4,825 research outputs found

    Increasing throughput in IEEE 802.11 by optimal selection of backoff parameters

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    Engineering and Physical Sciences Research Council. Grant Number: EP/G012628/

    A utility based framework for optimal network measurement

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    Packet level measurement is now routinely used to evaluate the loss and delay performance of broadband networks. In active measurement, probe packets provide samples of the loss and delay and from these samples the performance of the traffic as a whole can be deduced. However this is prone to errors: inaccuracy due to taking insufficient samples, self-interference due to injecting too many probe packets, and possible sample-correlation induced bias. In this paper we consider the optimisation of probing rate by treating all measurements as numerical experiments which can be optimally designed by using the statistical principles of design of experiments. We develop an analytical technique that quantifies an overall utility function associated with: (i) the disruption caused per probe packet, (ii) the bias and (iii) the variance as a function of the probing (sampling) rate. Our numerical results show that the optimal probing rate depends strongly on what parameter the network engineer seeks to measure.</p

    Towards an analysis of shear suspension flows using radial basis functions

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    In this paper, radial basis functions are utilised for numerical prediction of the bulk properties of particulate suspensions under simple shear conditions. The suspending fluid is Newtonian and the suspended particles are rigid. Results obtained are compared well with those based on finite elements in the literature

    Blood-brain barrier water exchange measurements using FEXI: Impact of modeling paradigm and relaxation time effects

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    PURPOSE: To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 T. METHODS: Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model (2CM) explicitly representing intra- and extravascular signal components, and (iii) a two-compartment model additionally accounting for finite compartmental T1 and T2 relaxation times (2CMr). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and 2CM models, as well as the accuracy and precision of all three models. The scan–rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23–52 years; five female) RESULTS: The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/2CM models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan–rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of RCAXR = 0.43 s −1, RC2CM = 0.51 s −1, and RC2CMr = 0.61 s −1. CONCLUSION: Compartmental modelling of BBB-FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model-dependent biases

    Water-exchange MRI detects subtle blood-brain barrier breakdown in Alzheimer's disease rats

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    Blood-brain barrier (BBB) breakdown has been hypothesized to play a key role in the onset and progression of Alzheimer's disease (AD). However, the question of whether AD itself contributes to loss of BBB integrity is still uncertain, as many in-vivo studies have failed to detect signs of AD-related BBB breakdown. We hypothesize AD-related BBB damage is subtle, and that these negative results arise from a lack of measurement sensitivity. With the aim of developing a more sensitive measure of BBB breakdown, we have designed a novel MRI scanning protocol to quantify the trans-BBB exchange of endogenous water. Using this method, we detect increased BBB water permeability in a rat model of AD that is associated with reduced expression of the tight junction protein occludin. BBB permeability to MRI contrast agent, assessed using dynamic contrast-enhanced (DCE)-MRI, did not differ between transgenic and wild-type animals and was uncorrelated with occludin expression. Our data supports the occurrence of AD-related BBB breakdown, and indicates that such BBB pathology is subtle and may be undetectable using existing ‘tracer leakage’ methods. Our validated water-exchange MRI method provides a new powerful tool with which to study BBB damage in-vivo

    Lateglacial and Early Holocene palaeoenvironmental change and human activity at Killerby Quarry, North Yorkshire, UK

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    The hunter-gatherers that entered the British peninsula after ice-retreat were exploiting a dynamic, rapidly changing environment. Records of vegetation change and human occupation during the Lateglacial to Early Holocene in northern Britain are more commonly found at upland and cave sites. However, recent research highlights many areas of the Swale–Ure Washlands that preserve extensive environmental sequences in low-lying ice-wastage basins, channels and depressions. The Lateglacial–Early Holocene environment of Killerby Quarry, North Yorkshire, is investigated here using a multi-proxy approach of sedimentary ancient DNA (sedaDNA), pollen, sedimentological (geochemistry and portable optically stimulated luminescence), and rare and well-preserved archaeology (Lavvu structures and lithics). Results show that the wetland basins and kettleholes were small lakes or ponds in the Lateglacial surrounded by sedge-fen and birch woodland. A gradual (centennial scale) succession to reed-swamp and then marsh is seen by the Early Holocene. This environment formed the resource-scape for hunter-gatherer transitory settlement in both the Lateglacial (Late Upper Palaeolithic) and Holocene (Early Mesolithic), attracted by the rich communities of pond-related flora and fauna as well as easy strategic landscape access by way of the River Swale, an arterial route through the landscape connecting the North Sea Basin with the Pennine uplands via the palaeolakes around Killerby

    Alzheimer's disease pathology is associated with earlier alterations to blood–brain barrier water permeability compared with healthy ageing in TgF344‐AD rats

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    From Wiley via Jisc Publications RouterHistory: received 2020-11-05, rev-recd 2021-02-06, accepted 2021-02-26, pub-electronic 2021-03-15, pub-print 2021-07Article version: VoRPublication status: PublishedFunder: Biotechnology and Biological Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/F011350Funder: Engineering and Physical Sciences Research Council; Id: http://dx.doi.org/10.13039/501100000266; Grant(s): EP/M005909/1Funder: European Union’s Seventh Framework Programme; Grant(s): FP7/2007‐2013, HEALTH‐F2‐2011‐278850, HEALTH‐F2‐2011‐278850The effects of Alzheimer's disease (AD) and ageing on blood–brain barrier (BBB) breakdown are investigated in TgF344‐AD and wild‐type rats aged 13, 18 and 21 months. Permeability surface area products of the BBB to water (PSw) and gadolinium‐based contrast agent (PSg) were measured in grey matter using multiflip angle multiecho dynamic contrast‐enhanced MRI. At 13 months of age, there was no significant difference in PSw between TgF344‐AD and wild‐types (p = 0.82). Between 13 and 18 months, PSw increased in TgF344‐AD rats (p = 0.027), but not in wild‐types (p = 0.99), leading to significantly higher PSw in TgF344‐AD rats at 18 months, as previously reported (p = 0.012). Between 18 and 21 months, PSw values increased in wild‐types (p = 0.050), but not in TgF344‐AD rats (p = 0.50). These results indicate that BBB water permeability is affected by both AD pathology and ageing, but that changes occur earlier in the presence of AD pathology. There were no significant genotype or ageing effects on PSg (p > 0.05). In conclusion, we detected increases in BBB water permeability with age in TgF344‐AD and wild‐type rats, and found that changes occurred at an earlier age in rats with AD pathology

    The evolution, diversity, and host associations of rhabdoviruses.

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    Metagenomic studies are leading to the discovery of a hidden diversity of RNA viruses. These new viruses are poorly characterized and new approaches are needed predict the host species these viruses pose a risk to. The rhabdoviruses are a diverse family of RNA viruses that includes important pathogens of humans, animals, and plants. We have discovered thirty-two new rhabdoviruses through a combination of our own RNA sequencing of insects and searching public sequence databases. Combining these with previously known sequences we reconstructed the phylogeny of 195 rhabdovirus sequences, and produced the most in depth analysis of the family to date. In most cases we know nothing about the biology of the viruses beyond the host they were identified from, but our dataset provides a powerful phylogenetic approach to predict which are vector-borne viruses and which are specific to vertebrates or arthropods. By reconstructing ancestral and present host states we found that switches between major groups of hosts have occurred rarely during rhabdovirus evolution. This allowed us to propose seventy-six new likely vector-borne vertebrate viruses among viruses identified from vertebrates or biting insects. Based on currently available data, our analysis suggests it is likely there was a single origin of the known plant viruses and arthropod-borne vertebrate viruses, while vertebrate- and arthropod-specific viruses arose at least twice. There are also few transitions between aquatic and terrestrial ecosystems. Viruses also cluster together at a finer scale, with closely related viruses tending to be found in closely related hosts. Our data therefore suggest that throughout their evolution, rhabdoviruses have occasionally jumped between distantly related host species before spreading through related hosts in the same environment. This approach offers a way to predict the most probable biology and key traits of newly discovered viruses.BL and FMJ are supported by a NERC grant (NE/L004232/1), a European Research Council grant (281668, DrosophilaInfection), a Junior Research Fellowship from Christ’s College, Cambridge (BL). GGRM is supported by an MRC studentship. The metagenomic sequencing of viruses from D. immigrans, D. tristis and S. deflexa was supported by a Wellcome Trust fellowship (WT085064) to DJO.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/ve/vev01
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