Fluid Shear Induces Conformation Change in Human Blood Protein von Willebrand Factor in Solution

Many of the physiological functions of von Willebrand Factor (VWF), including its binding interaction with blood platelets, are regulated by the magnitude of applied fluid/hydrodynamic stress. We applied two complementary strategies to study the effect of fluid forces on the solution structure of VWF. First, small-angle neutron scattering was used to measure protein conformation changes in response to laminar shear rates (G) up to 3000/s. Here, purified VWF was sheared in a quartz Couette cell and protein conformation was measured in real time over length scales from 2-140 nm. Second, changes in VWF structure up to 9600/s were quantified by measuring the binding of a fluorescent probe 1,1'-bis(anilino)-4-,4'-bis(naphtalene)-8,8'-disulfonate (bis-ANS) to hydrophobic pockets exposed in the sheared protein. Small angle neutron scattering studies, coupled with quantitative modeling, showed that VWF undergoes structural changes at G < 3000/s. These changes were most prominent at length scales <10 nm (scattering vector (q) range >0.6/nm). A mathematical model attributes these changes to the rearrangement of domain level features within the globular section of the protein. Studies with bis-ANS demonstrated marked increase in bis-ANS binding at G > 2300/s. Together, the data suggest that local rearrangements at the domain level may precede changes at larger-length scales that accompany exposure of protein hydrophobic pockets. Changes in VWF conformation reported here likely regulate protein function in response to fluid shear.

Using mixed-methods to examine teachers’ attitudes to educational change:The case of the Skills for Life strategy for improving adult literacy and numeracy skills in England.

This paper reports on a longitudinal study that examines how a national reform introduced in England in the field of adult literacy, language, and numeracy is affecting teachers. The paper focuses on the use of a mixed methodology to explore teachers' attitudes to the reform and how these change over time. The quantitative strand includes the construction and use of a Likert-type instrument for measuring the attitudes of a panel of 1,500 teachers. The qualitative strand builds on the quantitative results and includes focus groups and in-depth interviews with a subsample of teachers in the panel. As the study is still in its initial phase, the purpose is not to present findings, but to discuss how quantitative and qualitative evidence can be combined in evaluation research.

The relationship between breastfeeding and postpartum weight change-a systematic review and critical evaluation

Pregnancy and the postpartum period is a time of increased vulnerability for retention of excess body fat in women. Breastfeeding (BF) has been shown to have many health benefits for both mother and baby; however, its role in postpartum weight management is unclear. Our aim was to systematically review and critically appraise the literature published to date in relation to the impact of BF on postpartum weight change, weight retention and maternal body composition. Electronic literature searches were carried out using MEDLINE, EMBASE, PubMed, Web of Science, BIOSIS, CINAHL and British Nursing Index. The search covered publications up to 12 June 2012 and included observational studies (prospective and retrospective) carried out in BF mothers (either exclusively or as a subgroup), who were 2 years postpartum and with a body mass index (BMI) >18.5 kg m(-2), with an outcome measure of change in weight (including weight retention) and/or body composition. Thirty-seven prospective studies and eight retrospective studies were identified that met the selection criteria; studies were stratified according to study design and outcome measure. Overall, studies were heterogeneous, particularly in relation to sample size, measurement time points and in the classification of BF and postpartum weight change. The majority of studies reported little or no association between BF and weight change (n=27, 63%) or change in body composition (n=16, 89%), although this seemed to depend on the measurement time points and BF intensity. However, of the five studies that were considered to be of high methodological quality, four studies demonstrated a positive association between BF and weight change. This systematic review highlights the difficulties of examining the association between BF and weight management in observational research. Although the available evidence challenges the widely held belief that BF promotes weight loss, more robust studies are needed to reliably assess the impact of BF on postpartum weight management.International Journal of Obesity advance online publication, 20 August 2013; doi:10.1038/ijo.2013.132.

The effects of global climate change on the cycling and processes of persistent organic pollutants (POPs) in the North Sea

The fate and cycling of two selected legacy persistent organic pollutants (POPs), PCB 153 and gamma-HCH, in the North Sea in the 21st century have been modelled with combined hydrodynamic and fate and transport ocean models
(HAMSOM and FANTOM, respectively). To investigate the impact of climate variability on POPs in the North Sea in the 21st century, future scenario model runs for three 10-year periods to the year 2100 using plausible levels of both in
situ concentrations and atmospheric, river and open boundary inputs are performed. This slice mode under a moderate scenario (A1B) is sufficient to provide a basis for further analysis. For the HAMSOM and atmospheric forcing, results of the IPCC A1B (SRES) 21st century scenario are utilized, where surface forcing is provided by the REMO downscaling of the ECHAM5 global atmospheric model, and open boundary conditions are provided by the MPIOM global ocean model.
Dry gas deposition and volatilization of gamma-HCH increase in the future relative to the present by up to 20% (in the spring and summer months for deposition and in summer for volatilization). In the water column, total mass of
gamma-HCH and PCB 153 remain fairly steady in all three runs. In sediment,
gamma-HCH increases in the future runs, relative to the present, while PCB 153 in sediment decreases exponentially in all three runs, but even faster in the future, due to the increased number of storms, increased duration of gale wind conditions and increased water and air temperatures, all of which are the result of climate change. Annual net sinks exceed sources at the ends of all periods.
Overall, the model results indicate that the climate change scenarios considered here generally have a negligible influence on the simulated fate and transport of the two POPs in the North Sea, although the increased number and magnitude of storms in the 21st century will result in POP resuspension and ensuing revolatilization events. Trends in emissions from primary and secondary sources will remain the key driver of levels of these contaminants over time.

On sea level change in the North Sea influenced by the North Atlantic Oscillation: local and remote steric effects

In this study, contributions of both local steric and remote baroclinic effects (i.e., steric variations external to the region of interest) to the inter-annual variability of winter sea level in the North Sea, with respect to the North Atlantic Oscillation (NAO), for the period of 1953–2010 are investigated. On inter-annual time scales in this period, the NAO is significantly correlated to sea level variations in the North Sea only in the winter months (December–March), while its correlation to sea temperature over much of the North Sea is only significant in January and February. The discrepancy in sea level between observations and barotropic tide and surge models forced by tides and local atmospheric forcing, i.e., local atmospheric pressure effects and winds, in the present study are found to be consistent with previous studies. In the North Sea, local thermosteric effects caused by thermal expansion play a minor role on winter-mean NAO related sea level variability compared with atmospheric forcing. This is particularly true in the southeastern North Sea where water depths are mostly less than 25 m. Our calculations demonstrate that the discrepancy can be mostly explained by remote baroclinic effects, which appear as water mass exchanges on the continental shelf and are therefore only apparent in ocean bottom pressure. In the North Sea, NAO related sea level variations seem to be a hybrid of barotropic and baroclinic processes. Hence, they can only be adequately modelled with three-dimensional baroclinic ocean models that include contributions of baroclinic effects and large-scale atmospheric forcing external to the region of interest.

Use of Short Time-on-Stream Attenuated Total Internal Reflection Infrared Spectroscopy To Probe Changes in Adsorption Geometry for Determination of Selectivity in the Hydrogenation of Citral

Abstract Image

A new experimental procedure based on attenuated total reflection infrared spectroscopy has been developed to investigate surface species under liquid phase reaction conditions. The technique has been tested by investigating the enhanced selectivity in the hydrogenation of α,β-unsaturated aldehyde citral over a 5% Pt/SiO2 catalyst toward unsaturated alcohols geraniol/nerol, which occurs when citronellal is added to the reaction. The change in selectivity is proposed to be the result of a change in the citral adsorption mode in the presence of citronellal. Short time on stream attenuated total internal reflection infrared spectroscopy has allowed identification of the adsorption modes of citral. With no citronellal, citral adsorbs through both the C═C and C═O groups; however, in the presence of citronellal, citral adsorption occurs through the C═O group only, which is proposed to be the cause of the altered reaction selectivity.

Public management, Peace-building and Creating Change: Shifting the Lens of Analysis from the Macro to the Micro

Considerable time, research money and expertise has been spent exploring the complex reality of ethno nationalist conflict and the role that public management plays in supporting the transition from violent conflict to stability, order and prosperity (Esman 1999; Guelke and Milton-Edwards 2000; Brinkerhoff 2005; Brinkerhoff, Wetterberg et al. 2012; Rao 2014). However, there seems to be a gap in relation to the practical challenges of managing change within, through and beyond such conflict. This paper aims to begin the process of putting a framework around the real experience of public management in conflict and transition by shifting the lens of analysis from macros concerns about sequencing interventions (Rao 2014) and legitimate requirements of security, stability and service delivery (Brinkerhoff, Wetterberg et al. 2012) to a micro analysis of the attitudes, behaviours, challenges and compromises held and faced by those public servants on the front line of conflict management and conflict transformation processes. Using senior managers as the unit of analysis and Northern Ireland as an embryonic case study, this paper discusses the links between ethno nationalist societal conflict, public sector reform and manager behaviour. In doing so, it highlights some initial data from an early pilot study into the experiences of individuals in significant public service roles at various stages of the NI conflict / peace process and draws some tentative conclusions about the viability of a wider study.

Robust visual tracking using structurally random projection and weighted least squares

Sparse representation based visual tracking approaches have attracted increasing interests in the community in recent years. The main idea is to linearly represent each target candidate using a set of target and trivial templates while imposing a sparsity constraint onto the representation coefficients. After we obtain the coefficients using L1-norm minimization methods, the candidate with the lowest error, when it is reconstructed using only the target templates and the associated coefficients, is considered as the tracking result. In spite of promising system performance widely reported, it is unclear if the performance of these trackers can be maximised. In addition, computational complexity caused by the dimensionality of the feature space limits these algorithms in real-time applications. In this paper, we propose a real-time visual tracking method based on structurally random projection and weighted least squares techniques. In particular, to enhance the discriminative capability of the tracker, we introduce background templates to the linear representation framework. To handle appearance variations over time, we relax the sparsity constraint using a weighed least squares (WLS) method to obtain the representation coefficients. To further reduce the computational complexity, structurally random projection is used to reduce the dimensionality of the feature space while preserving the pairwise distances between the data points in the feature space. Experimental results show that the proposed approach outperforms several state-of-the-art tracking methods.

Tracking Change in Northern Ireland Policing: Temporal Phases and Key Themes

Purpose
– The purpose of this paper is to explore and explain the change process in Northern Ireland policing through an analysis of temporally bracketed change phases and key change delivery themes ranging from 1996 to 2012.

Design/methodology/approach
– The research approach adopted is process based, longitudinal and multi-method, utilising “temporal bracketing” to determine phases of change and conjunctural reasoning to unravel the systematic factors interacting over time, within the case.

Findings
– The paper identifies and temporally brackets four phases of change: “Tipping point”; “Implementation, Symbolic Modification and Resistance”; “Power Assisted Steering”; and “A Return to Turbulence”, identifies four themes that emerge from RUC-PSNI experience: the role of adaptive leadership; pace and sequencing of change implementation; sufficient resourcing; and the impact of external agents acting as boundary spanners, and comments on the prominence of these themes through the phases. The paper goes on to reflect upon how these phases and themes inform our understanding of organisational change within policing organisations generally and within politically pressurised transition processes.

Originality/value
– The contribution of the paper lies in the documentation of an almost unique organisational case in an environmentally forced change process. In this it contains lessons for other organisations facing similar, if less extreme challenges and presents an example of intense change analysed longitudinally.

Next-generation sequencing: a change of paradigm in molecular diagnostic validation

Next-generation sequencing (NGS) is beginning to show its full potential for diagnostic and therapeutic applications. In particular, it is enunciating its capacity to contribute to a molecular taxonomy of cancer, to be used as a standard approach for diagnostic mutation detection, and to open new treatment options that are not exclusively organ-specific. If this is the case, how much validation is necessary and what should be the validation strategy, when bringing NGS into the diagnostic/clinical practice? This validation strategy should address key issues such as: what is the overall extent of the validation? Should essential indicators of test performance such as sensitivity of specificity be calculated for every target or sample type? Should bioinformatic interpretation approaches be validated with the same rigour? What is a competitive clinical turnaround time for a NGS-based test, and when does it become a cost-effective testing proposition? While we address these and other related topics in this commentary, we also suggest that a single set of international guidelines for the validation and use of NGS technology in routine diagnostics may allow us all to make a much more effective use of resources.

High resolution monitoring of surface morphological change of building limestones in response to simulated salt weathering

A salt weathering simulation using a mix of sodium chloride (5%) and magnesium sulphate (5%) in a salt corrosion cabinet and five granular limestones is described. Progressive surface loss from vertical exposed faces was mapped using a high resolution (sub-millimetre) object scanner (Konica Minolta Vi9i). Patterns of loss are related to surface porosity/permeability measurements obtained using a hand-held gas permeameter. Introduction of this spatial dimension into damage assessment is seen as essential for understanding the initial conditions that allow surface loss to be triggered, and changes in surface characteristics as weathering proceeds which dictate subsequent decay in space and time. Preliminary observations suggest that scanning at this high resolution is particularly valuable in quantifying very subtle trends and distortions that are pre-cursors to material loss, including surface swelling and pore filling.

Demand response to improved walking infrastructure: A study into the economics of walking and health behaviour change

Walking is the most common form of moderate‐intensity physical activity among adults, is widely accessible and especially appealing to obese people. Most often policy makers are interested in valuing the effect on walking of changes in some characteristics of a neighbourhood, the demand response for walking, of infrastructure changes. A positive demand response to improvements in the walking environment could help meet the public health target of 150 minutes of at least moderate‐intensity physical activity per week. We model walking in an individual’s local neighbourhood as a ‘weak complement’ to the characteristics of the neighbourhood itself. Walking is affected by neighbourhood
characteristics, substitutes, and individual’s characteristics, including their opportunity cost of time.  Using compensating variation, we assess the economic benefits of walking and how walking behaviour is affected by improvements to the neighbourhood.  Using a sample of 1,209 respondents surveyed over a 12 month period (Feb 2010‐Jan 2011) in East Belfast, United Kingdom, we find that a policy that increased walkability and people’s perception of access to shops and facilities  would lead to an increase in walking of about 36 minutes/person/week, valued at £13.65/person/week. When focusing on inactive residents, a policy that improved the walkability of the area would lead to guidelines for physical activity being reached by only 12.8% of the population who are currently inactive. Additional interventions would therefore be needed to encourage inactive residents to
achieve the recommended levels of physical activity, as it appears that interventions that improve the walkability of an area are particularly effective in increasing walking among already active citizens, and, among the inactive ones, the best response is found among healthier, younger and wealthier citizens.

Time-dependent tegumental surface changes in juvenile Fasciola gigantica in response to triclabendazole treatment in goat

Triclabendazole (TCBZ), the anthelmintic drug active against both mature and immature liver flukes, was used to investigate the effect of in vivo treatment on the tegumental surface of juvenile Fasciola gigantica. Five goats were infected with 150 F. gigantica metacercariae each by oral gavage. Four of them were treated with single dose of TCBZ at 10mg/kg at four weeks post-infection. They were euthanized at 0 (untreated), 24, 48, 72 and 96h post treatment. Juvenile flukes were manually retrieved from the goat livers and processed for scanning electron microscopy. In control flukes, the anterior region was adorned with sharply pointed spines projecting away from the surface, while in the posterior region, spines become shorter and narrower, loosing serration and with the appearance of distinct furrows and papillae. The dorsal surface retained the same pattern of surface architecture similar to that of ventral surface. Flukes obtained from 24h post-treatment did not show any apparent change and were still very active. However, there were limited movements and some blebbing, swelling, deposition of tegumental secretions and some flattening displayed by the flukes of 48h post-treatment. All the worms were found dead 72h post-treatment and showed advanced level of tegumental disruptions, consisting of severe distortion of spines, sloughing off the tegument to expose the basal lamina, formation of pores and isolated patches of lesions. By 96h post-treatment, the disruption was extremely severe and the tegument was completely sheared off causing deeper lesions that exposed the underlying musculature. The disruption was more severe at posterior than anterior region and on ventral than dorsal surface. The present study further establishes the time-course of TCBZ action in vivo with 100% efficacy against the juvenile tropical liver fluke.

Doing Gendered Time: The Harms of Women's Imprisonment

This chapter focuses on women’s imprisonment in the context of gendered punishment inflicted by the State. It considers the gender-specific consequences of incarceration for women prisoners and the potential of gender-responsive alternatives to custodial sentences. Following a brief historical overview, it traces the rise and consolidation of women’s incarceration in UK jurisdictions, noting the significance of devolution on the prison systems of Scotland and Northern Ireland. In examining the impact of neo-liberal policies and globalisation on women’s imprisonment, it draws comparisons with other advanced democratic states. Analysing the rationale underpinning the disproportionate rise in women’s incarceration, particularly in the UK and the USA the chapter identifies the persistent tensions between retributivism/ incapacitation and reformism/rehabilitation. Drawing on international research demonstrating the complex needs and vulnerabilities of women and girl prisoners, the chapter reveals the gendered harm experienced within penal regimes and the recent development - and limitations - of official gender-specific policies and practices. The emergence of distinct but related political discourses on ‘risk’ and ‘responsibilisation’ as applied to women in conflict with the law, and their consequent criminalisation, is critiqued in the contexts of structural disadvantage, gender discrimination and institutionalised racism. Within these oppressive dynamics often severe deprivations are inflicted on women’s acts of resistance both inside prison and in their communities post-release, further confining the potential of individual and collective agency. Finally, the chapter proposes fundamental change through establishing women-centred alternatives to prison, alongside policies committed to decarceration, while working towards securing the abolition of women’s imprisonment.

Fast Byzantine Leader Election in Dynamic Networks

We study the fundamental Byzantine leader election problem in dynamic networks where the topology can change from round to round and nodes can also experience heavy {\em churn} (i.e., nodes can join and leave the network continuously over time). We assume the full information model where the Byzantine nodes have complete knowledge about the entire state of the network at every round (including random choices made by all the nodes), have unbounded computational power and can deviate arbitrarily from the protocol. The churn is controlled by an adversary that has complete knowledge and control over which nodes join and leave and at what times and also may rewire the topology in every round and has unlimited computational power, but is oblivious to the random choices made by the algorithm. Our main contribution is an $O(\log^3 n)$ round algorithm that achieves Byzantine leader election under the presence of up to $O({n}^{1/2 - \epsilon})$ Byzantine nodes (for a small constant $\epsilon > 0$) and a churn of up to \\$O(\sqrt{n}/\poly\log(n))$ nodes per round (where $n$ is the stable network size).The algorithm elects a leader with probability at least $1-n^{-\Omega(1)}$ and guarantees that it is an honest node with probability at least $1-n^{-\Omega(1)}$; assuming the algorithm succeeds, the leader's identity will be known to a $1-o(1)$ fraction of the honest nodes. Our algorithm is fully-distributed, lightweight, and is simple to implement. It is also scalable, as it runs in polylogarithmic (in $n$) time and requires nodes to send and receive messages of only polylogarithmic size per round.To the best of our knowledge, our algorithm is the first scalable solution for Byzantine leader election in a dynamic network with a high rate of churn; our protocol can also be used to solve Byzantine agreement in a straightforward way.We also show how to implement an (almost-everywhere) public coin with constant bias in a dynamic network with Byzantine nodes and provide a mechanism for enabling honest nodes to store information reliably in the network, which might be of independent interest.