Calibration and testing of a TLD dosemeter for area monitoring

The response of a TLD-600/TLD-700 area dosemeter has been characterized in neutron fields around the 590 MeV cyclotron ring at the Paul Scherrer Institute (PSI). The dosemeter is based on a cylindrical paraffin moderator with three of each type of TLD chip at the centre, and is intended to use for area monitoring around accelerator facilities. The dosemeter is calibrated in terms of ambient dose equivalent using a non-moderated 252Cf neutron source. The ambient dose equivalent response has been tested in five locations where the neutron fields and dose rates have been well characterized by Bonner sphere spectrometer and active neutron monitor measurements. The different spectrum shapes and dose rates in the five locations permit the comparison of the behavior of the active and passive dosemeters in these neutron field

Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg2+ homeostasis and cytoskeletal architecture

Mg2+ plays a vital role in platelet function, but despite implications for life-threatening conditions such as stroke or myocardial infarction, the mechanisms controlling [Mg2+](i) in megakaryocytes (MKs) and platelets are largely unknown. Transient receptor potential melastatin-like 7 channel (TRPM7) is a ubiquitous, constitutively active cation channel with a cytosolic alpha-kinase domain that is critical for embryonic development and cell survival. Here we report that impaired channel function of TRPM7 in MKs causes macrothrombocytopenia in mice (Trpm7(fl/fl-Pf4Cre)) and likely in several members of a human pedigree that, in addition, suffer from atrial fibrillation. The defect in platelet biogenesis is mainly caused by cytoskeletal alterations resulting in impaired proplatelet formation by Trpm7(fl/fl-Pf4Cre) MKs, which is rescued by Mg2+ supplementation or chemical inhibition of non-muscle myosin IIA heavy chain activity. Collectively, our findings reveal that TRPM7 dysfunction may cause macrothrombocytopenia in humans and mice

A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity

Polycrystalline diamond micro‐hotplates

Micro‐hotplate structures are increasingly being investigated for use in a host of applications ranging from broadband infra‐red sources within absorption‐based gas sensors to in situ heater stages for ultra‐high‐resolution imaging. With devices usually fabricated from a conductive electrode placed on top of a freestanding radiator element, coefficient of thermal expansion (CTE) mismatches between layers and electro‐migration within the heating element typically lead to failure upon exceeding temperatures of 1600 K. In an attempt to mitigate such issues, a series of hotplates of varying geometry have been fabricated from a single layer of mechanically robust, high thermal conductivity, and low CTE boron‐doped polycrystalline diamond. Upon testing under high vacuum conditions and characterization of the emission spectra, the resulting devices are shown to exhibit a grey‐body like emission response and reach temperatures vastly in excess of conventional geometries of up to 2731 K at applied powers of ⩽100 mW. Characterization of the thermalization time meanwhile demonstrates rapid millisecond response times, while Raman spectroscopy reveals the performance of the devices is dictated by cumulative graphitization at elevated temperatures. As such, both diamond and sp2 carbon are shown to be promising materials for the fabrication of next‐generation micro‐hotplates

Real time observation of glass-like carbon formation from SU-8 using X-ray and ultraviolet photoelectron spectroscopy

The structural development and change in elemental composition of SU-8 3005 photoresist into glass-like carbon due to pyrolysis up to 1000 C is investigated utilising in-situ x-ray and ultraviolet photoelectron spectroscopy (XPS/UPS) under ultra-high vacuum (UHV). XPS spectra were analysed in order to investigate changes to elemental composition and physical structure. Peak asymmetry in the measured C 1s spectra is found to be a clear indicator of a transition in both physical structure and increased electrical conductivity. The in-situ XPS measurement of pyrolysis is effective in isolating changes in oxygen composition solely due to the pyrolysis process. Oxygen concentration, C 1s peak asymmetry and C 1s peak positions are strong indicators of semiconducting SU-8 transitioning to conducting glass-like carbon. For SU-8 pyrolysed above temperatures of 500 C, a clear development is observed in the material structure and composition towards a carbon rich conducting network indicative of glass-like carbon. UPS spectra were analysed to investigate the changes in secondary electron cut-off (SECO) and valence band maximum (VBM) as the SU-8 layer is heated in UHV. The changes in SECO and VBM correlates well with the XPS data and a zero binding energy state is observed at 1000 C

Migration without interbreeding: Evolutionary history of a highly selfing Mediterranean grass inferred from whole genomes

Wild plant populations show extensive genetic subdivision and are far from the ideal of panmixia which permeates population genetic theory. Understanding the spatial and temporal scale of population structure is therefore fundamental for empirical population genetics –and of interest in itself, as it yields insights into the history and biology of a species. In this study we extend the genomic resources for the wild Mediterranean grass Brachypodium distachyon to investigate the scale of population structure and its underlying history at whole-genome resolution. A total of 86 accessions were sampled at local and regional scales in Italy and France, which closes a conspicuous gap in the collection for this model organism. The analysis of 196 accessions, spanning the Mediterranean from Spain to Iraq, suggests that the interplay of high selfing and seed dispersal rates has shaped genetic structure in B. distachyon. At the continental scale, the evolution in B. distachyon is characterized by the independent expansion of three lineages during the Upper Pleistocene. Today, these lineages may occur on the same meadow yet do not interbreed. At the regional scale, dispersal and selfing interact and maintain high genotypic diversity, thus challenging the textbook notion that selfing in finite populations implies reduced diversity. Our study extends the population genomic resources for B. distachyon and suggests that an important use of this wild plant model is to investigate how selfing and dispersal, two processes typically studied separately, interact in colonizing plant species

Genetic and Methylome Variation in Turkish Brachypodium Distachyon Accessions Differentiate Two Geographically Distinct Subpopulations

Brachypodium distachyon (Brachypodium) is a non-domesticated model grass species that can be used to test if variation in genetic sequence or methylation are linked to environmental differences. To assess this, we collected seeds from 12 sites within five climatically distinct regions of Turkey. Seeds from each region were grown under standardized growth conditions in the UK to preserve methylated sequence variation. At six weeks following germination, leaves were sampled and assessed for genomic and DNA methylation variation. In a follow-up experiment, phenomic approaches were used to describe plant growth and drought responses. Genome sequencing and population structure analysis suggested three ancestral clusters across the Mediterranean, two of which were geographically separated in Turkey into coastal and central subpopulations. Phenotypic analyses showed that the coastal subpopulation tended to exhibit relatively delayed flowering and the central, increased drought tolerance as indicated by reduced yellowing. Genome-wide methylation analyses in GpC, CHG and CHH contexts also showed variation which aligned with the separation into coastal and central subpopulations. The climate niche modelling of both subpopulations showed a significant influence from the “Precipitation in the Driest Quarter” on the central subpopulation and “Temperature of the Coldest Month” on the coastal subpopulation. Our work demonstrates genetic diversity and variation in DNA methylation in Turkish accessions of Brachypodium that may be associated with climate variables and the molecular basis of which will feature in ongoing analyses. View Full-Text Keywords: Brachypodium; DNA methylation; drought; flowering; genome; phenomic

Migration without interbreeding: evolutionary history of a highly selfing Mediterranean grass inferred from whole genomes

Wild plant populations show extensive genetic subdivision and are far from the ideal of panmixia which permeates population genetic theory. Understanding the spatial and temporal scale of population structure is therefore fundamental for empirical population genetics – and of interest in itself, as it yields insights into the history and biology of a species. In this study we extend the genomic resources for the wild Mediterranean grass Brachypodium distachyon to investigate the scale of population structure and its underlying history at whole-genome resolution. A total of 86 accessions were sampled at local and regional scales in Italy and France, which closes a conspicuous gap in the collection for this model organism. The analysis of 196 accessions, spanning the Mediterranean from Spain to Iraq, suggests that the interplay of high selfing and seed dispersal rates has shaped genetic structure in B. distachyon. At the continental scale, the evolution in B. distachyon is characterized by the independent expansion of three lineages during the Upper Pleistocene. Today, these lineages may occur on the same meadow yet do not interbreed. At the regional scale, dispersal and selfing interact and maintain high genotypic diversity, thus challenging the textbook notion that selfing in finite populations implies reduced diversity. Our study extends the population genomic resources for B. distachyon and suggests that an important use of this wild plant model is to investigate how selfing and dispersal, two processes typically studied separately, interact in colonizing plant species