T-cell epitope prediction and immune complex simulation using molecular dynamics:state of the art and persisting challenges

Atomistic Molecular Dynamics provides powerful and flexible tools for the prediction and analysis of molecular and macromolecular systems. Specifically, it provides a means by which we can measure theoretically that which cannot be measured experimentally: the dynamic time-evolution of complex systems comprising atoms and molecules. It is particularly suitable for the simulation and analysis of the otherwise inaccessible details of MHC-peptide interaction and, on a larger scale, the simulation of the immune synapse. Progress has been relatively tentative yet the emergence of truly high-performance computing and the development of coarse-grained simulation now offers us the hope of accurately predicting thermodynamic parameters and of simulating not merely a handful of proteins but larger, longer simulations comprising thousands of protein molecules and the cellular scale structures they form. We exemplify this within the context of immunoinformatics.

A hierarchical localization scheme for large scale underwater wireless sensor networks

In this paper, we study the localization problem in large-scale Underwater Wireless Sensor Networks (UWSNs). Unlike in the terrestrial positioning, the global positioning system (GPS) can not work efficiently underwater. The limited bandwidth, the severely impaired channel and the cost of underwater equipment all makes the localization problem very challenging. Most current localization schemes are not well suitable for deep underwater environment. We propose a hierarchical localization scheme to address the challenging problems. The new scheme mainly consists of four types of nodes, which are surface buoys, Detachable Elevator Transceivers (DETs), anchor nodes and ordinary nodes. Surface buoy is assumed to be equipped with GPS on the water surface. A DET is attached to a surface buoy and can rise and down to broadcast its position. The anchor nodes can compute their positions based on the position information from the DETs and the measurements of distance to the DETs. The hierarchical localization scheme is scalable, and can be used to make balances on the cost and localization accuracy. Initial simulation results show the advantages of our proposed scheme. © 2009 IEEE.

Large-scale molecular dynamics simulations of HLA-A*0201 complexed with a tumor-specific antigenic peptide:can the α3 and β2m domains be neglected?

Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histo-compatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVY-DGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available Large-scale massively parallel molecular dynamics (MD) simulations of the human class I major histocompatibility complex (MHC) protein HLA-A*0201 bound to a decameric tumor-specific antigenic peptide GVYDGREHTV were performed using a scalable MD code on high-performance computing platforms. Such computational capabilities put us in reach of simulations of various scales and complexities. The supercomputing resources available for this study allow us to compare directly differences in the behavior of very large molecular models; in this case, the entire extracellular portion of the peptide–MHC complex vs. the isolated peptide binding domain. Comparison of the results from the partial and the whole system simulations indicates that the peptide is less tightly bound in the partial system than in the whole system. From a detailed study of conformations, solvent-accessible surface area, the nature of the water network structure, and the binding energies, we conclude that, when considering the conformation of the α1–α2 domain, the α3 and β2m domains cannot be neglected. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1803–1813, 2004

Computational modelling approaches to vaccinology

Excepting the Peripheral and Central Nervous Systems, the Immune System is the most complex of somatic systems in higher animals. This complexity manifests itself at many levels from the molecular to that of the whole organism. Much insight into this confounding complexity can be gained through computational simulation. Such simulations range in application from epitope prediction through to the modelling of vaccination strategies. In this review, we evaluate selectively various key applications relevant to computational vaccinology: these include technique that operates at different scale that is, from molecular to organisms and even to population level.

High-performance liquid chromatography and pharmacokinetics of some antibiotics

The principles of High Performance Liquid Chromatography (HPLC) and pharmacokinetics were applied to the use of several clinically-important drugs at the East Birmingham Hospital. Amongst these was gentamicin, which was investigated over a two-year period by a multi-disciplinary team. It was found that there was considerable intra- and inter-patient variation that had not previously been reported and the causes and consequences of such variation were considered. A detailed evaluation of available pharmacokinetic techniques was undertaken and 1- and 2-compartment models were optimised with regard to sampling procedures, analytical error and model-error. The implications for control of therapy are discussed and an improved sampling regime is proposed for routine usage. Similar techniques were applied to trimethoprim, assayed by HPLC, in patients with normal renal function and investigations were also commenced into the penetration of drug into peritoneal dialysate. Novel assay techniques were also developed for a range of drugs including 4-aminopyridine, chloramphenicol, metronidazole and a series of penicillins and cephalosporins. Stability studies on cysteamine, reaction-rate studies on creatinine-picrate and structure-activity relationships in HPLC of aminopyridines are also reported.

High performance numerical modeling of ultra-short laser pulse propagation based on multithreaded parallel hardware

The focus of this study is development of parallelised version of severely sequential and iterative numerical algorithms based on multi-threaded parallel platform such as a graphics processing unit. This requires design and development of a platform-specific numerical solution that can benefit from the parallel capabilities of the chosen platform. Graphics processing unit was chosen as a parallel platform for design and development of a numerical solution for a specific physical model in non-linear optics. This problem appears in describing ultra-short pulse propagation in bulk transparent media that has recently been subject to several theoretical and numerical studies. The mathematical model describing this phenomenon is a challenging and complex problem and its numerical modeling limited on current modern workstations. Numerical modeling of this problem requires a parallelisation of an essentially serial algorithms and elimination of numerical bottlenecks. The main challenge to overcome is parallelisation of the globally non-local mathematical model. This thesis presents a numerical solution for elimination of numerical bottleneck associated with the non-local nature of the mathematical model. The accuracy and performance of the parallel code is identified by back-to-back testing with a similar serial version.

Leveraging employee creativity through high performance work systems:a multilevel perspective

Research has looked at single rather than a configuration of human resource management (HRM) practices to influence creativity so it is not yet clear how these practices synergistically facilitate creativity and organisational performance. I address this significant but unanswered question in a three-part study. In Study 1, I develop a high performance work system (HPWS) for creativity scale. I use Study 2 sample to test the validity of the new scale. In Study 3, I test a multilevel model of the intervening processes through which branch HPWS for creativity influences creativity and branch performance. Specifically, at the branch level, I draw on social context theory and hypothesise that branch HPWS for creativity relates to climate for creativity which, in turn, leads to creativity, and ultimately, to profit. Furthermore, I hypothesise environmental dynamism as a boundary condition of the creativity-profit relationship. At the individual level, I hypothesise a cross-level effect of branch HPWS for creativity on employee-perceived HPWS. I draw on self-determination theory and argue that perceived HPWS for creativity relate to need satisfaction and the psychological pathways of intrinsic motivation and creative process engagement to predict creativity. I also hypothesise climate for creativity as a cross-level moderator of the intrinsic motivation-creativity and creative process engagement-creativity relationships. Results of hierarchical linear modeling (HLM) indicate that ten out of the fifteen hypotheses were supported. The findings of this study respond to calls for HPWS to be designed around a strategic focus by developing and providing initial validity evidence of an HPWS for creativity scale. The results reveal the underlying mechanisms through which HPWS for creativity simultaneously influences individual and branch creativity leading to profit. Lastly, results indicate environmental dynamism to be an important boundary condition of the creativity-profit relationship and climate for creativity as a cross-level moderator of the creative process engagement-creativity.

High performance liquid level monitoring system based on polymer fiber Bragg gratings embedded in silicone rubber diaphragm

Liquid-level sensing technologies have attracted great prominence, because such measurements are essential to industrial applications, such as fuel storage, flood warning and in the biochemical industry. Traditional liquid level sensors are based on electromechanical techniques; however they suffer from intrinsic safety concerns in explosive environments. In recent years, given that optical fiber sensors have lots of well-established advantages such as high accuracy, costeffectiveness, compact size, and ease of multiplexing, several optical fiber liquid level sensors have been investigated which are based on different operating principles such as side-polishing the cladding and a portion of core, using a spiral side-emitting optical fiber or using silica fiber gratings. The present work proposes a novel and highly sensitive liquid level sensor making use of polymer optical fiber Bragg gratings (POFBGs). The key elements of the system are a set of POFBGs embedded in silicone rubber diaphragms. This is a new development building on the idea of determining liquid level by measuring the pressure at the bottom of a liquid container, however it has a number of critical advantages. The system features several FBG-based pressure sensors as described above placed at different depths. Any sensor above the surface of the liquid will read the same ambient pressure. Sensors below the surface of the liquid will read pressures that increase linearly with depth. The position of the liquid surface can therefore be approximately identified as lying between the first sensor to read an above-ambient pressure and the next higher sensor. This level of precision would not in general be sufficient for most liquid level monitoring applications; however a much more precise determination of liquid level can be made by linear regression to the pressure readings from the sub-surface sensors. There are numerous advantages to this multi-sensor approach. First, the use of linear regression using multiple sensors is inherently more accurate than using a single pressure reading to estimate depth. Second, common mode temperature induced wavelength shifts in the individual sensors are automatically compensated. Thirdly, temperature induced changes in the sensor pressure sensitivity are also compensated. Fourthly, the approach provides the possibility to detect and compensate for malfunctioning sensors. Finally, the system is immune to changes in the density of the monitored fluid and even to changes in the effective force of gravity, as might be obtained in an aerospace application. The performance of an individual sensor was characterized and displays a sensitivity (54 pm/cm), enhanced by more than a factor of 2 when compared to a sensor head configuration based on a silica FBG published in the literature, resulting from the much lower elastic modulus of POF. Furthermore, the temperature/humidity behavior and measurement resolution were also studied in detail. The proposed configuration also displays a highly linear response, high resolution and good repeatability. The results suggest the new configuration can be a useful tool in many different applications, such as aircraft fuel monitoring, and biochemical and environmental sensing, where accuracy and stability are fundamental. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Towards a multilevel model of the high performance work systems–workplace safety relationship

Human Resource (HR) systems and practices generally referred to as High Performance Work Practices (HPWPs), (Huselid, 1995) (sometimes termed High Commitment Work Practices or High Involvement Work Practices) have attracted much research attention in past decades. Although many conceptualizations of the construct have been proposed, there is general agreement that HPWPs encompass a bundle or set of HR practices including sophisticated staffing, intensive training and development, incentive-based compensation, performance management, initiatives aimed at increasing employee participation and involvement, job safety and security, and work design (e.g. Pfeffer, 1998). It is argued that these practices either directly and indirectly influence the extent to which employees’ knowledge, skills, abilities, and other characteristics are utilized in the organization. Research spanning nearly 20 years has provided considerable empirical evidence for relationships between HPWPs and various measures of performance including increased productivity, improved customer service, and reduced turnover (e.g. Guthrie, 2001; Belt & Giles, 2009). With the exception of a few papers (e.g., Laursen &Foss, 2003), this literature appears to lack focus on how HPWPs influence or foster more innovative-related attitudes and behaviours, extra role behaviors, and performance. This situation exists despite the vast evidence demonstrating the importance of innovation, proactivity, and creativity in its various forms to individual, group, and organizational performance outcomes. Several pertinent issues arise when considering HPWPs and their relationship to innovation and performance outcomes. At a broad level is the issue of which HPWPs are related to which innovation-related variables. Another issue not well identified in research relates to employees’ perceptions of HPWPs: does an employee actually perceive the HPWP –outcomes relationship? No matter how well HPWPs are designed, if they are not perceived and experienced by employees to be effective or worthwhile then their likely success in achieving positive outcomes is limited. At another level, research needs to consider the mechanisms through which HPWPs influence –innovation and performance. The research question here relates to what possible mediating variables are important to the success or failure of HPWPs in impacting innovative behaviours and attitudes and what are the potential process considerations? These questions call for theory refinement and the development of more comprehensive models of the HPWP-innovation/performance relationship that include intermediate linkages and boundary conditions (Ferris, Hochwarter, Buckley, Harrell-Cook, & Frink, 1999). While there are many calls for this type of research to be made a high priority, to date, researchers have made few inroads into answering these questions. This symposium brings together researchers from Australia, Europe, Asia and Africa to examine these various questions relating to the HPWP-innovation-performance relationship. Each paper discusses a HPWP and potential variables that can facilitate or hinder the effects of these practices on innovation- and performance- related outcomes. The first paper by Johnston and Becker explores the HPWPs in relation to work design in a disaster response organization that shifts quickly from business as usual to rapid response. The researchers examine how the enactment of the organizational response is devolved to groups and individuals. Moreover, they assess motivational characteristics that exist in dual work designs (normal operations and periods of disaster activation) and the implications for innovation. The second paper by Jørgensen reports the results of an investigation into training and development practices and innovative work behaviors (IWBs) in Danish organizations. Research on how to design and implement training and development initiatives to support IWBs and innovation in general is surprisingly scant and often vague. This research investigates the mechanisms by which training and development initiatives influence employee behaviors associated with innovation, and provides insights into how training and development can be used effectively by firms to attract and retain valuable human capital in knowledge-intensive firms. The next two papers in this symposium consider the role of employee perceptions of HPWPs and their relationships to innovation-related variables and performance. First, Bish and Newton examine perceptions of the characteristics and awareness of occupational health and safety (OHS) practices and their relationship to individual level adaptability and proactivity in an Australian public service organization. The authors explore the role of perceived supportive and visionary leadership and its impact on the OHS policy-adaptability/proactivity relationship. The study highlights the positive main effects of awareness and characteristics of OHS polices, and supportive and visionary leadership on individual adaptability and proactivity. It also highlights the important moderating effects of leadership in the OHS policy-adaptability/proactivity relationship. Okhawere and Davis present a conceptual model developed for a Nigerian study in the safety-critical oil and gas industry that takes a multi-level approach to the HPWP-safety relationship. Adopting a social exchange perspective, they propose that at the organizational level, organizational climate for safety mediates the relationship between enacted HPWS’s and organizational safety performance (prescribed and extra role performance). At the individual level, the experience of HPWP impacts on individual behaviors and attitudes in organizations, here operationalized as safety knowledge, skills and motivation, and these influence individual safety performance. However these latter relationships are moderated by organizational climate for safety. A positive organizational climate for safety strengthens the relationship between individual safety behaviors and attitudes and individual-level safety performance, therefore suggesting a cross-level boundary condition. The model includes both safety performance (behaviors) and organizational level safety outcomes, operationalized as accidents, injuries, and fatalities. The final paper of this symposium by Zhang and Liu explores leader development and relationship between transformational leadership and employee creativity and innovation in China. The authors further develop a model that incorporates the effects of extrinsic motivation (pay for performance: PFP) and employee collectivism in the leader-employee creativity relationship. The papers’ contributions include the incorporation of a PFP effect on creativity as moderator, rather than predictor in most studies; the exploration of the PFP effect from both fairness and strength perspectives; the advancement of knowledge on the impact of collectivism on the leader- employee creativity link. Last, this is the first study to examine three-way interactional effects among leader-member exchange (LMX), PFP and collectivism, thus, enriches our understanding of promoting employee creativity. In conclusion, this symposium draws upon the findings of four empirical studies and one conceptual study to provide an insight into understanding how different variables facilitate or potentially hinder the influence various HPWPs on innovation and performance. We will propose a number of questions for further consideration and discussion. The symposium will address the Conference Theme of ‘Capitalism in Question' by highlighting how HPWPs can promote financial health and performance of organizations while maintaining a high level of regard and respect for employees and organizational stakeholders. Furthermore, the focus on different countries and cultures explores the overall research question in relation to different modes or stages of development of capitalism.