Review of Electronic-nose Technologies and Algorithms to Detect Hazardous Chemicals in the Environment

Novel mobile electronic-nose (e-nose) devices and algorithms capable of real-time detection of industrial and municipal pollutants, released from point-sources, recently have been developed by scientists worldwide that are useful for monitoring specific environmental-pollutant levels for enforcement and implementation of effective pollution-abatement programs. E-nose devices are ideal instruments for measuring and monitoring carbon and greenhouse-gas emissions due to their sensitivity to a wide diversity of volatile organic compounds (VOCs). A large number of e-nose instrument types, based on a wide diversity of technologies and operational mechanisms, are available to monitor gaseous and particulate pollutants released into the atmosphere, or liquid and dissolved organic pollutants released into municipal and industrial waste-water systems. Some commonly used e-nose technologies include conducting polymers (CP), metal-oxide semiconductor (MOS), quartz crystal microbalance (QCM), and surface acoustic wave (SAW) sensors. Potential pollution-detection applications of e-noses range from atmospheric pollutant (gas-leak) detection of carbon emissions from biofuel production plants and fossil-fuel production sources in the oil and gas industry to VOC-releases from numerous other industries. E-nose technologies are potentially capable of monitoring all phases of industrial manufacturing processes to minimize production of pollutants and maintain efficient, clean production lines. E-nose devices are also useful in designing more environmentallyfriendly

Developing a pressure ulcer risk factor minimum data set and risk assessment framework

AIM: To agree a draft pressure ulcer risk factor Minimum Data Set to underpin the development of a new evidenced-based Risk Assessment Framework.BACKGROUND: A recent systematic review identified the need for a pressure ulcer risk factor Minimum Data Set and development and validation of an evidenced-based pressure ulcer Risk Assessment Framework. This was undertaken through the Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research and incorporates five phases. This article reports phase two, a consensus study.DESIGN: Consensus study.METHOD: A modified nominal group technique based on the Research and Development/University of California at Los Angeles appropriateness method. This incorporated an expert group, review of the evidence and the views of a Patient and Public Involvement service user group. Data were collected December 2010-December 2011.FINDINGS: The risk factors and assessment items of the Minimum Data Set (including immobility, pressure ulcer and skin status, perfusion, diabetes, skin moisture, sensory perception and nutrition) were agreed. In addition, a draft Risk Assessment Framework incorporating all Minimum Data Set items was developed, comprising a two stage assessment process (screening and detailed full assessment) and decision pathways.CONCLUSION: The draft Risk Assessment Framework will undergo further design and pre-testing with clinical nurses to assess and improve its usability. It will then be evaluated in clinical practice to assess its validity and reliability. The Minimum Data Set could be used in future for large scale risk factor studies informing refinement of the Risk Assessment Framework

Continued Development of the Advanced Stirling Convertor (ASC)

The Advanced Stirling Convertor (ASC) is being developed under contract with the NASA Glenn Research Center (GRC) and is supported by NASA s Science Mission Directorate for potential use in future radioisotope power systems having significantly increased efficiency and higher specific power compared to the current thermoelectric systems. An ASC with a lower temperature (approx.650 C) Inconel heater head is currently being substituted into the DOE/Lockheed Martin Advanced Stirling Radioisotope Generator (ASRG) program with a predicted convertor efficiency of 34 percent (AC electrical out to heat input ) at a temperature ratio of 2.7 and is expected to deliver approximately 75 W(sub ac). Continued development of the higher temperature (approx.850 C) version using existing materials and fabrication techniques in the hot portions is reported on here. The higher temperature ASC is expected to have 38 percent efficiency (AC electrical out to heat input) at a temperature ratio of 3.1 and is expected to deliver approximately 88 W(sub ac). The high temperature ASC also has approximately 30 C higher rejection temperature, which allows for further reduced system mass because of the reduced radiator size. Six higher temperature and hermetically sealed convertors are being built under this effort for extended life testing at GRC

AXTAR: Mission Design Concept

The Advanced X-ray Timing Array (AXTAR) is a mission concept for X-ray timing of compact objects that combines very large collecting area, broadband spectral coverage, high time resolution, highly flexible scheduling, and an ability to respond promptly to time-critical targets of opportunity. It is optimized for submillisecond timing of bright Galactic X-ray sources in order to study phenomena at the natural time scales of neutron star surfaces and black hole event horizons, thus probing the physics of ultradense matter, strongly curved spacetimes, and intense magnetic fields. AXTAR's main instrument, the Large Area Timing Array (LATA) is a collimated instrument with 2-50 keV coverage and over 3 square meters effective area. The LATA is made up of an array of supermodules that house 2-mm thick silicon pixel detectors. AXTAR will provide a significant improvement in effective area (a factor of 7 at 4 keV and a factor of 36 at 30 keV) over the RXTE PCA. AXTAR will also carry a sensitive Sky Monitor (SM) that acts as a trigger for pointed observations of X-ray transients in addition to providing high duty cycle monitoring of the X-ray sky. We review the science goals and technical concept for AXTAR and present results from a preliminary mission design study.Comment: 19 pages, 10 figures, to be published in Space Telescopes and Instrumentation 2010: Ultraviolet to Gamma Ray, Proceedings of SPIE Volume 773

Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study

BACKGROUND: Research on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT), and three traditional self-report measures. METHODS: 195 individuals (42% male) were recruited from a university campus and were assessed in small group sessions using personal computers. Genotyping was conducted using previously established protocols. For the DRD2 TaqI A locus, individuals were designated as possessing at least one copy of the A1 allele (A1+) or not (A1-), and for the DRD4 48-bp VNTR locus, individuals were designated as having at least one long allele (7 repeats or longer, L+) or not (L-). Principal analyses used multiple univariate factorial 2 (A1+/A1-) × 2 (L+/L-) analyses of variance. RESULTS: A significant main effect of A1+ status on DDT performance was evident (p = .006) as well as a significant interaction effect (p = .006) between both genes. No other significant effects were evident on the self-report measures, with the exception of a trend toward an interaction effect on the Sensation Seeking Scale. Exploratory analyses suggested that the significant effects were not a function of population stratification or gender. DISCUSSION: These data suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as measured with a delay discounting task. Specifically, these findings suggest that an interaction between the functional effects of the two unlinked genotypes results in significant difference in the balance of mesolimbic dopaminergic activation relative to frontal-parietal activation. However, these findings are also the first in this area and must be replicated. CONCLUSION: These findings suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR polymorphisms in the expression of impulsivity and provide initial support for the utility of using behavioral measures for clarifying genetic influences on impulsivity

A new fireworm (Amphinomidae) from the Cretaceous of Lebanon identified from three-dimensionally preserved myoanatomy

© 2015 Parry et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

Identification and Validation of Novel Small Molecule Disruptors of HuR-mRNA Interaction

HuR, an RNA binding protein, binds to adenine- and uridine-rich elements (ARE) in the 3′-untranslated region (UTR) of target mRNAs, regulating their stability and translation. HuR is highly abundant in many types of cancer, and it promotes tumorigenesis by interacting with cancer-associated mRNAs, which encode proteins that are implicated in different tumor processes including cell proliferation, cell survival, angiogenesis, invasion, and metastasis. Drugs that disrupt the stabilizing effect of HuR upon mRNA targets could have dramatic effects on inhibiting cancer growth and persistence. In order to identify small molecules that directly disrupt the HuR–ARE interaction, we established a fluorescence polarization (FP) assay optimized for high throughput screening (HTS) using HuR protein and an ARE oligo from Musashi RNA-binding protein 1 (Msi1) mRNA, a HuR target. Following the performance of an HTS of ~6000 compounds, we discovered a cluster of potential disruptors, which were then validated by AlphaLISA (Amplified Luminescent Proximity Homogeneous Assay), surface plasmon resonance (SPR), ribonucleoprotein immunoprecipitation (RNP IP) assay, and luciferase reporter functional studies. These compounds disrupted HuR–ARE interactions at the nanomolar level and blocked HuR function by competitive binding to HuR. These results support future studies toward chemical probes for a HuR function study and possibly a novel therapy for HuR-overexpressing cancers. NA-binding proteins (RBPs) are critical trans factors that associate with specific cis elements present in mRNAs, thereby regulating the fate of target mRNAs.1 The RBP Hu antigen R (HuR, also known as HuA; Hu references the patient's initials from whom an anti-HuR, autoinflammatory antibody was first isolated2) is a member of the embryonic lethal abnormal vision-like (ELAVL) protein family that binds to adenine- and uridine-rich elements (ARE) mainly located in the mRNA 3′-untranslated region (UTR).1,3,4 HuR is elevated in a broad range of cancer tissues compared with the corresponding normal tissues.5 In early reports, upregulated HuR in brain and colon cancers was linked to the enhanced expression of COX-2, VEGF, TGF-β, IL-8, and other cancer-associated proteins,6,7 Subsequent studies revealed that HuR was broadly overexpressed in virtually all malignancies tested, including cancers of the colon,5,8,9 prostate,10,11 breast,12 brain,6 ovaries,13 pancreas,14 and lung.15 Elevated cytoplasmic accumulation of HuR correlates with high-grade malignancy and serves as a prognostic factor of poor clinical outcome in those cancers.3,4,16 HuR is proposed to play a causal role in tumor development. Cultured carcinoma cells with elevated HuR produced significantly larger tumors than those arising from control populations in a mouse xenograft model,5 while reducing HuR by siRNA or microRNA led to decreased tumor size.5,17 HuR contains three RNA recognition motifs (RRM), of which RRM1 and RRM2 are involved in RNA binding, whereas RRM3 does not contribute to RNA binding but is needed for cooperative assembly of HuR oligomers on RNA.18 Many cytokine and proto-oncogene mRNAs have been identified as containing AREs within their 3′-UTRs, which confer a short mRNA half-life.19 Cytoplasmic binding of HuR to these ARE-containing mRNAs is generally accepted as leading to mRNA stabilization and increased translation.20,21 HuR promotes tumorigenesis by interacting with cancer-associated mRNAs which encode proteins implicated in different tumor processes including cell proliferation, cell survival, angiogenesis, invasion, and metastasis.3,4,16 HuR also promotes the translation of several target mRNAs encoding proteins that are involved in cancer treatment resistance.16,22–24 Taken together, these findings suggest that HuR is an attractive target for developing novel cancer therapies. RBPs have been considered “undruggable targets” due to the lack of a well-defined binding pocket for target mRNA. Indeed, there has globally been limited success in finding small molecules that directly disrupt the HuR interaction with AREs of target mRNAs, with limited reports indicating several active hits arising from screening for HuR inhibitors.25–27 Those reported hits are structurally independent, so they cannot provide information for later structure–activity relationship (SAR) analysis to design more potent and specific HuR inhibitors. Currently, the most potent hit reported (MS-444) acts via inhibition of HuR homodimerization, leading to disruption of the HuR–ARE interaction.25 Here, we try to identify HuR inhibitors, which competitively bind to HuR and directly disrupt the HuR–ARE interaction. In this study, we optimized a fluorescent polarization-based (FP-based) binding assay using human full-length HuR protein and an ARE region of Musashi1 (Msi1) 3′-UTR mRNA. HuR binds to and stabilizes the mRNA of Msi128 allowing for oncogenic overexpression of Msi1 and negative regulation of Numb and adenomatous polyposis coli (APC), which are involved in controlling Notch and Wnt signaling pathways.29 Using this FP-based HTS, we screened a library of ~6000 compounds and identified a set of HuR–ARE disruptors, which were validated by AlphaLISA assay, SPR, RNP IP, and luciferase reporter functional studies. The discovery of these inhibitors and related inactive compounds provides the impetus for rational design of more potent and specific HuR–ARE disruptors

Near Infrared Monitoring of Ultracool Dwarfs: Prospects for Searching for Transiting Companions

Stars of late-M and L spectral types, collectively known as Ultracool Dwarfs (UCDs), may be excellent targets for searches for extrasolar planets. Owing to their small radii, the signal from an Earth-size planet transiting a UCD is, in principle, readily detectable. We present results from a study designed to evaluate the feasibility of using precise near infrared (NIR) photometry to detect terrestrial extrasolar planets orbiting UCDs. We used the Peters Automated InfRared Imaging TELescope (PAIRITEL) to observe a sample of 13 UCDs over a period of 10 months. We consider several important systematic effects in NIR differential photometry and develop techniques for generating photometry with a precision of 0.01 mag and long-term stability. We simulate the planet detection efficiency of an extended campaign to monitor a large sample of UCDs with PAIRITEL. We find that both a targeted campaign with a single telescope lasting several years and a campaign making use of a network of telescopes distributed in longitude could provide significant sensitivity to terrestrial planets orbiting UCDs, potentially in the habitable zone.Comment: 22 pages, 5 figures, 3 tables. Accepted for publication in PAS

Affordances, constraints and information flows as ‘leverage points’ in design for sustainable behaviour

Copyright @ 2012 Social Science Electronic PublishingTwo of Donella Meadows' 'leverage points' for intervening in systems (1999) seem particularly pertinent to design for sustainable behaviour, in the sense that designers may have the scope to implement them in (re-)designing everyday products and services. The 'rules of the system' -- interpreted here to refer to affordances and constraints -- and the structure of information flows both offer a range of opportunities for design interventions to in fluence behaviour change, and in this paper, some of the implications and possibilities are discussed with reference to parallel concepts from within design, HCI and relevant areas of psychology

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein