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2021 ◽  
Author(s):  
Alp Bugra Aydin ◽  
Ahmet Baylar ◽  
Fahri Ozkan ◽  
Muhammed Cihat Tuna ◽  
Mualla Ozturk

Abstract When the researches on the gated conduits were examined, it was determined that the air-demand ratio changed according to the hydraulic and geometric parameters. However, no study investigated the effect of the cross-section geometry of gated conduits on the air-demand ratio. In this study, the effect of conduit cross-section geometry on the air-demand ratio was examined. Results showed that conduit cross-section geometry was an important effect on the air-demand ratio especially at 10% and 15% gate opening rates. It was seen that the effect of the conduit geometry on the air-demand ratio decreased at 20%, and greater gate opening rates. In addition, a design formula related to the gate opening rate, Froude number, hydraulic radius, and conduit length was presented for estimating the air-demand ratio.


2021 ◽  
Author(s):  
Janelle Chuah ◽  
Tifffany Thibaudeau ◽  
David Smith

Abstract Impairment of proteasomal function has been implicated in neurodegenerative diseases, justifying the need to understand how the proteasome is activated for protein degradation. Here, using biochemical and structural (cryo-EM) strategies in both archaeal and mammalian proteasomes, we further determine the HbYX(-motif)-dependent mechanism of proteasomal activation used by multiple proteasome-activating complexes including the 19S Particle. We identify multiple proteasome α subunit residues involved in HbYX-dependent activation, a point mutation that activates the proteasome by partially mimicking a HbYX-bound state, and conformational changes involved in gate-opening with a 2.0A structure. Through an iterative process of peptide synthesis, we successfully design a HbYX-like dipeptide mimetic as a robust tool to elucidate how the motif autonomously activates the proteasome. The mimetic induces near complete gate-opening at saturating concentration, activating mammalian proteasomal degradation of peptides and proteins. Findings using our peptide mimetic suggest the HbYX-dependent mechanism requires cooperative binding in at least two intersubunit pockets of the α ring. Collectively, the results presented here unambiguously demonstrate the lone role of the HbYX tyrosine in the allosteric mechanism of proteasome activation and offer proof of concept for the robust potential of HbYX-like small molecules to activate the proteasome.


2021 ◽  
Vol 118 (37) ◽  
pp. e2102036118
Author(s):  
Xiaoan Wu ◽  
Rosamary Ramentol ◽  
Marta E. Perez ◽  
Sergei Yu Noskov ◽  
H. Peter Larsson

Rhythmic activity in pacemaker cells, as in the sino-atrial node in the heart, depends on the activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. As in depolarization-activated K+ channels, the fourth transmembrane segment S4 functions as the voltage sensor in hyperpolarization-activated HCN channels. But how the inward movement of S4 in HCN channels at hyperpolarized voltages couples to channel opening is not understood. Using voltage clamp fluorometry, we found here that S4 in HCN channels moves in two steps in response to hyperpolarizations and that the second S4 step correlates with gate opening. We found a mutation in sea urchin HCN channels that separate the two S4 steps in voltage dependence. The E356A mutation in S4 shifts the main S4 movement to positive voltages, but channel opening remains at negative voltages. In addition, E356A reveals a second S4 movement at negative voltages that correlates with gate opening. Cysteine accessibility and molecular models suggest that the second S4 movement opens up an intracellular crevice between S4 and S5 that would allow radial movement of the intracellular ends of S5 and S6 to open HCN channels.


2021 ◽  
Vol 11 (17) ◽  
pp. 8118
Author(s):  
Cong Zhang ◽  
Yuqi Zhang ◽  
Huadong Zhao ◽  
Mao Wang ◽  
Tongtong Wang

There are many sand-laden waters in China, and the wear of hydraulic structures caused by sand-laden water diversion has been paid more and more attention. Taking the spillway of a reservoir as the research object, the numerical model of erosion wear caused by sediment-laden particle flows on the spillway was established by using the computational fluid dynamics (CFD) method, VOF (Volume of Fluid) multiphase flow model and DPM (Discrete Phase Model). Through the simulation analysis of the spillway’s overall erosion, the distribution of the spillway erosion wear was obtained. Then, according to the main wear parts, the single variable, such as sediment diameter, sediment concentration, flow velocity and gate opening degree, was changed to study the erosion amount of the spillway and the distribution law of the spillway erosion parts. The results show that the main erosion sites of the spillway are at the bottom of the gate chamber and the middle section of the spillway. The maximum erosion increases linearly with the increase in sediment concentration. With the increase in sediment concentration, the sediment concentration changed from 1 kg/m3 to 6 kg/m3, and the maximum erosion of the spillway increased from 2.58 × 10−7 kg/m2 to 1.53 × 10−6 kg/m2. The erosion at the bottom of the spillway and gate leaf increases first and then decreases with the increase in sediment diameter and reaches the maximum value when the particle size is 0.002 mm. The erosion at the bottom of the spillway and the gate leaf increases with different growth trends as the flow velocity increases, when the flow velocity increases from 2 m/s to 9 m/s and the maximum erosion amount at the bottom of the spillway increases from 3.66 × 10−7 kg/m2 to 1.14 × 10−6 kg/m2, and the maximum erosion of the gate leaf increased from 1.66 × 10−8 kg/m2 to 8.98 × 10−6 kg/m2. The erosion amount at the bottom of the spillway increases with the increase in the gate opening between 0 and 3 m and tends to be stable when the gate opening is greater than 3 m. The maximum erosion position moves to the rear part of the spillway with the change in the gate opening. The change in the gate opening has no obvious effect on the erosion amount of the gate leaf but only changes the area of the gate erosion part. Thus, the erosion wear distribution of spillway under different work conditions is summarized, and the qualitative study between the erosion wear and the distribution of sediment diameter, sediment concentration, flow velocity and gate opening degree is made.


2021 ◽  
Author(s):  
Mickaele Bonneau ◽  
Kunihisa Sugimoto ◽  
Ken‐ichi Otake ◽  
Yukiko Tsuji ◽  
Nanae Shimanaka ◽  
...  

2021 ◽  
pp. 016502542110239
Author(s):  
Lauren E. Altenburger ◽  
Sarah J. Schoppe-Sullivan

Maternal gatekeeping is characterized by the extent to which mothers engage in behaviors that ultimately serve to inhibit (i.e., gate close) or encourage (i.e., gate open) father involvement in childrearing. This study considered direct and indirect associations between observed and reported maternal gatekeeping and children’s social–emotional difficulties. Data come from a sample of 182 parents who transitioned to parenthood in 2008–2010 and their young children. Results of longitudinal path analyses indicated mothers’ perceptions of maternal gate closing at 3-months postpartum were associated with greater dysregulation (β = .21, 95% CI [.08, .35], p = .002) and externalizing (β = .25, 95% CI [.10, .41], p = .001) in 26-month-old toddlers. Observed maternal gate opening at 3-months postpartum predicted lower dysregulation (β = −.18, 95% CI [−.32, −.05], p = .008) in 26-month-old toddlers. Observed fathers’ parenting quality did not mediate associations between maternal gatekeeping and child social–emotional difficulties. However, a statistically significant interaction between infant negative affect and observed maternal gate opening emerged as a predictor of toddler dysregulation, such that the adjusted negative effect of observed maternal gate opening on toddler dysregulation was strongest when infant negative affect was low. Statistically significant interactions between fathers’ perceptions of gate closing and infant negative affect also emerged as predictors of toddler dysregulation and externalizing. Infants high in negative affect exposed to maternal gate closing were at the greatest risk for externalizing and dysregulation difficulties. Implications for maternal gatekeeping theory and research are discussed.


Author(s):  
Wang Lu ◽  
Hongliang Huang ◽  
Zhu Hejin ◽  
Chang Yanjiao ◽  
Guo Xiangyu ◽  
...  

Efficient and economical separation of 1,3-butadiene (C4H6) from C4 hydrocarbons is imperative yet challenging in industrial separation processes. Herein, a guest-induced flexible Mn-bpdc MOF has been employed to separate C4H6 from C4 hydrocarbons, including n-butene (n-C4H8), iso-butene (iso-C4H8), n-butane (n-C4H10) and iso-butane (iso-C4H10). Significantly, C4H6 can instantaneously induce gate-opening of Mn-bpdc MOF at 0.13 bar and 298 K, thus significant amounts of C4H6 can be adsorbed, while other C4 hydrocarbons cannot induce the gate-opening even at 1 bar. The uptake selectivities of Mn-bpdc MOF for C4H6/n-C4H8 and C4H6/iso-C4H8 are up to 40.0 and 45.0 at 298 K and 1 bar, respectively, both surpassing all the reported adsorbents. In addition, breakthrough experiments verified that C4H6/n-C4H8, C4H6/iso-C4H8, C4H6/n-C4H10 and C4H6/iso-C4H10 mixture can be efficiently separated. More importantly, Mn-bpdc possesses excellent water stability and outstanding regeneration ability for C4H6 separation, making it a new benchmark for C4H6 purification.


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