Analysis of Inertial Migration of Neutrally Buoyant Particle Suspensions in a Planar Poiseuille Flow with a Coupled Lattice Boltzmann Method-Discrete Element Method

In this study a hybrid numerical framework for modelling solid-liquid multiphase flow is established with a single-relaxation-time lattice Boltzmann method and the discrete element method implemented with the Hertz contact theory. The numerical framework is then employed to systematically explore the effect of particle concentration on the inertial migration of neutrally buoyant particle suspensions in planar Poiseuille flow. The results show that the influence of particle concentration on the migration is primarily determined by the characteristic channel Reynolds number Re0. For relatively low Re0 (Re0˂20), the migration behaviour can only be observed at a very low particle concentration (≤5%). However, when Re0˃20 the migration behaviour can be observed at a high concentration (≥20%). Furthermore, a focusing number Fc is proposed to characterise the degree of inertial migration. It was found that the inertial migration can be classified into three regimes depending on two critical values of the focusing number, Fc+ and Fc-: i) when Fc˃Fc+, a full inertial migration occurs; ii) when Fc˂Fc-, particles are laterally unfocused; iii) when Fc-˂Fc˂Fc+, a partially inertial migration takes place

Flavonoids activate pregnane × receptor-mediated CYP3A4 gene expression by inhibiting cyclin-dependent kinases in HepG2 liver carcinoma cells

<p>Abstract</p> <p>Background</p> <p>The expression of the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is regulated by the pregnane × receptor (PXR), which is modulated by numerous signaling pathways, including the cyclin-dependent kinase (Cdk) pathway. Flavonoids, commonly consumed by humans as dietary constituents, have been shown to modulate various signaling pathways (e.g., inhibiting Cdks). Flavonoids have also been shown to induce <it>CYPs </it>expression, but the underlying mechanism of action is unknown. Here, we report the mechanism responsible for flavonoid-mediated PXR activation and <it>CYP </it>expression.</p> <p>Results</p> <p>In a cell-based screen designed to identify compounds that activate PXR-mediated <it>CYP3A4 </it>gene expression in HepG2 human carcinoma cells, we identified several flavonoids, such as luteolin and apigenin, as PXR activators. The flavonoids did not directly bind to PXR, suggesting that an alternative mechanism may be responsible for flavonoid-mediated PXR activation. Consistent with the Cdk5-inhibitory effect of flavonoids, Cdk5 and p35 (a non-cyclin regulatory subunit required to activate Cdk5) were expressed in HepG2. The activation of Cdk5 attenuated PXR-mediated <it>CYP3A4 </it>expression whereas its downregulation enhanced it. The Cdk5-mediated downregulation of <it>CYP3A4 </it>promoter activity was restored by flavonoids, suggesting that flavonoids activate PXR by inactivating Cdk5. <it>In vitro </it>kinase assays showed that Cdk5 directly phosphorylates PXR. The Cdk kinase profiling assay showed that apigenin inhibits multiple Cdks, suggesting that several Cdks may be involved in activation of PXR by flavonoids.</p> <p>Conclusions</p> <p>Our results for the first time link the stimulatory effect of flavonoids on <it>CYP </it>expression to their inhibitory effect on Cdks, through a PXR-mediated mechanism. These results may have important implications on the pharmacokinetics of drugs co-administered with herbal remedy and herbal-drug interactions.</p

Fluctuations and correlations of reactive scalars near chemical equilibrium in incompressible turbulence

The statistical properties of species undergoing chemical reactions in a turbulent environment are studied. We focus on the case of reversible multi-component reactions of second and higher orders, in a condition close to chemical equilibrium sustained by random large-scale reactant sources, while the turbulent flow is highly developed. In such a state a competition exists between the chemical reaction that tends to dump reactant concentration fluctuations and enhance their correlation intensity and the turbulent mixing that on the contrary increases fluctuations and remove relative correlations. We show that a unique control parameter, the Damkh\"{o}ler number ($Da_\theta$) that can be constructed from the scalar Taylor micro-scale, the reactant diffusivity and the reaction rate characterises the functional dependence of fluctuations and correlations in a variety of conditions, i.e., at changing the reaction order, the Reynolds and the Schmidt numbers. The larger is such a Damkh\"{o}ler number the more depleted are the scalar fluctuations as compared to the fluctuations of a passive scalar field in the same conditions, and vice-versa the more intense are the correlations. A saturation in this behaviour is observed beyond $Da_\theta \simeq \mathcal{O}(10)$. We provide an analytical prediction for this phenomenon which is in excellent agreement with direct numerical simulation results.Comment: 17 pages , 9 figure

A Novel Prognostic Predictor of Immune Micro-environment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature

Background: Necroptosis, a cell death of caspase-independence, plays a pivotal role in cancer biological regulation. Although necroptosis is closely associated with oncogenesis, cancer metastasis, and immunity, there remains a lack of studies determining the role of necroptosis-related genes (NRGs) in the highly immunogenic cancer type, kidney renal clear cell carcinoma (KIRC). Methods: The information of clinicopathology and transcriptome was extracted from TCGA database. Following the division into the train and test cohorts, a three-NRGs (TLR3, FASLG, ZBP1) risk model was identified in train cohort by LASSO regression. The overall survival (OS) comparison was conducted between different risk groups through Kaplan-Meier analysis, which was further validated in test cohort. The Cox proportional hazards regression model was introduced to assess its impact of clinicopathological factors and risk score on survival. ESTIMATE and CIBERSORT algorithms were introduced to evaluate immune microenvironment, while enrichment analysis was conducted to explore the biological significance. Correlation analysis was applied for the correlation assessment between checkpoint gene expression and risk score, between gene expression and therapeutic response. Gene expressions from TCGA were verified by GEO datasets and immunohistochemistry (IHC) analysis. Results: This NRGs-related signature predicted poorer OS in high-risk group, which was also verified in test cohort. Risk score could also independently predict survival outcome of KIRC. Significant changes were also found in immune microenvironment and checkpoint gene expressions between different risk groups, with immune functional enrichment in high-risk group. Interestingly, therapeutic response was correlated with the expressions of NRGs. The expressions of NRGs from TCGA were consistent with those from GEO datasets and IHC analysis. Conclusion: The NRGs-related signature functions as a novel prognostic predictor of immune microenvironment and therapeutic response in KIRC

Dynamic Stiffness Method for Vibrations of Ship Structures

Initiated by the objective to address the dynamics of ship structures other than conventional finite element method, a dynamic stiffness method (DSM) is proposed systematically including that for three types of element models. A DSM element accounting for both in-plane and bending vibrations in flat rectangular plates is developed, which makes it possible for modeling wave conversion across junctions in built-up plates. In addition, a DSM element for stiffened plates is formulated, which considers all possible vibrations in plates and beams, i.e., bending, torsion, and extension motions. The third type of DSM plate element takes fluid loading into account, which is induced by vibrating plate. Finally, the proposed DSM method is extended to address vibration transmission in a built-up plate structure, which demonstrates the great potentials of DSM in application to more practical and more general engineering fields

In the Blink of an Eye: Event-based Emotion Recognition

We introduce a wearable single-eye emotion recognition device and a real-time approach to recognizing emotions from partial observations of an emotion that is robust to changes in lighting conditions. At the heart of our method is a bio-inspired event-based camera setup and a newly designed lightweight Spiking Eye Emotion Network (SEEN). Compared to conventional cameras, event-based cameras offer a higher dynamic range (up to 140 dB vs. 80 dB) and a higher temporal resolution. Thus, the captured events can encode rich temporal cues under challenging lighting conditions. However, these events lack texture information, posing problems in decoding temporal information effectively. SEEN tackles this issue from two different perspectives. First, we adopt convolutional spiking layers to take advantage of the spiking neural network's ability to decode pertinent temporal information. Second, SEEN learns to extract essential spatial cues from corresponding intensity frames and leverages a novel weight-copy scheme to convey spatial attention to the convolutional spiking layers during training and inference. We extensively validate and demonstrate the effectiveness of our approach on a specially collected Single-eye Event-based Emotion (SEE) dataset. To the best of our knowledge, our method is the first eye-based emotion recognition method that leverages event-based cameras and spiking neural network

Targeted suppression of heme oxygenase-1 by small interference RNAs inhibits the production of bilirubin in neonatal rat with hyperbilirubinemia

<p>Abstract</p> <p>Background</p> <p>Excessive accumulation of bilirubin contributes to neonatal hyperbilirubinemia in rats. Heme oxygenase (HO) is one of the rate-limiting enzymes in catabolizing heme to bilirubin. In the present study, we investigated whether suppression of rat HO-1 (rHO-1) expression by small interference RNAs (siRNAs) reduces bilirubin levels in hyperbilirubinemic rats.</p> <p>Results</p> <p>Four pairs of siRNA targeting rHO-1 mRNA were introduced into BRL cells and compared for their inhibitory effect on the expression of <it>rHO-1 </it>gene and production of rHO-1 protein. The siRNA exhibiting the most potent effect on HO-1 expression and activity was then administered intraperitoneally to 7 to 9-day-old rats with hyperbilirubinemia. The siRNA distributed mostly in the liver and spleen of neonatal rat. Serum bilirubin levels and hepatic HO-1 expression were further evaluated. Systemic treatment of siRNA targeting rHO-1 reduced hepatic HO-1 expression and decreased the serum bilirubin levels in a time- and dose-dependent manner, and siRNA decreased the indirect bilirubin levels more effectively than Sn-protoporphyrin (SnPP), an HO-1 inhibitor.</p> <p>Conclusion</p> <p>siRNA targeting rHO-l attenuates hepatic HO-1 expression and serum bilirubin levels. Thus this study provides a novel therapeutic rationale for the prevention and treatment of neonatal hyperbilirubinemia.</p

Desipramine Pretreatment Improves Sympathetic Remodeling and Ventricular Fibrillation Threshold after Myocardial Ischemia

Abnormal increase in sympathetic nerve sprouting was responsible for the ventricular arrhythmogenesis after myocardial infarction. This study investigated whether the norepinephrine transporter inhibitor, desipramine, can modulate sympathetic remodeling and ventricular fibrillation threshold (VFT) after myocardial ischemia-reperfusion. Rats were administered desipramine (0.8 mg/kg, IV) before or after myocardial ischemia. VFT, infarct size, tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43)-positive nerve fibers were measured after one week. The VFT of preischemic treatment group was 11.0±2.65 V and significantly higher than that of control ischemic group (7.2±1.30 V, P<0.05). Infarct size in the preischemic treatment group (23.3±2.4%) was significantly lower than that in the control ischemic group (30.8±1.3%, P<0.05) and the delayed application group (27.1±2.6%, P<0.05). The density of TH and GAP43-positive nerve fibers in the control ischemic group was significantly higher than that in the other three groups (P<0.05). The density of nerve fibers improved after desipramine treatment. Moreover, there was a negative correlation between the VFT and both TH and GAP43-positive nerve fiber density in the infarct border zone (P<0.05). Desipramine treatment before acute myocardial ischemia can decrease infarct size, improve sympathetic remodeling, and increase VFT and electrical stability of ischemic hearts. Desipramine appears to cause myocardial ischemic preconditioning