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.

House price dynamics and bank herding: European empirical evidence

This paper investigates the behavior of residential property and examines the linkages between house price dynamics and bank herding behavior. The analysis presents evidence that irrational behaviour may have played a significant role in several countries, including; United Kingdom, Spain, Denmark, Sweden and Ireland. In addition, we also provide evidence indicative of herding behaviour in the European residential mortgage loan market. Granger Causality tests indicate that non-fundamentally justified prices dynamics contributed to herding by lenders and that this behaviour was a response by the banks as a group to common information on residential property assets. In contrast, in Germany, Portugal and Austria, residential property prices were largely explained by fundamentals. Furthermore, these countries show no evidence of either irrational price bubbles or herd behaviour in the mortgage market. Granger Causality tests indicate that both variables are independent.

Comparative in situ analyses of cell wall matrix polysaccharide dynamics in developing rice and wheat grain

Cell wall polysaccharides of wheat and rice endosperm are an important source of dietary fibre. Monoclonal antibodies specific to cell wall polysaccharides were used to determine polysaccharide dynamics during the development of both wheat and rice grain. Wheat and rice grain present near synchronous developmental processes and significantly different endosperm cell wall compositions, allowing the localisation of these polysaccharides to be related to developmental changes. Arabinoxylan (AX) and mixed-linkage glucan (MLG) have analogous cellular locations in both species, with deposition of AX and MLG coinciding with the start of grain filling. A glucuronoxylan (GUX) epitope was detected in rice, but not wheat endosperm cell walls. Callose has been reported to be associated with the formation of cell wall outgrowths during endosperm cellularisation and xyloglucan is here shown to be a component of these anticlinal extensions, occurring transiently in both species. Pectic homogalacturonan (HG) was abundant in cell walls of maternal tissues of wheat and rice grain, but only detected in endosperm cell walls of rice in an unesterified HG form. A rhamnogalacturonan-I (RG-I) backbone epitope was observed to be temporally regulated in both species, detected in endosperm cell walls from 12 DAA in rice and 20 DAA in wheat grain. Detection of the LM5 galactan epitope showed a clear distinction between wheat and rice, being detected at the earliest stages of development in rice endosperm cell walls, but not detected in wheat endosperm cell walls, only in maternal tissues. In contrast, the LM6 arabinan epitope was detected in both species around 8 DAA and was transient in wheat grain, but persisted in rice until maturity.

Interventions in social networks: impact on mood and network dynamics

Results from two studies on longitudinal friendship networks are presented, exploring the impact of a gratitude intervention on positive and negative affect dynamics in a social network. The gratitude intervention had been previously shown to increase positive affect and decrease negative affect in an individual but dynamic group effects have not been considered. In the first study the intervention was administered to the whole network. In the second study two social networks are considered and in each only a subset of individuals, initially low/high in negative affect respectively received the intervention as `agents of change'. Data was analyzed using stochastic actor based modelling techniques to identify resulting network changes, impact on positive and negative affect and potential contagion of mood within the group. The first study found a group level increase in positive and a decrease in negative affect. Homophily was detected with regard to positive and negative affect but no evidence of contagion was found. The network itself became more volatile along with a fall in rate of change of negative affect. Centrality measures indicated that the best broadcasters were the individuals with the least negative affect levels at the beginning of the study. In the second study, the positive and negative affect levels for the whole group depended on the initial levels of negative affect of the intervention recipients. There was evidence of positive affect contagion in the group where intervention recipients had low initial level of negative affect and contagion in negative affect for the group where recipients had initially high level of negative affect.

Consumer attitudes to injurious pecking in free range egg production

Free range egg producers face continuing problems from injurious pecking (IP) which has financial consequences for farmers and poor welfare implications for birds. Beak trimming has been practised for many years to limit the damage caused by IP, but with the UK Government giving notification that they intend to ban beak trimming in 2016, considerable efforts have been made to devise feasible housing, range and management strategies to reduce IP. A recent research project investigated the efficacy of a range of IP reducing management strategies, the mean costs of which came to around 5 pence per bird. Here, the results of the above project’s consumer survey are presented: consumers’ attitudes to free range egg production are detailed showing that, whilst consumers had a very positive attitude towards free range eggs, they were especially uninformed about some aspects of free range egg production. The contingent valuation technique was used to estimate the price premium consumers would be prepared to pay to ensure that hens do not suffer from IP: this was calculated as just over 3% on top of the prevailing retail price of free range eggs. These findings reinforce other studies that have found that whilst consumers are not generally well-informed about certain specific welfare problems faced by animals under free range conditions, they are prepared to pay to improve animal welfare. Indeed, the study findings suggest that producers could obtain an additional price premium if they demonstrate the welfare provenance of their eggs, perhaps through marketing the eggs as coming from birds with intact beaks. This welfare provenance issue could usefully be assured to consumers by the introduction of a mandatory, single, accredited EU-wide welfare-standards labelling scheme.

Negative priming in free recall reconsidered

Recent investigations of the phenomenon of forgetting have been driven mostly by the development of a novel theoretical framework which places great emphasis on inhibitory control (Anderson, 2003; Anderson & Spellman, 1995; Bjork, 1989). Whereas traditional, interference-based theories consider forgetting to be a by-product of storing new information, the inhibitory framework postulates a specialized mechanism, or a group of mechanisms, that serves the function of ‘deactivating’ information which is currently irrelevant. This process of inhibiting currently irrelevant information is thought to have lasting consequences, affecting memory for the irrelevant information on subsequent tests. The active and functional perspective on forgetting embedded in the inhibitory framework opens new fields for examining the role of forgetting in cognitive functioning. Differences in the ability to inhibit irrelevant information have been postulated to play important roles in a range of clinical conditions (e.g., Soriano, Jiménez, Román, & Bajo, 2009; Storm & White, 2010) and the trajectory of cognitive development (e.g., Aslan & Bäuml, 2010) as well as contributing to individual differences in many other cognitive and social domains (Redick, Heitz, & Engle, 2007).

The dynamics of temperature extremes

Changes in the occurrence of atmospheric circulation patterns are not well understood. A study finds that these have been a big factor in observed changes in regional temperature extremes during recent decades.

EU free movement law and the legal recognition of same-sex relationships: the case for mutual recognition

This article seeks to examine the cross-border legal recognition of same-sex relationships in the EU. Although the Member States maintain an exclusive competence in the field of family law and, thus, it is up to them to determine whether they will provide a legal status to same-sex couples within their territory, they need to exercise their powers in that field in a way that does not violate EU law. This, it is suggested, requires that Member States mutually recognize the legal status of same-sex couples and do not treat same-sex couples worse than opposite-sex couples, if the basis of the differentiation is, merely, the (homosexual) sexual orientation of the two spouses/partners. Nonetheless, the current legal framework does not make it clear that Member States are under such an obligation. The main argument of the article, therefore, is that the EU must adopt a more hands-on approach towards this issue.

The grass-free lawn: floral performance and management implications

Grass lawns are a ubiquitous feature of urban green-space throughout much of the temperate world. Species poor and intensively managed, lawns are ecologically impoverished, however environmentally aware lawn owners are reluctant to implement alternatives due to aesthetic concerns. Developing an alternative lawn format which is both biodiversity friendly and aesthetically pleasing is an imperative for urban greening. We suggest that such an alternative can be provided by replacing the grass lawn by a forb-based mix. To advance this, we tested the floral performance of three groups of clonal perennial forbs (native, non-native and mixed), each maintained using standard lawn management mowing regimes. Our findings show that both the frequency of mowing and the height at which mowing is applied influence floral performance and lawn aesthetics. Species origin was found to influence floral productivity, floral visibility and floral variety within grass-free lawns, with native species providing the greatest floral performance. The behaviour and management of grass lawns was not found to be a suitable analogue for the management of grass-free lawns and grass-free lawns are sufficiently different from grass lawns to require an entirely original management approach. We suggest that the grass-free lawn can provide an aesthetically and environmentally relevant replacement for the ubiquitous and ecologically-poor grass lawn.

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.

Molecular insights of p47phox phosphorylation dynamics in the regulation of NADPH oxidase activation and superoxide production

Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47phox is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47phox phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47phox protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47phox is critical for stabilizing its autoinhibited structure. Ser-379 phosphorylation disrupts H-bonds that link the C-terminal tail to the autoinhibitory region (AIR) and the tandem Src homology 3 (SH3) domains, allowing the AIR to undergo phosphorylation to expose the SH3 pocket for p22phox binding. These findings were confirmed by site-directed mutagenesis and gene transfection of p47phox_/_ coronary microvascular cells. Compared with wild-type p47phoxcDNAtransfected cells, the single mutation of S379A completely blocked p47phox membrane translocation, binding to p22phox and endothelial O2 . production in response to acute stimulation of PKC. p47phox C-terminal tail plays a key role in stabilizing intramolecular interactions at rest. Ser-379 phosphorylation is a molecular switch which initiates p47phox conformational changes and NADPH oxidase-dependent superoxide production by cells.

An annotation-free method for evaluating privacy protection techniques in videos

While several privacy protection techniques are pre- sented in the literature, they are not complemented with an established objective evaluation method for their assess- ment and comparison. This paper proposes an annotation- free evaluation method that assesses the two key aspects of privacy protection that are privacy and utility. Unlike some existing methods, the proposed method does not rely on the use of subjective judgements and does not assume a spe- cific target type in the image data. The privacy aspect is quantified as an appearance similarity and the utility aspect is measured as a structural similarity between the original raw image data and the privacy-protected image data. We performed an extensive experimentation using six challeng- ing datasets (including two new ones) to demonstrate the effectiveness of the evaluation method by providing a per- formance comparison of four state-of-the-art privacy pro- tection techniques.

Managing the complexity of information flow for construction small and medium-sized enterprises (CSMEs) using system dynamics and collaborative technologies

With the increase in e-commerce and the digitisation of design data and information,the construction sector has become reliant upon IT infrastructure and systems. The design and production process is more complex, more interconnected, and reliant upon greater information mobility, with seamless exchange of data and information in real time. Construction small and medium-sized enterprises (CSMEs), in particular,the speciality contractors, can effectively utilise cost-effective collaboration-enabling technologies, such as cloud computing, to help in the effective transfer of information and data to improve productivity. The system dynamics (SD) approach offers a perspective and tools to enable a better understanding of the dynamics of complex systems. This research focuses upon system dynamics methodology as a modelling and analysis tool in order to understand and identify the key drivers in the absorption of cloud computing for CSMEs. The aim of this paper is to determine how the use of system dynamics (SD) can improve the management of information flow through collaborative technologies leading to improved productivity. The data supporting the use of system dynamics was obtained through a pilot study consisting of questionnaires and interviews from five CSMEs in the UK house-building sector.