23,225 research outputs found

    Interpreting interpolation: the pattern of interpolation errors in digital surface models derived from laser scanning data

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    Errors within height models have, in the past, been communicated in terms of global measures ofaccuracy for the model. Such quantification ignores the spatial structure of errors across thesurface, hindering subsequent analysis. This paper demonstrates the importance ofunderstanding the spatial structure of error using, as an example, the creation of a DigitalSurface Model (DSM) from laser scanner data

    Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.

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    Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation

    An investigation of the effects of the common cold on simulated driving performance and detection of collisions

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    The aim of the present research was to investigate whether individuals with a common cold showed impaired ability on a simulated driving task and the ability to detect potential collisions between moving objects. The study involved comparison of a healthy group with a group with colds. These scores were adjusted for individual differences by collecting further data when both groups were healthy and using these scores as covariates. On both occasions volunteers rated their symptoms, carried out a laboratory task measuring collision detection and also a simulated driving session. Twenty five students from the University of Leeds. 10 volunteers were healthy on both occasions and 15 had a cold on the first session and were healthy on the second. In the collision detection task the main outcomes were correct detections and response to a secondary identification task. In the simulated driving task the outcomes were: speed; lateral control; gap acceptance; overtaking behaviour; car following; vigilance and traffic light violations. Those with a cold detected fewer collisions and had a higher divided attention error than those who were healthy. Many basic driving skills were unimpaired by the illness. However, those with a cold were slower at responding to unexpected events and drove closer to the car in front. The finding that having a common cold reduces the ability to detect collisions and respond quickly to unexpected events is of practical importance. Further research is now required to examine the efficacy of information campaigns and countermeasures such as caffeine

    The consequences of replicating in the wrong orientation: Bacterial chromosome duplication without an active replication origin

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    Chromosome replication is regulated in all organisms at the assembly stage of the replication machinery at specific origins. In Escherichia coli the DnaA initiator protein regulates the assembly of replication forks at oriC. This regulation can be undermined by defects in nucleic acid meta¬bolism. In cells lacking RNase HI replication initiates indepen¬dently of DnaA and oriC, presumably at persisting R-loops. A similar mechanism was assumed for origin-independent synthesis in cells lacking RecG. However, recently we suggested that this synthesis initiates at intermediates resulting from replication fork fusions. Here we present data suggesting that in cells lacking RecG or RNase HI origin-independent synthesis arises by different mechanisms, indicative of these two proteins having different roles in vivo. Our data support the idea that RNase HI processes R-loops, while RecG is required to process replication fork fusion intermediates. However, regardless of how origin-independent synthesis is initiated, a fraction of forks will proceed in an orientation opposite to normal. We show that the resulting head-on encounters with transcription threaten cell viability, especially if taking place in highly-transcribed areas. Thus, despite their different functions, RecG and RNase HI are both important factors for maintaining replication control and orientation. Their absence causes severe replication problems, highlighting the advantages of the normal chromosome arrangement, which exploits a single origin to control the number of forks and their orientation relative to transcription, and a defined termination area to contain fork fusions. Any changes to this arrangement endanger cell cycle control, chromosome dynamics and, ultimately, cell viability.This work was supported by the Royal Society (RG110414 to C.J.R.) and The Biotechnology and Biological Sciences Research Council (BB/K015729/1 to C.J.R.)

    Strong Lefschetz elements of the coinvariant rings of finite Coxeter groups

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    For the coinvariant rings of finite Coxeter groups of types other than H4_4, we show that a homogeneous element of degree one is a strong Lefschetz element if and only if it is not fixed by any reflections. We also give the necessary and sufficient condition for strong Lefschetz elements in the invariant subrings of the coinvariant rings of Weyl groups.Comment: 18 page

    The James Clerk Maxwell telescope dense gas survey of the Perseus molecular cloud

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    This is the final version of the article. Available from the publisher via the DOI in this record.We present the results of a large-scale survey of the very dense (n > 106 cm-3) gas in the Perseus molecular cloud using HCO+ and HCN (J = 4 → 3) transitions. We have used this emission to trace the structure and kinematics of gas found in pre- and protostellar cores, as well as in outflows. We compare the HCO+/HCN data, highlighting regions where there is a marked discrepancy in the spectra of the two emission lines. We use the HCO+ to identify positively protostellar outflows and their driving sources, and present a statistical analysis of the outflow properties that we derive from this tracer. We find that the relations we calculate between the HCO+ outflow driving force and the Menv and Lbol of the driving source are comparable to those obtained from similar outflow analyses using 12CO, indicating that the two molecules give reliable estimates of outflow properties. We also compare the HCO+ and the HCN in the outflows, and find that the HCN traces only the most energetic outflows, the majority of which are driven by young Class 0 sources. We analyse the abundances of HCN and HCO+ in the particular case of the IRAS 2A outflows, and find that the HCN is much more enhanced than the HCO+ in the outflow lobes. We suggest that this is indicative of shock enhancement of HCN along the length of the outflow; this process is not so evident for HCO+, which is largely confined to the outflow base. © 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.SLW-S and JH are funded by the Science and Technology Facilities Council of the UK. The James Clerk Maxwell Telescope is operated by the Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the National Research Council of Canada and (until 2013 March 31) the Netherlands Organisation for Scientific Researc

    Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

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    Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease

    Historical geography II: traces remain

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    The second report in this series turns to focus on the trace in relation to life-writing and biography in historical geography and beyond. Through attention to tracing journeys, located moments and listening to the presence of ghosts (Ogborn, 2005), this report seeks to highlight the range of different ways in which historical geographers have explored lives, deaths, and their transient traces through varied biographical terrains. Continuing to draw attention in historical geography to the darkest of histories, this piece will pivot on moments of discovering the dead to showcase the nuanced ways in which historical geography is opening doors into uncharted lives and unspoken histories

    Wolbachia and DNA barcoding insects: patterns, potential and problems

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    Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region
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