57 research outputs found

    Modeling a New Water Channel That Allows SET9 to Dimethylate p53

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    SET9, a protein lysine methyltransferase, has been thought to be capable of transferring only one methyl group to target lysine residues. However, some reports have pointed out that SET9 can dimethylate Lys372 of p53 (p53-K372) and Lys4 of histone H3 (H3-K4). In order to understand how p53 can be dimethylated by SET9, we measured the radius of the channel that surrounds p53-K372, first on the basis of the crystal structure of SET9, and we show that the channel is not suitable for water movement. Second, molecular dynamic (MD) simulations were carried out for 204 ns on the crystal structure of SET9. The results show that water leaves the active site of SET9 through a new channel, which is made of G292, A295, Y305 and Y335. In addition, the results of molecular docking and MD simulations indicate that the new water channel continues to remain open when S-adenosyl-L-methionine (AdoMet) or S-adenosyl-L-homocysteine (AdoHcy) is bound to SET9. The changes in the radii of these two channels were measured in the equilibrium phase at the constant temperature of 300 K. The results indicate that the first channel still does not allow water to get into or out of the active site, but the new channel is large enough to allow this water to circulate. Our results indicate that water can be removed from the active site, an essential process for allowing the dimethylation reaction to occur

    Emergence and Spread of the SARS-CoV-2 Omicron Variant in Alberta Communities Revealed by Wastewater Monitoring

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    Wastewater monitoring of SARS-CoV-2 allows for early detection and monitoring of COVID-19 burden in communities and can track specific variants of concern. Targeted assays enabled relative proportions of SARS-CoV-2 Omicron and Delta variants to be determined across 30 municipalities covering >75% of the province of Alberta (pop. 4.5M) in Canada, from November 2021 to January 2022. Larger cities like Calgary and Edmonton exhibited a more rapid emergence of Omicron relative to smaller and more remote municipalities. Notable exceptions were Banff, a small international resort town, and Fort McMurray, a more remote northern city with a large fly-in worker population. The integrated wastewater signal revealed that the Omicron variant represented close to 100% of SARS-CoV-2 burden prior to the observed increase in newly diagnosed clinical cases throughout Alberta, which peaked two weeks later. These findings demonstrate that wastewater monitoring offers early and reliable population-level results for establishing the extent and spread of emerging pathogens including SARS-CoV-2 variants.Alberta Healt

    Intrinsically Motivated Self-supervised Learning in Reinforcement Learning

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    In vision-based reinforcement learning (RL) tasks, it is prevalent to assign auxiliary tasks with a surrogate self-supervised loss so as to obtain more semantic representations and improve sample efficiency. However, abundant information in self-supervised auxiliary tasks has been disregarded, since the representation learning part and the decision-making part are separated. To sufficiently utilize information in auxiliary tasks, we present a simple yet effective idea to employ self-supervised loss as an intrinsic reward, called Intrinsically Motivated Self-Supervised learning in Reinforcement learning (IM-SSR). We formally show that the self-supervised loss can be decomposed as exploration for novel states and robustness improvement from nuisance elimination. IM-SSR can be effortlessly plugged into any reinforcement learning with self-supervised auxiliary objectives with nearly no additional cost. Combined with IM-SSR, the previous underlying algorithms achieve salient improvements on both sample efficiency and generalization in various vision-based robotics tasks from the DeepMind Control Suite, especially when the reward signal is sparse

    Influence of Wind Pressure on the Carbonation of Concrete

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    Carbonation is one of the major deteriorations that accelerate steel corrosion in reinforced concrete structures. Many mathematical/numerical models of the carbonation process, primarily diffusion-reaction models, have been established to predict the carbonation depth. However, the mass transfer of carbon dioxide in porous concrete includes molecular diffusion and convection mass transfer. In particular, the convection mass transfer induced by pressure difference is called penetration mass transfer. This paper presents the influence of penetration mass transfer on the carbonation. A penetration-reaction carbonation model was constructed and validated by accelerated test results under high pressure. Then the characteristics of wind pressure on the carbonation were investigated through finite element analysis considering steady and fluctuating wind flows. The results indicate that the wind pressure on the surface of concrete buildings results in deeper carbonation depth than that just considering the diffusion of carbon dioxide. In addition, the influence of wind pressure on carbonation tends to increase significantly with carbonation depth

    A Series of Frequency Shift Antennas Based on Shape Blending

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    In this paper, an automatic antenna design method based on the shape blending algorithm is proposed. The algorithm is used to construct the shape of the wide slot of a CPW-fed antenna. Firstly, two basic shapes are chosen as the initial shape and the target shape. The shape blending process is then applied on them to get a series of shapes, which are used as the geometry structure of the wide slot. In this way, a series of CPW-fed wide slot antennas are obtained. And they have similar but gradually changing characteristics. The bandwidth ranges are 8.00–9.24 GHz, 7.95–9.05 GHz, 7.05–8.55 GHz, 6.95–8.13 GHz, and 6.55–7.50 GHz, respectively. The overall size of the antenna is 26 mm ∗ 20 mm ∗ 0.6 mm. Experimental results show that the resonant frequencies vary (via translation) with the change of slot shape in a specific frequency band. The experiments also validate that the antennas have omnidirectional radiation characteristics. The radiation gains and aperture efficiencies of the antennas are about 3.8–5.5 dBi and 57.7–83.0% at their centre frequencies, respectively. The experiment results show that the proposed antennas could be used in C-band and X-band radar applications
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