Engineering-Driven Statistical Adjustment and Calibration

<div><p>Engineering model development involves several simplifying assumptions for the purpose of mathematical tractability, which are often not realistic in practice. This leads to discrepancies in the model predictions. A commonly used statistical approach to overcome this problem is to build a statistical model for the discrepancies between the engineering model and observed data. In contrast, an engineering approach would be to find the causes of discrepancy and fix the engineering model using first principles. However, the engineering approach is time consuming, whereas the statistical approach is fast. The drawback of the statistical approach is that it treats the engineering model as a black box and therefore, the statistically adjusted models lack physical interpretability. This article proposes a new framework for model calibration and statistical adjustment. It tries to open up the black box using simple main effects analysis and graphical plots and introduces statistical models inside the engineering model. This approach leads to simpler adjustment models that are physically more interpretable. The approach is illustrated using a model for predicting the cutting forces in a laser-assisted mechanical micro-machining process. This article has supplementary material online.</p></div

Turn-on Room Temperature Phosphorescence Assay of Heparin with Tunable Sensitivity and Detection Window Based on Target-Induced Self-Assembly of Polyethyleneimine Capped Mn-Doped ZnS Quantum Dots

Room-temperature phosphorescence (RTP) turn-on assay of heparin with tunable sensitivity and detection window was demonstrated on the basis of the target induced self-assembly of polyethyleneimine capped Mn-doped ZnS (PEI-Mn-ZnS) QDs. The proposed method can cover the whole therapeutic dosing concentration range in postoperation and long-term therapy (0.2–1.2 U/mL, 1.7–10 μM) and cardiovascular surgery (2–8 U/mL, 17–67 μM) in 10 mM Tris–HCl (pH 7.4) buffer and can be applied for heparin determination in 100-fold diluted human serum samples. The tunable sensitivity and detection window was ascribed to the tunable particle size and ligand loading amount of PEI-Mn-ZnS QD arising from the chain length (or molecule weight) and feed amount of PEI. The chain length of PEI exhibited significant effect on the particle size and ligand loading amount and ultimately had important influence on both the sensitivity and detection window. The feeding amount of PEI, however, greatly affected the ligand loading amount alone and, in turn, affected only the detection window

Thermoresponsive Gelatin Nanogels

We present a novel tunable thermoresponsive gelatin nanogel that shows a volume transition at ∼32 °C. A thermally induced volume reduction of more than 30× is observed due to the helix to random coil transition of gelatin chains confined in the nanogels. The physical process and key factors influencing thermoresponsive properties are investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and polarimetry. The thermoresponsive properties of this nanogel can be exploited in the development of new types of stimuli-responsive, biomedically relevant materials based on natural polymers

Shizukaol D inhibits lipid accumulation in HepG2 cells.

<p>HepG2 cells were starved in serum-free medium overnight and then treated with shizukaol D at the indicated concentrations for 24 h. Metformin (2 mM) was used as a positive control. Western blotting analysis showing phosphorylated AMPK and ACC (A). The triglyceride content (B) and cholesterol content (C) were measured (Results correspond to the mean ± SD of six independent experiments, statistical analysis was performed using one-way ANOVA followed by post- hoc test. *, p<0.05; **, p<0.01 versus the DMSO control). The cells were starved in serum-free medium overnight and then treated with shizukaol D at the indicated concentrations in the presence of 5.5 mM or 30 mM glucose for an additional 24 hours. The expression of AMPK and ACC was detected by western blotting (D), and the triglyceride content (E) and cholesterol content (F) were measured (graphics represent the mean ± SD from six independent experiments. *, p<0.05; **, p<0.01 versus the DMSO control).</p

Chemical structure of shizukaol D from <i>Chloranthus</i><i>japonicas</i>.

<p>Chemical structure of shizukaol D from <i>Chloranthus</i><i>japonicas</i>.</p

Shizukaol D increases AMPK and ACC phosphorylation in HepG2 cells.

<p>Western blotting analysis showing the levels of phosphorylated AMPK and ACC in HepG2 cells treated with shizukaol D. (A) HepG2 cells were treated with shizukaol D at the indicated concentrations for 1 h. Metformin (2 mM) was used as a positive control. (D) The cells were treated with 2 µM shizukaol D for the indicated time points. (B) (C), (E) and (F) the levels of phosphorylated AMPK and ACC were quantified from three independent experiments. *, p<0.05; **, p<0.01 compared to treatment with DMSO (one-way ANOVA).</p

Shizukaol D inhibits lipid accumulation in HepG2 cells in an AMPK-dependent manner.

<p>HepG2 cells were transfected with AMPK siRNA or a control siRNA for 24 h followed by incubation with 2 µM shizukaol D or 2 mM metformin for an additional 24 h. AMPK and ACC phosphorylation was analyzed by western blotting (A), and the triglyceride content (B) and cholesterol content (C) were measured (n = 3). (D) The cells were pretreated with 20 µM compound C (an AMPK inhibitor) followed by treatment with 2 µM shizukaol D. AMPK and ACC phosphorylation was analyzed by western blotting (D), and the triglyceride content (E) and cholesterol content (F) were measured (n = 3). Statistical analysis was performed using two-way ANOVA followed by Tukey’ post-hoc test *, p<0.05; **, p<0.01.</p

Shizukaol D inhibits cellular respiration.

<p>(A) Dose-dependent inhibition of HepG2 cell respiration by treatment with shizukaol D at the indicated concentrations (n = 4). (B) Effect of shizukaol D on the respiration of mitochondria isolated from HepG2 cells (n = 3). Shizukaol D did not inhibit mitochondrial respiration either in the presence of complex I (glutamate + malate) or complex II (succinate) substrates. (C) And (D) Lactate concentrations were measured in HepG2 cells treated with shizukaol D as indicated time (1 h and 4 h) (n = 3). *, p<0.05; **, p<0.01 compared to the DMSO control (one-way ANOVA).</p

Shizukaol D inhibits the mitochondrial membrane potential and increases the AMP/ATP ratio in HepG2 cells.

<p>(A) HepG2 cells were incubated with shizukaol D for 10 min, and the mitochondrial membrane potential was measured. Treatment with CCCP was used as a positive control (n = 4). (B) HepG2 cells were treated with shizukaol D at the indicated concentrations for 1 h, and then the AMP/ATP ratio was measured (n = 3). (C) The cells were treated with 2 µM shizukaol D for the indicated time-points, and then the AMP/ATP ratio was measured (n = 3). *, p<0.05; **, p<0.01 compared to the DMSO control (one-way ANOVA).</p

Shizukaol D Isolated from <i>Chloranthus</i><i> japonicas</i> Inhibits AMPK-Dependent Lipid Content in Hepatic Cells by Inducing Mitochondrial Dysfunction

<div><p>This study is the first to demonstrate that shizukaol D, a natural compound isolated from <i>Chloranthus</i><i>japonicus</i>, can activate AMP- activated protein kinase (AMPK), a key sensor and regulator of intracellular energy metabolism, leading to a decrease in triglyceride and cholesterol levels in HepG2 cells. Furthermore, we found that shizukaol D induces mitochondrial dysfunction by depolarizing the mitochondrial membrane and suppressing energy production, which may result in AMPK activation. Our results provide a possible link between mitochondrial dysfunction and AMPK activation and suggest that shizukaol D might be used to treat metabolic syndrome.</p> </div