246 research outputs found

    Passive suspensions for ride quality improvement of two-axle railway vehicles

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    The aim of this paper is to investigate the possibility of improving the ride quality of a two-axle railway vehicle with a single-stage suspension by means of passive suspensions employing an inerter device. The inerter is a mechanical one-port element that is analogous to a capacitor in electrical circuits. The goal is to improve the ride quality in both the vertical and lateral motions in response to track irregularities. Performance benefits for several simple passive suspension layouts are demonstrated and compared with the conventional scheme. The elastic effects of the damper and inerter device are then taken into consideration for practical purposes. The optimum parameter values of the damper, inerter and the parameters representing the elastic effects provide guidance for mechanical design purposes

    Predictive coupled-cluster isomer orderings for some Sin{}_nCm{}_m (m,n12m, n\le 12) clusters; A pragmatic comparison between DFT and complete basis limit coupled-cluster benchmarks

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    The accurate determination of the preferred Si12C12{\rm Si}_{12}{\rm C}_{12} isomer is important to guide experimental efforts directed towards synthesizing SiC nano-wires and related polymer structures which are anticipated to be highly efficient exciton materials for opto-electronic devices. In order to definitively identify preferred isomeric structures for silicon carbon nano-clusters, highly accurate geometries, energies and harmonic zero point energies have been computed using coupled-cluster theory with systematic extrapolation to the complete basis limit for set of silicon carbon clusters ranging in size from SiC3_3 to Si12C12{\rm Si}_{12}{\rm C}_{12}. It is found that post-MBPT(2) correlation energy plays a significant role in obtaining converged relative isomer energies, suggesting that predictions using low rung density functional methods will not have adequate accuracy. Utilizing the best composite coupled-cluster energy that is still computationally feasible, entailing a 3-4 SCF and CCSD extrapolation with triple-ζ\zeta (T) correlation, the {\it closo} Si12C12{\rm Si}_{12}{\rm C}_{12} isomer is identified to be the preferred isomer in support of previous calculations [J. Chem. Phys. 2015, 142, 034303]. Additionally we have investigated more pragmatic approaches to obtaining accurate silicon carbide isomer energies, including the use of frozen natural orbital coupled-cluster theory and several rungs of standard and double-hybrid density functional theory. Frozen natural orbitals as a way to compute post MBPT(2) correlation energy is found to be an excellent balance between efficiency and accuracy

    Performance of a dual-stage inerter-based vibration isolator

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    This paper investigates the dynamic behaviour and performance of a dual-stage inerter-based vibration isolator. Force transmissi-bility and vibration power flow variables are used as performance indices to evaluate the effectiveness of the inerter-based vibration isolator. Vibration power input, transmission and dissipation characteristics of the system are examined. It is found that the inclusion of inerters in dual-stage vibration isolator can reduce force and vibration power flow transmission over a larger band of excitation frequencies. The addition of inerters can also introduce notches in the curves of force transmissibility and time-averaged transmitted power such that the vibration transmission may be greatly suppressed at pre-determined excitation frequencies. These findings demonstrate the potential benefits of employing inerters in vibration isolation and facilitate better understanding of vibration mitigation systems with such element

    Risk Factors for Heart Failure in Patients With Chronic Kidney Disease: The CRIC (Chronic Renal Insufficiency Cohort) Study.

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    Background Heart failure is common in patients with chronic kidney disease. We studied risk factors for incident heart failure among 3557 participants in the CRIC (Chronic Renal Insufficiency Cohort) Study. Methods and Results Kidney function was assessed by estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C, or both, and 24‐hour urine albumin excretion. During an average of 6.3 years of follow‐up, 452 participants developed incident heart failure. After adjustment for age, sex, race, and clinical site, hazard ratio (95% CI) for heart failure associated with 1 SD lower creatinine‐based eGFR was 1.67 (1.49, 1.89), 1 SD lower cystatin C‐based‐eGFR was 2.43 (2.10, 2.80), and 1 SD higher log‐albuminuria was 1.65 (1.53, 1.78), all P\u3c0.001. When all 3 kidney function measures were simultaneously included in the model, lower cystatin C‐based eGFR and higher log‐albuminuria remained significantly and directly associated with incidence of heart failure. After adjusting for eGFR, albuminuria, and other traditional cardiovascular risk factors, anemia (1.37, 95% CI 1.09, 1.72, P=0.006), insulin resistance (1.16, 95% CI 1.04, 1.28, P=0.006), hemoglobin A1c (1.27, 95% CI 1.14, 1.41, P\u3c0.001), interleukin‐6 (1.15, 95% CI 1.05, 1.25, P=0.002), and tumor necrosis factor‐α (1.10, 95% CI 1.00, 1.21, P=0.05) were all significantly and directly associated with incidence of heart failure. Conclusions Our study indicates that cystatin C‐based eGFR and albuminuria are better predictors for risk of heart failure compared to creatinine‐based eGFR. Furthermore, anemia, insulin resistance, inflammation, and poor glycemic control are independent risk factors for the development of heart failure among patients with chronic kidney disease

    Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

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    Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

    Wolbachia Infections in Anopheles gambiae Cells: Transcriptomic Characterization of a Novel Host-Symbiont Interaction

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    The endosymbiotic bacterium Wolbachia is being investigated as a potential control agent in several important vector insect species. Recent studies have shown that Wolbachia can protect the insect host against a wide variety of pathogens, resulting in reduced transmission of parasites and viruses. It has been proposed that compromised vector competence of Wolbachia-infected insects is due to up-regulation of the host innate immune system or metabolic competition. Anopheles mosquitoes, which transmit human malaria parasites, have never been found to harbor Wolbachia in nature. While transient somatic infections can be established in Anopheles, no stable artificially-transinfected Anopheles line has been developed despite numerous attempts. However, cultured Anopheles cells can be stably infected with multiple Wolbachia strains such as wAlbB from Aedes albopictus, wRi from Drosophila simulans and wMelPop from Drosophila melanogaster. Infected cell lines provide an amenable system to investigate Wolbachia-Anopheles interactions in the absence of an infected mosquito strain. We used Affymetrix GeneChip microarrays to investigate the effect of wAlbB and wRi infection on the transcriptome of cultured Anopheles Sua5B cells, and for a subset of genes used quantitative PCR to validate results in somatically-infected Anopheles mosquitoes. Wolbachia infection had a dramatic strain-specific effect on gene expression in this cell line, with almost 700 genes in total regulated representing a diverse array of functional classes. Very strikingly, infection resulted in a significant down-regulation of many immune, stress and detoxification-related transcripts. This is in stark contrast to the induction of immune genes observed in other insect hosts. We also identified genes that may be potentially involved in Wolbachia-induced reproductive and pathogenic phenotypes. Somatically-infected mosquitoes had similar responses to cultured cells. The data show that Wolbachia has a profound and unique effect on Anopheles gene expression in cultured cells, and has important implications for mechanistic understanding of Wolbachia-induced phenotypes and potential novel strategies to control malaria

    High-Throughput Sequencing of Arabidopsis microRNAs: Evidence for Frequent Birth and Death of MIRNA Genes

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    In plants, microRNAs (miRNAs) comprise one of two classes of small RNAs that function primarily as negative regulators at the posttranscriptional level. Several MIRNA genes in the plant kingdom are ancient, with conservation extending between angiosperms and the mosses, whereas many others are more recently evolved. Here, we use deep sequencing and computational methods to identify, profile and analyze non-conserved MIRNA genes in Arabidopsis thaliana. 48 non-conserved MIRNA families, nearly all of which were represented by single genes, were identified. Sequence similarity analyses of miRNA precursor foldback arms revealed evidence for recent evolutionary origin of 16 MIRNA loci through inverted duplication events from protein-coding gene sequences. Interestingly, these recently evolved MIRNA genes have taken distinct paths. Whereas some non-conserved miRNAs interact with and regulate target transcripts from gene families that donated parental sequences, others have drifted to the point of non-interaction with parental gene family transcripts. Some young MIRNA loci clearly originated from one gene family but form miRNAs that target transcripts in another family. We suggest that MIRNA genes are undergoing relatively frequent birth and death, with only a subset being stabilized by integration into regulatory networks
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