TNF-α influences the lateral dynamics of TNF receptor I in living cells

In mammalian cells, inflammation is mainly mediated by the binding of tumor necrosis factor alpha to tumor necrosis factor receptor 1. In this study, we investigated lateral dynamics of TNF-R1 before and after ligand binding using high-density single-particle tracking in combination with photoactivated localization microscopy. Our single-molecule data indicates the presence of tumor necrosis factor receptor 1 with different mobilities in the plasma membrane, suggesting different molecular organizations. Cholesterol depletion led to a decrease of slow receptor species and a strong increase in the average diffusion coefficient. Moreover, as a consequence of tumor necrosis factor-alpha treatment, the mean diffusion coefficient moderately increased while its distribution narrowed. Based on our observation, we propose a refined mechanism on the structural arrangement and activation of tumor necrosis factor receptor 1 in the plasma membrane.

A traceable physical calibration of the vertical advection-diffusion equation for modelling ocean heat uptake

The classic vertical advection-diffusion (VAD) balance is a central concept in studying the ocean heat budget, in particular in simple climate models (SCMs). Here we present a new framework to calibrate the parameters of the VAD equation to the vertical ocean heat balance of two fully-coupled climate models that is traceable to the models’ circulation as well as to vertical mixing and diffusion processes. Based on temperature diagnostics, we derive an effective vertical velocity w∗ and turbulent diffusivity k∗ for each individual physical process. In steady-state, we find that the residual vertical velocity and diffusivity change sign in mid-depth, highlighting the different regional contributions of isopycnal and diapycnal diffusion in balancing the models’ residual advection and vertical mixing. We quantify the impacts of the time-evolution of the effective quantities under a transient 1%CO2 simulation and make the link to the parameters of currently employed SCMs.

POZylation: a new approach to enhance nanoparticle diffusion through mucosal barriers

The increasing use of nanoparticles in the pharmaceutical industry is generating concomitant interest in developing nanomaterials that can rapidly penetrate into, and permeate through, biological membranes to facilitate drug delivery and improve the bioavailability of active pharmaceutical ingredients. Here, we demonstrate that the permeation of thiolated silica nanoparticles through porcine gastric mucosa can be significantly enhanced by their functionalization with either 5 kDa poly(2-ethyl-2-oxazoline) or poly(ethylene glycol). Nanoparticle diffusion was assessed using two independent techniques; Nanoparticle Tracking Analysis, and fluorescence microscopy. Our results show that poly(2-ethyl-2-oxazoline) and poly(ethylene glycol) have comparable abilities to enhance diffusion of silica nanoparticles in mucin dispersions and through the gastric mucosa. These findings provide a new strategy in the design of nanomedicines, by surface modification or nanoparticle core construction, for enhanced transmucosal drug delivery.

A method for merging nadir-sounding climate records, with an application to the global-mean stratospheric temperature data sets from SSU and AMSU

A method is proposed for merging different nadir-sounding climate data records using measurements from high-resolution limb sounders to provide a transfer function between the different nadir measurements. The two nadir-sounding records need not be overlapping so long as the limb-sounding record bridges between them. The method is applied to global-mean stratospheric temperatures from the NOAA Climate Data Records based on the Stratospheric Sounding Unit (SSU) and the Advanced Microwave Sounding Unit-A (AMSU), extending the SSU record forward in time to yield a continuous data set from 1979 to present, and providing a simple framework for extending the SSU record into the future using AMSU. SSU and AMSU are bridged using temperature measurements from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS), which is of high enough vertical resolution to accurately represent the weighting functions of both SSU and AMSU. For this application, a purely statistical approach is not viable since the different nadir channels are not sufficiently linearly independent, statistically speaking. The near-global-mean linear temperature trends for extended SSU for 1980–2012 are −0.63 ± 0.13, −0.71 ± 0.15 and −0.80 ± 0.17 K decade−1 (95 % confidence) for channels 1, 2 and 3, respectively. The extended SSU temperature changes are in good agreement with those from the Microwave Limb Sounder (MLS) on the Aura satellite, with both exhibiting a cooling trend of ~ 0.6 ± 0.3 K decade−1 in the upper stratosphere from 2004 to 2012. The extended SSU record is found to be in agreement with high-top coupled atmosphere–ocean models over the 1980–2012 period, including the continued cooling over the first decade of the 21st century.

The creation and diffusion of innovation in developing countries: a systematic literature review

In this study, we review the literature on the creation and diffusion of innovation in the private sectors (industry and services) in developing countries. In particular, we collect evidence on what are the barriers to innovation creation and diffusion and the channels of innovation diffusion to and within developing countries. We find that innovation in developing countries is about creation or adoption of new ideas and technologies; but the capacity for innovation is embedded in and constituted by dynamics between geographical, socio-economic, political and legal subsystems. We contextualize the findings from the review in the current theoretical framework of diffusion of innovations, and we emphasize how the institutional context typical of developing countries impacts the diffusion itself.

Innovation diffusion across firms

This chapter seeks to add to the study of innovation diffusion as enacted within the UK construction sector. Whereas using relevant theoretical frames as touch points, the chapter maps out challenges associated with understanding innovation diffusion within the UK construction sector. Central to the argument developed here is just how diverse the UK construction sector is, resulting in the need to focus upon a specific constituent perspective within the sector. It is argued that constituents of the UK construction sector experience the reality of innovation diffusion differently. The chosen focus here is medium-size and typically regionally based construction firms rather than the big guns, because statistics continually demonstrate that this group of smaller firms undertake more than 80% of the sector’s output. As is pointed out in other chapters in the present volume, and as argued theoretically in the industrial network perspective of chapter 7, firms do not innovate in a vacuum. Innovation and diffusion occur within networks of firms typically around a project. A framework drawing upon empirical data is provided to additional insight on the process and the interconnections. It is argued here that the unit of analysis or level of understanding termed the firm can actually be fairly unhelpful for understanding innovation and its manifestation and diffusion within the broader UK construction sector, because this occurs across networks of firms.

Diffusion of digital innovation in construction: a case study of a UK engineering firm

The UK government is mandating the use of building information modelling (BIM) in large public projects by 2016. As a result, engineering firms are faced with challenges related to embedding new technologies and associated working practices for the digital delivery of major infrastructure projects. Diffusion of innovations theory is used to investigate how digital innovations diffuse across complex firms. A contextualist approach is employed through an in-depth case study of a large, international engineering project-based firm. The analysis of the empirical data, which was collected over a four-year period of close interaction with the firm, reveals parallel paths of diffusion occurring across the firm, where both the innovation and the firm context were continually changing. The diffusion process is traced over three phases: centralization of technology management, standardization of digital working practices, and globalization of digital resources. The findings describe the diffusion of a digital innovation as multiple and partial within a complex social system during times of change and organizational uncertainty, thereby contributing to diffusion of innovations studies in construction by showing a range of activities and dynamics of a non-linear diffusion process.

What does global mean temperature tell us about local climate?

The subject of climate feedbacks focuses attention on global mean surface air temperature (GMST) as the key metric of climate change. But what does knowledge of past and future GMST tell us about the climate of specific regions? In the context of the ongoing UNFCCC process, this is an important question for policy-makers as well as for scientists. The answer depends on many factors, including the mechanisms causing changes, the timescale of the changes, and the variables and regions of interest. This paper provides a review and analysis of the relationship between changes in GMST and changes in local climate, first in observational records and then in a range of climate model simulations, which are used to interpret the observations. The focus is on decadal timescales, which are of particular interest in relation to recent and near-future anthropogenic climate change. It is shown that GMST primarily provides information about forced responses, but that understanding and quantifying internal variability is essential to projecting climate and climate impacts on regional-to-local scales. The relationship between local forced responses and GMST is often linear but may be nonlinear, and can be greatly complicated by competition between different forcing factors. Climate projections are limited not only by uncertainties in the signal of climate change but also by uncertainties in the characteristics of real-world internal variability. Finally, it is shown that the relationship between GMST and local climate provides a simple approach to climate change detection, and a useful guide to attribution studies.

Recent progress in understanding and projecting regional and global mean sea-level change

Considerable progress has been made in understanding the present and future regional and global sea level in the 2 years since the publication of the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change. Here, we evaluate how the new results affect the AR5’s assessment of (i) historical sea level rise, including attribution of that rise and implications for the sea level budget, (ii) projections of the components and of total global mean sea level (GMSL), and (iii) projections of regional variability and emergence of the anthropogenic signal. In each of these cases, new work largely provides additional evidence in support of the AR5 assessment, providing greater confidence in those findings. Recent analyses confirm the twentieth century sea level rise, with some analyses showing a slightly smaller rate before 1990 and some a slightly larger value than reported in the AR5. There is now more evidence of an acceleration in the rate of rise. Ongoing ocean heat uptake and associated thermal expansion have continued since 2000, and are consistent with ocean thermal expansion reported in the AR5. A significant amount of heat is being stored deeper in the water column, with a larger rate of heat uptake since 2000 compared to the previous decades and with the largest storage in the Southern Ocean. The first formal detection studies for ocean thermal expansion and glacier mass loss since the AR5 have confirmed the AR5 finding of a significant anthropogenic contribution to sea level rise over the last 50 years. New projections of glacier loss from two regions suggest smaller contributions to GMSL rise from these regions than in studies assessed by the AR5; additional regional studies are required to further assess whether there are broader implications of these results. Mass loss from the Greenland Ice Sheet, primarily as a result of increased surface melting, and from the Antarctic Ice Sheet, primarily as a result of increased ice discharge, has accelerated. The largest estimates of acceleration in mass loss from the two ice sheets for 2003–2013 equal or exceed the acceleration of GMSL rise calculated from the satellite altimeter sea level record over the longer period of 1993–2014. However, when increased mass gain in land water storage and parts of East Antarctica, and decreased mass loss from glaciers in Alaska and some other regions are taken into account, the net acceleration in the ocean mass gain is consistent with the satellite altimeter record. New studies suggest that a marine ice sheet instability (MISI) may have been initiated in parts of the West Antarctic Ice Sheet (WAIS), but that it will affect only a limited number of ice streams in the twenty-first century. New projections of mass loss from the Greenland and Antarctic Ice Sheets by 2100, including a contribution from parts of WAIS undergoing unstable retreat, suggest a contribution that falls largely within the likely range (i.e., two thirds probability) of the AR5. These new results increase confidence in the AR5 likely range, indicating that there is a greater probability that sea level rise by 2100 will lie in this range with a corresponding decrease in the likelihood of an additional contribution of several tens of centimeters above the likely range. In view of the comparatively limited state of knowledge and understanding of rapid ice sheet dynamics, we continue to think that it is not yet possible to make reliable quantitative estimates of future GMSL rise outside the likely range. Projections of twenty-first century GMSL rise published since the AR5 depend on results from expert elicitation, but we have low confidence in conclusions based on these approaches. New work on regional projections and emergence of the anthropogenic signal suggests that the two commonly predicted features of future regional sea level change (the increasing tilt across the Antarctic Circumpolar Current and the dipole in the North Atlantic) are related to regional changes in wind stress and surface heat flux. Moreover, it is expected that sea level change in response to anthropogenic forcing, particularly in regions of relatively low unforced variability such as the low-latitude Atlantic, will be detectable over most of the ocean by 2040. The east-west contrast of sea level trends in the Pacific observed since the early 1990s cannot be satisfactorily accounted for by climate models, nor yet definitively attributed either to unforced variability or forced climate change.

The diffusion of grassroots innovations for sustainability in Italy and Great Britain: an exploratory spatial data analysis

Little research so far has been devoted to understanding the diffusion of grassroots innovation for sustainability across space. This paper explores and compares the spatial diffusion of two networks of grassroots innovations, the Transition Towns Network (TTN) and Gruppi di Acquisto Solidale (Solidarity Purchasing Groups – GAS), in Great Britain and Italy. Spatio-temporal diffusion data were mined from available datasets, and patterns of diffusion were uncovered through an exploratory data analysis. The analysis shows that GAS and TTN diffusion in Italy and Great Britain is spatially structured, and that the spatial structure has changed over time. TTN has diffused differently in Great Britain and Italy, while GAS and TTN have diffused similarly in central Italy. The uneven diffusion of these grassroots networks on the one hand challenges current narratives on the momentum of grassroots innovations, but on the other highlights important issues in the geography of grassroots innovations for sustainability, such as cross-movement transfers and collaborations, institutional thickness, and interplay of different proximities in grassroots innovation diffusion.

Reliable but not home free? What framing effects mean for moral intuitions

Various studies show moral intuitions to be susceptible to framing effects. Many have argued that this susceptibility is a sign of unreliability and that this poses a methodological challenge for moral philosophy. Recently, doubt has been cast on this idea. It has been argued that extant evidence of framing effects does not show that moral intuitions have a unreliability problem. I argue that, even if the extant evidence suggests that moral intuitions are fairly stable with respect to what intuitions we have, the effect of framing on the strength of those intuitions still needs to be taken into account. I argue that this by itself poses a methodological challenge for moral philosophy.

Frontal networks in adults with autism spectrum disorder

It has been postulated that autism spectrum disorder is underpinned by an ‘atypical connectivity’ involving higher-order association brain regions. To test this hypothesis in a large cohort of adults with autism spectrum disorder we compared the white matter networks of 61 adult males with autism spectrum disorder and 61 neurotypical controls, using two complementary approaches to diffusion tensor magnetic resonance imaging. First, we applied tract-based spatial statistics, a ‘whole brain’ non-hypothesis driven method, to identify differences in white matter networks in adults with autism spectrum disorder. Following this we used a tract-specific analysis, based on tractography, to carry out a more detailed analysis of individual tracts identified by tract-based spatial statistics. Finally, within the autism spectrum disorder group, we studied the relationship between diffusion measures and autistic symptom severity. Tract-based spatial statistics revealed that autism spectrum disorder was associated with significantly reduced fractional anisotropy in regions that included frontal lobe pathways. Tractography analysis of these specific pathways showed increased mean and perpendicular diffusivity, and reduced number of streamlines in the anterior and long segments of the arcuate fasciculus, cingulum and uncinate—predominantly in the left hemisphere. Abnormalities were also evident in the anterior portions of the corpus callosum connecting left and right frontal lobes. The degree of microstructural alteration of the arcuate and uncinate fasciculi was associated with severity of symptoms in language and social reciprocity in childhood. Our results indicated that autism spectrum disorder is a developmental condition associated with abnormal connectivity of the frontal lobes. Furthermore our findings showed that male adults with autism spectrum disorder have regional differences in brain anatomy, which correlate with specific aspects of autistic symptoms. Overall these results suggest that autism spectrum disorder is a condition linked to aberrant developmental trajectories of the frontal networks that persist in adult life.

The diffusion of the Transition Network in four European countries

The Transition Network exemplifies the potential of social movements to create spaces of possibility for alternatives to emerge in the interstices of mainstream, neoliberal economies. Yet, little work has been carried out so far on the Transition Network or other grassroots innovations for sustainability in a way that reveals their actual patterns of diffusion. This graphic of the diffusion of the Transition Network visualises its spatial structure and compare diffusion patterns across Italy, France, Great Britain and Germany. The graphics show that the number of transition initiatives in the four countries has steadily increased over the past eight years, but the rate of increase has slowed down in all countries. The maps clearly show that in all four countries the diffusion of the Transition Network has not been spatially even. The graphic suggests that in each country transition initiatives are more likely to emerge in some geographical areas (hotspots) than in others (cold spots). While the existence of a spatial structure of the Transition Network may result from the combination of place-specific factors and diffusion mechanisms, these graphics illustrate the importance of better comprehending where grassroots innovations emerge.

Small global-mean cooling due to volcanic radiative forcing

In both the observational record and atmosphere-ocean general circulation model (AOGCM) simulations of the last ∼∼ 150 years, short-lived negative radiative forcing due to volcanic aerosol, following explosive eruptions, causes sudden global-mean cooling of up to ∼∼ 0.3 K. This is about five times smaller than expected from the transient climate response parameter (TCRP, K of global-mean surface air temperature change per W m−2 of radiative forcing increase) evaluated under atmospheric CO2 concentration increasing at 1 % yr−1. Using the step model (Good et al. in Geophys Res Lett 38:L01703, 2011. doi:10.​1029/​2010GL045208), we confirm the previous finding (Held et al. in J Clim 23:2418–2427, 2010. doi:10.​1175/​2009JCLI3466.​1) that the main reason for the discrepancy is the damping of the response to short-lived forcing by the thermal inertia of the upper ocean. Although the step model includes this effect, it still overestimates the volcanic cooling simulated by AOGCMs by about 60 %. We show that this remaining discrepancy can be explained by the magnitude of the volcanic forcing, which may be smaller in AOGCMs (by 30 % for the HadCM3 AOGCM) than in off-line calculations that do not account for rapid cloud adjustment, and the climate sensitivity parameter, which may be smaller than for increasing CO2 (40 % smaller than for 4 × CO2 in HadCM3).