As a classic issue, structural seismic bearing capacity could not be accurately predicted since it was based on a structural ultimate state with inherent uncertainty. This result led to rare research ...efforts to discover structures' general and definite working laws from their experimental data. This study is to reveal the seismic working law of a bottom frame structure from its shaking table strain data by applying structural stressing state theory: (1) The tested strains are transformed into generalized strain energy density (GSED) values. (2) The method is proposed to express the stressing state mode and the corresponding characteristic parameter. (3) According to the natural law of quantitative and qualitative change, the Mann-Kendall criterion detects the mutation feature in the evolution of characteristic parameters versus seismic intensity. Moreover, it is verified that the stressing state mode also presents the corresponding mutation feature, which reveals the starting point in the seismic failure process of the bottom frame structure. (4) The Mann-Kendall criterion distinguishes the elastic-plastic branch (EPB) feature in the bottom frame structure's normal working process, which could be taken as the design reference. This study presents a new theoretical basis to determine the bottom frame structure's seismic working law and update the design code. Meanwhile, this study opens up the application of seismic strain data in structural analysis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment ...outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate-an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tyre wet skid resistance greatly affects vehicle safety, and it is dependent on the frictional behaviour at the tyre–road interface; however, the currently available numerical models, using the ...finite element method, either neglect the road roughness or obtain the rightness using expensive computed tomography scans, rendering them inefficient and complex. This study aims to present an estimation method of rubber slides on a rough road, to study tyre wet skid resistance. A three-dimensional rough road model was established, using the harmonic superposition method; the sealing effect of the water film on a wet road was modelled in terms of the pseudo-hydrodynamic bearing effect; the contact pressure, hysteresis friction, and water film hydrodynamic lift force were calculated. Subsequently, a friction model was established that accounted for the road surface morphology, tyre properties, sliding speed, and contact pressure. The accuracy of the friction model was experimentally validated, using the published experimental results. The friction model was then adopted, to conduct a study of the wet skid resistance of a 205/55R16 tyre with two different tread patterns. The simulation results were consistent with the experimental results of braking distance on a wet road. Finally, the effects of road roughness, tread rubber, load, and inflation pressure on wet skid resistance were carried out and analysed. The works in this paper have important significance and practical value for the development of high-performance tyres.
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This paper investigates numerically the collapses of both a single cavitation bubble and a cluster consisting of 8 bubbles, concerning mainly on the conversions between different forms of energy. ...Direct numerical simulation (DNS) with volume of fluid (VOF) method is applied, considering the detailed resolution of the vapor-liquid interfaces. First, for a single bubble near a solid wall, we find that the peak value of the wave energy, or equivalently the energy conversion rate decreases when the distance between the bubble and the wall is reduced. However, for the collapses of multiple bubbles, this relationship between the bubble-wall distance and the conversion rate reverses, implying a distinct physical mechanism. The evolutions of individual bubbles during the collapses of multiple bubbles are examined. We observe that when the bubbles are placed far away from the solid wall, the jetting flows induced by all bubbles point towards the cluster centre, while the focal point shifts towards the solid wall when the cluster is very close to the wall. We note that it is very challenging to consider thermal and acoustic damping mechanisms in the current numerical methods, which might be significant contributions to the energy budget, and we leave it open to the future studies.
As vehicle speed increases, the aerodynamic drag reduction becomes increasingly significant. The aim of this paper is to find out the effects of the wheelhouse shapes on the aerodynamics of an Ahmed ...body with a 35 slant angle. In this paper, based on the detached-eddy simulation method, the effects of the three classic different wheelhouse on the aerodynamic performance and near wake of the Ahmed body are presented. The mesh resolution and methodology are validated against the published test results. The results show that the front wheelhouse has a significant impact on the aerodynamic performance of the Ahmed body, leading to different aerodynamic drag forces and flow fields. Enlarging the wheelhouse cavity volume could result in a gradual increase in aerodynamic drag coefficients, the ratio of the wheelhouse cavity volume increased by 2.9% and 9.8%, the drag coefficients increased by 2.5% and 4.5% respectively. The increase in aerodynamic drag was primarily caused by flow separation in the large cavity volume wheelhouse.
Herein we described the clinical, radiological, histological, and molecular characteristics of seven soft tissue aneurysmal bone cysts (STABCs) diagnosed and managed at a tertiary cancer center and ...to elucidate their relationship with myositis ossificans (MO). All cases had established imaging and histopathological diagnosis of STABC and were subject to fluorescence in situ hybridization (FISH) for USP6 rearrangement and Archer® FusionPlex® targeted RNA sequencing (RNASeq) analysis to identify the fusion partner. A thorough literature review of STABC and MO was conducted. The patients presented with painful masses unpreceded by trauma, occurring most commonly in the deep soft tissue of the thigh/gluteus (4/7), and also in the supraclavicular region, the axilla, and the hand. On imaging, the lesions were frequently associated with peripheral calcification on conventional radiographs and CT (6/7), cystic components on ultrasound, as well as perilesional edema (7/7) and fluid levels (3/7) on MRI. Bone scan (1/1) showed intense radiotracer uptake. Histologically, 6/7 cases demonstrated zonal arrangements reminiscent of MO. USP6 rearrangement was found in all seven cases by FISH and/or RNASeq. RNASeq further detected COL1A1-USP6 fusion in six cases and a novel ANGPTL2-USP6 fusion in one case. Four patients underwent resection of the tumors and were disease free at their last follow-up. Three patients who underwent incisional or needle biopsies had no evidence of disease progression on imaging studies. In conclusion, the clinical, radiological, and pathological overlap between STABC and MO suggests that they are closely related entities. A novel fusion ANGPTL2-USP6 is associated with distinct clinical and pathological presentation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A pressure-based compressible-medium numerical method is developed and applied to the computation of cavitating flow. The cavitating flow is regarded as a homogeneous mixture with the density of the ...mixture being a function of the void volume fraction. The void volume fraction is governed by a transfer equation, in which the finite phase change rate is considered. To include the compressibility effect, the equation of state of each phase is introduced into the numerical modeling. The governing equations are solved using a pressure–velocity coupling approach, where finally an implicit pressure correction equation is obtained and solved. Our calculation demonstrates that the present compressible-medium numerical method is capable of simulating the dynamics of unsteady cavitating flow. In addition, this method is applicable to the study of the wave propagation in the flow fields, such as waves induced by the collapse of the cavitation cloud, or the presence of imposed external pressure waves.
•Development of an implicit pressure-based algorithm for the computation of unsteady compressible cavitating flow.•Implementation of the algorithm in the open-source program, OpenFOAM.•Computations of both partial and super cavitating flows over cylinders.•Study of the unsteady feature of pressure waves in cavitating flows.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reponses of structures subjected to severe earthquakes sometimes significantly surpass what was considered in the design. It is important to investigate the failure mechanism and collapse margin of ...structures beyond design, especially for high-rise buildings. In this study, steel high-rise buildings using either square concrete-filled-tube (CFT) columns or steel tube columns are designed. A detailed three-dimensional (3D) structural model is developed to analyze the seismic behavior of a steel high-rise towards a complete collapse. The effectiveness is verified by both component tests and a full-scale shaking table test. The collapse margin, which is defined as the ratio of PGA between the collapse level to the design major earthquake level (Level 2), is quantified by a series of numerical simulations using incremental dynamic analyses (IDA). The baseline building using CFT columns collapsed with a weak first story mechanism and presented a collapse margin ranging from 10 to 20. The significant variation in the collapse margin was caused by the different characteristics of the input ground motions. The building using equivalent steel columns collapsed earlier due to the significant shortening of the locally buckled columns, exhibiting only 57% of the collapse margin of the baseline building. The influence of reducing the height of the first story was quite significant. The shortened first story not only enlarged the collapse margin by 20%, but also changed the collapse mode.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
(
) is an important transmembrane hepatic uptake transporter. Genetic variants in the
gene have been associated with altered protein folding, resulting in protein degradation and decreased ...transporter activity. Next-generation sequencing (NGS) of pharmacogenes is being applied increasingly to associate variation in drug response with genetic sequence variants. However, it is difficult to link variants of unknown significance with functional phenotypes using "one-at-a-time" functional systems. Deep mutational scanning (DMS) using a "landing pad cell-based system" is a high-throughput technique designed to analyze hundreds of gene open reading frame (ORF) missense variants in a parallel and scalable fashion. We have applied DMS to analyze 137 missense variants in the
ORF obtained from the Exome Aggregation Consortium project. ORFs containing these variants were fused to green fluorescent protein and were integrated into "landing pad" cells. Florescence-activated cell sorting was performed to separate the cells into four groups based on fluorescence readout indicating protein expression at the single cell level. NGS was then performed and
variant frequencies were used to determine protein abundance. We found that six variants not previously characterized functionally displayed less than 25% and another 12 displayed approximately 50% of wild-type protein expression. These results were then functionally validated by transporter studies. Severely damaging variants identified by DMS may have clinical relevance for
dependent drug transport, but we need to exercise caution since the relatively small number of severely damaging variants identified raise questions with regard to the application of DMS to intrinsic membrane proteins such as organic anion transporter protein 1B1. SIGNIFICANCE STATEMENT: The functional implications of a large numbers of open reading frame (ORF) "variants of unknown significance" (VUS) in transporter genes have not been characterized. This study applied deep mutational scanning to determine the functional effects of VUS that have been observed in the ORF of
(
). Several severely damaging variants were identified, studied, and validated. These observations have implications for both the application of deep mutational scanning to intrinsic membrane proteins and for the clinical effect of drugs and endogenous compounds transported by
.
Tire contour design theory has always been studied because of its significant effect on tire performance. Based on the new non-natural equilibrium contour theory, the influence of belt pressure share ...ratio on the carcass contour is studied. The type of 385/65R22.5 all-steel radial tire was chosen as the research object and the finite element analysis technique was adopted to calculate the belt pressure share ratio. The results show that with the increase of the belt pressure share ratio, the clamping effect of belt layer on the carcass is strengthened, the curvature of tire crown in carcass contour increases and the crown curve tends to be rounded. The influence of belt pressure share ratio on wear, footprint, rolling resistance and grip performance was also explored with the finite element technology. It turned out that with the increase of the belt pressure share ratio, the tire wear increased, rolling resistance reduced, grip performance enhanced.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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