995 resultados para American society
Resumo:
Monitoring of the integrity of rolling element bearings in the traction system of high speed trains is a fundamental operation in order to avoid catastrophic failures and to implement effective condition-based maintenance strategies. Diagnostics of rolling element bearings is usually based on vibration signal analysis by means of suitable signal processing techniques. The experimental validation of such techniques has been traditionally performed by means of laboratory tests on artificially damaged bearings, while their actual effectiveness in industrial applications, particularly in the field of rail transport, remains scarcely investigated. This paper will address the diagnostics of bearings taken from the service after a long term operation on a high speed train. These worn bearings have been installed on a test-rig, consisting of a complete full-scale traction system of a high speed train, able to reproduce the effects of wheel-track interaction and bogie-wheelset dynamics. The results of the experimental campaign show that suitable signal processing techniques are able to diagnose bearing failures even in this harsh and noisy application. Moreover, the most suitable location of the sensors on the traction system is also proposed.
Resumo:
Fault identification in industrial machine is a topic of major importance under engineering point of view. In fact, the possibility to identify not only the type, but also the severity and the position of a fault occurred along a shaft-line allows quick maintenance and shorten the downtime. This is really important in the power generation industry where the units are often of several tenths of meters long and where the rotors are enclosed by heavy and pressure-sealed casings. In this paper, an industrial experimental case is presented related to the identification of the unbalance on a large size steam turbine of about 1.3 GW, belonging to a nuclear power plant. The case history is analyzed by considering the vibrations measured by the condition monitoring system of the unit. A model-based method in the frequency domain, developed by the authors, is introduced in detail and it is then used to identify the position of the fault and its severity along the shaft-line. The complete model of the unit (rotor – modeled by means of finite elements, bearings – modeled by linearized damping and stiffness coefficients and foundation – modeled by means of pedestals) is analyzed and discussed before being used for the fault identification. The assessment of the actual fault was done by inspection during a scheduled maintenance and excellent correspondence was found with the identified one by means of authors’ proposed method. Finally a complete discussion is presented about the effectiveness of the method, even in presence of a not fine tuned machine model and considering only few measuring planes for the machine vibration.
Resumo:
In the electricity market environment, load-serving entities (LSEs) will inevitably face risks in purchasing electricity because there are a plethora of uncertainties involved. To maximize profits and minimize risks, LSEs need to develop an optimal strategy to reasonably allocate the purchased electricity amount in different electricity markets such as the spot market, bilateral contract market, and options market. Because risks originate from uncertainties, an approach is presented to address the risk evaluation problem by the combined use of the lower partial moment and information entropy (LPME). The lower partial moment is used to measure the amount and probability of the loss, whereas the information entropy is used to represent the uncertainty of the loss. Electricity purchasing is a repeated procedure; therefore, the model presented represents a dynamic strategy. Under the chance-constrained programming framework, the developed optimization model minimizes the risk of the electricity purchasing portfolio in different markets because the actual profit of the LSE concerned is not less than the specified target under a required confidence level. Then, the particle swarm optimization (PSO) algorithm is employed to solve the optimization model. Finally, a sample example is used to illustrate the basic features of the developed model and method.
Resumo:
The aim of this paper is to determine the strain-rate-dependent mechanical behavior of living and fixed osteocytes and chondrocytes, in vitro. Firstly, Atomic Force Microscopy (AFM) was used to obtain the force-indentation curves of these single cells at four different strain-rates. These results were then employed in inverse finite element analysis (FEA) using Modified Standard neo-Hookean Solid (MSnHS) idealization of these cells to determine their mechanical properties. In addition, a FEA model with a newly developed spring element was employed to accurately simulate AFM evaluation in this study. We report that both cytoskeleton (CSK) and intracellular fluid govern the strain-rate-dependent mechanical property of living cells whereas intracellular fluid plays a predominant role on fixed cells’ behavior. In addition, through the comparisons, it can be concluded that osteocytes are stiffer than chondrocytes at all strain-rates tested indicating that the cells could be the biomarker of their tissue origin. Finally, we report that MSnHS is able to capture the strain-rate-dependent mechanical behavior of osteocyte and chondrocyte for both living and fixed cells. Therefore, we concluded that the MSnHS is a good model for exploration of mechanical deformation responses of single osteocytes and chondrocytes. This study could open a new avenue for analysis of mechanical behavior of osteocytes and chondrocytes as well as other similar types of cells.
Resumo:
The paper examines the knowledge of pedestrian movements, both in real scenarios, and from more recent years, in the virtual 4 simulation realm. Aiming to verify whether it is possible to learn from the study of virtual environments how people will behave in real 5 environments, it is vital to understand what is already known about behavior in real environments. Besides the walking interaction among 6 pedestrians, the interaction between pedestrians and the built environment in which they are walking also have greatest relevance. Force-based 7 models were compared with the other three major microscopic models of pedestrian simulation to demonstrate a more realistic and capable 8 heuristic approach is needed for the study of the dynamics of pedestrians.
Resumo:
Ubiquitin (Ub)-conjugating enzymes (E2s) and ubiquitin ligases (E3s) catalyze the attachment of Ub to lysine residues in substrates and Ub during monoubiquitination and polyubiquitination. Lysine selection is important for the generation of diverse substrate-Ub structures, which provides versatility to this pathway in the targeting of proteins to different fates. The mechanisms of lysine selection remain poorly understood, with previous studies suggesting that the ubiquitination site(s) is selected by the E2/E3-mediated positioning of a lysine(s) toward the E2/E3 active site. By studying the polyubiquitination of Sic1 by the E2 protein Cdc34 and the RING E3 Skp1/Cul1/F-box (SCF) protein, we now demonstrate that in addition to E2/E3-mediated positioning, proximal amino acids surrounding the lysine residues in Sic1 and Ub are critical for ubiquitination. This mechanism is linked to key residues composing the catalytic core of Cdc34 and independent of SCF. Changes to these core residues altered the lysine preference of Cdc34 and specified whether this enzyme monoubiquitinated or polyubiquitinated Sic1. These new findings indicate that compatibility between amino acids surrounding acceptor lysine residues and key amino acids in the catalytic core of ubiquitin-conjugating enzymes is an important mechanism for lysine selection during ubiquitination.
Resumo:
Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosageand RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperaturesensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.
Resumo:
Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs.
Resumo:
Amplification of the Plasmodium falciparum multidrug resistance 1 gene (pfmdr1) has been implicated in multidrug resistance, including in vitro resistance to artelinic acid (AL). The stability and fitness of having multiple copies of pfmdr1 are important factors due to their potential effects on the resistance phenotype of parasites. These factors were investigated by using an AL-resistant line of P. falciparum (W2AL80) and clones originating from W2AL80. A rapid reduction in pfmdr1 copy number (CN) was observed in the uncloned W2AL80 line; 63% of this population reverted to a CN of <3 without exposure to the drug. Deamplification of the pfmdr1 amplicon was then determined in three clones, each initially containing three copies of pfmdr1. Interestingly, two outcomes were observed during 3 months without drug pressure. In one clone, parasites with fewer than 3 copies of pfmdr1 emerged rapidly. In two other clones, the reversion was significantly delayed. In all subclones, the reduction in pfmdr1 CN involved the deamplification of the entire amplicon (19 genes). Importantly, deamplification of the pfmdr1 amplicon resulted in partial reversal of resistance to AL and increased susceptibility to mefloquine. These results demonstrate that multiple copies of the pfmdr1-containing amplicon in AL-resistant parasites are unstable when drug pressure is withdrawn and have practical implications for the maintenance and spread of parasites resistant to artemisinin derivatives.
Resumo:
Chloroquine-resistant Plasmodium falciparum was highly prevalent in Hainan, China, in the 1970s. Twenty-five years after cessation of chloroquine therapy, the prevalence of P. falciparum wild-type Pfcrt alleles has risen to 36% (95% confidence interval, 22.1 to 52.4%). The diverse origins of wild-type alleles indicate that there was no genetic bottleneck caused by high chloroquine resistance.
Resumo:
The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family
Resumo:
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT(2B), is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT(2B) receptors by circulating c-kit(+) precursor cells, whereas mice lacking 5-HT(2B) receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT(2B) receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT(2B) receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34(+) or mice c-kit(+) progenitor cells in the presence of a 5-HT(2B) receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT(2B) receptors on bone marrow lineage progenitors is critical for the development of PAH.
Resumo:
Managing sewer blockages represents a significant operational challenge for water utilities. In Australia, company-level blockage rates are used to compare the effectiveness of the management strategies of different utilities. Anecdotal evidence suggests this may not be a fair basis for comparison because blockages are influenced by a range of factors beyond management control and that vary from company to company. This issue was investigated as part of a broader research effort on sewer blockage management undertaken in conjunction with the Water Services Association of Australia (WSAA) and its members. A Web-based survey was used to collate expert opinion on factors that influence blockage rate. The identified factors were then investigated in an exploratory analysis of blockage-related data provided by two participating utilities, supported by literature reviews. The results indicate that blockage rate is influenced by a range of factors, including asset attributes, climatic conditions, water consumption, and soil type. Since these factors vary from utility to utility, this research supports the assertion that company-level blockage rate is not in itself an appropriate metric for comparing management effectiveness.
Resumo:
Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET domain protein G9a. We found that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression was unchanged at the domains analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is impaired in the absence of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3. These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast.
Resumo:
Cold-formed steel lipped channel beams (LCB) are used extensively in residential, industrial and commercial buildings as load bearing structural elements. Their shear capacities are considerably reduced when web openings are included for the purpose of locating building services. Past research has shown that the shear capacities of LCBs were reduced by up to 70% due to the inclusion of these web openings. Hence there is a need to improve the shear capacities of LCBs with web openings. A cost effective way of eliminating the detrimental effects of large web openings is to attach suitable stiffeners around the web openings and restore the original shear strength and stiffness of LCBs. Hence detailed experimental studies were undertaken to investigate the behaviour and strength of LCBs with stiffened web openings subject to shear, and combined bending and shear actions. Both plate and stud stiffeners with varying sizes and thicknesses were attached to the web elements of LCBs using different screw-fastening arrangements. Simply supported test specimens of LCBs with aspect ratios of 1.0 and 1.5 were loaded at mid-span until failure. Numerical studies were also undertaken to investigate the strength of LCBs with stiffened web openings. Finite element models of LCBs with stiffened web openings under shear, combined bending and shear actions were developed to simulate the behaviour of tested LCBs. The developed models were then validated by comparing their results with experimental results and used in further studies. Both experimental and finite element analysis results showed that the stiffening arrangements recommended by past research and available design guidelines are not adequate to restore the original shear strengths of LCBs. Therefore new stiffener arrangements were proposed based on screw fastened plate stiffeners. This paper presents the details of this research study and the results.