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.

Servitization:revisiting the state-of-the-art and research priorities

Purpose – This paper consolidates the servitization knowledge base from an organisational change perspective, identifying developed, developing and undeveloped topics to provide a platform that directs future research. Design/methodology/approach – This paper addresses three objectives : a) it comprehensively examines organisational change management literature for selection of a theoretical framework, b) it classifies extant studies within the framework through a systemic literature review, and (c) it analyses 232 selected papers and proposes a research agenda. Findings – Analysis suggests increasing global awareness of the importance of services to manufacturers. However, some topics, especially related to servitization transformation, remain undeveloped. Research limitations/implications – Although the authors tried to include all publications relevant to servitization, some might not have been captured. Evaluation and interpretation relied on the research team and subsequent research workshops. Practical implications - One of the most significant challenges for practitioners of servitization is how to transform a manufacturing organisation to exploit the opportunity. This paper consolidates literature regarding servitization, identifying progress concerning key research topics and contributing a platform for future research. The goal is to inform research to result eventually in a roadmap for practitioners seeking to servitize. Originality/value - Although extant reviews of servitization identify themes that are examined well, they struggle to identify unanswered questions. This paper addresses this gap by focusing on servitization as a process of organisational change.

Constructing communism in the Romanian People's Republic. Orthodoxy and state, 1948 - 49

This article analyses the ambiguous and contradictory relationship between the Orthodox Church and the communist regime during the first two years of the Romanian People's Republic. The installation of communism and the process of Stalinisation led to an unprecedented control of the church. The church was actively employed in propaganda and the regime imposed its own people in the hierarchy. On the one hand, Romanian communists followed the Soviet model regarding the place of the church in the communist state while, on the other hand, the church hierarchy adapted to the new political system by creating a theory of 'social apostolate'. Lacking popular support, the communists used the church as an instrument through which they could acquire the political support of the masses. The church thus enjoyed a favoured position in society mainly because the communists employed it in their ideological expansionism and confrontation with the West.

Bottom-up risk regulation? How nanotechnology risk knowledge gaps challenge federal and state environmental agencies

Nanotechnologies have been called the "Next Industrial Revolution." At the same time, scientists are raising concerns about the potential health and environmental risks related to the nano-sized materials used in nanotechnologies. Analyses suggest that current U.S. federal regulatory structures are not likely to adequately address these risks in a proactive manner. Given these trends, the premise of this paper is that state and local-level agencies will likely deal with many "end-of-pipe" issues as nanomaterials enter environmental media without prior toxicity testing, federal standards, or emissions controls. In this paper we (1) briefly describe potential environmental risks and benefits related to emerging nanotechnologies; (2) outline the capacities of the Toxic Substances Control Act, the Clean Air Act, the Clean Water Act, and the Resources Conservation and Recovery Act to address potential nanotechnology risks, and how risk data gaps challenge these regulations; (3) outline some of the key data gaps that challenge state-level regulatory capacities to address nanotechnologies' potential risks, using Wisconsin as a case study; and (4) discuss advantages and disadvantages of state versus federal approaches to nanotechnology risk regulation. In summary, we suggest some ways government agencies can be better prepared to address nanotechnology risk knowledge gaps and risk management.

Evolutionary neurobiology and art

In his important book on evolutionary theory, Darwin's Dangerous Idea, Daniel Dennett warns that Darwin's idea seeps through every area of human discourse like a "universal acid" (Dennett, 1995). Art and the aesthetic response cannot escape its influence. So my approach in this chapter is essentially naturalistic. Friedrich Nietzsche writes of observing the human comedy from afar, "like a cold angel...without anger, but without warmth" (Nietzsche, 1872, p. 164). Whether Nietzsche, of all people, could have done this is a matter of debate. But we know what he means. It describes a stance outside the human world as if looking down on human folly from Mount Olympus. From this stance, humans, their art and neurology are all part of the natural world, all part of the evolutionary process, the struggle for existence. The anthropologist David Dutton, in his contribution to the Routledge Companion to Aesthetics, says that all humans have an aesthetic sense (Dutton, 2001). It is a human universal. Biologists argue that such universals have an evolutionary basis. Furthermore, many have argued that not only humans but also animals, at least the higher mammals and birds, have an appreciation of the beautiful and the ugly (Eibl-Eibesfeldt, 1988).11Charles Darwin indeed writes "Birds appear to be the most aesthetic of all animals, excepting, of course, man, and they have nearly the same sense of the beautiful that we have" (1871, The Descent of Man and Selection in Relation to Sex, London: John Murray, vol.2, xiii, 39). This again suggests that aesthetics has an evolutionary origin. In parenthesis here, I should perhaps say that I am well aware of the criticism leveled at evolutionary psychology. I am well aware that it has been attacked as just so many "just-so" stories. This is neither the time nor the place to mount a defense but simply just to say that I believe that a defense is eminently feasible. © 2006 Elsevier Inc. All rights reserved.

Mathematical modelling and control of agitated extraction columns

Liquid-liquid extraction has long been known as a unit operation that plays an important role in industry. This process is well known for its complexity and sensitivity to operation conditions. This thesis presents an attempt to explore the dynamics and control of this process using a systematic approach and state of the art control system design techniques. The process was studied first experimentally under carefully selected. operation conditions, which resembles the ranges employed practically under stable and efficient conditions. Data were collected at steady state conditions using adequate sampling techniques for the dispersed and continuous phases as well as during the transients of the column with the aid of a computer-based online data logging system and online concentration analysis. A stagewise single stage backflow model was improved to mimic the dynamic operation of the column. The developed model accounts for the variation in hydrodynamics, mass transfer, and physical properties throughout the length of the column. End effects were treated by addition of stages at the column entrances. Two parameters were incorporated in the model namely; mass transfer weight factor to correct for the assumption of no mass transfer in the. settling zones at each stage and the backmixing coefficients to handle the axial dispersion phenomena encountered in the course of column operation. The parameters were estimated by minimizing the differences between the experimental and the model predicted concentration profiles at steady state conditions using non-linear optimisation technique. The estimated values were then correlated as functions of operating parameters and were incorporated in·the model equations. The model equations comprise a stiff differential~algebraic system. This system was solved using the GEAR ODE solver. The calculated concentration profiles were compared to those experimentally measured. A very good agreement of the two profiles was achieved within a percent relative error of ±2.S%. The developed rigorous dynamic model of the extraction column was used to derive linear time-invariant reduced-order models that relate the input variables (agitator speed, solvent feed flowrate and concentration, feed concentration and flowrate) to the output variables (raffinate concentration and extract concentration) using the asymptotic method of system identification. The reduced-order models were shown to be accurate in capturing the dynamic behaviour of the process with a maximum modelling prediction error of I %. The simplicity and accuracy of the derived reduced-order models allow for control system design and analysis of such complicated processes. The extraction column is a typical multivariable process with agitator speed and solvent feed flowrate considered as manipulative variables; raffinate concentration and extract concentration as controlled variables and the feeds concentration and feed flowrate as disturbance variables. The control system design of the extraction process was tackled as multi-loop decentralised SISO (Single Input Single Output) as well as centralised MIMO (Multi-Input Multi-Output) system using both conventional and model-based control techniques such as IMC (Internal Model Control) and MPC (Model Predictive Control). Control performance of each control scheme was. studied in terms of stability, speed of response, sensitivity to modelling errors (robustness), setpoint tracking capabilities and load rejection. For decentralised control, multiple loops were assigned to pair.each manipulated variable with each controlled variable according to the interaction analysis and other pairing criteria such as relative gain array (RGA), singular value analysis (SVD). Loops namely Rotor speed-Raffinate concentration and Solvent flowrate Extract concentration showed weak interaction. Multivariable MPC has shown more effective performance compared to other conventional techniques since it accounts for loops interaction, time delays, and input-output variables constraints.

"Comparing the incomparable":hospital costing and the art of medicine in post-war Britain

This paper examines the relationship between medical and hospital accounting discourses during the two decades after the 1946 National Health Service (NHS) Act for England and Wales. It argues that the departmental costing system introduced into the NHS in 1957 was concerned with the administrative aspects of hospital costliness as contemporary hospital accountants suggested that the perceived incomparability, immeasurability and uncontrollability of medical practice precluded the application of cost accounting to the clinical functions of hospitals. The paper links these suggestions to medical discourses which portrayed the practice of medicine as an intuitive and experience-based art and argues that post-war conceptions of clinical medicine represented this domain in a manner that was neither susceptible to the calculations of cost accountants nor to calculating and normalising intervention more generally. The paper concludes by suggesting that a closer engagement with medical discourses may enhance our understanding of historical as well as present day attempts to make medicine calculable.

From art for arts sake to art as means of knowing:a rationale for advancing arts-based methods in research, practice and pedagogy

This paper advances a philosophically informed rationale for the broader, reflexive and practical application of arts-based methods to benefit research, practice and pedagogy. It addresses the complexity and diversity of learning and knowing, foregrounding a cohabitative position and recognition of a plurality of research approaches, tailored and responsive to context. Appreciation of art and aesthetic experience is situated in the everyday, underpinned by multi-layered exemplars of pragmatic visual-arts narrative inquiry undertaken in the third, creative and communications sectors. Discussion considers semi-guided use of arts-based methods as a conduit for topic engagement, reflection and intersubjective agreement; alongside observation and interpretation of organically employed approaches used by participants within daily norms. Techniques span handcrafted (drawing), digital (photography), hybrid (cartooning), performance dimensions (improvised installations) and music (metaphor and structure). The process of creation, the artefact/outcome produced and experiences of consummation are all significant, with specific reflexivity impacts. Exploring methodology and epistemology, both the "doing" and its interpretation are explicated to inform method selection, replication, utility, evaluation and development of cross-media skills literacy. Approaches are found engaging, accessible and empowering, with nuanced capabilities to alter relationships with phenomena, experiences and people. By building a discursive space that reduces barriers; emancipation, interaction, polyphony, letting-go and the progressive unfolding of thoughts are supported, benefiting ways of knowing, narrative (re)construction, sensory perception and capacities to act. This can also present underexplored researcher risks in respect to emotion work, self-disclosure, identity and agenda. The paper therefore elucidates complex, intricate relationships between form and content, the represented and the representation or performance, researcher and participant, and the self and other. This benefits understanding of phenomena including personal experience, sensitive issues, empowerment, identity, transition and liminality. Observations are relevant to qualitative and mixed methods researchers and a multidisciplinary audience, with explicit identification of challenges, opportunities and implications.