural techniques that are briefly described show promise for improving the performance of future plantations. Examples of silvicultural control are reviewed with reference to these mechanisms.

Emergence and artistic visualisation

This research draws on theories of emergence to inform the creation of an artistic and direct visualization. This is an interactive artwork and drawing tool for creative participant experiences. As is discussed, emergence is characteristically creative. It is also debated across and within disciplines, resulting in a range of understandings as well as models. This paper shows how one field’s understanding of emergence (complexity theory) can be used to facilitate emergence in another domain (design research) and, importantly provide the opportunity for someone to act creatively. This paper begins with a brief review of some theories of emergence to show how they interrelate and can effect the perception of emergent structures in an observer, and, correspondingly, the design for creative experience. This is subsequently demonstrated in the second section of the paper where an interactive artwork and drawing application, Of me with me, is presented. This artwork by the author was created during collaboration with community artists from Cerebral Palsy League. The discussion covers the application of emergence theories to create this visualization in order facilitate the perception of structures and creative behaviours in a participant and to facilitate self-efficacy in the community artist user group.

12 minute dances

A collection of short works which are the result of a year-long period of movement reflection and investigation by Liz Roche with a core group of Rex Levitates dancers. The works appear as a wash of colour, movement, rhythm and emotion; human embodiment as a dynamic event. The audience completes the picture. A picture lives by companionship, expanding and quickening in the eyes of the sensitive observer - Mark Rothko (Painter, 1903 - 1970)."

Public space and the marginalisation of children and young people

Throughout Australia (and elsewhere in the world) public spaces are under attack by developers and also attempts by civic authorities to regulate, restrict and reframe them. A consequence of the increasingly security driven, privatised and surveilled nature of public space is the exclusion and displacement of those considered flawed and unwelcome in the “spectacular” consumption spaces of major urban centres. In this context of monitoring and control procedures, children and young people’s use of public space in parks, neighbourhoods, shopping malls and streets is often viewed as a threat to social order, requiring various forms of punitive and/or remedial action. This paper discusses developments in the surveillance, governance and control of public space used by children and young people in particular and the capacity for their displacement and marginality, diminishing their sense of belonging, wellbeing and right to public space as an expression of social, political and civil citizenship.

DNA adduction by the potent carcinogen aflatoxin B1 : mechanistic studies

Aflatoxin B1, a potently carcinogenic fungal metabolite, is converted to the biologically active form by chemical oxidation using dimethyldioxirane and enzymatically by cytochrome P450 mixed-function oxidases. Both processes give rise to mixtures of the exo- and endo-8,9-epoxides. Methanolysis studies reveal exclusive trans opening of both epoxides under neutral conditions in CH3OH and CH3OH/H2O mixtures; an SN2 mechanism is postulated. Under acidic conditions, the exo isomer gives mixtures of trans and cis solvolysis products, suggesting that the reaction is, at least in part, SN1; the endo isomer gives only the trans product. The exo isomer reacts with DNA by attack of the nitrogen atom at the 7 position of guanine on C8 of the epoxide to give the trans adduct; the endo epoxide fails to form an adduct at this or any other site in DNA. The exo isomer is strongly mutagenic in a base-pair reversion assay employing Salmonella typhimurium; the endo isomer is essentially nonmutagenic. Aflatoxin B1 and its derivatives intercalate in DNA. These results are consistent with a mechanism in which intercalation of the exo epoxide optimally orients the epoxide for an SN2 reaction with guanine but intercalation of the endo isomer places the epoxide in an orientation which precludes reaction. Thus, while the exo epoxide is a potent mutagen, the endo epoxide fails to react with DNA.

Evolution to a chronic disease niche correlates with increased sensitivity to tryptophan availability for the obligate intracellular bacterium Chlamydia pneumoniae

The chlamydiae are obligate intracellular parasites that have evolved specific interactions with their various hosts and host cell types to ensure their successful survival and consequential pathogenesis. The species Chlamydia pneumoniae is ubiquitous, with serological studies showing that most humans are infected at some stage in their lifetime. While most human infections are asymptomatic, C. pneumoniae can cause more-severe respiratory disease and pneumonia and has been linked to chronic diseases such as asthma, atherosclerosis, and even Alzheimer's disease. The widely dispersed animal-adapted C. pneumoniae strains cause an equally wide range of diseases in their hosts. It is emerging that the ability of C. pneumoniae to survive inside its target cells, including evasion of the host's immune attack mechanisms, is linked to the acquisition of key metabolites. Tryptophan and arginine are key checkpoint compounds in this host-parasite battle. Interestingly, the animal strains of C. pneumoniae have a slightly larger genome, enabling them to cope better with metabolite restrictions. It therefore appears that as the evolutionarily more ancient animal strains have evolved to infect humans, they have selectively become more "susceptible" to the levels of key metabolites, such as tryptophan. While this might initially appear to be a weakness, it allows these human C. pneumoniae strains to exquisitely sense host immune attack and respond by rapidly reverting to a persistent phase. During persistence, they reduce their metabolic levels, halting progression of their developmental cycle, waiting until the hostile external conditions have passed before they reemerge.