Dynamic coupling modelling and application case analysis of high-slip motors and pumping units

To solve the issues and difficulties in the high-coupling modelling of beam pumping units and high-slip motors, external characteristic experiments of high-slip motors were performed where the external database and characteristic correlation equations of the motors were obtained through data regression analysis. Based on the analysis of the kinematics, dynamics and driving characteristics of the beam pumping unit, a fully coupled mathematical model of a motor, pumping unit, sucker rod and oil pump was established. The differential pumping equation system of the pumping unit used a cyclic iteration method to solve the problem of high coupling among the motor, pumping unit, sucker rod and the pumping pump. The model was verified by experimental data of field l pumping wells. Theoretical calculations and experimental tests showed that the soft characteristic of the high-slip motor can reduce the peak suspension load of the sucker rod, peak net torque of the gearbox and peak power of the motor. In addition, the results show that the soft characteristic can also decrease the high-frequency fluctuation of the motor power curve and the torque curve of the gearbox. The highslip motor can improve the smoothness and safety of the pumping well system

Sampling biases shape our view of the natural world

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Combination Therapy Strategy of Quorum Quenching Enzyme and Quorum Sensing Inhibitor in Suppressing Multiple Quorum Sensing Pathways of P. <i>aeruginosa</i>

Abstract The threat of antibiotic resistant bacteria has called for alternative antimicrobial strategies that would mitigate the increase of classical resistance mechanism. Many bacteria employ quorum sensing (QS) to govern the production of virulence factors and formation of drug-resistant biofilms. Targeting the mechanism of QS has proven to be a functional alternative to conventional antibiotic control of infections. However, the presence of multiple QS systems in individual bacterial species poses a challenge to this approach. Quorum sensing inhibitors (QSI) and quorum quenching enzymes (QQE) have been both investigated for their QS interfering capabilities. Here, we first simulated the combination effect of QQE and QSI in blocking bacterial QS. The effect was next validated by experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P. aeruginosa las and rhl QS systems. Our findings provide a potential chemical biology application strategy for bacterial QS disruption

Heterogeneous blood-brain barrier dysfunction in cerebral small vessel diseases

INTRODUCTION: We explored how blood-brain barrier (BBB) leakage rate of gadolinium chelates (K trans) and BBB water exchange rate (k w) varied in cerebral small vessel disease (cSVD) subtypes. METHODS: Thirty sporadic cSVD, 40 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 13 high-temperature requirement factor A serine peptidase 1 (HTRA) -related cSVD subjects were investigated parallel to 40 healthy individuals. Subjects underwent clinical, cognitive, and MRI assessment.RESULTS: In CADASIL, no difference in K trans, but lower k w was observed in multiple brain regions. In sporadic cSVD, no difference in k w, but higher K trans was found in the whole brain and normal-appearing white matter. In HTRA1-related cSVD, both higher K trans in the whole brain and lower k w in multiple brain regions were observed. In each patient group, the altered BBB measures were correlated with lesion burden or clinical severity. DISCUSSION: In cSVD subtypes, distinct alterations of k w and K trans were observed. The combination of K trans and k w can depict the heterogeneous BBB dysfunction. HIGHLIGHTS: We measured BBB leakage to gadolinium-based contrast agent (K trans) and water exchange rate (k w) across BBB in three subtypes of cSVD. CADASIL is characterized by lower k w, HTRA1-related cSVD exhibits both higher K trans and lower k w, while sporadic cSVD is distinguished by higher K trans. There are distinct alterations in k w and K trans among subtypes of cSVD, indicating the heterogeneous nature of BBB dysfunction. </p

Reservoir Permeability Prediction Based on Analogy and Machine Learning Methods: Field Cases in DLG Block of Jing’an Oilfield, China

AbstractReservoir permeability, generally determined by experimental or well testing methods, is an essential parameter in the oil and gas field development. In this paper, we present a novel analogy and machine learning method to predict reservoir permeability. Firstly, the core test and production data of other 24 blocks (analog blocks) are counted according to the DLG block (target block) of Jing’an Oilfield, and the permeability analogy parameters including porosity, shale content, reservoir thickness, oil saturation, liquid production, and production pressure difference are optimized by Pearson and principal component analysis. Then, the fuzzy matter element method is used to calculate the similarity between the target block and analog blocks. According to the similarity calculation results, reservoir permeability of DLG block is predicted by reservoir engineering method (the relationship between core permeability and porosity of QK-D7 in similar blocks) and machine learning method (random forest, gradient boosting decision tree, light gradient boosting machine, and categorical boosting). By comparing the prediction accuracy of the two methods through the evaluation index determination coefficient (R2) and root mean square error (RMSE), the CatBoost model has higher accuracy in predicting reservoir permeability, with R2 of 0.951 and RMSE of 0.139. Finally, the CatBoost model is selected to predict reservoir permeability of 121 oil wells in the DLG block. This work uses simple logging and production data to quickly and accurately predict reservoir permeability without coring and testing. At the same time, the prediction results are well applied to the formulation of DLG block development technology strategy, which provides a new idea for the application of machine learning to predict oilfield parameters

Enhanced metabolic flux of methylerythritol phosphate (MEP) pathway by overexpression of Ginkgo biloba 1-Hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate Reductase 1 (GbHDR1) gene in poplar

Terpenoids are of great interests in a broad range of health-beneficial biological activities and various industrial applications. In plants, terpenoids are synthesized by two distinct pathways, methylerythritol phosphate (MEP) and mevalonate pathways in a separate location. MEP pathway supplies isoprene precursors isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP) of terpenoid biosynthesis in plant plastids. The MEP pathway has been an engineering target to increase the metabolic flux towards higher terpenoid production in plants. 1-Hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) is the terminal step of the MEP pathway to regulate the terpenoid biosynthesis and is encoded by three paralogous genes in Ginkgo biloba. In this study, we assessed the effect of overexpression of GbHDR1 on terpenoid metabolism in poplar plants. Overexpression of GbHDR1 in poplar plants accelerated growth and delayed winter-bud formation. Transcript levels of gibberellin, chlorophylls, and carotenoid biosynthetic genes in GbHDR1-overexpressing (GbHDR1ox) poplars were up-regulated, suggesting metabolic flux enhancement. Moreover, enhanced contents of chlorophylls and carotenoids in the leaves of the GbHDR1ox plants resulted in a higher photosynthetic rate as a consequence. Therefore, we expect the GbHDR1 overexpression will be a desirable engineering point of the MEP pathway for enhancing terpenoid metabolic flux and production in plants.This work was supported by the National Research Foundation of Korea (NRF) grant (2021R1A5A8029490); the Korea Foundation for Women In Science, Engineering and Technology (WISET) Returners into R&D Program grant; the intramural grant (2Z06670) from the Korea Institute of Science and Technology (KIST), Republic of Korea

Downregulation of p16 Decreases Biliary Damage and Liver Fibrosis in the Mdr2 / Mouse Model of Primary Sclerosing Cholangitis

Biliary senescence and hepatic fibrosis are hallmarks of cholangiopathies including primary sclerosing cholangitis (PSC). Senescent cholangiocytes display senescence-associated secretory phenotypes [SASPs, e.g., transforming growth factor-1 (TGF-1)] that further increase biliary senescence (by an autocrine loop) and trigger liver fibrosis by paracrine mechanisms. The aim of this study was to determine the effect of p16 inhibition and role of the TGF-1/microRNA (miR)-34a/sirtuin 1 (SIRT1) axis in biliary damage and liver fibrosis in the Mdr2/ mouse model of PSC. We treated (i) in vivo male wild-type (WT) and Mdr2/ mice with p16 Vivo-Morpholino or controls before measuring biliary mass [intrahepatic bile duct mass (IBDM)] and senescence, biliary SASP levels, and liver fibrosis, and (ii) in vitro intrahepatic murine cholangiocyte lines (IMCLs) with small interfering RNA against p16 before measuring the mRNA expression of proliferation, senescence, and fibrosis markers. p16 and miR-34a increased but SIRT1 decreased in Mdr2/ mice and PSC human liver samples compared to controls. p16 immunoreactivity and biliary senescence and SASP levels increased in Mdr2/ mice but decreased in Mdr2/ mice treated with p16 Vivo-Morpholino. The increase in IBDM and hepatic fibrosis (observed in Mdr2/ mice) returned to normal values in Mdr2/ mice treated with p16 Vivo-Morpholino. TGF-1 immunoreactivity and biliary SASPs levels were higher in Mdr2/ compared to those of WT mice but returned to normal values in Mdr2/ mice treated with p16 Vivo-Morpholino. The expression of fibrosis/senescence markers decreased in cholangiocytes from Mdr2/ mice treated with p16 Vivo-Morpholino (compared to Mdr2/ mice) and in IMCLs (after p16 silencing) compared to controls. Modulation of the TGF-1/miR-34a/SIRT1 axis may be important in the management of PSC phenotypes

Glucose and Palmitate Differentially Regulate PFKFB3/iPFK2 and Inflammatory Responses in Mouse Intestinal Epithelial Cells

The gene PFKFB3 encodes for inducible 6-phosphofructo-2-kinase, a glycolysis-regulatory enzyme that protects against diet-induced intestine inflammation. However, it is unclear how nutrient overload regulates PFKFB3 expression and inflammatory responses in intestinal epithelial cells (IECs). In the present study, primary IECs were isolated from small intestine of C57BL/6J mice fed a low-fat diet (LFD) or high-fat diet (HFD) for 12 weeks. Additionally, CMT-93 cells, a cell line for IECs, were cultured in low glucose (LG, 5.5 mmol/L) or high glucose (HG, 27.5 mmol/L) medium and treated with palmitate (50 mu mol/L) or bovine serum albumin (BSA) for 24 hr. These cells were analyzed for PFKFB3 and inflammatory markers. Compared with LFD, HFD feeding decreased IEC PFKFB3 expression and increased IEC proinflammatory responses. In CMT-93 cells, HG significantly increased PFKFB3 expression and proinflammatory responses compared with LG. Interestingly, palmitate decreased PFKFB3 expression and increased proinflammatory responses compared with BSA, regardless of glucose concentrations. Furthermore, HG significantly increased PFKFB3 promoter transcription activity compared with LG. Upon PFKFB3 overexpression, proinflammatory responses in CMT-93 cells were decreased. Taken together, these results indicate that in IECs glucose stimulates PFKFB3 expression and palmitate contributes to increased proinflammatory responses. Therefore, PFKFB3 regulates IEC inflammatory status in response to macronutrients.National Institutes of Health [HL108922, HL095556, R01DK095828, R01DK095862]; National Natural Science Foundation of China [81100562/H0711]; Hatch Program of National Institutes of Food and Agriculture (NIFA)SCI(E)[email protected]; [email protected]

Palmitoleate Induces Hepatic Steatosis but Suppresses Liver Inflammatory Response in Mice

The interaction between fat deposition and inflammation during obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD). The present study examined the effects of palmitoleate, a monounsaturated fatty acid (16∶1n7), on liver metabolic and inflammatory responses, and investigated the mechanisms by which palmitoleate increases hepatocyte fatty acid synthase (FAS) expression. Male wild-type C57BL/6J mice were supplemented with palmitoleate and subjected to the assays to analyze hepatic steatosis and liver inflammatory response. Additionally, mouse primary hepatocytes were treated with palmitoleate and used to analyze fat deposition, the inflammatory response, and sterol regulatory element-binding protein 1c (SREBP1c) activation. Compared with controls, palmitoleate supplementation increased the circulating levels of palmitoleate and improved systemic insulin sensitivity. Locally, hepatic fat deposition and SREBP1c and FAS expression were significantly increased in palmitoleate-supplemented mice. These pro-lipogenic events were accompanied by improvement of liver insulin signaling. In addition, palmitoleate supplementation reduced the numbers of macrophages/Kupffer cells in livers of the treated mice. Consistently, supplementation of palmitoleate decreased the phosphorylation of nuclear factor kappa B (NF-κB, p65) and the expression of proinflammatory cytokines. These results were recapitulated in primary mouse hepatocytes. In terms of regulating FAS expression, treatment of palmitoleate increased the transcription activity of SREBP1c and enhanced the binding of SREBP1c to FAS promoter. Palmitoleate also decreased the phosphorylation of NF-κB p65 and the expression of proinflammatory cytokines in cultured macrophages. Together, these results suggest that palmitoleate acts through dissociating liver inflammatory response from hepatic steatosis to play a unique role in NAFLD

A Complete Analysis of HA and NA Genes of Influenza A Viruses

BACKGROUND: More and more nucleotide sequences of type A influenza virus are available in public databases. Although these sequences have been the focus of many molecular epidemiological and phylogenetic analyses, most studies only deal with a few representative sequences. In this paper, we present a complete analysis of all Haemagglutinin (HA) and Neuraminidase (NA) gene sequences available to allow large scale analyses of the evolution and epidemiology of type A influenza. METHODOLOGY/PRINCIPAL FINDINGS: This paper describes an analysis and complete classification of all HA and NA gene sequences available in public databases using multivariate and phylogenetic methods. CONCLUSIONS/SIGNIFICANCE: We analyzed 18,975 HA sequences and divided them into 280 subgroups according to multivariate and phylogenetic analyses. Similarly, we divided 11,362 NA sequences into 202 subgroups. Compared to previous analyses, this work is more detailed and comprehensive, especially for the bigger datasets. Therefore, it can be used to show the full and complex phylogenetic diversity and provides a framework for studying the molecular evolution and epidemiology of type A influenza virus. For more than 85% of type A influenza HA and NA sequences into GenBank, they are categorized in one unambiguous and unique group. Therefore, our results are a kind of genetic and phylogenetic annotation for influenza HA and NA sequences. In addition, sequences of swine influenza viruses come from 56 HA and 45 NA subgroups. Most of these subgroups also include viruses from other hosts indicating cross species transmission of the viruses between pigs and other hosts. Furthermore, the phylogenetic diversity of swine influenza viruses from Eurasia is greater than that of North American strains and both of them are becoming more diverse. Apart from viruses from human, pigs, birds and horses, viruses from other species show very low phylogenetic diversity. This might indicate that viruses have not become established in these species. Based on current evidence, there is no simple pattern of inter-hemisphere transmission of avian influenza viruses and it appears to happen sporadically. However, for H6 subtype avian influenza viruses, such transmissions might have happened very frequently and multiple and bidirectional transmission events might exist