39 research outputs found

    Merged two-level optimization for optimal pump operation of large scale urban water distribution system

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    Subsequent to the least cost design problem of water distribution systems (WDSs), optimal operation is probably the most explored topic. Since 1970 a variety of methods have been developed to address this problem. Although the proposed methods give theoretic ways for solving optimal operation problems of WDSs, there are little successful application cases in practice, especially when the methods were used to large scale WDSs due to too many decision variables. In consideration of using fewer decision variables, the two-level optimal method is adopted in this paper. By abstracting pump stations into high level reservoirs, the water distribution system hydraulic model can be modified into a modality, which can be used in first optimal level of two-level optimal method. Also, by building on feasible pump combination database, a new optimal method in the second optimal level will be proposed, and the proposed new method in the second optimal level will be embedded into the first optimal level, so that the problem of results discordant in different levels will be solved. By introducing new concepts and improving present optimal methods, a more practical optimal operation method of water distribution system will be established. By applying in a large scale practical water distribution system, the proposed method has been evaluated

    Transduction of Adeno-Associated Virus Vectors Targeting Hair Cells and Supporting Cells in the Neonatal Mouse Cochlea

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    Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expression patterns of AAV with different serotypes or promoters in hair cells and supporting cells in the neonatal mouse cochlea, we examined the expression of enhanced green fluorescent protein (eGFP) for five different types of AAV vectors [serotypes 2, 9, and Anc80L65 with promoter cytomegalovirus (CMV)-beta-Globin and serotypes 2 and 9 with promoter chicken beta-actin (CBA)] in in vitro cochlear explant cultures and we tested the transduction of AAV2/2-CBA, AAV2/9-CBA, and AAV2/Anc80L65-CMV by in vivo microinjection into the scala media of the cochlea. We found that each AAV vector had its own transduction and expression characteristics in hair cells and supporting cells in different regions of the cochlea. There was a tonotopic gradient for the in vitro transduction of AAV2/2-CBA, AAV2/9-CBA, AAV2/2-CMV, and AAV2/9-CMV in outer hair cells (OHCs), with more OHCs expressing eGFP at the base of the cochlea than at the apex. AAV2/2-CBA in vitro and AAV2/Anc80L65-CMV in vivo induced more supporting cells expressing eGFP at the apex than in the base. We found that AAV vectors with different promoters had different expression efficacies in hair cells and supporting cells of the auditory epithelium. The CMV-beta-Globin promoter could drive the expression of the delivered construct more efficiently in hair cells, while the CBA promoter was more efficient in supporting cells. The in vitro and in vivo experiments both demonstrated that AAV2/Anc80L65-CMV was a very promising vector for gene therapy of deafness because of its high transduction rates in hair cells. These results might be useful for selecting the appropriate vectors for gene delivery into different types of inner ear cells and thus improving the effectiveness of gene therapy

    Genome of the rams horn snail Biomphalaria straminea : an obligate intermediate host of schistosomiasis

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    This work was supported by the Hong Kong Research Grant Council Collaborative Research Fund (C4015-20EF), General Research Fund (14100919), NSFC/RGC Joint Research Scheme (N_CUHK401/21), and The Chinese University of Hong Kong Direct Grant (4053433, 4053489). Y.Y., W.L.S., C.F.W., S.T.S.L., and Y.L. were supported by the Ph.D. studentships of The Chinese University of Hong Kong. A.H. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/N020146/1). T.B. is supported by a studentship from the Biotechnology and Biological Sciences Research Council-funded South West Biosciences Doctoral Training Partnership (BB/M009122/1). M.E.A.R. is supported by a Ph.D. studentship from the School of Biology and St Andrews University.Background: Schistosomiasis, or bilharzia, is a parasitic disease caused by trematode flatworms of the genus Schistosoma. Infection by Schistosoma mansoni in humans results when cercariae emerge into water from freshwater snails in the genus Biomphalaria and seek out and penetrate human skin. The snail Biomphalaria straminea is native to South America and is now also present in Central America and China, and represents a potential vector host for spreading schistosomiasis. To date, genomic information for the genus is restricted to the neotropical species Biomphalaria glabrata. This limits understanding of the biology and management of other schistosomiasis vectors, such as B. straminea. Findings: Using a combination of Illumina short‐read, 10X Genomics linked‐read, and Hi‐C sequencing data, our 1.005 Gb B. straminea genome assembly is of high contiguity, with a scaffold N50 of 25.3 Mb. Transcriptomes from adults were also obtained. Developmental homeobox genes, hormonal genes, and stress-response genes were identified, and repeat content was annotated (40.68% of genomic content). Comparisons with other mollusc genomes (including Gastropoda, Bivalvia, and Cephalopoda) revealed syntenic conservation, patterns of homeobox gene linkage indicative of evolutionary changes to gene clusters, expansion of heat shock protein genes, and the presence of sesquiterpenoid and cholesterol metabolic pathway genes in Gastropoda. In addition, hormone treatment together with RT-qPCR assay reveal a sesquiterpenoid hormone responsive system in B. straminea, illustrating that this renowned insect hormonal system is also present in the lophotrochozoan lineage. Conclusion: This study provides the first genome assembly for the snail B. straminea and offers an unprecedented opportunity to address a variety of phenomena related to snail vectors of schistosomiasis, as well as evolutionary and genomics questions related to molluscs more widely.Publisher PDFPeer reviewe

    Macrophage-mediated trogocytosis contributes to destroying human schistosomes in a non-susceptible rodent host, Microtus fortis

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    Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control

    Optimal placement of pressure monitors in water supply network with elitist genetic algorithm

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    Optimisation of pressure monitoring in a water distribution network is essential for water companies to provide safe and reliable water supply to customers. With analysis of pressure pertinence and its quantified criteria of nodes in a water supply network, a mathematical model has been established for optimal placement of pressure monitoring. The elitist genetic algorithm (GA) method was adopted for solving this model. The model is evaluated by solving an example network and improves the accuracy and feasibility of this optimal model

    Ruthenium(III) Chloride Catalyzed Acylation of Alcohols, Phenols, and Thiols in Room Temperature Ionic Liquids

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    Ruthenium(III) chloride-catalyzed acylation of a variety of alcohols, phenols, and thiols was achieved in high yields under mild conditions (room temperature) in the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]). The ionic liquid and ruthenium catalyst can be recycled at least 10 times. Our system not only solves the basic problem of ruthenium catalyst reuse, but also avoids the use of volatile acetonitrile as solvent

    Association between serum uric acid and homocysteine levels among adults in the United States: a cross-sectional study

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    Abstract Background Many studies have shown that both elevated serum uric acid (SUA) levels and hyperhomocysteinemia are risk factors for atherosclerosis. However, the relationship between the two has not been thoroughly investigated. Objective This study aimed to explore the possible link between SUA levels and homocysteine (Hcy) levels. Methods In this cross-sectional study, 17,692 adults aged > 19 years in National Health and Nutrition Examination Survey from 1999 to 2006 were analyzed. Multivariable linear regression analysis was performed to assess the association between SUA and Hcy levels. In addition, smooth curve fitting (penalized spline method) and threshold effect analysis were performed. Results Multivariable linear analysis showed that Hcy levels increased by 0.48 µmol/L (β = 0.48, 95%CI: 0.43–0.53) for every 1 mg/dL increase in SUA levels. We found a nonlinear relationship between SUA and Hcy levels. The results of threshold effect analysis showed that the inflection point for SUA levels was 7.1 mg/dL (β = 0.29, 95% CI: 0.23–0.36 and β = 1.05, 95% CI: 0.67–1.43 on the left and right sides of the inflection point, respectively). The p-values was less than 0.001 when using the log likelihood ratio test. This nonlinear relationship was also found in both sexes. The inflection point for SUA levels was 5.4 mg/dL in males and 7.3 mg/dL in females, respectively. Conclusions This cross-sectional study showed that the SUA levels were positively correlated with Hcy levels. And we found a nonlinear relationship between SUA and Hcy levels

    Exercise Training Enhances Myocardial Mitophagy and Improves Cardiac Function via Irisin/FNDC5-PINK1/Parkin Pathway in MI Mice

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    Myocardial infarction is the major cause of death in cardiovascular disease. In vitro and in vivo models are used to find the exercise mode which has the most significant effect on myocardial irisin/FNDC5 expression and illuminate the cardioprotective role and mechanisms of exercise-activated myocardial irisin/FNDC5-PINK1/Parkin-mediated mitophagy in myocardial infarction. The results indicated that expression of irisin/FNDC5 in myocardium could be up-regulated by different types of exercise and skeletal muscle electrical stimulation, which then promotes mitophagy and improves cardiac function and the effect of resistance exercise. Resistance exercise can improve cardiac function by activating the irisin/FNDC5-PINK1/Parkin-LC3/P62 pathway, regulating mitophagy and inhibiting oxidative stress. OPA1 may play an important role in the improvement of cardiac function and mitophagy pathway in myocardial infarction mice by irisin-mediated resistance exercise. Resistance exercise is expected to become an effective therapeutic way to promote myocardial infarction rehabilitation
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