42 research outputs found

    Recommended Selective Maintenance and Rehabilitation Treatment Approach for Air Force Primary Rigid Runway Pavement Systems

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    The Air Force is facing the challenge to preserve the current inventory of 154 million square yards of paved airfield assets while at the same time reducing the budget by $36.2 billion between fiscal years 2015-2019. This research sought to determine a selective maintenance and rehabilitation treatment approach that allocates resources efficiently to preserve the degrading pavement assets in the financially constrained environment. Air Force pavement inspection reports from the past five years provided 4289 observed pavement distress data points for this research. The data was inputted into the pavement management software, PAVER, to calculate the Pavement Condition Index (PCI) deduct values for every pavement distress combinations. A pavement distress prioritization list was created from the 111 PCI deduct value calculations to rank the impact that different distresses have on the condition of pavement systems. The analysis led to the recommended selective maintenance and rehabilitation treatment approach of treating all medium and high severity joint seal damage with joint seal repair, repairing all pavement slabs with slab replacement that had a PCI less than 70 and with a PCI deduct greater than 10, and using all remaining resources on the Air Force recommended treatments. The recommended approach minimizes the potential of Foreign Object Damage, uses corrective measures in the form of slab replacement to repair the worst conditioned and highest priority slabs, and reduces further pavement degradation with the Air Force recommended treatments

    Application performance of elements in a floating–gate FPAA

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    Field–programmable analog arrays (FPAAs) provide a method for rapidly prototyping analog systems. Currently available commercial and academic FPAAs are typically based on operational amplifiers (or other similar analog primitives) with only a few computational elements per chip. While their specific architectures vary, their small sizes and often restrictive interconnect designs leave current FPAAs limited in functionality, flexibility, and usefulness. In this paper, we explore the use of floating–gate devices as the core programmable element in a signal processing FPAA. A generic FPAA architecture is presented that offers increased functionality and flexibility in realizing analog systems. In addition, the computational analog elements are shown to be widely and accurately programmable while remaining small in area. 1. LOW–POWER SIGNAL PROCESSING The future of FPAAs lie in their ability to speed the implementatio

    Developing large-scale field-programmable analog arrays for rapid prototyping

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    Field-programmable analog arrays (FPAAs) provide a method for rapidly prototyping analog systems. While currently available FPAAs vary in architecture and interconnect design, they are often limited in size and flexibility. For FPAAs to be as useful and marketable as modern digital reconfigurable devices, new technologies must be explored to provide area efficient, accurately programmable analog circuitry that can be easily integrated into a larger digital/mixed signal system. By leveraging recent advances in floating gate transistors, a new generation of FPAAs are achievable that will dramatically advance the current state of the art in terms of size, functionality, and flexibility

    A Versatile, Portable Intravital Microscopy Platform for Studying Beta-cell Biology In Vivo

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    The pancreatic islet is a complex micro-organ containing numerous cell types, including endocrine, immune, and endothelial cells. The communication of these systems is lost upon isolation of the islets, and therefore the pathogenesis of diabetes can only be fully understood by studying this organized, multicellular environment in vivo. We have developed several adaptable tools to create a versatile platform to interrogate β-cell function in vivo. Specifically, we developed β-cell-selective virally-encoded fluorescent protein biosensors that can be rapidly and easily introduced into any mouse. We then coupled the use of these biosensors with intravital microscopy, a powerful tool that can be used to collect cellular and subcellular data from living tissues. Together, these approaches allowed the observation of in vivo β-cell-specific ROS dynamics using the Grx1-roGFP2 biosensor and calcium signaling using the GcAMP6s biosensor. Next, we utilized abdominal imaging windows (AIW) to extend our in vivo observations beyond single-point terminal measurements to collect longitudinal physiological and biosensor data through repeated imaging of the same mice over time. This platform represents a significant advancement in our ability to study β-cell structure and signaling in vivo, and its portability for use in virtually any mouse model will enable meaningful studies of β-cell physiology in the endogenous islet niche

    Microbial sophorolipids inhibit colorectal tumour cell growth in vitro and restore haematocrit in Apcmin+/− mice

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    Sophorolipids are glycolipid biosurfactants consisting of a carbohydrate sophorose head with a fatty acid tail and exist in either an acidic or lactonic form. Sophorolipids are gaining interest as potential cancer chemotherapeutics due to their inhibitory effects on a range of tumour cell lines. Currently, most anti-cancer studies reporting the effects of sophorolipids have focused on lactonic preparations with the effects of acidic sophorolipids yet to be elucidated. We produced a 94% pure acidic sophorolipid preparation which proved to be non-toxic to normal human colonic and lung cells. In contrast, we observed a dose-dependent reduction in viability of colorectal cancer lines treated with the same preparation. Acidic sophorolipids induced apoptosis and necrosis, reduced migration, and inhibited colony formation in all cancer cell lines tested. Furthermore, oral administration of 50 mg kg(-1) acidic sophorolipids over 70 days to Apc(min+/-) mice was well tolerated and resulted in an increased haematocrit, as well as reducing splenic size and red pulp area. Oral feeding did not affect tumour numbers or sizes in this model. This is the first study to show that acidic sophorolipids dose-dependently and specifically reduces colon cancer cell viability in addition to reducing tumour-associated bleeding in the Apc(min+/-) mouse model

    Changing supersites: Assessing the impact of the southern UK EMEP supersite relocation on measured atmospheric composition

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    In January 2016 the United Kingdom's southern European Monitoring and Evaluation Programme (EMEP) level-2 air pollution monitoring 'supersite' was relocated from Harwell, Oxfordshire to Chilbolton Observatory, Hampshire. As no co-location study was undertaken, this work retrospectively investigates whether the supersite relocation has led to discontinuities in the time series of concentrations of commonly studied gaseous pollutants (NOx, NH3, SO2 and O3) and particulate matter (PM2.5 and PM10). Two years of measurements pre- and post-relocation (2014–15 and 2016–17 respectively) were analysed in conjunction with meteorological variables and local emission data. The deweather package was applied to the concatenated time series to minimise the influence of meteorology. Similar average concentrations of PM2.5, PM10, SO2 and O3 were observed, but there were substantial differences in that of NOx and NH3 (increase by factors of ~1.6 and ~3, respectively). The considerably higher NH3 concentrations at Chilbolton are attributed to the close proximity of mixed farmland, in particular to a strong south-westerly source contributing to ~50% of the annual average. NOx and PM concentrations in easterly winds arriving at Chilbolton are ~2.7 and ~1.5 times larger than at Harwell, from sources including the M3 motorway and Greater London. Westerly concentrations of NOx remain similar, therefore despite a higher frequency of westerly wind, annual mean concentrations are larger. Lower concentrations of PM arriving from the west result in similar annual averages. The secondary inorganic and black carbon components of PM were broadly similar between the sites. The differences in average NOx and NH3 at Chilbolton must be taken into account when considering long-term regional trends based on the southern UK supersite data

    A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis

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    Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4-MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4-MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency

    Regional and hemispheric influences on measured spring peroxyacetyl nitrate (PAN) mixing ratios at the Auchencorth UK EMEP supersite

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    AbstractThis work presents 15-min averaged measurements of peroxyacetyl nitrate (PAN) obtained during spring 2014 (24/04/2014 – 06/05/2014) at the Auchencorth UK EMEP supersite (southeast Scotland). The aim of this analysis was to investigate the conditions producing the distribution of PAN mixing ratios at the supersite in spring 2014. Air mass back trajectories showed the majority of air masses to have spent substantial time over the UK, continental Europe or Scandinavia prior to arrival at Auchencorth. The median and 95th percentile PAN mixing ratios observed were 0.46ppb and 1.03ppb, respectively. The median mixing ratio was elevated compared with previous PAN measurements during springtime (April–May) in southeast Scotland (corresponding median mixing ratios April–May 1994–1998: 0.1–0.3ppb), which is hypothesised to be due to conditions conducive to regional (European) photochemical PAN production. Additionally, PAN mixing ratios during regionally influenced conditions (0.4–1.5ppb) were substantially more elevated from hemispheric background mixing ratios (0.4–0.6ppb) than for ozone (O3, regional: 10–45ppb, hemispheric: 30–40ppb). PAN and O3 both impact upon vegetation and human health and it is necessary to understand the extent to which hemispheric and regional processes contribute to their abundances in different locations. Regional processes can both increase and decrease PAN and O3 mixing ratios compared to imported hemispheric background mixing ratios. This study concludes that during the measurement period in spring 2014 at the Auchencorth supersite, regional PAN and O3 modifying processes enhanced PAN mixing ratios more than for O3
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