Novel method to measure the intrinsic spatial resolution in PET detectors based on monolithic crystals

[EN] The main aim of this work is to provide a method to retrieve the intrinsic spatial resolution of a gamma-ray detector block based on monolithic crystals within an assembled scanner. This method consists on a discrimination of the data using a software collimation process. The results are compared with an alternative method of separating two detector blocks far enough to produce a "virtual" source collimation due to the geometric constraints on the allowed coincidence event angles. A theoretical model has been deduced to fit the measured light distribution profiles, allowing estimating the detector intrinsic spatial resolution. The detector intrinsic spatial resolution is expected to follow a Gaussian distribution and the positron-emitter source shape, given the small size of a Na-22 source with 0.25 mm in diameter, can be assumed to follow a Lorentzian profile. However, the collimation of the data modifies the source shape that is no longer a pure Lorentzian distribution. Therefore, the model is based on the convolution of a Gaussian shaped distribution (contribution of the detector) and a modified Lorentzian distribution (contribution of the collimated source profile) that takes into account the collimation effect. Three LYSO crystals geometries have been studied in the present work, namely a 10 mm thick trapezoidal monolithic block, and two rectangular monolithic blocks with thicknesses of 15 mm and 20 mm, respectively. All the blocks have size dimensions of 50 mm x 50 mm. The experimental results yielded an intrinsic detector spatial resolution of 0.64 +/- 0.02 mm, 0.82 +/- 0.02 and 1.07 +/- 0.03 mm, for the 10 mm, 15 mm and 20 mm thick blocks, respectively, when the source was placed at the center of the detector. The detector intrinsic spatial resolution was moreover evaluated across one of the axis of each crystal. These values worsen to an average value of 0.68 +/- 0.04 mm, 0.90 +/- 0.14 and 1.29 +/- 0.19 mm, respectively, when the whole crystal size is considered, as expected. These tests show an accurate method to determine the intrinsic spatial resolution of monolithic-based detector blocks, once assembled in the PET system.This project has received funding from the European Research Council, Spain (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the EU, Spain Grant 603002 under the FP7 program, and by the Spanish Ministerio de Economia, Industria y Competitividad under Grant TEC2016-79884-C2-1-R and through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad, Spain.González, A.; Sanchez, F.; Bruyndonckx, P.; Cañizares-Ledo, G.; Benlloch Baviera, JM.; González Martínez, AJ. (2019). Novel method to measure the intrinsic spatial resolution in PET detectors based on monolithic crystals. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 920:58-67. https://doi.org/10.1016/j.nima.2018.12.056S586792

High levels of auxin signalling define the stem-cell organizer of the vascular cambium

Wood, a type of xylem tissue, originates from cell proliferation of the vascular cambium. Xylem is produced inside, and phloem outside, of the cambium(1). Morphogenesis in plants is typically coordinated by organizer cells that direct the adjacent stem cells to undergo programmed cell division and differentiation. The location of the vascular cambium stem cells and whether the organizer concept applies to the cambium are currently unknown(2). Here, using lineage-tracing and molecular genetic studies in the roots of Arabidopsis thaliana, we show that cells with a xylem identity direct adjacent vascular cambial cells to divide and function as stem cells. Thus, these xylem-identity cells constitute an organizer. A local maximum of the phytohormone auxin, and consequent expression of CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP III) transcription factors, promotes xylem identity and cellular quiescence of the organizer cells. Additionally, the organizer maintains phloem identity in a non-cell-autonomous fashion. Consistent with this dual function of the organizer cells, xylem and phloem originate from a single, bifacial stem cell in each radial cell file, which confirms the classical theory of a uniseriate vascular cambium(3). Clones that display high levels of ectopically activated auxin signalling differentiate as xylem vessels; these clones induce cell divisions and the expression of cambial and phloem markers in the adjacent cells, which suggests that a local auxin-signalling maximum is sufficient to specify a stem-cell organizer. Although vascular cambium has a unique function among plant meristems, the stem-cell organizer of this tissue shares features with the organizers of root and shoot meristems.Peer reviewe

PET detector block with accurate 4D capabilities

[EN] In this contribution, large SiPM arrays (8 x 8 elements of 6 x 6 mm(2) each) are processed with an ASIC-based readout and coupled to a monolithic LYSO crystal to explore their potential use for TOF-PET applications. The aim of this work is to study the integration of this technology in the development of clinical PET systems reaching sub-300 ps coincidence resolving time (CRT). The SiPM and readout electronics have been evaluated first, using a small size 1.6 mm (6 mm height) crystal array (32 x 32 elements). All pixels were well resolved and they exhibited an energy resolution of about 20% (using Time-over-Threshold methods) for the 511 keV photons. Several parameters have been scanned to achieve the optimum readout system performance, obtaining a CRT as good as 330 +/- 5 ps FWHM. When using a black-painted monolithic block, the spatial resolution was measured to be on average 2.6 +/- 0.5 mm, without correcting for the source size. Energy resolution appears to be slightly above 20%. CRT measurements with the monolithic crystal detector were also carried out. Preliminary results as well as calibration methods specifically designed to improve timing performance, are being analyzed in the present manuscript.This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 695536). It has also been supported by the Spanish Ministerio de Economia, Industria y Competitividad under Grants No. FIS2014-62341-EXP and TEC2016-79884-C2-1-R.Lamprou, E.; Aguilar -Talens, A.; Gonzalez-Montoro, A.; Monzó Ferrer, JM.; Cañizares-Ledo, G.; Iranzo-Egea, S.; Vidal San Sebastian, LF.... (2018). PET detector block with accurate 4D capabilities. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 912:132-136. https://doi.org/10.1016/j.nima.2017.11.002S13213691

The role of a Mediterranean diet on the risk of oral and pharyngeal cancer.

BACKGROUND: The Mediterranean diet has a beneficial role on various neoplasms, but data are scanty on oral cavity and pharyngeal (OCP) cancer. METHODS: We analysed data from a case-control study carried out between 1997 and 2009 in Italy and Switzerland, including 768 incident, histologically confirmed OCP cancer cases and 2078 hospital controls. Adherence to the Mediterranean diet was measured using the Mediterranean Diet Score (MDS) based on the major characteristics of the Mediterranean diet, and two other scores, the Mediterranean Dietary Pattern Adherence Index (MDP) and the Mediterranean Adequacy Index (MAI). RESULTS: We estimated the odds ratios (ORs), and the corresponding 95% confidence intervals (CI), for increasing levels of the scores (i.e., increasing adherence) using multiple logistic regression models. We found a reduced risk of OCP cancer for increasing levels of the MDS, the ORs for subjects with six or more MDS components compared with two or less being 0.20 (95% CI 0.14-0.28, P-value for trend <0.0001). The ORs for the highest vs the lowest quintile were 0.20 (95% CI 0.14-0.28) for the MDP score (score 66.2 or more vs less than 57.9), and 0.48 (95% CI 0.33-0.69) for the MAI score (score value 2.1 or more vs value less 0.92), with significant trends of decreasing risk for both scores. The favourable effect of the Mediterranean diet was apparently stronger in younger subjects, in those with a higher level of education, and in ex-smokers, although it was observed in other strata as well. CONCLUSIONS: Our study provides strong evidence of a beneficial role of the Mediterranean diet on OCP cancer

Evaluation of model refinement in CASP14

We report here an assessment of the model refinement category of the 14th round of Critical Assessment of Structure Prediction (CASP14). As before, predictors submitted up to five ranked refinements, along with associated residue-level error estimates, for targets that had a wide range of starting quality. The ability of groups to accurately rank their submissions and to predict coordinate error varied widely. Overall only four groups out-performed a “naïve predictor” corresponding to resubmission of the starting model. Among the top groups there are interesting differences of approach and in the spread of improvements seen: some methods are more conservative, others more adventurous. Some targets were “double-barrelled” for which predictors were offered a high-quality AlphaFold 2 (AF2)-derived prediction alongside another of lower quality. The AF2-derived models were largely unimprovable, many of their apparent errors being found to reside at domain and, especially, crystal lattice contacts. Refinement is shown to have a mixed impact overall on structure-based function annotation methods to predict nucleic acid binding, spot catalytic sites and dock protein structures

Tertiary structure assessment at CASP15

The results of tertiary structure assessment at CASP15 are reported. For the first time, recognizing the outstanding performance of AlphaFold 2 (AF2) at CASP14, all single-chain predictions were assessed together, irrespective of whether a template was available. At CASP15, there was no single stand-out group, with most of the best-scoring groups-led by PEZYFoldings, UM-TBM, and Yang Server-employing AF2 in one way or another. Many top groups paid special attention to generating deep Multiple Sequence Alignments (MSAs) and testing variant MSAs, thereby allowing them to successfully address some of the hardest targets. Such difficult targets, as well as lacking templates, were typically proteins with few homologues. Local divergence between prediction and target correlated with localization at crystal lattice or chain interfaces, and with regions exhibiting high B-factor factors in crystal structure targets, and should not necessarily be considered as representing error in the prediction. However, analysis of exposed and buried side chain accuracy showed room for improvement even in the latter. Nevertheless, a majority of groups produced high-quality predictions for most targets, which are valuable for experimental structure determination, functional analysis, and many other tasks across biology. These include those applying methods similar to those used to generate major resources such as the AlphaFold Protein Structure Database and the ESM Metagenomic atlas: the confidence estimates of the former were also notably accurate

ConPlot: web-based application for the visualization of protein contact maps integrated with other data

SummaryCovariance-based predictions of residue contacts and inter-residue distances are an increasingly popular data type in protein bioinformatics. Here we present ConPlot, a web-based application for convenient display and analysis of contact maps and distograms. Integration of predicted contact data with other predictions is often required to facilitate inference of structural features. ConPlot can therefore use the empty space near the contact map diagonal to display multiple coloured tracks representing other sequence-based predictions. Popular file formats are natively read and bespoke data can also be flexibly displayed. This novel visualization will enable easier interpretation of predicted contact maps.Availability and implementationavailable online at www.conplot.org, along with documentation and examples. Alternatively, ConPlot can be installed and used locally using the docker image from the project's Docker Hub repository. ConPlot is licensed under the BSD 3-Clause.Supplementary informationSupplementary data are available at Bioinformatics online