Queuing analysis of delayed differentiation system

2021 ◽  
pp. 1-11
Author(s):  
Jack C. P. Su ◽  
Wilson Wang ◽  
Weimin Chow
Keyword(s):  
Queuing Analysis ◽  
Delayed Differentiation

Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2617-2627 ◽  
Author(s):  
P.J. Miettinen ◽  
M. Huotari ◽  
T. Koivisto ◽  
J. Ustinov ◽  
J. Palgi ◽  
...  
Keyword(s):  
Beta Cells ◽  
Islet Cells ◽  
Branching Morphogenesis ◽  
Late Gestation ◽  
Pancreatic Ducts ◽  
Egf Receptors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pancreatic Acini ◽  
Delayed Differentiation ◽  
Pai 1

Pancreatic acini and islets are believed to differentiate from common ductal precursors through a process requiring various growth factors. Epidermal growth factor receptor (EGF-R) is expressed throughout the developing pancreas. We have analyzed here the pancreatic phenotype of EGF-R deficient (−/−) mice, which generally die from epithelial immaturity within the first postnatal week. The pancreata appeared macroscopically normal. The most striking feature of the EGF-R (−/−) islets was that instead of forming circular clusters, the islet cells were mainly located in streak-like structures directly associated with pancreatic ducts. Based on BrdU-labelling, proliferation of the neonatal EGF-R (−/−) beta-cells was significantly reduced (2.6+/−0.4 versus 5.8+/−0.9%, P<0.01) and the difference persisted even at 7–11 days of age. Analysis of embryonic pancreata revealed impaired branching morphogenesis and delayed islet cell differentiation in the EGF-R (−/−) mice. Islet development was analyzed further in organ cultures of E12.5 pancreata. The proportion of insulin-positive cells was significantly lower in the EGF-R (−/−) explants (27+/−6 versus 48+/−8%, P<0.01), indicating delayed differentiation of the beta cells. Branching of the epithelium into ducts was also impaired. Matrix metalloproteinase (MMP-2 and MMP-9) activity was reduced 20% in EGF-R (−/−) late-gestation pancreata, as measured by gelatinase assays. Furthermore, the levels of secreted plasminogen activator inhibitor-1 (PAI-1) were markedly higher, while no apparent differences were seen in the levels of active uPA and tPa between EGF-R (−/−) and wild-type pancreata. Our findings suggest that the perturbation of EGF-R-mediated signalling can lead to a generalized proliferation defect of the pancreatic epithelia associated with a delay in beta cell development and disturbed migration of the developing islet cells as they differentiate from their precursors. Upregulated PAI-1 production and decreased gelatinolytic activity correlated to this migration defect. An intact EGF-R pathway appears to be a prerequisite for normal pancreatic development.

scholarly journals Elevated CO2 Levels Delay Skeletal Muscle Repair by Increasing Fatty Acid Oxidation

2021 ◽  
Vol 11 ◽  
Author(s):  
Ermelinda Ceco ◽  
Diego Celli ◽  
Samuel Weinberg ◽  
Masahiko Shigemura ◽  
Lynn C. Welch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Acid Oxidation ◽  
Chronic Obstructive ◽  
C2c12 Myoblasts ◽  
Delayed Differentiation ◽  
Chronic Obstructive Pulmonary Diseases

Muscle dysfunction often occurs in patients with chronic obstructive pulmonary diseases (COPD) and affects ventilatory and non-ventilatory skeletal muscles. We have previously reported that hypercapnia (elevated CO2 levels) causes muscle atrophy through the activation of the AMPKα2-FoxO3a-MuRF1 pathway. In the present study, we investigated the effect of normoxic hypercapnia on skeletal muscle regeneration. We found that mouse C2C12 myoblasts exposed to elevated CO2 levels had decreased fusion index compared to myoblasts exposed to normal CO2. Metabolic analyses of C2C12 myoblasts exposed to high CO2 showed increased oxidative phosphorylation due to increased fatty acid oxidation. We utilized the cardiotoxin-induced muscle injury model in mice exposed to normoxia and 10% CO2 for 21 days and observed that muscle regeneration was delayed. High CO2-delayed differentiation in both mouse C2C12 myoblasts and skeletal muscle after injury and was restored to control levels when cells or mice were treated with a carnitine palmitoyltransfearse-1 (CPT1) inhibitor. Taken together, our data suggest that hypercapnia leads to changes in the metabolic activity of skeletal muscle cells, which results in impaired muscle regeneration and recovery after injury.

scholarly journals A delayed differentiation multiproduct model with the outsourcing of common parts, overtime strategy for end products, and quality reassurance

2021 ◽  
pp. 143-158 ◽  
Author(s):  
Singa Wang Chiu ◽  
Victoria Chiu ◽  
Ming-Hon Hwang ◽  
Yuan-Shyi Peter Chiu
Keyword(s):  
Cost Effective ◽  
Sensitivity Analyses ◽  
Optimization Approach ◽  
Limited Capacity ◽  
Numerical Illustration ◽  
Delayed Differentiation ◽  
Modeling Analysis ◽  
End Products ◽  
Effective Decision ◽  
Effective Decision Making

Production planners today must simultaneously face with the time and quality demands of various goods externally and meet limited capacity internally. This study presents a two-stage delayed- differentiation multiproduct model that considers the outsourcing options for common parts, overtime strategy for end products, and quality reassurance to assist in making fabrication runtime decisions that are cost-effective. Stage one produces all necessary common intermediate components for end products. To reduce stage one’s utilization/uptime, this study adopts a partial outsourcing option. Stage two uses an overtime strategy to fabricate end products that further shorten the uptime. The production processes in both phases are assumed to be imperfect. This study employs the reworking/scrapping of random faulty items to reassure product quality. The researchers build a model to depict the proposed problem’s characteristics and used the mathematical modeling, analysis, and optimization approach to determine the best rotation cycle length that minimizes the system’s expenses. Further, in this study, the researchers provide sensitivity analyses and a numerical illustration, which validate the result’s applicability and exhibit its capability. This result contributes to practical multiproduct-fabrication by (1) deriving the optimal manufacturing policy for a delayed-differentiation multiproduct system with dual uptime reduction policies and quality reassurance; and (2) offering a decisional model that allows production planners to explore the collective/separate effect of a quality-ensured and dual uptime reduction strategy on a problem’s operating policy and crucial system performance indicators, which assists in cost-effective decision-making.

scholarly journals Knockdown of a disintegrin A metalloprotease 12 (ADAM12) during adipogenesis reduces cell numbers, delays differentiation, and increases lipid accumulation in 3T3-L1 cells

2018 ◽  
Vol 29 (15) ◽  
pp. 1839-1855 ◽  
Author(s):  
Chantal A. Coles ◽  
Jovana Maksimovic ◽  
Jenny Wadeson ◽  
Fahri T. Fahri ◽  
Tracie Webster ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lipid Accumulation ◽  
Tissue Growth ◽  
Mtor Signaling ◽  
Gene Profiling ◽  
Insulin Like Growth Factor ◽  
Cell Numbers ◽  
Delayed Differentiation ◽  
Ppar Signaling ◽  
Enzymatic Markers

Mouse models have shown that a disintegrin A metalloprotease 12 (ADAM12) is implicated during adipogenesis; the molecular pathways are not well understood. Stealth RNA interference was used to knock down ADAM12 in 3T3-L1 cells. Using gene profiling and metabolic enzymatic markers, we have identified signaling pathways ADAM12 impacts upon during proliferation, differentiation, and maturation of adipocytes. ADAM12 reduced cell numbers in proliferating preadipocytes, delayed differentiation of preadipocytes to adipocytes, and increased lipid accumulation in mature adipocytes. The pathway most affected by ADAM12 knockdown was regulation of insulin-like growth factor (IGF) activity by insulin-like growth factor binding proteins (IGFBPs); ADAM12 is known to cleave IGFBP3 and IGFBP5. The IGF/mTOR signaling pathway was down-regulated, supporting a role for ADAM12 in the IGFBP/IGF/mTOR-growth pathway. PPARγ signaling was also down-regulated by ADAM12 knockdown. Gene ontology (GO) analysis revealed that the extracellular matrix was the cellular compartment most impacted. Filtering for matrisome genes, connective tissue growth factor ( Ctgf) was up-regulated. CTGF and IGBP3 can interact with PPARγ to hinder its regulation. Increased expression of these molecules could have influenced PPARγ signaling reducing differentiation and an imbalance of lipids. We believe ADAM12 regulates cell proliferation of preadipocytes through IGFBP/IGF/mTOR signaling and delays differentiation through altered PPAR signaling to cause an imbalance of lipids within mature adipocytes.

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