88 research outputs found

    On Modeling and Constrained Model Predictive Control of Open Irrigation Canals

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    This paper proposes a model predictive control of open irrigation canals with constraints. The Saint-Venant equations are widely used in hydraulics to model an open canal. As a set of hyperbolic partial differential equations, they are not solved explicitly and difficult to design optimal control algorithms. In this work, a prediction model of an open canal is developed by discretizing the Saint-Venant equations in both space and time. Based on the prediction model, a constrained model predictive control was firstly investigated for the case of one single-pool canal and then generalized to the case of a cascaded canal with multipools. The hydraulic software SICC was used to simulate the canal and test the algorithms with application to a real-world irrigation canal of Yehe irrigation area located in Hebei province

    Down-regulation of E-cadherin enhances prostate cancer chemoresistance via Notch signaling

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    Abstract Background The chemoresistance of prostate cancer (PCa) is invariably associated with the aggressiveness and metastasis of this disease. New emerging evidence indicates that the epithelial-to-mesenchymal transition (EMT) may play pivotal roles in the development of chemoresistance and metastasis. As a hallmark of EMT, E-cadherin is suggested to be a key marker in the development of chemoresistance. However, the molecular mechanisms underlying PCa chemoresistance remain unclear. The current study aimed to explore the association between EMT and chemoresistance in PCa as well as whether changing the expression of E-cadherin would affect PCa chemoresistance. Methods Parental PC3 and DU145 cells and their chemoresistant PC3-TxR and DU145-TxR cells were analyzed. PC3-TxR and DU145-TxR cells were transfected with E-cadherin-expressing lentivirus to overexpress E-cadherin; PC3 and DU145 cells were transfected with small interfering RNA to silence E-cadherin. Changes of EMT phenotype-related markers and signaling pathways were assessed by Western blotting and quantitative real-time polymerase chain reaction. Tumor cell migration, invasion, and colony formation were then evaluated by wound healing, transwell, and colony formation assays, respectively. The drug sensitivity was evaluated using MTS assay. Results Chemoresistant PC3-TxR and DU145-TxR cells exhibited an invasive and metastatic phenotype that associated with EMT, including the down-regulation of E-cadherin and up-regulation of Vimentin, Snail, and N-cadherin, comparing with that of parental PC3 and DU145 cells. When E-cadherin was overexpressed in PC3-TxR and DU145-TxR cells, the expression of Vimentin and Claudin-1 was down-regulated, and tumor cell migration and invasion were inhibited. In particular, the sensitivity to paclitaxel was reactivated in E-cadherin-overexpressing PC3-TxR and DU145-TxR cells. When E-cadherin expression was silenced in parental PC3 and DU145 cells, the expression of Vimentin and Snail was up-regulated, and, particularly, the sensitivity to paclitaxel was decreased. Interestingly, Notch-1 expression was up-regulated in PC3-TxR and DU145-TxR cells, whereas the E-cadherin expression was down-regulated in these cells comparing with their parental cells. The use of γ-secretase inhibitor, a Notch signaling pathway inhibitor, significantly increased the sensitivity of chemoresistant cells to paclitaxel. Conclusion The down-regulation of E-cadherin enhances PCa chemoresistance via Notch signaling, and inhibiting the Notch signaling pathway may reverse PCa chemoresistance.https://deepblue.lib.umich.edu/bitstream/2027.42/136217/1/40880_2017_Article_203.pd

    Alterations to the Lung Microbiome in Idiopathic Pulmonary Fibrosis Patients

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    Lung microbiome ecosystem homeostasis in idiopathic pulmonary fibrosis (IPF) remains uncharacterized. The aims of this study were to identify unique microbial signatures of the lung microbiome and analyze microbial gene function in IPF patients. DNA isolated from BALF samples was obtained for high-throughput gene sequencing. Microbial metagenomic data were used for principal component analysis (PCA) and analyzed at different taxonomic levels. Shotgun metagenomic data were annotated using the KEGG database and were analyzed for functional and metabolic pathways. In this study, 17 IPF patients and 38 healthy subjects (smokers and non-smokers) were recruited. For the PCA, the first and the second principal component explained 16.3 and 13.4% of the overall variability, respectively. The β diversity of microbiome was reduced in the IPF group. Signature of IPF's microbes was enriched of Streptococcus, Pseudobutyrivibrio, and Anaerorhabdus. The translocation of lung microbiome was shown that 32.84% of them were from oral. After analysis of gene function, ABC transporter systems, biofilm formation, and two-component regulatory system were enriched in IPF patients' microbiome. Here we shown the microbiology characteristics in IPF patients. The microbiome may participate in altering internal conditions and involving in generating antibiotic resistance in IPF patients

    Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

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    Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development

    Malignant B Cells Induce the Conversion of CD4+CD25− T Cells to Regulatory T Cells in B-Cell Non-Hodgkin Lymphoma

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    Recent evidence has demonstrated that regulatory T cells (Treg) were enriched in the tumor sites of patients with B-cell non-Hodgkin lymphoma (NHL). However, the causes of enrichment and suppressive mechanisms need to be further elucidated. Here we demonstrated that CD4+CD25+FoxP3+CD127lo Treg were markedly increased and their phenotypes were different in peripheral blood (PB) as well as bone marrow (BM) from newly diagnosed patients with B-cell NHL compared with those from healthy volunteers (HVs). Involved lymphatic tissues also showed higher frequencies of Treg than benign lymph nodes. Moreover, the frequencies of Treg were significantly higher in involved lymphatic tissues than those from PB as well as BM in the same patients. Suppression mediated by CD4+CD25+ Treg co-cultured with allogeneic CFSE-labeled CD4+CD25− responder cells was also higher in involved lymphatic tissues from B-cell NHL than that mediated by Treg from HVs. In addition, we found that malignant B cells significantly induced FoxP3 expression and regulatory function in CD4+CD25− T cells in vitro. In contrast, normal B cells could not induce the conversion of CD4+CD25− T cells to Treg. We also showed that the PD-1/B7-H1 pathway might play an important role in Treg induction. Taken together, our results suggest that malignant B cells induce the conversion of CD4+CD25− T cells to Treg, which may play a role in the pathogenesis of B-cell NHL and represent a promising therapeutic target

    Explaining the Paradox of Leader Narcissism – How does Leader Narcissism Interact with Intrapersonal and Contextual Factors?

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    Narcissism is a personality trait that is associated with an exaggerated preoccupation of the self, lack of empathy, power-striving, and grandiose fantasies. This PhD thesis includes four empirical studies that investigated the intrapersonal and the organizational factors influencing how leader narcissism manifests in attitudes and behaviors. Two empirical chapters, each with two studies, focus on different aspects of leader narcissism. Study 1 (N = 73) and Study 2 (N = 157) in Chapter 2 examine how intrapersonal factors affect trait manifestation. Specifically, I distinguished two subtypes of narcissism – grandiosity and vulnerability – and investigated how they interact with levels of identity, thereby influencing leadership outcomes (abusive supervision, workplace incivility, workplace deviance, and transformational leadership). Levels of identity refers to the extent to which one constructs their self-concept in relation to themselves (individual), and to a group (collective). While the research that was conducted during the peak of the Covid-19 pandemic produced null results, Chapter 2 provides a valuable blueprint for future research that distinguishes leaders’ grandiose and vulnerable narcissism. Chapter 3 investigates the role of organizational factors in affecting how leader narcissism manifests. I studied if the interplay between leader narcissism and motivational climates affects the trust followers have in their leaders (Study 3, N = 546 leaders, 1717 = followers). I focused specifically on performance climates (fostering competition) and mastery climates (fostering cooperation). Study 3 found that there was no direct relationship between leader narcissism and follower trust. However, such a relationship was significant and negative when performance climates were strong rather than weak. Similarly, the relationship between leader narcissism and follower trust was negative and significant when the mastery climates were weak. In addition, a follow-up study provided further insights into the intrapersonal processes: I investigated how narcissistic leaders’ self-enhancement in the agentic and the communal domains was affected by their perceptions of the motivational climates (Study 4a, N = 100; Study 4b, N = 101). The findings showed that different levels of abusive supervision occurred depending on whether leader narcissism interacted with performance or mastery climates, respectively. It was found that higher, rather than lower performance climates triggered narcissistic leaders’ agentic tendencies that resulted in abusive supervision. However, there was no interaction effect between leader narcissism and mastery climates that led to a mediating effect of self-enhancement in the communal domain. Chapter 4 summarizes the studies in this thesis and discusses the implications in relation to future research and management practice

    GA Optimization Model for Time/cost Trade-off Problem in Repetitive Projects Considering Resource Continuity

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    Discrete time/cost trade-off problem (DTCTP) is very common in project scheduling. In repetitive projects, some activities are required to maintain resource continuity. This paper proposes an optimization model which is based on the genetic algorithm for DTCTP in repetitive projects considering different requirements for resource continuity of activities. First, two kinds of resource continuity are defined, namely, the constraint of work continuity and resource consistency. Impact of resource continuity on time and cost is analyzed. Then the model which includes five modules is described in details. The model can provide a set of Pareto near optimal solutions to represent the time/cost trade-off in repetitive projects. It can also deal with all kinds of situations where the resource continuity of activities is differently required. A project from the pertinent literature has demonstrated its capabilities
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