IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms

Interleukin(IL)-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa) was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM)/B4H7-luc. RM1 and RM1(BM)/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4). IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ) completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4+ and CD8+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1−/− mice or in mice depleted of CD4+ and/or CD8+ cells than in normal mice. The tumors in RAG1−/− mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

Context-aware rate-adaptive beaconing for efficient and scalable vehicular safety communication

Vehicular safety applications, such as cooperative collision warning systems, rely on beaconing to provide situational awareness that is needed to predict and therefore to avoid possible collisions. Beaconing is the continual exchange of vehicle motion-state information, such as position, speed, and heading, which enables each vehicle to track its neighboring vehicles in real time. This work presents a context-aware adaptive beaconing scheme that dynamically adapts the beaconing repetition rate based on an estimated channel load and the danger severity of the interactions among vehicles. The safety, efficiency, and scalability of the new scheme is evaluated by simulating vehicle collisions caused by inattentive drivers under various road traffic densities. Simulation results show that the new scheme is more efficient and scalable, and is able to improve safety better than the existing non-adaptive and adaptive rate schemes.

Adaptive subcarrier allocation in multiuser OFDM system using forced cost based decisions

Subcarrier allocation scheme for Orthogonal Frequency Division Multiplexing(OFDM) based multiuser system is proposed. Most previous algorithms use greedy approach as a subcarrier allocation scheme until a conflict occurs or as an initial first round allocation with improvement steps carried out in next rounds. Our algorithm uses information obtained by the forced costs of a system that incur by a current allocation to make assignment decisions. This algorithm does not rely on greedy approach and therefore can also be considered as a substitute for first layer Greedy algorithms. Simulation results show that for two user case this algorithm gives better or equal allocation 80-90 percent of the time when compared with the greedy allocation.

Adaptive evolution of color vision as seen through the eyes of butterflies

Butterflies and primates are interesting for comparative color vision studies, because both have evolved middle- (M) and long-wavelength- (L) sensitive photopigments with overlapping absorbance spectrum maxima (lambda(max) values). Although positive selection is important for the maintenance of spectral variation within the primate pigments, it remains an open question whether it contributes similarly to the diversification of butterfly pigments. To examine this issue, we performed epimicrospectrophotometry on the eyes of five Limenitis butterfly species and found a 31-nm range of variation in the lambda(max) values of the L-sensitive photopigments (514-545 nm). We cloned partial Limenitis L opsin gene sequences and found a significant excess of replacement substitutions relative to polymorphisms among species. Mapping of these L photopigment lambda(max) values onto a phylogeny revealed two instances within Lepidoptera of convergently evolved L photopigment lineages whose lambda(max) values were blue-shifted. A codon-based maximum-likelihood analysis indicated that, associated with the two blue spectral shifts, four amino acid sites (Ile17Met, Ala64Ser, Asn70Ser, and Ser137Ala) have evolved substitutions in parallel and exhibit significant d(N)/d(S) >1. Homology modeling of the full-length Limenitis arthemis astyanax L opsin placed all four substitutions within the chromophore-binding pocket. Strikingly, the Ser137Ala substitution is in the same position as a site that in primates is responsible for a 5- to 7-nm blue spectral shift. Our data show that some of the same amino acid sites are under positive selection in the photopigments of both butterflies and primates, spanning an evolutionary distance >500 million years.

Tangible cultural heritage and adaptive reuse: the Old Government House, Brisbane, Australia

The Old Government House, a former residence of the Queen’s representatives in Brisbane, Australia, symbolises British cultural heritage of Colonial Queensland. Located on the campus of the Queensland University of Technology, it is one of the oldest surviving examples of a stately residence in Queensland. Built in 1860s, the Old Government House was originally intended as a temporary residence for the first governor of the newly independent colony of Queensland. However, it remained the vice-regal residence until 1909, serving eleven succeeding governors. Nearly seven decades later, it became the first building in Queensland to be protected under heritage legislation. Thus its importance, as an excellent exemplar that demonstrates the significance of cultural heritage, was established. The Old Government House has survived 150 years of restoration work, refurbishments, and additions. Through these years, it has served the people of Queensland in a multitude of roles. This paper aims to investigate the survival of heritage listed buildings through their adaptive re-use. Its focus will be on the adaptive reuse of the Old Government House through its refurbishments and additions over a period of 150 years. Through a qualitative research process this paper will endeavour to establish the significance of restoration work on the Old Government house; the new opportunities that has opened up as a result of the restoration work; the continued maintenance and management of the building through adaptive re-use; the economic benefits of restoration work; and its contribution to the on-going interest in the preservation of the Tangible Cultural Heritage.

Recombination hotspots and host susceptibility modulate the adaptive value of recombination during maize streak virus evolution

Background Maize streak virus -strain A (MSV-A; Genus Mastrevirus, Family Geminiviridae), the maize-adapted strain of MSV that causes maize streak disease throughout sub-Saharan Africa, probably arose between 100 and 200 years ago via homologous recombination between two MSV strains adapted to wild grasses. MSV recombination experiments and analyses of natural MSV recombination patterns have revealed that this recombination event entailed the exchange of the movement protein - coat protein gene cassette, bounded by the two genomic regions most prone to recombination in mastrevirus genomes; the first surrounding the virion-strand origin of replication, and the second around the interface between the coat protein gene and the short intergenic region. Therefore, aside from the likely adaptive advantages presented by a modular exchange of this cassette, these specific breakpoints may have been largely predetermined by the underlying mechanisms of mastrevirus recombination. To investigate this hypothesis, we constructed artificial, low-fitness, reciprocal chimaeric MSV genomes using alternating genomic segments from two MSV strains; a grass-adapted MSV-B, and a maize-adapted MSV-A. Between them, each pair of reciprocal chimaeric genomes represented all of the genetic material required to reconstruct - via recombination - the highly maize-adapted MSV-A genotype, MSV-MatA. We then co-infected a selection of differentially MSV-resistant maize genotypes with pairs of reciprocal chimaeras to determine the efficiency with which recombination would give rise to high-fitness progeny genomes resembling MSV-MatA. Results Recombinants resembling MSV-MatA invariably arose in all of our experiments. However, the accuracy and efficiency with which the MSV-MatA genotype was recovered across all replicates of each experiment depended on the MSV susceptibility of the maize genotypes used and the precise positions - in relation to known recombination hotspots - of the breakpoints required to re-create MSV-MatA. Although the MSV-sensitive maize genotype gave rise to the greatest variety of recombinants, the measured fitness of each of these recombinants correlated with their similarity to MSV-MatA. Conclusions The mechanistic predispositions of different MSV genomic regions to recombination can strongly influence the accessibility of high-fitness MSV recombinants. The frequency with which the fittest recombinant MSV genomes arise also correlates directly with the escalating selection pressures imposed by increasingly MSV-resistant maize hosts.

An interactive and adaptive building layer : strategies for allowing people to become advanced building-users

This paper reports outcomes of a pilot study to develop a conceptual framework to allow people to retrofit a building-layer to gain better control of their own built- environments. The study was initiated by the realisation that discussions surrounding the improvement of building performances tend to be about top-down technological solutions rather than to help and encourage bottom-up involvement of building-users. While users are the ultimate beneficiaries and their feedback is always appreciated, their direct involvements in managing buildings would often be regarded as obstruction or distraction. This is largely because casual interventions by uninformed building-users tend to disrupt the system. Some earlier researches showed however that direct and active participation of users could improve the building performance if appropriate training and/or systems were introduced. We also speculate this in long run would also make the built environment more sustainable. With this in mind, we looked for opportunities to retrofit our own office with an interactive layer to study how we could introduce ad-hoc systems for building-users. The aim of this paper is to describe our vision and initial attempts followed by discussion.

Adaptive sizing of populations and number of islands in distributed genetic algorithms

Deciding the appropriate population size and number of is- lands for distributed island-model genetic algorithms is often critical to the algorithm’s success. This paper outlines a method that automatically searches for good combinations of island population sizes and the number of islands. The method is based on a race between competing parameter sets, and collaborative seeding of new parameter sets. This method is applicable to any problem, and makes distributed genetic algorithms easier to use by reducing the number of user-set parameters. The experimental results show that the proposed method robustly and reliably finds population and islands settings that are comparable to those found with traditional trial-and-error approaches.

Threshold concepts in property education : a case study

First year Property Economics students enrolled in the Bachelor of Urban Development at QUT are required to undertake a number of compulsory subjects, alongside students undertaking studies in other disciplines. One such common unit is ‘Stewardship of Land’, an interdisciplinary unit that introduces students to the characteristics of land and land tenure with a focus on land use and property rights. It covers a range of issues including: native title, land contamination, heritage values, alternative uses, the property development process, impact of environmental and social factors, and the management of land, both urban and regional. Teaching such a diverse content to a diverse audience has in previous years proved difficult, from the perspectives of relevance, engagement and content overload. In 2011 a project was undertake to redevelop this unit to reflect ‘threshold concepts’, concepts that are “transformative, probably irreversible, integrative, often troublesome and probably bounded” (Meyer & Land, 2003) . This project involved the development of a new set of underlying concepts students should draw from the unit, application of these to the unit curriculum, and a survey of the student response to these changes. This paper reports on the threshold concepts developed for this unit, the changes this made to the unit curriculum, and a preliminary report on survey responses. Recommendations for other educators seeking to incorporate threshold concepts into their curricula are provided.

Linear adaptive channel equalization for multiuser MIMO-OFDM systems

Linear adaptive channel equalization using the least mean square (LMS) algorithm and the recursive least-squares(RLS) algorithm for an innovative multi-user (MU) MIMOOFDM wireless broadband communications system is proposed. The proposed equalization method adaptively compensates the channel impairments caused by frequency selectivity in the propagation environment. Simulations for the proposed adaptive equalizer are conducted using a training sequence method to determine optimal performance through a comparative analysis. Results show an improvement of 0.15 in BER (at a SNR of 16 dB) when using Adaptive Equalization and RLS algorithm compared to the case in which no equalization is employed. In general, adaptive equalization using LMS and RLS algorithms showed to be significantly beneficial for MU-MIMO-OFDM systems.

The other side of the threshold : Strindberg's experiments in creative dissection

A 1500-word review of Strindberg: A Life by Sue Prideaux (Yale UP, 2012). One way of classifying biographies is to divide them into those that apply their own interpretative framework – be it psychoanalytic, gender-based, socio-historical, and so on – to a given subject and those that aim to meet the subject, on their own terms, or at least in terms that the subject would recognise...

Adaptive radiotherapy for virally mediated head and neck cancer : predicting which patients may benefit most

Background: Recent clinical studies have demonstrated an emerging subgroup of head and neck cancers that are virally mediated. This disease appears to be a distinct clinical entity with patients presenting younger and with more advanced nodal disease, having lower tobacco and alcohol exposure and highly radiosensitive tumours. This means they are living longer, often with the debilitating functional side effects of treatment. The primary objective of this study was to determine how virally mediated nasopharyngeal and oropharyngeal cancers respond to radiation therapy treatment. The aim was to determine risk categories and corresponding adaptive treatment management strategies to proactively manage these patients. Method/Results: 121 patients with virally mediated, node positive nasopharyngeal or oropharyngeal cancer who received radiotherapy treatment with curative intent between 2005 and 2010 were studied. Relevant patient demographics including age, gender, diagnosis, TNM stage, pre-treatment nodal size and dose delivered was recorded. Each patient’s treatment plan was reviewed to determine if another computed tomography (re-CT) scan was performed and at what time point (dose/fraction) this occurred. The justification for this re-CT was determined using four categories: tumour and/or nodal regression, weight loss, both or other. Patients who underwent a re-CT were further investigated to determine whether a new plan was calculated. If a re-plan was performed, the dosimetric effect was quantified by comparing dose volume histograms of planning target volumes and critical structures from the actual treatment delivered and the original treatment plan. Preliminary results demonstrated that 25/121 (20.7%) patients required a re-CT and that these re-CTs were performed between fractions 20 to 25 of treatment. The justification for these re-CTs consisted of a combination of tumour and/or nodal regression and weight loss. 16/25 (13.2%) patients had a replan calculated. 9 (7.4%) of these replans were implemented clinically due to the resultant dosimetric effect calculated. The data collected from this assessment was statistically analysed to identify the major determining factors for patients to undergo a re-CT and/or replan. Specific factors identified included nodal size and timing of the required intervention (i.e. how when a plan is to be adapted). This data was used to generate specific risk profiles that will form the basis of a biologically guided adaptive treatment management strategy for virally mediated head and neck cancer. Conclusion: Preliminary data indicates that virally mediated head and neck cancers respond significantly during radiation treatment (tumour and/or nodal regression and weight loss). Implications of this response are the potential underdosing or overdosing of tumour and/or surrounding critical structures. This could lead to sub-optimal patient outcomes and compromised quality of life. Consequently, the development of adaptive treatment strategies that improve organ sparing for this patient group is important to ensure delivery of the prescribed dose to the tumour volume whilst minimizing the dose received to surrounding critical structures. This could reduce side effects and improve overall patient quality of life. The risk profiles and associated adaptive treatment approaches developed in this study will be tested prospectively in the clinical setting in Phase 2 of this investigation.

Adaptive radiotherapy for virally mediated head and neck cancer

Introduction: Clinical investigation has revealed a subgroup of head and neck cancers that are virally mediated. The relationship between nasopharyngeal cancer and Epstein Barr Virus (EBV) has long been established and more recently, the association between oropharyngeal cancer and Human Papillomavirus (HPV) has been revealed1,2 These cancers often present with nodal involvement and generally respond well to radiation treatment, evidenced by tumour regression1. This results in the need for treatment plan adaptation or re-planning in a subset of patients. Adaptive techniques allow the target region of the radiotherapy treatment plan to be altered in accordance with treatment-induced changes to ensure that under or over dosing does not occur3. It also assists in limiting potential overdosing of surrounding critical normal tissues4. We sought to identify a high-risk group based on nodal size to be evaluated in a future prospective adaptive radiotherapy trial. Method: Between 2005-2010, 121 patients with virally mediated, node positive nasopharyngeal (EBV positive) or oropharyngeal (HPV positive) cancers, receiving curative intent radiotherapy treatment were reviewed. Patients were analysed based on maximum size of the dominant node at diagnosis with a view to grouping them in varying risk categories to determine the need of re-planning. The frequency and timing of the re-planning scans were also evaluated. Results: Sixteen nasopharyngeal and 105 oropharyngeal tumours were reviewed. Twenty-five (21%) patients underwent a re-planning CT at a median of 22 (range, 0-29) fractions with 1 patient requiring re-planning prior to the commencement of treatment. Based on the analysis, patients were subsequently placed into risk categories; ≤35mm (Group 1), 36-45mm (Group 2), ≥46mm (Group 3). Re-planning CT’s were performed in Group 1- 8/68 (11.8%), Group 2- 4/28 (14.3%), Group 3- 13/25 (52%). Conclusion: In this series, patients with virally mediated head and neck cancer and nodal size > 46mm appear to be a high-risk group for the need of re-planning during a course of curative radiotherapy. This finding will now be tested in a prospective adaptive radiotherapy study. ‘Real World’ Implications: This research identifies predictive factors for those patients with virally mediated head and neck cancer that will benefit most from treatment adaptation. This will assist in minimising the side effects experienced by these patients thereby improving their quality of life after treatment.