An endemic hantavirus in field voles in northern England

We report a PCR survey of hantavirus infection in the extensive field vole (Microtus agrestis) populations occurring in the Kielder Forest, northern England. A Tatenale virus-like lineage was frequently detected (~ 15% prevalence) in liver tissue. Such lineages are likely to be endemic in northern England

In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immuno-biology of Allogeneic Transplantation

Donor T cell mediated graft vs. host effects may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA) presented by the HLA in each donor-recipient pair (DRP) undergoing stem cell transplantation (SCT). Whole exome sequencing has demonstrated extensive nucleotide sequence variation in HLA-matched DRP. Non-synonymous single nucleotide polymorphisms (nsSNPs) in the GVH direction (polymorphisms present in recipient and absent in donor) were identified in 4 HLA-matched related and 5 unrelated DRP. The nucleotide sequence flanking each SNP was obtained utilizing the ANNOVAR software package. All possible nonameric-peptides encoded by the non-synonymous SNP were then interrogated in-silico for their likelihood to be presented by the HLA class I molecules in individual DRP, using the Immune-Epitope Database (IEDB) SMM algorithm. The IEDB-SMM algorithm predicted a median 18,396 peptides/DRP which bound HLA with an IC50 of <500nM, and 2254 peptides/DRP with an IC50 of <50nM. Unrelated donors generally had higher numbers of peptides presented by the HLA. A similarly large library of presented peptides was identified when the data was interrogated using the Net MHCPan algorithm. These peptides were uniformly distributed in the various organ systems. The bioinformatic algorithm presented here demonstrates that there may be a high level of minor histocompatibility antigen variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential. These data provide a possible explanation for how relatively minor adjustments in GVHD prophylaxis yield relatively similar outcomes in HLA matched and mismatched SCT recipients.Comment: Abstract: 235, Words: 6422, Figures: 7, Tables: 3, Supplementary figures: 2, Supplementary tables:

Comparison of four dimensional computed tomography and magnetic resonance imaging in abdominal radiotherapy planning

Background and Purpose: Four-dimensional (4D) computed tomography (CT) is widely used in radiotherapy (RT) planning and remains the current standard for motion evaluation. We assess a 4D magnetic resonance imaging (MRI) sequence in terms of motion and image quality in a phantom, healthy volunteers and patients undergoing RT. Materials and Methods: The 4D-MRI sequence is a prototype T1-weighted 3D gradient echo with radial acquisition with self-gating. The accuracy of the 4D-MRI respiratory sorting based method was assessed using a MRICT compatible respiratory simulation phantom. In volunteers, abdominal viscera were evaluated for artefact, noise, structure delineation and overall image quality using a previously published four-point scoring system. In patients undergoing abdominal RT, the tumour (or a surrogate) was utilized to assess the range of motion on both 4D-CT and 4D-MRI. Furthermore, imaging quality was evaluated for both 4D-CT and 4D-MRI. Results: In phantom studies 4D-MRI demonstrated amplitude of motion error of less than 0.2mm for five, seven and ten bins. 4D-MRI provided excellent image quality for liver, kidney and pancreas. In patients, the median amplitude of motion seen on 4D-CT and 4D-MRI was 11.2mm (range 2.8-20.3 mm) and 10.1mm (range 0.7-20.7 mm) respectively. The median difference in amplitude between 4D-CT and 4D-MRI was −0.6mm (range −3.4-5.2 mm). 4D-MRI demonstrated superior edge detection (median score 3 versus 1) and overall image quality (median score 2 versus 1) compared to 4D-CT. Conclusions: The prototype 4D-MRI sequence demonstrated promising results and may be used in abdominal targeting, motion gating, and towards implementing MRI-based adaptive RT

Applicability and usage of dose mapping/accumulation in radiotherapy

Dose mapping/accumulation (DMA) is a topic in radiotherapy (RT) for years, but has not yet found its widespread way into clinical RT routine. During the ESTRO Physics workshop 2021 on "commissioning and quality assurance of deformable image registration (DIR) for current and future RT applications", we built a working group on DMA from which we present the results of our discussions in this article. Our aim in this manuscript is to shed light on the current situation of DMA in RT and to highlight the issues that hinder consciously integrating it into clinical RT routine. As a first outcome of our discussions, we present a scheme where representative RT use cases are positioned, considering expected anatomical variations and the impact of dose mapping uncertainties on patient safety, which we have named the DMA landscape (DMAL). This tool is useful for future reference when DMA applications get closer to clinical day-to-day use. Secondly, we discussed current challenges, lightly touching on first-order effects (related to the impact of DIR uncertainties in dose mapping), and focusing in detail on second-order effects often dismissed in the current literature (as resampling and interpolation, quality assurance considerations, and radiobiological issues). Finally, we developed recommendations, and guidelines for vendors and users. Our main point include: Strive for context-driven DIR (by considering their impact on clinical decisions/judgements) rather than perfect DIR; be conscious of the limitations of the implemented DIR algorithm; and consider when dose mapping (with properly quantified uncertainties) is a better alternative than no mapping

Information management for high content live cell imaging.

BACKGROUND: High content live cell imaging experiments are able to track the cellular localisation of labelled proteins in multiple live cells over a time course. Experiments using high content live cell imaging will generate multiple large datasets that are often stored in an ad-hoc manner. This hinders identification of previously gathered data that may be relevant to current analyses. Whilst solutions exist for managing image data, they are primarily concerned with storage and retrieval of the images themselves and not the data derived from the images. There is therefore a requirement for an information management solution that facilitates the indexing of experimental metadata and results of high content live cell imaging experiments. RESULTS: We have designed and implemented a data model and information management solution for the data gathered through high content live cell imaging experiments. Many of the experiments to be stored measure the translocation of fluorescently labelled proteins from cytoplasm to nucleus in individual cells. The functionality of this database has been enhanced by the addition of an algorithm that automatically annotates results of these experiments with the timings of translocations and periods of any oscillatory translocations as they are uploaded to the repository. Testing has shown the algorithm to perform well with a variety of previously unseen data. CONCLUSION: Our repository is a fully functional example of how high throughput imaging data may be effectively indexed and managed to address the requirements of end users. By implementing the automated analysis of experimental results, we have provided a clear impetus for individuals to ensure that their data forms part of that which is stored in the repository. Although focused on imaging, the solution provided is sufficiently generic to be applied to other functional proteomics and genomics experiments. The software is available from: fhttp://code.google.com/p/livecellim/RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Baryon masses in a chiral expansion with meson-baryon form factors

The chiral expansion of the one-loop corrections to baryon masses is examined in a generic meson-cloud model with meson-baryon form factors. For pion loops, the expansion is rapidly convergent and at fourth order in $m_\pi$ accurately reproduces the full integral. In contrast, the expansion is found to converge very slowly for kaon loops, raising questions about the usefulness of chiral expansions for kaon-baryon physics. Despite the importance of high-order terms, relations like that of Gell-Mann and Okubo are well satisfied by the baryon masses calculated with the full integral. The pion cloud cloud makes a significant contribution to the $\pi N$ sigma commutator, while kaon cloud gives a very small strangeness content in the nucleon.Comment: 20 pages (RevTeX), 2 figures (attached

Near and Mid-IR Photometry of the Pleiades, and a New List of Substellar Candidate Members

We make use of new near and mid-IR photometry of the Pleiades cluster in order to help identify proposed cluster members. We also use the new photometry with previously published photometry to define the single-star main sequence locus at the age of the Pleiades in a variety of color-magnitude planes. The new near and mid-IR photometry extend effectively two magnitudes deeper than the 2MASS All-Sky Point Source catalog, and hence allow us to select a new set of candidate very low mass and sub-stellar mass members of the Pleiades in the central square degree of the cluster. We identify 42 new candidate members fainter than Ks =14 (corresponding to 0.1 Mo). These candidate members should eventually allow a better estimate of the cluster mass function to be made down to of order 0.04 solar masses. We also use new IRAC data, in particular the images obtained at 8 um, in order to comment briefly on interstellar dust in and near the Pleiades. We confirm, as expected, that -- with one exception -- a sample of low mass stars recently identified as having 24 um excesses due to debris disks do not have significant excesses at IRAC wavelengths. However, evidence is also presented that several of the Pleiades high mass stars are found to be impacting with local condensations of the molecular cloud that is passing through the Pleiades at the current epoch.Comment: Accepted to ApJS; data tables and embedded-figure version available at http://spider.ipac.caltech.edu/staff/stauffer/pleiades07

Whole Exome Sequencing to Estimate Alloreactivity Potential Between Donors and Recipients in Stem Cell Transplantation

Whole exome sequencing was performed on HLA-matched stem cell donors and transplant recipients to measure sequence variation contributing to minor histocompatibility antigen differences between the two. A large number of nonsynonymous single nucleotide polymorphisms were identified in each of the nine unique donor-recipient pairs tested. This variation was greater in magnitude in unrelated donors as compared with matched related donors. Knowledge of the magnitude of exome variation between stem cell transplant recipients and donors may allow more accurate titration of immunosuppressive therapy following stem cell transplantation.Comment: 12 pages- main article, 29 pages total, 5 figures, 1 supplementary figur

Unsteady Interaction Between a Transonic Turbine Stage and Downstream Components

Results from a numerical simulation of the unsteady flow through one quarter of the circumference of a transonic high-pressure turbine stage, transition duct, and low-pressure turbine first vane are presented and compared with experimental data. Analysis of the unsteady pressure field resulting from the simulation shows the effects of not only the rotor/stator interaction of the high-pressure turbine stage but also new details of the interaction between the blade and the downstream transition duct and low-pressure turbine vane. Blade trailing edge shocks propagate downstream, strike, and reflect off of the transition duct hub and/or downstream vane leading to high unsteady pressure on these downstreamcomponents. The reflection of these shocks from the downstream components back into the blade itself has also been found to increase the level of unsteady pressure fluctuations on the uncovered portion of the blade suction surface. In addition, the blade tip vortex has been found to have a moderately strong interaction with the downstream vane even with the considerable axial spacing between the two blade-rows. Fourier decomposition of the unsteady surface pressure of the blade and downstream low-pressure turbine vane shows the magnitude of the various frequencies contributing to the unsteady loads. Detailed comparisons between the computed unsteady surface pressure spectrum and the experimental data are shown along with a discussion of the various interaction mechanisms between the blade, transition duct, and downstream vane. These comparisons show-overall good agreement between the simulation and experimental data and identify areas where further improvements in modeling are needed