Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8+ T-cell epitopes

Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. ‘EBV-positive DLBCL of the elderly’ (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EBNA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.

Positively playful : when videogames lead to player wellbeing

Videogames are an increasingly popular entertainment choice, yet we have a limited understanding of their potential wellbeing benefits. The current research used an online survey (N = 429) to investigate how gameplay choices and the psychological experience of gameplay impact on player wellbeing. Specifically, a hierarchical multiple regression was conducted to determine if, controlling for age and gender, current gameplay choices (amount of play, game genre, mode of play) and play experience (flow, psychological need satisfaction) predicted current wellbeing. Results indicated that age, social play, relatedness during gameplay and flow were positively associated with player wellbeing. Implications for our understanding of player wellbeing, as well as directions for future research are discussed.

Aqueous phase synthesis of copper nanoparticles : a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems

We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii. This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase. Electrochemical analysis of bacterial cells exposed to Cu2+ ions provides new insights into the mechanistic aspect of Cu2+ ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction. The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.

“Who decides?” Security and privacy in the wild

Even though web security protocols are designed to make computer communication secure, it is widely known that there is potential for security breakdowns at the human-machine interface. This paper examines findings from a qualitative study investigating the identification of security decisions used on the web. The study was designed to uncover how security is perceived in an individual user's context. Study participants were tertiary qualified individuals, with a focus on HCI designers, security professionals and the general population. The study identifies that security frameworks for the web are inadequate from an interaction perspective, with even tertiary qualified users having a poor or partial understanding of security, of which they themselves are acutely aware. The result is that individuals feel they must protect themselves on the web. The findings contribute a significant mapping of the ways in which individuals reason and act to protect themselves on the web. We use these findings to highlight the need to design for trust at three levels, and the need to ensure that HCI design does not impact on the users' main identified protection mechanism: separation.

Understanding player threat responses in FPS games

This paper describes the results of a study designed to understand the components contributing to a participant's assessment of threatening situations in a competitive First Person Shooter (FPS) game Quake III: Arena. The analysis process described compares theoretical, questionnaire based data with that of actual game play footage and identifies how skill and experience can affect a player's ability to accurately assess threat. This research also identifies relationships between variables contributing to a participant's threat assessment process which are not usually acknowledged in game AI design. A suggestion for integrating player-like threat based decision making processes is proposed.

Curiosity to cupboard : self reported disengagement with energy use feedback over time

This paper discusses findings made during a study of energy use feedback in the home (eco-feedback), well after the novelty has worn off. Contributing towards four important knowledge gaps in the research, we explore eco-feedback over longer time scales, focusing on instances where the feedback was not of lasting benefit to users rather than when it was. Drawing from 23 semi-structured interviews with Australian householders, we found that an initially high level of engagement gave way over time to disinterest, neglect and in certain cases, technical malfunction. Additionally, preconceptions concerned with the “purpose” of the feedback were found to affect use. We propose expanding the scope of enquiry for eco-feedback in several ways, and describe how eco-feedback that better supports decision-making in the “maintenance phase”, i.e. once the initial novelty has worn off, may be key to longer term engagement.

Redisplacement by design

Recently, researchers have noted that traditional knowledge systems (TKSs) can inspire technology design. They have also noted that the interdependency between Aboriginal culture and “landscape” provides insight into an embodied approach to HCI [1]: People’s experience of place and construction of space does not separate the mind, the body, and the surroundings [2]. However, we notice that increased recognition of Aboriginal TKS is no easy panacea for the constraints on design prescribed by the way the “technology race” (pun intended) abstracts spaces. Instead, paradoxes for the cultural “localization” of technology, mentioned in previous columns in this series, emerge from complex power relations between TKSs and dominant knowledge.

The role of epigenetics in resistance to cisplatin chemotherapy in lung cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

C. elegans RNA-dependent RNA polymerases rrf-1 and ego-1 silence Drosophila transgenes by differing mechanisms

Drosophila possesses the core gene silencing machinery but, like all insects, lacks the canonical RNA-dependent RNA polymerases (RdRps) that in C. elegans either trigger or enhance two major small RNA-dependent gene silencing pathways. Introduction of two different nematode RdRps into Drosophila showed them to be functional, resulting in differing silencing activities. While RRF-1 enhanced transitive dsRNA-dependent silencing, EGO-1 triggered dsRNA-independent silencing, specifically of transgenes. The strain w; da-Gal4; UAST-ego-1, constitutively expressing ego-1, is capable of silencing transgene including dsRNA hairpin upon a single cross, which created a powerful tool for research in Drosophila. In C. elegans, EGO-1 is involved in transcriptional gene silencing (TGS) of chromosome regions that are unpaired during meiosis. There was no opportunity for meiotic interactions involving EGO-1 in Drosophila that would explain the observed transgene silencing. Transgene DNA is, however, unpaired during the pairing of chromosomes in embryonic mitosis that is an unusual characteristic of Diptera, suggesting that in Drosophila, EGO-1 triggers transcriptional silencing of unpaired DNA during embryonic mitosis. © 2012 Springer Basel.

The Enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation

The P0 protein of poleroviruses and P1 protein of sobemoviruses suppress the plant's RNA silencing machinery. Here we identified a silencing suppressor protein (SSP), P0PE, in the Enamovirus Pea enation mosaic virus-1 (PEMV-1) and showed that it and the P0s of poleroviruses Potato leaf roll virus and Cereal yellow dwarf virus have strong local and systemic SSP activity, while the P1 of Sobemovirus Southern bean mosaic virus supresses systemic silencing. The nuclear localized P0PE has no discernable sequence conservation with known SSPs, but proved to be a strong suppressor of local silencing and a moderate suppressor of systemic silencing. Like the P0s from poleroviruses, P0PE destabilizes AGO1 and this action is mediated by an F-box-like domain. Therefore, despite the lack of any sequence similarity, the poleroviral and enamoviral SSPs have a conserved mode of action upon the RNA silencing machinery. © 2012 Elsevier Inc.

Testing second order cyclostationarity in the squared envelope spectrum of non-white vibration signals

Cyclostationary models for the diagnostic signals measured on faulty rotating machineries have proved to be successful in many laboratory tests and industrial applications. The squared envelope spectrum has been pointed out as the most efficient indicator for the assessment of second order cyclostationary symptoms of damages, which are typical, for instance, of rolling element bearing faults. In an attempt to foster the spread of rotating machinery diagnostics, the current trend in the field is to reach higher levels of automation of the condition monitoring systems. For this purpose, statistical tests for the presence of cyclostationarity have been proposed during the last years. The statistical thresholds proposed in the past for the identification of cyclostationary components have been obtained under the hypothesis of having a white noise signal when the component is healthy. This need, coupled with the non-white nature of the real signals implies the necessity of pre-whitening or filtering the signal in optimal narrow-bands, increasing the complexity of the algorithm and the risk of losing diagnostic information or introducing biases on the result. In this paper, the authors introduce an original analytical derivation of the statistical tests for cyclostationarity in the squared envelope spectrum, dropping the hypothesis of white noise from the beginning. The effect of first order and second order cyclostationary components on the distribution of the squared envelope spectrum will be quantified and the effectiveness of the newly proposed threshold verified, providing a sound theoretical basis and a practical starting point for efficient automated diagnostics of machine components such as rolling element bearings. The analytical results will be verified by means of numerical simulations and by using experimental vibration data of rolling element bearings.

Dynamic effects of electrical pitting in steam-turbine tilting-pad thrust-bearings

This paper merges the analysis of a case history and the simplified theoretical model related to a rather singular phenomenon that may happen in rotating machinery. Starting from the first, a small industrial steam turbine experienced a very strange behavior during megawatt load. When the unit was approaching the maximum allowed power, the temperature of the babbitt metal of the pads of the thrust bearing showed constant increase with an unrecoverable drift. Bearing inspection showed that pad trailing edge had the typical aspect of electrical pitting. This kind of damage was not reparable and bearing pads had to replaced. This problem occurred several times in sequence and was solved only by adding further ground brushes to the shaft-line. Failure analysis indicated electrodischarge machining as the root fault. A specific model, able to take into consideration the effect of electrical pitting and loading capacity decreasing as a consequence of the damage of the babbitt metal, is proposed in the paper and shows that the phenomenon causes the irretrievable failure of the thrust bearing.

Order tracking for discrete-random separation in variable speed conditions

The transmission path from the excitation to the measured vibration on the surface of a mechanical system introduces a distortion both in amplitude and in phase. Moreover, in variable speed conditions, the amplification/attenuation and the phase shift, due to the transfer function of the mechanical system, varies in time. This phenomenon reduces the effectiveness of the traditionally tachometer based order tracking, compromising the results of a discrete-random separation performed by a synchronous averaging. In this paper, for the first time, the extent of the distortion is identified both in the time domain and in the order spectrum of the signal, highlighting the consequences for the diagnostics of rotating machinery. A particular focus is given to gears, providing some indications on how to take advantage of the quantification of the disturbance to better tune the techniques developed for the compensation of the distortion. The full theoretical analysis is presented and the results are applied to an experimental case.

Signal Processing Diagnostic Tool for Rolling Element Bearings Using EMD and MED

The signal processing techniques developed for the diagnostics of mechanical components operating in stationary conditions are often not applicable or are affected by a loss of effectiveness when applied to signals measured in transient conditions. In this chapter, an original signal processing tool is developed exploiting some data-adaptive techniques such as Empirical Mode Decomposition, Minimum Entropy Deconvolution and the analytical approach of the Hilbert transform. The tool has been developed to detect localized faults on bearings of traction systems of high speed trains and it is more effective to detect a fault in non-stationary conditions than signal processing tools based on envelope analysis or spectral kurtosis, which represent until now the landmark for bearings diagnostics.

Diagnostic of Rolling Element Bearings with Envelope Analysis in Non-Stationary Conditions

In the field of rolling element bearing diagnostics, envelope analysis has gained in the last years a leading role among the different digital signal processing techniques. The original constraint of constant operating speed has been relaxed thanks to the combination of this technique with the computed order tracking, able to resample signals at constant angular increments. In this way, the field of application of this technique has been extended to cases in which small speed fluctuations occur, maintaining high effectiveness and efficiency. In order to make this algorithm suitable to all industrial applications, the constraint on speed has to be removed completely. In fact, in many applications, the coincidence of high bearing loads, and therefore high diagnostic capability, with acceleration-deceleration phases represents a further incentive in this direction. This chapter presents a procedure for the application of envelope analysis to speed transients. The effect of load variation on the proposed technique will be also qualitatively addressed.