4,879 research outputs found

    The strong weak convergence of the quasi-EA

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    In this paper, we investigate the convergence of a novel simulation scheme to the target diffusion process. This scheme, the Quasi-EA, is closely related to the Exact Algorithm (EA) for diffusion processes, as it is obtained by neglecting the rejection step in EA. We prove the existence of a myopic coupling between the Quasi-EA and the diffusion. Moreover, an upper bound for the coupling probability is given. Consequently we establish the convergence of the Quasi-EA to the diffusion with respect to the total variation distance

    Degradation of a quantum directional reference frame as a random walk

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    We investigate if the degradation of a quantum directional reference frame through repeated use can be modeled as a classical direction undergoing a random walk on a sphere. We demonstrate that the behaviour of the fidelity for a degrading quantum directional reference frame, defined as the average probability of correctly determining the orientation of a test system, can be fit precisely using such a model. Physically, the mechanism for the random walk is the uncontrollable back-action on the reference frame due to its use in a measurement of the direction of another system. However, we find that the magnitude of the step size of this random walk is not given by our classical model and must be determined from the full quantum description.Comment: 5 pages, no figures. Comments are welcome. v2: several changes to clarify the key results. v3: journal reference added, acknowledgements and references update

    Mathematical modelling of nanoparticle delivery to vascular tumours

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    This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The goal of any cancer therapy is to achieve efficient, tissue-specific targeting of drugs to cancer cells. However, most anticancer agents act on healthy and malignant tissue alike, potentially resulting in side effects to healthy tissue. This has motivated the development of treatment strategies that are cancer-cell specific; one approach uses biomimetic polymer vesicles (BPV) to deliver chemotherapeutic drugs into cells before releasing them. BPVs are synthetic membrane enclosed, nanometre-sized structures, and provide ideal drug delivery vectors because specific targeting to cancer cells can be achieved by coating with tumourspecific molecules. We present several mathematical models covering a wide range of length-scales pertinent to BPV-mediated delivery protocols and focus on capturing the in vivo environment by evaluating the impact of the underlying vascular structure upon the governing transport mechanisms. Firstly, we present models of specific binding of BPVs to cancer cells. Subsequently we examine the implications of these model outputs in the contexts of both discrete capillary architectures and higher level homogenized-models that track blood and BPV transport at the tissue scale (both intra- and extra-tumorally). Numerical solutions are discussed, and recommendations are presented on that optimal integration of the models to generate quantitative predictions associated with BPV treatment efficacy

    Exposure of benthic invertebrates to sediment vibration: From laboratory experiments to outdoor simulated pile-driving

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    This is the final version of the article. Available from Acoustical Society of America via the DOI in this record.Fourth International Conference on the Effects of Noise on Aquatic Life, Dublin, Ireland, 10-16 July 2016Activities directly interacting with the seabed, such as pile-driving, can produce vibrations that have the potential to impact benthic invertebrates within their vicinity. This stimuli may interfere with crucial behaviors such as foraging and predator avoidance, and the sensitivity to vibration is largely unknown. Here, the responsiveness of benthic invertebrates to sediment vibration is discussed in relation to laboratory and semi-field trials with two marine species: the mussel (Mytilus edulis) and hermit crab (Pagurus bernhardus). Sensory threshold curves were produced for both species in controlled laboratory conditions, followed by small-scale pile-driving exposures in the field. The merits of behavioral indicators are discussed, in addition to using physiological measures, as a method of determining reception and measuring responses. The measurement and sensors required for sediment vibration quantification are also discussed. Response and threshold data were related to measurements taken in the vicinity of anthropogenic sources, allowing a link between responsiveness and actual operations. The impact of pile-driving on sediment-dwelling invertebrates has received relatively little research, yet the data here suggest that such activities are likely to impact key coastal species which play important roles within the marine environment.LR would like to thank the organizers and sponsors of the 2016 conference for supporting her attendance for which she is extremely grateful. This study was partially funded by a research award from the Malacological Society of London to LR. The authors would also like to acknowledge Defra and NERC who funded the laboratory and field work aspects respectively, and the staff at the OREC field site, Blyth

    Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation

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    When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal

    The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

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    P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

    You turn me cold: evidence for temperature contagion

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    Introduction During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in the observer. Methods Thirty-six healthy participants (age; 22.9±3.1 yrs) each observed, then rated, eight purpose-made videos (3 min duration) that depicted actors with either their right or left hand in visibly warm (warm videos) or cold water (cold videos). Four control videos with the actors' hand in front of the water were also shown. Temperature of participant observers' right and left hands was concurrently measured using a thermistor within a Wheatstone bridge with a theoretical temperature sensitivity of <0.0001°C. Temperature data were analysed in a repeated measures ANOVA (temperature × actor's hand × observer's hand). Results Participants rated the videos showing hands immersed in cold water as being significantly cooler than hands immersed in warm water, F(1,34) = 256.67, p0.1). There was however no evidence of left-right mirroring of these temperature effects p>0.1). Sensitivity to temperature contagion was also predicted by inter-individual differences in self-report empathy. Conclusions We illustrate physiological contagion of temperature in healthy individuals, suggesting that empathetic understanding for primary low-level physiological challenges (as well as more complex emotions) are grounded in somatic simulation

    Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

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    &lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt

    Multifrequency Strategies for the Identification of Gamma-Ray Sources

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    More than half the sources in the Third EGRET (3EG) catalog have no firmly established counterparts at other wavelengths and are unidentified. Some of these unidentified sources have remained a mystery since the first surveys of the gamma-ray sky with the COS-B satellite. The unidentified sources generally have large error circles, and finding counterparts has often been a challenging job. A multiwavelength approach, using X-ray, optical, and radio data, is often needed to understand the nature of these sources. This chapter reviews the technique of identification of EGRET sources using multiwavelength studies of the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer Academic Press, 2004. For complete article and higher resolution figures, go to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd
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