Assessing the ability of rural agrarian areas to provide Cultural Ecosystem Services (CES): a Multi Scale Social Indicator Framework (MSIF)

Assessing the ways in which rural agrarian areas provide Cultural Ecosystem Services (CES) is proving difficult to achieve. This research has developed an innovative methodological approach named as Multi Scale Indicator Framework (MSIF) for capturing the CES embedded into the rural agrarian areas. This framework reconciles a literature review with a trans-disciplinary participatory workshop. Both of these sources reveal that societal preferences diverge upon judgemental criteria which in turn relate to different visual concepts that can be drawn from analysing attributes, elements, features and characteristics of rural areas. We contend that it is now possible to list a group of possible multi scale indicators for stewardship, diversity and aesthetics. These results might also be of use for improving any existing European indicators frameworks by also including CES. This research carries major implications for policy at different levels of governance, as it makes possible to target and monitor policy instruments to the physical rural settings so that cultural dimensions are adequately considered. There is still work to be developed on regional specific values and thresholds for each criteria and its indicator set. In practical terms, by developing the conceptual design within a common framework as described in this paper, a considerable step forward towards the inclusion of the cultural dimension in European wide assessments can be made.

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays.

Le credit au Moyen Age: les prets a la couronne D'Angleterre entre 1272 et 1345

A summary of some of the key findings of a recent ESRC-funded project based at the ICMA centre, University of Reading. This study applied modern financial analysis and theories to the early history of sovereign debt, in this case the credit arrangements between the ‘Three Edwards’, kings of England 1272-1377, and a succession of Italian merchant societies.

Atmospheric rivers do not explain UK summer extreme rainfall

Extreme rainfall events continue to be one of the largest natural hazards in the UK. In winter, heavy precipitation and floods have been linked with intense moisture transport events associated with atmospheric rivers (ARs), yet no large-scale atmospheric precursors have been linked to summer flooding in the UK. This study investigates the link between ARs and extreme rainfall from two perspectives: 1) Given an extreme rainfall event, is there an associated AR? 2) Given an AR, is there an associated extreme rainfall event? We identify extreme rainfall events using the UK Met Office daily rain-gauge dataset and link these to ARs using two different horizontal resolution atmospheric datasets (ERA-Interim and 20th Century Re-analysis). The results show that less than 35% of winter ARs and less than 15% of summer ARs are associated with an extreme rainfall event. Consistent with previous studies, at least 50% of extreme winter rainfall events are associated with an AR. However, less than 20% of the identified summer extreme rainfall events are associated with an AR. The dependence of the water vapor transport intensity threshold used to define an AR on the years included in the study, and on the length of the season, is also examined. Including a longer period (1900-2012) compared to previous studies (1979-2005) reduces the water vapor transport intensity threshold used to define an AR.

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.

Targeted activation of toll-like receptors: conjugation of a toll-like receptor 7 agonist to a monoclonal antibody maintains antigen binding and specificity

Therapeutic activation of Toll-like receptors (TLR) has potential for cancer immunotherapy, for augmenting the activity of anti-tumor monoclonal antibodies (mAbs), and for improved vaccine adjuvants. A previous attempt to specifically target TLR agonists to dendritic cells (DC) using mAbs failed because conjugation led to non-specific binding and mAbs lost specificity. We demonstrate here for the first time the successful conjugation of a small molecule TLR7 agonist to an anti-tumour mAb (the anti-hCD 20 rituximab) without compromising antigen specificity. The TLR7 agonist UC-1V150 was conjugated to rituximab using two conjugation methods and yield, molecular substitution ratio, retention of TLR7 activity and specificity of antigen binding were compared. Both conjugation methods produced rituximab-UC-1V150 conjugates with UC-1V150 : rituximab ratio ranging from 1:1 to 3:1 with drug loading quantified by UV spectroscopy and drug substitution ratio verified by MALDI TOF mass spectroscopy. The yield of purified conjugates varied with conjugation method, and dropped as low as 31% using a method previously described for conjugating UC-1V150 to proteins, where a bifunctional crosslinker was firstly reacted with rituximab, and secondly to the TLR7 agonist. We therefore developed a direct conjugation method by producing an amine-reactive UV active version of UC-1V150, termed NHS:UC-1V150. Direct conjugation with NHS:UC-1V150 was quick and simple and gave improved conjugate yields of 65-78%. Rituximab-UC-1V150 conjugates had the expected pro-inflammatory activity in vitro (EC50 28-53 nM) with a significantly increased activity over unconjugated UC-1V150 (EC50 547 nM). Antigen binding and specificity of the rituxuimab-UC-1V150 conjugates was retained, and after incubation with human peripheral blood leukocytes, all conjugates bound strongly only to CD20-expressing B cells whilst no non-specific binding to CD20-negative cells was observed. Selective targeting of Toll-like receptor activation directly within tumors or to DC is now feasible.

Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex

The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organization and function. Here we use electron microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterize the structural organization and signalling pathways associated with nodule formation. Nodules are composed of up to four actin-rich structures linked together by actin bundles. They are enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phosphorylated proteins and are depleted of integrins at the plasma membrane. Nodule formation is dependent on Wiskott-Aldrich syndrome protein (WASp) and the ARP2/3 complex. WASp(-/-) mouse blood displays impaired platelet aggregate formation at arteriolar shear rates. We propose actin nodules are platelet podosome-related structures required for platelet-platelet interaction and their absence contributes to the bleeding diathesis of Wiskott-Aldrich syndrome.

A comparison of greenhouse gas emissions in the residential sector of major Canadian cities

One of the most significant sources of greenhouse gas (GHG) emissions in Canada is the buildings sector, with over 30% of national energy end-use occurring in buildings. Energy use must be addressed to reduce emissions from the buildings sector, as nearly 70% of all Canada’s energy used in the residential sector comes from fossil sources. An analysis of GHG emissions from the existing residential building stock for the year 2010 has been conducted for six Canadian cities with different climates and development histories: Vancouver, Edmonton, Winnipeg, Toronto, Montreal, and Halifax. Variation across these cities is seen in their 2010 GHG emissions, due to climate, characteristics of the building stock, and energy conversion technologies, with Halifax having the highest per capita emissions at 5.55 tCO2e/capita and Montreal having the lowest at 0.32 tCO2e/capita. The importance of the provincial electricity grid’s carbon intensity is emphasized, along with era of construction, occupancy, floor area, and climate. Approaches to achieving deep emissions reductions include innovative retrofit financing and city level residential energy conservation by-laws; each region should seek location-appropriate measures to reduce energy demand within its residential housing stock, as well as associated GHG emissions.

Sea-breeze dynamics and convection initiation: the influence of convective parameterization in weather and climate model biases

There are some long-established biases in atmospheric models that originate from the representation of tropical convection. Previously, it has been difficult to separate cause and effect because errors are often the result of a number of interacting biases. Recently, researchers have gained the ability to run multiyear global climate model simulations with grid spacings small enough to switch the convective parameterization off, which permits the convection to develop explicitly. There are clear improvements to the initiation of convective storms and the diurnal cycle of rainfall in the convection-permitting simulations, which enables a new process-study approach to model bias identification. In this study, multiyear global atmosphere-only climate simulations with and without convective parameterization are undertaken with the Met Office Unified Model and are analyzed over the Maritime Continent region, where convergence from sea-breeze circulations is key for convection initiation. The analysis shows that, although the simulation with parameterized convection is able to reproduce the key rain-forming sea-breeze circulation, the parameterization is not able to respond realistically to the circulation. A feedback of errors also occurs: the convective parameterization causes rain to fall in the early morning, which cools and wets the boundary layer, reducing the land–sea temperature contrast and weakening the sea breeze. This is, however, an effect of the convective bias, rather than a cause of it. Improvements to how and when convection schemes trigger convection will improve both the timing and location of tropical rainfall and representation of sea-breeze circulations.

Diagnosing links between atmospheric moisture and extreme daily precipitation over the UK

Atmospheric moisture characteristics associated with the heaviest 1% of daily rainfall events affecting regions of the British Isles are analysed over the period 1997–2008. A blended satellite/rain-gauge data set (GPCP-1DD) and regionally averaged daily rain-gauge observations (HadUKP) are combined with the ERA Interim reanalysis. These are compared with simulations from the HadGEM2-A climate model which applied observed sea surface temperature and realistic radiative forcings. Median extreme daily rainfall across the identified events and locations is larger for GPCP (32 mm day−1) than HadUKP and the simulations (∼25 mm day−1). The heaviest observed and simulated daily rainfall events are associated with increased specific humidity and horizontal transport of moisture (median 850 hPa specific humidity of ∼6 g kg−1 and vapour transport of ∼150 g kg−1 m s−1 for both observed and simulated events). Extreme daily rainfall events are less common during spring and summer across much of the British Isles, but in the south east region, they contribute up to 60% of the total number of distinct extreme daily rainfall events during these months. Compared to winter events, the summer events over south east Britain are associated with a greater magnitude and more southerly location of moisture maxima and less spatially extensive regions of enhanced moisture transport. This contrasting dependence of extreme daily rainfall on moisture characteristics implies a range of driving mechanisms that depend upon location and season. Higher spatial and temporal resolution data are required to explore these processes further, which is vital in assessing future projected changes in rainfall and associated flooding.

Cognitive effects following acute wild blueberry supplementation in 7 – 10 year old children

Purpose: Previously, anthocyanin-rich blueberry treatments have shown positive effects on cognition in both animals and human adults. However, little research has considered whether these benefits transfer to children. Here we describe an acute time-course and dose–response investigation considering whether these cognitive benefits extend to children. Methods: Using a double-blind cross-over design, on three occasions children (n = 21; 7–10 years) consumed placebo (vehicle) or blueberry drinks containing 15 or 30 g freeze-dried wild blueberry (WBB) powder. A cognitive battery including tests of verbal memory, word recognition, response interference, response inhibition and levels of processing was performed at baseline, and 1.15, 3 and 6 h following treatment. Results: Significant WBB-related improvements included final immediate recall at 1.15 h, delayed word recognition sustained over each period, and accuracy on cognitively demanding incongruent trials in the interference task at 3h. Importantly, across all measures, cognitive performance improved, consistent with a dose–response model, with the best performance following 30 g WBB and the worst following vehicle. Conclusion: Findings demonstrate WBB-related cognitive improvements in 7- to 10-year-old children. These effects would seem to be particularly sensitive to the cognitive demand of task.

CDASH: a cloud-enabled program for structure solution from powder diffraction data

The simulated annealing approach to crystal structure determination from powder diffraction data, as implemented in the DASH program, is readily amenable to parallelization at the individual run level. Very large scale increases in speed of execution can be achieved by distributing individual DASH runs over a network of computers. The CDASH program delivers this by using scalable on-demand computing clusters built on the Amazon Elastic Compute Cloud service. By way of example, a 360 vCPU cluster returned the crystal structure of racemic ornidazole (Z0 = 3, 30 degrees of freedom) ca 40 times faster than a typical modern quad-core desktop CPU. Whilst used here specifically for DASH, this approach is of general applicability to other packages that are amenable to coarse-grained parallelism strategies.

Aspects of particle filtering in high-dimensional spaces

Nonlinear data assimilation is high on the agenda in all fields of the geosciences as with ever increasing model resolution and inclusion of more physical (biological etc.) processes, and more complex observation operators the data-assimilation problem becomes more and more nonlinear. The suitability of particle filters to solve the nonlinear data assimilation problem in high-dimensional geophysical problems will be discussed. Several existing and new schemes will be presented and it is shown that at least one of them, the Equivalent-Weights Particle Filter, does indeed beat the curse of dimensionality and provides a way forward to solve the problem of nonlinear data assimilation in high-dimensional systems.

Copyright exceptions and contract in the UK: the impact of recent amendments

In June and October 2014 a number of amendments to the Copyright, Designs and Patents Act 1988 came into effect, introducing new copyright exceptions and amending several existing exceptions. Whilst following recent judicial review the private copying exception has been quashed, many of the remaining new exceptions significantly alter the relationship between copyright exceptions and contract, making contractual terms unenforceable where those terms restrict users from taking advantage of an exception. This paper explores the rationale for the UK amendments and considers whether the changes, as implemented, prevent rightsholders from contracting out of exceptions and whether they increase the clarity of the copyright system.