Topology Preservation and Cooperative Learning in Identification of Multiple Model Systems

2008 ◽  
Vol 19 (12) ◽  
pp. 2065-2072 ◽  
Author(s):  
Jianbo Liu ◽  
Dragan Djurdjanovic
2020 ◽  
Author(s):  
Tamara Madácsy ◽  
Árpad Varga ◽  
Noémi Papp ◽  
Barnabás Deák ◽  
Bálint Tél ◽  
...  

ABSTRACTExocrine pancreatic damage is a common complication of cystic fibrosis (CF), which can significantly debilitate the quality of life and life expectancy of CF patients. The cystic fibrosis transmembrane conductance regulator (CFTR) has a major role in pancreatic ductal ion secretion, however, it presumably has an influence on intracellular signaling as well. Here we describe in multiple model systems, including iPSC-derived human pancreatic organoids from CF patients, that the activity of PMCA4 is impaired by the decreased expression of CFTR in ductal cells. The regulation of PMCA4, which colocalizes and physically interacts with CFTR on the apical membrane of the ductal cells, is dependent on the calmodulin binding ability of CFTR. Moreover, CFTR seems to be involved in the process of the apical recruitment of calmodulin, which enhances its role in calcium signaling and homeostasis. Sustained intracellular Ca2+ elevation in CFTR KO cells undermined the mitochondrial function and increased apoptosis. Based on these, the prevention of sustained intracellular Ca2+ overload may improve the exocrine pancreatic function and may have a potential therapeutic aspect in CF.


Author(s):  
Jianbo Liu ◽  
Dragan Djurdjanovic ◽  
Kenneth Marko ◽  
Jun Ni

A new anomaly detection scheme based on growing structure multiple model system (GSMMS) is proposed in this paper to detect and quantify the effects of anomalies. The GSMMS algorithm combines the advantages of growing self-organizing networks with efficient local model parameter estimation into an integrated framework for modeling and identification of general nonlinear dynamic systems. The identified model then serves as a foundation for building an effective anomaly detection and fault diagnosis system. By utilizing the information about system operation region provided by the GSMMS, the residual errors can be analyzed locally within each operation region. This local decision making scheme can accommodate for unequally distributed residual errors across different operational regions. The performance of the newly proposed method is evaluated through anomaly detection and quantification in an electronically controlled throttle system, which is simulated using a high-fidelity engine simulation software package provided by a major automotive manufacturer for control system development.


2019 ◽  
Vol 12 ◽  
Author(s):  
Erik Svensson ◽  
John Apergis-Schoute ◽  
Geoffrey Burnstock ◽  
Michael P. Nusbaum ◽  
David Parker ◽  
...  
Keyword(s):  

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S833-S833
Author(s):  
Christy S Carter ◽  
Michal Masternak ◽  
Thomas W Buford

Abstract The human intestinal tract (i.e., “gut”) is inhabited by over 100 trillion microorganisms; including over 1000 species of known bacteria. These organisms have co-evolved with humans over millennia to live together for mutual benefit. Though long overlooked in considerations of human health and disease treatment, gut microorganisms are highly involved in numerous metabolic reactions which influence normal host physiology. A variety of biologic, medical, and lifestyle factors appear to contribute to gut dysbiosis in late-life, and interventions specifically designed to target these factors may be useful in restoring microbial balance. Evidence from both clinical and preclinical studies suggests that gut dysbiosis is related to age-related inflammation as well as age-related conditions including frailty, Alzheimer’s disease, and perhaps even longevity. Crosstalk between the gut and multiple organ systems (brain, heart, muscle etc.) may lead to the development of age-related diseases and loss of physiological function, although the signals are not well understood. In this symposium we address the broad topic of the Gut Microbiome and Aging by presenting evidence from multiple model systems (mice, rats and monkeys) and provide a forum to discuss critical areas of research for moving forward.


2020 ◽  
Author(s):  
Anas M Khanshour ◽  
Yared H Kidane ◽  
Julia Kozlitina ◽  
Reuel Cornelia ◽  
Alexandra Rafipay ◽  
...  

Abstract Talipes equinovarus (clubfoot, TEV) is a congenital rotational foot deformity occurring in 1 per 1000 births with increased prevalence in males compared with females. The genetic etiology of isolated clubfoot (iTEV) remains unclear. Using a genome-wide association study, we identified a locus within FSTL5, encoding follistatin-like 5, significantly associated with iTEV. FSTL5 is an uncharacterized gene whose potential role in embryonic and postnatal development was previously unstudied. Utilizing multiple model systems, we found that Fstl5 was expressed during later stages of embryonic hindlimb development, and, in mice, expression was restricted to the condensing cartilage anlage destined to form the limb skeleton. In the postnatal growth plate, Fstl5 was specifically expressed in prehypertrophic chondrocytes. As Fstl5 knockout rats displayed no gross malformations, we engineered a conditional transgenic mouse line (Fstl5LSL) to overexpress Fstl5 in skeletal osteochondroprogenitors. We observed that hindlimbs were slightly shorter and that bone mineral density was reduced in adult male, but not female, Prrx1-cre;Fstl5LSL mice compared with control. No overt clubfoot-like deformity was observed in Prrx1-cre;Fstl5LSL mice, suggesting FSTL5 may function in other cell types to contribute to iTEV pathogenesis. Interrogating published mouse embryonic single-cell expression data showed that Fstl5 was expressed in cell lineage subclusters whose transcriptomes were associated with neural system development. Moreover, our results suggest that lineage-specific expression of the Fstl genes correlates with their divergent roles as modulators of transforming growth factor beta and bone morphogenetic protein signaling. Results from this study associate FSTL5 with iTEV and suggest a potential sexually dimorphic role for Fstl5 in vivo.


Oncotarget ◽  
2018 ◽  
Vol 9 (34) ◽  
pp. 23462-23481 ◽  
Author(s):  
Danielle Brooks ◽  
Alexandra Zimmer ◽  
Lalage Wakefield ◽  
L. Tiffany Lyle ◽  
Simone Difilippantonio ◽  
...  

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