Structure determination from powder diffraction data

Advances made over the past decade in structure determination from powder diffraction data are reviewed with particular emphasis on algorithmic developments and the successes and limitations of the technique. While global optimization methods have been successful in the solution of molecular crystal structures, new methods are required to make the solution of inorganic crystal structures more routine. The use of complementary techniques such as NMR to assist structure solution is discussed and the potential for the combined use of X-ray and neutron diffraction data for structure verification is explored. Structures that have proved difficult to solve from powder diffraction data are reviewed and the limitations of structure determination from powder diffraction data are discussed. Furthermore, the prospects of solving small protein crystal structures over the next decade are assessed.

Voices from the aid 'chain': The personal dynamics of care

This paper uses a simplified model of the aid 'chain' to explore some causes and consequences of breakdown in communication. Although the rhetoric of Northern-based donors is awash with words such as 'partnership' and 'inclusion' when dealing with their Southern-based partners, the situation in practice is different. Unequal power relationships sometimes result in donor imposition of Perspectives and values. It is our contention, based on a collective experience of fifty-four years in a Nigerian-based non-governmental development organization (NGDO), the Diocesan Development Services (DDS), that much of the driving force behind the successes and problems faced by the institution was founded on relationships that evolved between individuals. In order to understand why things happened the way they did it is necessary to begin with the human element that cannot be condensed into objects or categories. While injudicious donor interference bad damaging repercussions, our experience suggests that care and consideration flow throughout the aid chain and actions are not malevolent. Breakdowns can be attributed to a number of factors, with the over-riding one being pressures operating at the personal level that emanate from within the institution itself and the larger community. The paper analyses three experiences using institutional ethnography theory and methodologies as a basis. Examples taken address the influence key donor personnel had in the function of DDS, and how these changed with time. The mission, policies and even procedures of the donor did not change markedly over thirty-two years, but each changing desk officer had their own philosophy and approach and a different interpretation of their own institutional policies. Hence while the 'macro' has an influence it is mediated via individual interpretation. In our view, the importance of people-people relationships is particularly understated in development literature where emphasis gravitates towards the aggregate and global.

Predictability and skill of boreal winter forecasts made with the ECMWF Seasonal Forecasting System II

The performance of boreal winter forecasts made with the European Centre for Medium-Range Weather Forecasts (ECMWF) System 11 Seasonal Forecasting System is investigated through analyses of ensemble hindcasts for the period 1987-2001. The predictability, or signal-to-noise ratio, associated with the forecasts, and the forecast skill are examined. On average, forecasts of 500 hPa geopotential height (GPH) have skill in most of the Tropics and in a few regions of the extratropics. There is broad, but not perfect, agreement between regions of high predictability and regions of high skill. However, model errors are also identified, in particular regions where the forecast ensemble spread appears too small. For individual winters the information provided by t-values, a simple measure of the forecast signal-to-noise ratio, is investigated. For 2 m surface air temperature (T2m), highest t-values are found in the Tropics but there is considerable interannual variability, and in the tropical Atlantic and Indian basins this variability is not directly tied to the El Nino Southern Oscillation. For GPH there is also large interannual variability in t-values, but these variations cannot easily be predicted from the strength of the tropical sea-surface-temperature anomalies. It is argued that the t-values for 500 hPa GPH can give valuable insight into the oceanic forcing of the atmosphere that generates predictable signals in the model. Consequently, t-values may be a useful tool for understanding, at a mechanistic level, forecast successes and failures. Lastly, the extent to which t-values are useful as a predictor of forecast skill is investigated. For T2m, t-values provide a useful predictor of forecast skill in both the Tropics and extratropics. Except in the equatorial east Pacific, most of the information in t-values is associated with interannual variability of the ensemble-mean forecast rather than interannual variability of the ensemble spread. For GPH, however, t-values provide a useful predictor of forecast skill only in the tropical Pacific region.

Predicting magnetospheric dynamics with a coupled sun-to-Earth model: challenges and first results

Results from the first Sun-to-Earth coupled numerical model developed at the Center for Integrated Space Weather Modeling are presented. The model simulates physical processes occurring in space spanning from the corona of the Sun to the Earth's ionosphere, and it represents the first step toward creating a physics-based numerical tool for predicting space weather conditions in the near-Earth environment. Two 6- to 7-d intervals, representing different heliospheric conditions in terms of the three-dimensional configuration of the heliospheric current sheet, are chosen for simulations. These conditions lead to drastically different responses of the simulated magnetosphere-ionosphere system, emphasizing, on the one hand, challenges one encounters in building such forecasting tools, and on the other hand, emphasizing successes that can already be achieved even at this initial stage of Sun-to-Earth modeling.

Large-scale functional expression of WT and truncated human adenosine A(2A) receptor in Pichia pastoris bioreactor cultures

Background: The large-scale production of G-protein coupled receptors (GPCRs) for functional and structural studies remains a challenge. Recent successes have been made in the expression of a range of GPCRs using Pichia pastoris as an expression host. P. pastoris has a number of advantages over other expression systems including ability to post-translationally modify expressed proteins, relative low cost for production and ability to grow to very high cell densities. Several previous studies have described the expression of GPCRs in P. pastoris using shaker flasks, which allow culturing of small volumes (500 ml) with moderate cell densities (OD600 similar to 15). The use of bioreactors, which allow straightforward culturing of large volumes, together with optimal control of growth parameters including pH and dissolved oxygen to maximise cell densities and expression of the target receptors, are an attractive alternative. The aim of this study was to compare the levels of expression of the human Adenosine 2A receptor (A(2A)R) in P. pastoris under control of a methanol-inducible promoter in both flask and bioreactor cultures. Results: Bioreactor cultures yielded an approximately five times increase in cell density (OD600 similar to 75) compared to flask cultures prior to induction and a doubling in functional expression level per mg of membrane protein, representing a significant optimisation. Furthermore, analysis of a C-terminally truncated A2AR, terminating at residue V334 yielded the highest levels (200 pmol/mg) so far reported for expression of this receptor in P. pastoris. This truncated form of the receptor was also revealed to be resistant to C-terminal degradation in contrast to the WT A(2A)R, and therefore more suitable for further functional and structural studies. Conclusion: Large-scale expression of the A(2A)R in P. pastoris bioreactor cultures results in significant increases in functional expression compared to traditional flask cultures.

Structure determination from powder diffraction data

Advances made over the past decade in structure determination from powder diffraction data are reviewed with particular emphasis on algorithmic developments and the successes and limitations of the technique. While global optimization methods have been successful in the solution of molecular crystal structures, new methods are required to make the solution of inorganic crystal structures more routine. The use of complementary techniques such as NMR to assist structure solution is discussed and the potential for the combined use of X-ray and neutron diffraction data for structure verification is explored. Structures that have proved difficult to solve from powder diffraction data are reviewed and the limitations of structure determination from powder diffraction data are discussed. Furthermore, the prospects of solving small protein crystal structures over the next decade are assessed.

An examination of actors that impact technology introduction to FM

Developing and implementing a technology for Facilities Management (FM) can be a complex process. This is particularly the case when a technology impacts on an organisation as a whole. There are often a number of relevant actors, internal and external to FM, who should be engaged. This engagement is guided by the strategy of the organisation which is led by top management decisions. Indeed, it is top management who have the final decision to implement a technology. Actors of top management and other relevant actors will have their own discourses toward the implementation of the technology based on how they foresee the technology befittingly benefitting the organisation. This paper examines actors who play a relevant and necessary part in supporting and implementing a technology to FM. It examines how an actor’s discourse toward the project inhibits or speeds up the implementation of a technology. The methods used for this paper are based on a two year case study in a FM department where a technology development was observed and interviews with key participants were conducted. Critical discourse analysis is used to analyse the data. Prominent discourses that emerge from the data are emphasised during the process of introducing the technology. This research moves beyond focusing purely on project successes but examines the difficulties and the hurdles that must be overcome to reach a successful technology implementation.

Dynamic knowledge representation in connectionist systems

One of the most pervading concepts underlying computational models of information processing in the brain is linear input integration of rate coded uni-variate information by neurons. After a suitable learning process this results in neuronal structures that statically represent knowledge as a vector of real valued synaptic weights. Although this general framework has contributed to the many successes of connectionism, in this paper we argue that for all but the most basic of cognitive processes, a more complex, multi-variate dynamic neural coding mechanism is required - knowledge should not be spacially bound to a particular neuron or group of neurons. We conclude the paper with discussion of a simple experiment that illustrates dynamic knowledge representation in a spiking neuron connectionist system.

Extracting quantitative structural parameters for disordered polymers from neutron scattering data

The organization of non-crystalline polymeric materials at a local level, namely on a spatial scale between a few and 100 a, is still unclear in many respects. The determination of the local structure in terms of the configuration and conformation of the polymer chain and of the packing characteristics of the chain in the bulk material represents a challenging problem. Data from wide-angle diffraction experiments are very difficult to interpret due to the very large amount of information that they carry, that is the large number of correlations present in the diffraction patterns.We describe new approaches that permit a detailed analysis of the complex neutron diffraction patterns characterizing polymer melts and glasses. The coupling of different computer modelling strategies with neutron scattering data over a wide Q range allows the extraction of detailed quantitative information on the structural arrangements of the materials of interest. Proceeding from modelling routes as diverse as force field calculations, single-chain modelling and reverse Monte Carlo, we show the successes and pitfalls of each approach in describing model systems, which illustrate the need to attack the data analysis problem simultaneously from several fronts.

Modelling the structure of a polymer glass poly(methylmethacrylate) through neutron scattering experiments

Determination of the local structure of a polymer glass by scattering methods is complex due to the number of spatial and orientational correlations, both from within the polymer chain (intrachain) and between neighbouring chains (interchain), from which the scattering arises. Recently considerable advances have been made in the structural analysis of relatively simple polymers such as poly(ethylene) through the use of broad Q neutron scattering data tightly coupled to atomistic modelling procedures. This paper presents the results of an investigation into the use of these procedures for the analysis of the local structure of a-PMMA which is chemically more complex with a much greater number of intrachain structural parameters. We have utilised high quality neutron scattering data obtained using SANDALS at ISIS coupled with computer models representing both the single chain and bulk polymer system. Several different modelling approaches have been explored which encompass such techniques as Reverse Monte Carlo refinement and energy minimisation and their relative merits and successes are discussed. These different approaches highlight structural parameters which any realistic model of glassy atactic PMMA must replicate.

Keeping Hertfordshire green: the implementation of strategic environmental policy 1983-1993

This paper evaluates the implementation of environmental policy in the County of Hertfordshire during the 1980's and early 1990's. It emphasises that the recent growth of interest in environmental policy and sustainable planning initiatives should not cause researchers and practitioners to ignore the long history and experience of environmental policy implementation in local government. By looking at the experience of strategic environmental policy in Hertfordshire, the paper identifies the successes and failures of a range of implementation tools utilised by the County and district planning authorities to progress policies concerned with the conservation and improvement of urban and rural environments. It concludes that the planning authorities of Hertfordshire have stabilised the deterioration in the County's environment and have established some programmes which provide good examples of coordinated action in environmental policy implementation. These types of mechanism will need to be built upon in the new policy epoch where environmental sustainability and capacity planning take centre stage.

Population based models of cortical drug response: insights from anaesthesia

A great explanatory gap lies between the molecular pharmacology of psychoactive agents and the neurophysiological changes they induce, as recorded by neuroimaging modalities. Causally relating the cellular actions of psychoactive compounds to their influence on population activity is experimentally challenging. Recent developments in the dynamical modelling of neural tissue have attempted to span this explanatory gap between microscopic targets and their macroscopic neurophysiological effects via a range of biologically plausible dynamical models of cortical tissue. Such theoretical models allow exploration of neural dynamics, in particular their modification by drug action. The ability to theoretically bridge scales is due to a biologically plausible averaging of cortical tissue properties. In the resulting macroscopic neural field, individual neurons need not be explicitly represented (as in neural networks). The following paper aims to provide a non-technical introduction to the mean field population modelling of drug action and its recent successes in modelling anaesthesia.

Entertainment education theory and practice in HIV/AIDS communication: a South Africa / United Kingdom comparison

Within development communication, gaps remain in theory and practice: communication innovations are taking place which either do not incorporate theory or fail to challenge the assumptions of development communication and HIV/AIDS theory. This can lead to the implementation of unsuccessful interventions that lack theoretical frameworks or to uninformed practice, making it difficult to replicate. Further, research has demonstrated that Entertainment Education (EE) interventions have a measurable impact on behaviour in areas such as HIV/AIDS prevention. Given the transitions in EE practice and evidence of its impact, EE theory and practice can contribute insight into these challenges. A pilot study investigated these dilemmas within the context of the monitoring and evaluation of development communication. Framing this discussion is the concept of South-North dialogue, using comparative analysis of EE interventions to distil lessons through contrasting experiences in two diverse settings. It holds as a principle that lessons from the experience of EE in the Southern context can inform lessons for the North. Further, comparison of the case studies can generate insights for the broader development communication field. We present four case studies, informed by key informant interviews, of EE interventions in the UK and South Africa. We address how communication is defined in planning, implementation and evaluation, highlighting how it often misses the importance of 'listening'. The case studies show that HIV/AIDS communication, and development communication more broadly, has not internalised ideas of evaluation and listening in communication. Successes in the case studies can be partially attributed to responsiveness and context-specificity rather than following rigid planning templates, such as those found in some development communication literature. This indicates the importance of flexibility and responsiveness to context for both development communication and HIV/AIDS communication.

Texture, realism, performance: exploring the intersection of transtexts and the contemporary sitcom

Contemporary US sitcom is at an interesting crossroads: it has received an increasing amount of scholarly attention (e.g. Mills 2009; Butler 2010; Newman and Levine 2012; Vermeulen and Whitfield 2013), which largely understands it as shifting towards the aesthetically and narratively complex. At the same time, in the post-broadcasting era, US networks are particularly struggling for their audience share. With the days of blockbuster successes like Must See TV’s Friends (NBC 1994-2004) a distant dream, recent US sitcoms are instead turning towards smaller, engaged audiences. Here, a cult sensibility of intertextual in-jokes, temporal and narrational experimentation (e.g. flashbacks and alternate realities) and self-reflexive performance styles have marked shows including Community (NBC 2009-2015), How I Met Your Mother (CBS 2005-2014), New Girl (Fox 2011-present) and 30 Rock (NBC 2006-2013). However, not much critical attention has so far been paid to how these developments in textual sensibility in contemporary US sitcom may be influenced by, and influencing, the use of transmedia storytelling practices, an increasingly significant industrial concern and rising scholarly field of enquiry (e.g. Jenkins 2006; Mittell 2015; Richards 2010; Scott 2010; Jenkins, Ford and Green 2013). This chapter investigates this mutual influence between sitcom and transmedia by taking as its case studies two network shows that encourage invested viewership through their use of transtexts, namely How I Met Your Mother (hereafter HIMHM) and New Girl (hereafter NG). As such, it will pay particular attention to the most transtextually visible character/actor from each show: HIMYM’s Barney Stinson, played by Neil Patrick Harris, and NG’s Schmidt, played by Max Greenfield. This chapter argues that these sitcoms do not simply have their particular textual sensibility and also (happen to) engage with transmedia practices, but that the two are mutually informing and defining. This chapter explores the relationships and interplay between sitcom aesthetics, narratives and transmedia storytelling (or industrial transtexts), focusing on the use of multiple delivery channels in order to disperse “integral elements of a fiction” (Jenkins, 2006 95-6), by official entities such as the broadcasting channels. The chapter pays due attention to the specific production contexts of both shows and how these inform their approaches to transtexts. This chapter’s conceptual framework will be particularly concerned with how issues of texture, the reality envelope and accepted imaginative realism, as well as performance and the actor’s input inform and illuminate contemporary sitcoms and transtexts, and will be the first scholarly research to do so. It will seek out points of connections between two (thus far) separate strands of scholarship and will move discussions on transtexts beyond the usual genre studied (i.e. science-fiction and fantasy), as well as make a contribution to the growing scholarship on contemporary sitcom by approaching it from a new critical angle. On the basis that transmedia scholarship stands to benefit from widening its customary genre choice (i.e. telefantasy) for its case studies and from making more use of in-depth close analysis in its engagement with transtexts, the chapter argues that notions of texture, accepted imaginative realism and the reality envelope, as well as performance and the actor’s input deserve to be paid more attention to within transtext-related scholarship.