The causes of pediatric cancers' distinctiveness compared to adult-onset tumors of the same type are not completely clear and not fully explained by their genomes. In this study, we used an optimized ...multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. Tumor entities were sometimes unexpectedly grouped due to common lineages, drivers or stemness profiles. Some established entities were divided into subgroups that predicted outcome better than current diagnostic approaches. These definitions account for inter-tumoral and intra-tumoral heterogeneity and have the potential of enabling reproducible, quantifiable diagnostics. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort. If further validated, this framework could be extended to derive molecular definitions for all cancer types.
Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and ...tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.
The design and development of a monolithic system-on-chip dosimeter fabricated in a standard 180 nm CMOS technology is described. The device is intended for real time In Vivo measurement of dose of ...radiation during radiotherapy sessions. Owing to its proposed small size, of approximately 1 mm3, such solution could be made in-body implantable and, as such, provide a much-enhanced high-resolution, real-time dose measurement for quality assurance in radiation therapy. The device transmits the related information on dose of radiation wirelessly to an external receiver operating in the MICS band. The various phases of this two years project, started in 2011, including the design and development of radiation sensors and integrated RF to perform the readout, will be described.
•A novel monolithic CMOS dosimeter of size of 1 mm3 has been proposed.•Three different fabrications using a CMOS 180 nm technology have been carried out.•Radiation tests results showed a sensitivity of 1 cGy with accuracy better than 3%.•Preliminary RF tests showed that an RF signal is detectable in free air.
The design, fabrication and testing of a novel monolithic system-on-chip dosimeter fabricated in a standard 180 nm CMOS technology is described. The device, implementing a radiation sensor and an RF ...transmitter, is proposed to address the need for real-time In Vivo Dosimetry (IVD) of radiation during Linac radiotherapy sessions. Owing to its small size, of approximately 1 mm3, such solution could be made in-body implantable and, as such, provide a much-enhanced high-resolution, real-time dose measurement to improve Quality Assurance (QA) in radiation therapy. The device transmits the related information on dose of radiation wirelessly to a remote receiver operating in the Medical Implant Communication Service (MICS) band. Comprehensive description of the various phases of this project, including the development of the radiation sensors and integrated RF transmitter to perform the readout, along with the final test results using a radiation beam, will be given.
•A Monolithic Dosimeter for real time dosimetry during radiotherapy is proposed.•The proposed device is 1 mm3 in size and could potentially be body implantable.•The device includes a radiation sensor and RF readout, operating in the MICS band.•Detailed tests have been performed under radiation beam in a clinical environment.•Reported sensitivity is 1 cGy over 50 Gy, with an accuracy of better than 3%.
Arctic warming and permafrost degradation are modifying northern
ecosystems through changes in microtopography, soil water dynamics, nutrient
availability, and vegetation succession. Upon permafrost ...degradation, the
release of deep stores of nutrients, such as nitrogen and phosphorus, from
newly thawed permafrost stimulates Arctic vegetation production. More
specifically, wetter lowlands show an increase in sedges (as part of
graminoids), whereas drier uplands favor shrub expansion. These shifts in
the composition of vegetation may influence local mineral element cycling
through litter production. In this study, we evaluate the influence of
permafrost degradation on mineral element foliar stocks and potential annual
fluxes upon litterfall. We measured the foliar elemental composition (Al,
Ca, Fe, K, Mn, P, S, Si, and Zn) of ∼ 500 samples of typical
tundra plant species from two contrasting Alaskan tundra sites, i.e., an
experimental sedge-dominated site (Carbon in Permafrost Experimental Heating Research, CiPEHR) and natural shrub-dominated site
(Gradient). The foliar concentration of these mineral elements was species specific, with sedge leaves having relatively high Si concentration and
shrub leaves having relatively high Ca and Mn concentrations. Therefore,
changes in the species biomass composition of the Arctic tundra in response
to permafrost thaw are expected to be the main factors that dictate changes
in elemental composition of foliar stocks and maximum potential foliar
fluxes upon litterfall. We observed an increase in the mineral element
foliar stocks and potential annual litterfall fluxes, with Si increasing
with sedge expansion in wetter sites (CiPEHR), and Ca and Mn increasing with
shrub expansion in drier sites (Gradient). Consequently, we expect that
sedge and shrub expansion upon permafrost thaw will lead to changes in
litter elemental composition and therefore affect nutrient cycling across
the sub-Arctic tundra with potential implications for further vegetation
succession.
LGAD devices from Teledyne e2v (a long-established commercial manufacturer of scientific imaging sensors) have been fully characterised before and after irradiation. Irradiations were performed with ...27MeV protons at the MC40 cyclotron in Birmingham to deliver a fluence from 5.6 × 1013 up to 8.3 × 10141MeVneq/cm2 to seven LGADs. Te2v LGADs were shown to exhibit the expected trends in breakdown voltage, gain and time resolution as seen in literature. Time resolution and gain performance before and after irradiation are reported here and compared with published results for other manufacturers of such devices.
The need for ultra-fast timing is a result of the expected pile-up at the High-Luminosity LHC General-Purpose Detectors. Track timing resolution of the order of tens of picoseconds is required to ...sufficiently resolve individual vertices. In collaboration with Teledyne e2v, 22 six-inch wafers with Low Gain Avalanche Detectors, featuring a 50μm thick high-resistivity epitaxial layer and different gain layer implants, have been completed successfully. Using transient current technique, the charge gain of a 1 × 1 mm 2 LGAD device from one of the wafers was found to be higher than 10, with jitter reaching 10 ps when biased at 240 V. Tests with other wafers are under way.
Permafrost ecosystems are limited in nutrients for
vegetation development and constrain the biological activity to the active
layer. Upon Arctic warming, permafrost thaw exposes large amounts of soil
...organic carbon (SOC) to decomposition and minerals to weathering but also
releases organic and mineral soil material that may directly influence the
soil exchange properties (cation exchange capacity, CEC, and base saturation,
BS). The soil exchange properties are key for nutrient base cation supply
(Ca2+, K+, Mg2+, and Na+) for vegetation growth and
development. In this study, we investigate the distributions of soil exchange
properties within Arctic tundra permafrost soils at Eight Mile Lake
(Interior Alaska, USA) because they will dictate the potential reservoir of
newly thawed nutrients and thereby influence soil biological activity and
vegetation nutrient sources. Our results highlight much lower CEC density in
surface horizons (∼9400 cmolc m−3) than in the mineral
horizons of the active layer (∼16 000 cmolc m−3)
or in permafrost soil horizons (∼12 000 cmolc m−3). Together, with the overall increase in CEC density with depth and
the overall increase in BS (percentage of CEC occupied by exchangeable base
cations Ca2+, K+, Mg2+, and Na+) with depth (from
∼19 % in organic surface horizons to 62 % in permafrost soil
horizons), the total exchangeable base cation density (Ca2+, K+,
Mg2+, and Na+ in g m−3) is up to 5 times higher in the
permafrost than in the active layer. More specifically, the exchangeable
base cation density in the 20 cm upper part of permafrost about to thaw is
∼850 g m−3 for Caexch, 45 g m−3 for
Kexch, 200 g m−3 for Mgexch, and 150 g m−3 for
Naexch. This estimate is needed for future ecosystem prediction models
to provide constraints on the size of the reservoir in exchangeable
nutrients (Ca, K, Mg, and Na) about to thaw. All data described in this paper are stored in Dataverse, the online repository of Université catholique de Louvain, and are accessible through the following DOI: https://doi.org/10.14428/DVN/FQVMEP (Mauclet et al., 2022b).
The DECAL sensor is a depleted monolithic active pixel sensor (DMAPS) being developed to explore technological solutions for digital electromagnetic calorimeters. For this application, the number of ...pixels above threshold is used to estimate the shower energy and therefore the pixel size is required to be sufficiently small to avoid hit saturation. The DECAL and DECAL Fully Depleted (FD) sensors have been designed and fabricated in the TowerJazz 180 nm CMOS standard and modified imaging processes, respectively. The latter uses modifications to the implant configuration that improve charge collection and radiation hardness, including to the levels required for barrel ECAL regions of FCC-hh (few 1015 neq/cm2). Both DECAL variants feature a matrix of 64 × 64 pixels with a pitch of 55μm, read out every 25 ns. For DECAL FD, the logic has been modified to extend the in-pixel comparator threshold trim range from five to six bits, with the sixth bit used to de-activate the comparator. Characterisation results for the DECAL FD, including the pixel equalisation matrix, threshold scans testing under monochromatic X-rays and 90Sr source, are presented.
