1,645 research outputs found

    Structural-acoustic coupling and psychophysical effects in the active control of noise in vehicles

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    Active noise control systems offer a potential method of reducing the weight of passive acoustic treatment and, therefore, increasing vehicles' fuel efficiency. These can be particularly cost-efficient if integrated with the entertainment system. A combined system is presented employing feedforward control of engine noise and feedback control of road noise, using a `modal' error signal. Due to the dependence of the feedback system on the modal response of the vehicle cabin, the influence of structural-acoustic coupling on this response and the consequent effects on the control performance are investigated. Simulations of the performance of the control systems in rigid and non-rigid enclosures show that the feedforward component is largely unaffected by structural-acoustic coupling, whilst the modal feedback performance is reduced by 3 dB due to the shift in the frequency of the targeted acoustic mode. The simulation results are confirmed through experiments conducted in a structural-acoustic coupled enclosure

    Too good to be true: when overwhelming evidence fails to convince

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    Is it possible for a large sequence of measurements or observations, which support a hypothesis, to counterintuitively decrease our confidence? Can unanimous support be too good to be true? The assumption of independence is often made in good faith, however rarely is consideration given to whether a systemic failure has occurred. Taking this into account can cause certainty in a hypothesis to decrease as the evidence for it becomes apparently stronger. We perform a probabilistic Bayesian analysis of this effect with examples based on (i) archaeological evidence, (ii) weighing of legal evidence, and (iii) cryptographic primality testing. We find that even with surprisingly low systemic failure rates high confidence is very difficult to achieve and in particular we find that certain analyses of cryptographically-important numerical tests are highly optimistic, underestimating their false-negative rate by as much as a factor of 2802^{80}

    Reading instruction in first-grade classrooms: Do basals control teachers?

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    This study describes first-grade teachers beliefs and practices about reading instruction. Drawing from interview and observational data, 16 teachers from four districts were placed on a continuum from skills-based to literature-based in relationship to their use of the basal. Only 2 teachers were found to rely solely on the basal, while 3 teachers enhanced the basal with literature, and 4 teachers used only literature in their reading instruction. Six teachers enhanced their basal use with additional skills and 1 teacher relied on skills only in her reading instruction. This diversity\u27 of teaching beliefs and practices was corroborated by questionnaire data from a larger sample of teachers. Next, a framework developed by Belenky, Clinchy, Goldberger, and Tarule (1986) was used to categorize teachers\u27 ways of knowing. The findings showed 1 teacher to be a silent knower, 6 were received knowers, 1 was a subjective knower, 7 were procedural knowers, and 1 was a connected knower. Results challenge Shannon\u27s (1987) hypothesis that basals deskill teachers while supporting Sosniak and Stodolskv\u27s (1993) view that teachers are more autonomous in their use of textbook materials

    In and out of Madagascar : dispersal to peripheral islands, insular speciation and diversification of Indian Ocean daisy trees (Psiadia, Asteraceae)

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    This study was supported by the European Union’s HOTSPOTS Training Network (MEST-2005-020561)Madagascar is surrounded by archipelagos varying widely in origin, age and structure. Although small and geologically young, these archipelagos have accumulated disproportionate numbers of unique lineages in comparison to Madagascar, highlighting the role of waif-dispersal and rapid in situ diversification processes in generating endemic biodiversity. We reconstruct the evolutionary and biogeographical history of the genus Psiadia (Asteraceae), a plant genus with near equal numbers of species in Madagascar and surrounding islands. Analyzing patterns and processes of diversification, we explain species accumulation on peripheral islands and aim to offer new insights on the origin and potential causes for diversification in the Madagascar and Indian Ocean Islands biodiversity hotspot. Our results provide support for an African origin of the group, with strong support for non-monophyly. Colonization of the Mascarenes took place by two evolutionary distinct lineages from Madagascar, via two independent dispersal events, each unique for their spatial and temporal properties. Significant shifts in diversification rate followed regional expansion, resulting in co-occurring and phenotypically convergent species on high-elevation volcanic slopes. Like other endemic island lineages, Psiadia have been highly successful in dispersing to and radiating on isolated oceanic islands, typified by high habitat diversity and dynamic ecosystems fuelled by continued geological activity. Results stress the important biogeographical role for Rodrigues in serving as an outlying stepping stone from which regional colonization took place. We discuss how isolated volcanic islands contribute to regional diversity by generating substantial numbers of endemic species on short temporal scales. Factors pertaining to the mode and tempo of archipelago formation and its geographical isolation strongly govern evolutionary pathways available for species diversification, and the potential for successful diversification of dispersed lineages, therefore, appears highly dependent on the timing of arrival, as habitat and resource properties change dramatically over the course of oceanic island evolution.Publisher PDFPeer reviewe

    Late Holocene Sedimentation and Paleoenvironmental History for the Tidal Marshes of the Potomac and Rappahannock Rivers, Tributaries to Chesapeake Bay

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    Instrumental tide gauge records indicate that the modern rates of sea-level rise in the Chesapeake Bay more than double the global average of 1.2-1.5 mm yr-1. The primary objective for this study is to establish a relative depositional history for the tidal marshes of the Potomac and Rappahannock Rivers that will help us improve our understanding of processes that influence sedimentation in the proximal tributaries of Chesapeake Bay. Marsh cores were collected from Blandfield Point VA, Tappahannock VA, and Potomac Creek VA. The sedimentary facies include: 1) a lower unit of organic-poor, grey clay with fine sand and silt layers and estuarine foraminifera; and 2) an upper unit of organic-rich clay and peat with abundant brackish to freshwater marsh foraminifera and thecamoebians. AMS 14C dating of bulk marsh sediments yield sedimentation rates at Potomac Creek ranging from 3.04-4.20 mm yr-1 for the past 2500 years. Rates of sedimentation calculated for Blandfield Point indicate 1.37-2.19 mm yr-1 in the basal clays and peat for the past ~3000 years. Foraminiferal census counts indicate a freshening upward trend with a transition from an estuarine Ammobaculites crassus assemblage to a marsh Ammoastuta salsa assemblage with abundant freshwater thecamoebians. The late Holocene history of sedimentation for the marshes indicates that differential compaction, recent land use practices, and climate change have contributed to the resultant freshening-upward environmental trend and variability in sediment accumulation rates between coring sites

    Use of a ‘molecular tug’ to overcome limitations in the production of ‘difficult to express’ recombinant proteins

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    In recent years there has been an increased drive towards the production of recombinant proteins in large amounts using rapid cell culture processes. Mammalian expression systems such as Chinese Hamster Ovary (CHO) cells have remained the preferred choice for large-scale recombinant protein production (Walsh, 2014). However, in mammalian cells certain recombinant targets can prove to be ‘difficult to express’ and require extensive upstream process optimisation which can have a negative impact on industrial processes. This study has investigated the molecular mechanisms that are responsible for poor recombinant protein production. Model proteins from the Tissue Inhibitors of Metalloproteinase (TIMP) family, TIMP-2, TIMP-3 and TIMP-4, were subject to detailed study to characterise the molecular mechanisms that limit production of recombinant proteins with high sequence homology (Hussain et al., 2017). TIMP-2, -3 and -4, share significant sequence/structural homology (Douglas et al., 1997, Garcia et al., 2012), but show differences when produced in a transient CHO expression system (Hussain et al., 2017) . A systematic screen of the protein expression pathway showed all three TIMPs were detectable at the mRNA and protein level within the cell but only TIMP-2 was secreted in significant amounts into the culture medium. Analysis of the intracellular protein suggested the post-translational processing of poorly expressed TIMPs was limiting. A protein engineering approach was employed to overcome challenges in the production of these ‘difficult to express’ TIMP proteins. This approach involved the attachment of a furin-cleavable pro-sequence from a secretory growth factor to recombinant targets. The pro-sequence was predicted to act as a ‘molecular tug’ to aid transit through the protein expression pathway and/or promote correct post-translational processing. Initially, the furin-cleavable pro-sequence was added to TIMP-3 (non-secreted), which resulted in secretion of TIMP-3, however incomplete processing of the pro-sequence was observed. The protein engineering approach was optimised further and applied in combination with cell engineering (furin overexpression) to TIMP-4 (poorly secreted), which was also successfully detected in significantly higher amounts in the culture medium (Hussain et al., 2017). Together, the described protein engineering approach presents a novel strategy to increase the production of ‘difficult-to-express’ recombinant targets. References: Douglas, D. A., Shi, Y. E. & Sang, Q. X. A. 1997. Computational sequence analysis of the tissue inhibitor of metalloproteinase family. Journal of Protein Chemistry, 16, 237-255. Garcia, M. P. S., Suarez-Penaranda, J. M., Gayoso-Diz, P., Barros-Angueira, F., Gandara-Rey, J. M. & Garcia-Garcia, A. 2012. Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas - A therapeutic target? Cancer Letters, 323, 11-19. Hussain, H., Fisher, D. I., Abbott, W. M., Roth, R. G. & Dickson, A. J. 2017. Use of a protein engineering strategy to overcome limitations in the production of Difficult to Express recombinant proteins. Biotechnology and Bioengineering, 114, 2348-2359. Walsh, G. 2014. Biopharmaceutical benchmarks 2014. Nature Biotechnology, 32, 992-1000

    Does a Healthy Weight Body Mass Index at Onset of Idiopathic Intracranial Hypertension Change the Outcomes? A United Kingdom Prospective Cohort Study

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    Idiopathic intracranial hypertension (IIH) predominantly affects reproductive-aged females with obesity. However, the prevalence and impact of a healthy weight body mass index (BMI) at disease presentation is not known. This study aimed to evaluate the visual and headache outcomes stratified by the presenting BMI. This was a longitudinal prospective cohort study (IIH Life) based on a tertiary neuro-ophthalmology IIH service, University Hospitals Birmingham NHS Trust, United Kingdom, recruiting consecutive patients living with IIH between 2012 and 2021. Those with a presenting BMI were included. The outcome measures included visual outcomes of LogMAR visual acuity, Humphrey visual field perimetric mean deviation (PMD), optical coherence tomography (OCT) measurements, and headache outcomes of frequency, severity, and Headache Impact Test-6 score. Three hundred seventy-five people with IIH and a documented baseline BMI. About 3.7% of the entire cohort had a healthy weight BMI at IIH presentation and 15.5% BMI < 30 kg/m2. The baseline PMD was worse in patients without obesity; however, OCT papilloedema measures were similar. The presence of obesity was associated with a small but significant greater worsening in visual acuity but slower macular ganglion cell layer loss. There was no impact on PMD or papilloedema prognosis related to baseline obesity. The headache outcomes showed heterogeneity, with worse baseline headache frequency in patients with obesity. No BMI group was associated with worse headache outcomes. Patients with a healthy weight BMI or those without obesity at baseline make up a small proportion of IIH patients. BMI at presentation does not appear to influence long-term visual or headache outcomes
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