Enzymatically-triggered, isothermally responsive polymers: re-programming poly(oligoethylene glycols) to respond to phosphatase

Polymers which can respond to externally applied stimuli have found much application in the biomedical field due to their (reversible) coil–globule transitions. Polymers displaying a lower critical solution temperature are the most commonly used, but for blood-borne (i.e., soluble) biomedical applications the application of heat is not always possible, nor practical. Here we report the design and synthesis of poly(oligoethylene glycol methacrylate)-based polymers whose cloud points are easily varied by alkaline phosphatase-mediated dephosphorylation. By fine-tuning the density of phosphate groups on the backbone, it was possible to induce an isothermal transition: A change in solubility triggered by removal of a small number of phosphate esters from the side chains activating the LCST-type response. As there was no temperature change involved, this serves as a model of a cell-instructed polymer response. Finally, it was found that both polymers were non cytotoxic against MCF-7 cells (at 1 mg·mL–1), which confirms promise for biomedical applications.

Entrepreneurial failure and economic crisis: an historical perspective

This chapter analyses the major UK economic crises that have occurred since the speculative bubbles of the seventeenth century. It integrates insights from economic history and business history to analyse both the general economic conditions and the specific business and financial practices that led to these crises. The analysis suggests a significant reinterpretation of the evidence – one that questions economists’ conventional views.

Application of data assimilation to ocean and climate prediction

Ocean prediction systems are now able to analyse and predict temperature, salinity and velocity structures within the ocean by assimilating measurements of the ocean’s temperature and salinity into physically based ocean models. Data assimilation combines current estimates of state variables, such as temperature and salinity, from a computational model with measurements of the ocean and atmosphere in order to improve forecasts and reduce uncertainty in the forecast accuracy. Data assimilation generally works well with ocean models away from the equator but has been found to induce vigorous and unrealistic overturning circulations near the equator. A pressure correction method was developed at the University of Reading and the Met Office to control these circulations using ideas from control theory and an understanding of equatorial dynamics. The method has been used for the last 10 years in seasonal forecasting and ocean prediction systems at the Met Office and European Center for Medium-range Weather Forecasting (ECMWF). It has been an important element in recent re-analyses of the ocean heat uptake that mitigates climate change.

Understanding ENSO diversity

El Niño–Southern Oscillation (ENSO) is a naturally occurring mode of tropical Pacific variability, with global impacts on society and natural ecosystems. While it has long been known that El Niño events display a diverse range of amplitudes, triggers, spatial patterns, and life cycles, the realization that ENSO’s impacts can be highly sensitive to this event-to-event diversity is driving a renewed interest in the subject. This paper surveys our current state of knowledge of ENSO diversity, identifies key gaps in understanding, and outlines some promising future research directions.

Increased frequency of extreme La Niña events under greenhouse warming

The El Niño/Southern Oscillation is Earth’s most prominent source of interannual climate variability, alternating irregularly between El Niño and La Niña, and resulting in global disruption of weather patterns, ecosystems, fisheries and agriculture1, 2, 3, 4, 5. The 1998–1999 extreme La Niña event that followed the 1997–1998 extreme El Niño event6 switched extreme El Niño-induced severe droughts to devastating floods in western Pacific countries, and vice versa in the southwestern United States4, 7. During extreme La Niña events, cold sea surface conditions develop in the central Pacific8, 9, creating an enhanced temperature gradient from the Maritime continent to the central Pacific. Recent studies have revealed robust changes in El Niño characteristics in response to simulated future greenhouse warming10, 11, 12, but how La Niña will change remains unclear. Here we present climate modelling evidence, from simulations conducted for the Coupled Model Intercomparison Project phase 5 (ref. 13), for a near doubling in the frequency of future extreme La Niña events, from one in every 23 years to one in every 13 years. This occurs because projected faster mean warming of the Maritime continent than the central Pacific, enhanced upper ocean vertical temperature gradients, and increased frequency of extreme El Niño events are conducive to development of the extreme La Niña events. Approximately 75% of the increase occurs in years following extreme El Niño events, thus projecting more frequent swings between opposite extremes from one year to the next.

Increasing frequency of extreme El Niño events due to greenhouse warming

El Niño events are a prominent feature of climate variability with global climatic impacts. The 1997/98 episode, often referred to as ‘the climate event of the twentieth century’1, 2, and the 1982/83 extreme El Niño3, featured a pronounced eastward extension of the west Pacific warm pool and development of atmospheric convection, and hence a huge rainfall increase, in the usually cold and dry equatorial eastern Pacific. Such a massive reorganization of atmospheric convection, which we define as an extreme El Niño, severely disrupted global weather patterns, affecting ecosystems4, 5, agriculture6, tropical cyclones, drought, bushfires, floods and other extreme weather events worldwide3, 7, 8, 9. Potential future changes in such extreme El Niño occurrences could have profound socio-economic consequences. Here we present climate modelling evidence for a doubling in the occurrences in the future in response to greenhouse warming. We estimate the change by aggregating results from climate models in the Coupled Model Intercomparison Project phases 3 (CMIP3; ref. 10) and 5 (CMIP5; ref. 11) multi-model databases, and a perturbed physics ensemble12. The increased frequency arises from a projected surface warming over the eastern equatorial Pacific that occurs faster than in the surrounding ocean waters13, 14, facilitating more occurrences of atmospheric convection in the eastern equatorial region.

Sahel decadal rainfall variability and the role of model horizontal resolution

Substantial low-frequency rainfall fluctuations occurred in the Sahel throughout the twentieth century, causing devastating drought. Modeling these low-frequency rainfall fluctuations has remained problematic for climate models for many years. Here we show using a combination of state-of-the-art rainfall observations and high-resolution global climate models that changes in organized heavy rainfall events carry most of the rainfall variability in the Sahel at multiannual to decadal time scales. Ability to produce intense, organized convection allows climate models to correctly simulate the magnitude of late-twentieth century rainfall change, underlining the importance of model resolution. Increasing model resolution allows a better coupling between large-scale circulation changes and regional rainfall processes over the Sahel. These results provide a strong basis for developing more reliable and skilful long-term predictions of rainfall (seasons to years) which could benefit many sectors in the region by allowing early adaptation to impending extremes.

Steric sea level variability (1993-2010) in an ensemble of ocean reanalyses and objective analyses

Quantifying the effect of the seawater density changes on sea level variability is of crucial importance for climate change studies, as the sea level cumulative rise can be regarded as both an important climate change indicator and a possible danger for human activities in coastal areas. In this work, as part of the Ocean Reanalysis Intercomparison Project, the global and regional steric sea level changes are estimated and compared from an ensemble of 16 ocean reanalyses and 4 objective analyses. These estimates are initially compared with a satellite-derived (altimetry minus gravimetry) dataset for a short period (2003–2010). The ensemble mean exhibits a significant high correlation at both global and regional scale, and the ensemble of ocean reanalyses outperforms that of objective analyses, in particular in the Southern Ocean. The reanalysis ensemble mean thus represents a valuable tool for further analyses, although large uncertainties remain for the inter-annual trends. Within the extended intercomparison period that spans the altimetry era (1993–2010), we find that the ensemble of reanalyses and objective analyses are in good agreement, and both detect a trend of the global steric sea level of 1.0 and 1.1 ± 0.05 mm/year, respectively. However, the spread among the products of the halosteric component trend exceeds the mean trend itself, questioning the reliability of its estimate. This is related to the scarcity of salinity observations before the Argo era. Furthermore, the impact of deep ocean layers is non-negligible on the steric sea level variability (22 and 12 % for the layers below 700 and 1500 m of depth, respectively), although the small deep ocean trends are not significant with respect to the products spread.

Intercomparison and validation of the mixed layer depth fields of global ocean syntheses

Intercomparison and evaluation of the global ocean surface mixed layer depth (MLD) fields estimated from a suite of major ocean syntheses are conducted. Compared with the reference MLDs calculated from individual profiles, MLDs calculated from monthly mean and gridded profiles show negative biases of 10–20 m in early spring related to the re-stratification process of relatively deep mixed layers. Vertical resolution of profiles also influences the MLD estimation. MLDs are underestimated by approximately 5–7 (14–16) m with the vertical resolution of 25 (50) m when the criterion of potential density exceeding the 10-m value by 0.03 kg m−3 is used for the MLD estimation. Using the larger criterion (0.125 kg m−3) generally reduces the underestimations. In addition, positive biases greater than 100 m are found in wintertime subpolar regions when MLD criteria based on temperature are used. Biases of the reanalyses are due to both model errors and errors related to differences between the assimilation methods. The result shows that these errors are partially cancelled out through the ensemble averaging. Moreover, the bias in the ensemble mean field of the reanalyses is smaller than in the observation-only analyses. This is largely attributed to comparably higher resolutions of the reanalyses. The robust reproduction of both the seasonal cycle and interannual variability by the ensemble mean of the reanalyses indicates a great potential of the ensemble mean MLD field for investigating and monitoring upper ocean processes.

Interannual-decadal variability of wintertime mixed layer depths in the North Pacific detected by an ensemble of ocean syntheses

The interannual-decadal variability of the wintertime mixed layer depths (MLDs) over the North Pacific is investigated from an empirical orthogonal function (EOF) analysis of an ensemble of global ocean reanalyses. The first leading EOF mode represents the interannual MLD anomalies centered in the eastern part of the central mode water formation region in phase opposition with those in the eastern subtropics and the central Alaskan Gyre. This first EOF mode is highly correlated with the Pacific decadal oscillation index on both the interannual and decadal time scales. The second leading EOF mode represents the MLD variability in the subtropical mode water (STMW) formation region and has a good correlation with the wintertime West Pacific (WP) index with time lag of 3 years, suggesting the importance of the oceanic dynamical response to the change in the surface wind field associated with the meridional shifts of the Aleutian Low. The above MLD variabilities are in basic agreement with previous observational and modeling findings. Moreover the reanalysis ensemble provides uncertainty estimates. The interannual MLD anomalies in the first and second EOF modes are consistently represented by the individual reanalyses and the amplitudes of the variabilities generally exceed the ensemble spread of the reanalyses. Besides, the resulting MLD variability indices, spanning the 1948–2012 period, should be helpful for characterizing the North Pacific climate variability. In particular, a 6-year oscillation including the WP teleconnection pattern in the atmosphere and the oceanic MLD variability in the STMW formation region is first detected.

Future, Fortune, and the graphic design of information

This is a study of graphic information designed for Future Books/Future magazine (UK) and Fortune magazine (USA) in the years immediately after the Second World War. It highlights work made by the Isotype Institute for Future, which is then situated against contributions by Abram Games and F. H. K. Henrion. Similar work in Fortune under the art editorship of Will Burtin is discussed in a parallel account, drawing on examples by him and by others including György Kepes, Matthew Liebowitz, Alex Steinweiss and Ladislav Sutnar. Attention is drawn to links and relationships between to the two periodicals and the graphic information published in both. Further comparisons are made between underlying editorial and design strategies pursued by Otto Neurath (Isotype Institute) and Will Burtin. An argument is made for recognising the little-known innovations of Future alongside the long-acknowledged innovations of Fortune.

Designing care bundle documentation to support the recognition and treatment of acute kidney injury: a route to quality improvement

The chapter describes development of care bundle documentation, through an iterative, user-centred design process, to support the recognition and treatment of acute kidney injury (AKI). The chapter details stages of user and stakeholder consultation, employed to develop a design response that was sensitive to user experience and need, culminating in simulation testing of a near final prototype. The development of supplementary awareness-raising materials, relating to the main care bundle tool is also discussed. This information design response to a complex clinical decision-making process is contrasted to other approaches to promoting AKI care. The need for different but related approaches to the working tool itself and the tool’s communication are discussed. More general recommendations are made for the development of communication tools to support complex clinical processes.

Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range

BACKGROUND:The Salmonella enterica serovar Derby is frequently isolated from pigs and turkeys whereas serovar Mbandaka is frequently isolated from cattle, chickens and animal feed in the UK. Through comparative genomics, phenomics and mutant construction we previously suggested possible mechanistic reasons why these serovars demonstrate apparently distinct host ranges. Here, we investigate the genetic and phenotypic diversity of these two serovars in the UK. We produce a phylogenetic reconstruction and perform several biochemical assays on isolates of S. Derby and S. Mbandaka acquired from sites across the UK between the years 2000 and 2010. RESULTS:We show that UK isolates of S. Mbandaka comprise of one clonal lineage which is adapted to proficient utilisation of metabolites found in soya beans under ambient conditions. We also show that this clonal lineage forms a biofilm at 25 °C, suggesting that this serovar maybe well adapted to survival ex vivo, growing in animal feed. Conversely, we show that S. Derby is made of two distinct lineages, L1 and L2. These lineages differ genotypically and phenotypically, being divided by the presence and absence of SPI-23 and the ability to more proficiently invade porcine jejunum derived cell line IPEC-J2. CONCLUSION:The results of this study lend support to the hypothesis that the differences in host ranges of S. Derby and S. Mbandaka are adaptations to pathogenesis, environmental persistence, as well as utilisation of metabolites abundant in their respective host environments.

Libraries and networks of influence in the Roman world

This paper is concerned with the ways in which libraries – in this case public libraries in Rome and the Roman world – acted as points of connectivity and communication.