The Mont-Blanc prototype: an alternative approach for high-performance computing systems

High-performance computing (HPC) is recognized as one of the pillars for further advance of science, industry, medicine, and education. Current HPC systems are being developed to overcome emerging challenges in order to reach Exascale level of performance,which is expected by the year 2020. The much larger embedded and mobile market allows for rapid development of IP blocks, and provides more flexibility in designing an application-specific SoC, in turn giving possibility in balancing performance, energy-efficiency and cost. In the Mont-Blanc project, we advocate for HPC systems be built from such commodity IP blocks, currently used in embedded and mobile SoCs. As a first demonstrator of such approach, we present the Mont-Blanc prototype; the first HPC system built with commodity SoCs, memories, and NICs from the embedded and mobile domain, and off-the-shelf HPC networking, storage, cooling and integration solutions. We present the system’s architecture, and evaluation including both performance and energy efficiency. Further, we compare the system’s abilities against a production level supercomputer. At the end, we discuss parallel scalability, and estimate the maximum scalability point of this approach across a set of HPC applications.Postprint (published version

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Biodosimetry of radiation-induced effects on DNA damage and cell cycle.

Molecular biological markers of radiation response are thought to be of potential use to monitor the progress of radiation therapy and also to predict at an early stage the outcome of a radiotherapeutical treatment. They might also be a tool to monitor the populations potentially exposed after a radiological accident or a "dirty bomb" incident but also to monitor astronauts during a spaceflight during which they are submitted to cosmic radiations. The bone marrow and the blood are the most radiation sensitive tissues of the human body. Therefore, the specific study of the radiation effects on mononuclear cells is of particular importance to find radiation-induced biological markers. The study of radiation biomarkers includes DNA mutation, chromosome aberrations, apoptosis as well as protein, gene expression by the array technologies and cell cycle after propidium iodide staining. However, additional studies are needed to validate candidate biomarkers (molecular and/or proteic) for applied biological dosimetry applications and that could provide early and rapid information after exposure to radiation. In human mononuclear cells, we studied the effects of X- and gamma rays at low doses (from 0.015625, 0.03125, 0.0625, 0.125 to 0.25 Gy) to high doses (0.25, 0.5, 1, 2, 4, 6, 10, 15 and 20 Gy) on DNA damage and cell cycle. DNA damage was monitored by the 8-oxyDNA assay and the apoptosis by cell cycle analysis after Propidium Iodide staining and size reduction. The results show that X or gamma radiations induced a dose-dependent increase of DNA damage in mononuclear cells in comparison with the control samples. Moreover, cell cycle and the size reduction showed a higher number of cells in the sub-G1 phase (caracterising the apoptotic cells) in irradiated cells in comparison with the control. However, the pattern of the induction of the radiation-induced effects is different in function of the protocol applied (DNA damage, the cell cycle and the size reduction). This can be explained by the different radiosensitivities of the subpopulations amongst mononuclear cells and also the variation in intrinsic radiation sensitivities between individuals. This work is supported by a Belspo contract (BL/52/C43) and an ESA-Belspo contract (CO-90-2141)

A biodegradable starch based coating to waterproof hydrophilic materials

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Experimental uncertainty analysis for ice tank ship resistance experiments using a model for a Canadian Icebreaker "Terry Fox"

Experimental Uncertainty Analysis (EUA) is an analytical process for estimating uncertainties in the results of a given experimental program. Fundamentally, through the EUA process, experimentalists in the laboratory can quantify the agreement (the closeness or the difference) between the measured results and their "true" values.Peer reviewed: YesNRC publication: Ye

Apoptosis and inflammation induced by exposure radiation on the whole blood

In this study, we were interested in the effects on the immune system and the cytokine network induced by the ionizing radiations (X rays) at the low debit dose (0,005 Gy/s) from low to high doses, by focusing on the apoptosis of mononuclear cells 24 hours after the irradiation. Parallely, the levels of 10 cytokines in the plasma 4 hours after irradiation were monitored by using the Luminex technology. The cell counting by flow cytometry revealed a significant decrease of the living cells and increase of the apoptotic cells in comparison with the controls at high dose of irradiation. The measurement of the apoptosis involving the Bcl-2 shows a significant increase of the apoptotic cells at all doses. The same results were found with the caspase-3 experiments at most of the doses. The results from the double staining by AnnexinV/Propidium Iodide show that necrosis was higher than the apoptosis, like in the case of the radiotherapy for the tumour treatment. Concerning the cytokine experiments, the levels of pro-inflammatory cytokines, IL-2, IL-5, IL-6, IFN-gamma and TNF alpha were higher at high doses than in the controls but not significantly, except for IL-1 beta. In parallel, the levels of the anti-inflammatory cytokine, the levels of IL-10 were higher for the doses of 2, 15 and 20 Gy than the control. These modifications on the cytokine network might not involve the decrease of the cytokine, but rather the selective alterations of the specific cytokine functions. In conclusion, these results suggest that the ionizing radiations increase the apoptosis on the lymphocytes, in high doses in comparison with the control and that there are the selective alterations for some cytokine levels. This work is supported by a Belspo contract (BL/52/C43) and an ESA-Belspo contract (CO-90-2141)

Influence of a P53 Mutation on the Radiation Sensitivity of Mouse Zygotes

The aim of studies under way in our laboratory is to investigate whether heterozygous mutations in genes involved in such important cellular processes as cell cycle regulation, apoptosis and DNA repair may influence the radiation sensitivity of early mammalian embryos. The embryonic stage chosen for our first investigations is the zygote (first day of gestation). This stage occurs while women cannot be aware of pregnancy. Moreover, in contradiction with a long standing dogma of teratology, various kinds of malformations were previously found in mouse fetuses from particular (wild-type) strains after X-irradiation at the zygote stage. Our studies mainly concentrate on external congenital anomalies, cytokine secretion in the amniotic fluid and chromosomal instability. Measuring cytokines in the amniotic will enable us to determine whether developmental abnormalities are accompanied by changes in the levels of particular cytokines, as suggested by the few available data. On the other hand, chromosome instability has been recently reported in mouse fetuses from different strains, after x-irradiation at the zygote stage. The gene currently under study is P53, the "genome guardian". The P53 mutation was introduced in the CF1 strain, whose wild-type zygotes had been previously shown by us to be sensitive to radiation induction of congenital anomalies (Jacquet et al., Mutation Res., 332, 73-87, 1995). P53 (+/+ x -/-) or P53 (+/+ x +/-) matings were performed from 7.30 till 9.30 am and the females showing a vaginal plug were x-irradiated with either 0.2 or 0.4 Gy 2 h after presumed fertilization. A number of them were sacrificed on day 8 of gestation, their gastrula stage embryos were collected and their embryonic parts were cultured for 7 h in the presence of colchicine. The cells were then fixed and cytogenetically analyzed. Other females were sacrificed on day 19 of gestation. Pre- and post-implantation losses were recorded, amniotic fluid surrounding the fetuses was collected for cytokine analysis and the living fetuses were weighed and examined under the stereomicroscope for the presence of congenital anomalies. When needed (+/+ x +/- matings), the tails of the fetuses were collected for genotype analysis. So far, and although our results have still to be completed, the P53 mutation did not seem to result into the development of a chromosomal instability and/or to higher levels of congenital anomalies in irradiated embryos. (Partially funded by the research contract n° CO-90 06 2024.00 between SCKCEN and the Federal Agency for Nuclear Control)