Discrete-time contraction constrained nonlinear model predictive control using graph-based geodesic computation

Modern chemical processes need to operate around time-varying operating conditions to optimize plant economy, in response to dynamic supply chains (e.g., time-varying specifications of product and energy costs). As such, the process control system needs to handle a wide range of operating conditions whilst optimizing system performance and ensuring stability during transitions. This article presents a reference-flexible nonlinear model predictive control approach using contraction based constraints. Firstly, a contraction condition that ensures convergence to any feasible state trajectories or setpoints is constructed. This condition is then imposed as a constraint on the optimization problem for model predictive control with a general (typically economic) cost function, utilizing Riemannian weighted graphs and shortest path techniques. The result is a reference flexible and fast optimal controller that can trade-off between the rate of target trajectory convergence and economic benefit (away from the desired process objective). The proposed approach is illustrated by a simulation study on a CSTR control problem.     

Enhanced calcium–magnesium–aluminosilicate (CMAS) resistance of GdAlO3 (GAP) for composite thermal barrier coatings

The impact of calcium–magnesium–alumino-silicate (CMAS) degradation is a critical factor for development of new thermal and environmental barrier coatings. Several methods of preventing damage have been explored in the literature, with formation of an infiltration inhibiting reaction layer generally given the most attention. Gd₂Zr₂O₇ (GZO) exemplifies this reaction with the rapid precipitation of apatite when in contact with CMAS. The present study compares the CMAS behavior of GZO to an alternative thermal barrier coating (TBC) material, GdAlO₃ (GAP), which possesses high temperature phase stability through its melting point as well as a significantly higher toughness compared with GZO. The UCSB laboratory CMAS (35CaO–10MgO–7Al₂O₃–48SiO₂) was utilized to explore equilibrium behavior with 50:50 mol% TBC:CMAS ratios at 1200, 1300, and 1400°C for various times. In addition, 8 and 35 mg/cm² CMAS surface exposures were performed at 1425°C on dense pellets of each material to evaluate the infiltration and reaction in a more dynamic test. In the equilibrium tests, it was found that GAP appears to dissolve slower than GZO while producing an equivalent or higher amount of pore blocking apatite. In addition, GAP induces the intrinsic crystallization of the CMAS into a gehlenite phase, due in part to the participation of the Al₂O₃ from GAP. In surface exposures, GAP experienced a substantially thinner reaction zone compared with GZO after 10 h (87 ± 10 vs. 138 ± 4 μm) and a lack of strong sensitivity to CMAS loading when tested at 35 mg/cm² after 10 h (85 ± 13 versus 246 ± 10 μm). The smaller reaction zone, loading agnostic behavior, and intrinsic crystallization of the glass suggest this material warrants further evaluation as a potential CMAS barrier and inclusion into composite TBCs.     

Fragmentation and granular transition of ceramics for high rate loading

The paper presents a numerical model to study the transition of brittle materials from a cracked solid to a granular medium under impact loading. The model addresses competitive crack coalescence in the transition regime and provides insight into the onset of comminution and the initial conditions for subsequent granular flow. Crack statistics obtained from initial flaws using a wing crack growth-based damage model have been used to discretely model elliptical cracks in three dimensions. These discrete cracks are either generated randomly in space or with a constraint that minimizes the intersection between neighboring cracks. These cracks are then allowed to coalesce with nearby cracks along with favorable directions and the output fragment statistics are predicted. A simple statistical model is proposed that suggests a transition criterion resembling the one obtained from the numerical model. Initial fragments are power-law distributed similarly to experimental observations and particle-based models. A generalized form of a microstructure-dependent granular transition criterion based on a threshold measure of crack lengths has been proposed. This model can be implemented in numerical codes to activate granular physics and calibrate the initial conditions of granular flow, such as fragment size and morphology.     

Insights into the industrial growth of cyanobacteria from a model of the carbon‐concentrating mechanism

With the advent of modern bioengineering tools, photosynthetic organisms are increasingly being engineered to produce chemicals from CO₂ sources, thereby creating a potential route of sustainable chemical production. Cyanobacteria have evolved a carbon‐concentrating mechanism (CCM) that enables growth at low‐environmental carbon concentrations. However at high‐carbon concentrations these benefits may not outweigh synthesis costs. Here, mass transport and kinetic modeling analyses were performed on two species of cyanobacteria as well as a hypothetical no‐CCM mutant. Modeling results correlated with published experimental data. Three conclusions were drawn from the analysis. Carboxysome geometry was unimportant due to the fast relative rate of diffusion of carbon species. Interspecies variations were largely due to active transporters. The no‐carboxysome cell approaches the wild‐type at 10% CO₂. Therefore, in high CO₂ environments the carboxysome and active bicarbonate transporters provide no benefit and a metabolic advantage could be achieved by eliminating the energy‐intensive CCM proteins. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1269–1277, 2014     

Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRAS^Q61K and NRAS^Q61R drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133. MACS-sorted CD133(+) BAKP cells were conditionally reprogrammed to derive BAKR cells with sustained CD133 expression and MIC features. Compared to BAKP, CD133(+) BAKR exhibit increased cell survival and reduced apoptosis in response to trametinib or the chemotherapeutic dacarbazine (DTIC). CRISPR-Cas9-mediated CD133 knockout in BAKR cells (BAKR-KO) re-sensitized cells to trametinib. CD133 knockout in BAKP and POT cells increased trametinib-induced apoptosis by reducing anti-apoptotic BCL-xL, p-AKT, and p-BAD and increasing pro-apoptotic BAX. Conversely, Dox-induced CD133 expression diminished apoptosis in both trametinib-treated cell lines, coincident with elevated p-AKT, p-BAD, BCL-2, and BCL-xL and decreased activation of BAX and caspases-3 and -9. AKT1/2 siRNA knockdown or inhibition of BCL-2 family members with navitoclax (ABT-263) in BAKP-KO cells further enhanced caspase-mediated apoptotic PARP cleavage. CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the CD133, AKT, or BCL-2 survival pathways with trametinib highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma.     

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

The cAMP-dependent aquaporin-2 (AQP2) redistribution from intracellular vesicles into the plasma membrane of renal collecting duct principal cells induces water reabsorption and fine-tunes body water homeostasis. However, the mechanisms controlling the localization of AQP2 are not understood in detail. Using immortalized mouse medullary collecting duct (MCD4) and primary rat inner medullary collecting duct (IMCD) cells as model systems, we here discovered a key regulatory role of Aurora kinase A (AURKA) in the control of AQP2. The AURKA-selective inhibitor Aurora-A inhibitor I and novel derivatives as well as a structurally different inhibitor, Alisertib, prevented the cAMP-induced redistribution of AQP2. Aurora-A inhibitor I led to a depolymerization of actin stress fibers, which serve as tracks for the translocation of AQP2-bearing vesicles to the plasma membrane. The phosphorylation of cofilin-1 (CFL1) inactivates the actin-depolymerizing function of CFL1. Aurora-A inhibitor I decreased the CFL1 phosphorylation, accounting for the removal of the actin stress fibers and the inhibition of the redistribution of AQP2. Surprisingly, Alisertib caused an increase in actin stress fibers and did not affect CFL1 phosphorylation, indicating that AURKA exerts its control over AQP2 through different mechanisms. An involvement of AURKA and CFL1 in the control of the localization of AQP2 was hitherto unknown.     

Assembly and Characterization of Biocompatible Coenzyme Q10-Enriched Lipid Nanoparticles

Coenzyme Q₁₀ (CoQ₁₀) is a strongly hydrophobic lipid that functions in the electron transport chain and as an antioxidant. CoQ₁₀ was conferred with aqueous solubility by incorporation into nanoparticles containing phosphatidylcholine (PtdCho) and apolipoprotein (apo) A-I. These particles, termed CoQ₁₀ nanodisks (ND), contain 1.0 mg CoQ₁₀/5 mg PtdCho/2 mg apoA-I (97% CoQ₁₀ solubilization efficiency). UV/Vis absorbance spectroscopy of CoQ₁₀ ND revealed a characteristic absorbance peak centered at 275 nm. Incorporation of CoQ₁₀ into ND resulted in quenching of apoA-I tryptophan fluorescence emission. Gel filtration chromatography of CoQ₁₀ ND gave rise to a single major absorbance peak and HPLC of material extracted from this peak confirmed the presence of CoQ₁₀. Incubation of cultured cells with CoQ₁₀ ND, but not empty ND, resulted in a significant increase in the CoQ₁₀ content of mitochondria as well as enhanced oxidative phosphorylation, as observed by a ~24% increase in maximal oxygen consumption rate. Collectively, a facile method to solubilize significant quantities of CoQ₁₀ in lipid nanoparticles has been developed. The availability of CoQ₁₀ ND provides a novel means to investigate biochemical aspects of CoQ₁₀ uptake by cells and/or administer it to subjects deficient in this key lipid as a result of inborn errors of metabolism, statin therapy, or otherwise.     

A cathode support structure for use in a magnetron oscillator experiment

A low temperature co-fired ceramic (LTCC) material system has been used to develop a protype field emission cathode structure for use in an experimental magnetron oscillator. The structure is designed for used with 30 gated field emission array (GFEA) die electrically connected through silver metal traces and electrical vias. To approximate a cylinder, the cathode structure (48 mm long and 13.7 mm in diameter) is comprised of 10 faceted plates which cover the GFEA dies. Slits in the facet plates allow electron injection. The GFEA die (3 mm × 8 mm) are placed in axial columns of 3 and spaced azimuthally around a cylindrical support structure in a staggered configuration resulting in 10 azimuthal locations. LTCC manufacturing techniques were developed in order to fabricate the newly designed cathode with seven layers wrapped to form the cylinder with electrical traces and vias. Two different cathode wrapping techniques and two different via filling techniques were studied and compared. Two different facet plate manufacturing techniques were studied. Finally, four different support stand configurations for firing the cylindrical structure were also compared with a square post stand having the best circularity and linearity measurements of the fired structure.     

Two-phase flow pressure drop hysteresis in parallel channels of a proton exchange membrane fuel cell

Two-phase flow pressure drop hysteresis was studied in a non-operational PEM fuel cell to understand the effect of stoichiometry, GDL characteristics, operating range, and initial conditions (dry vs. flooded) for flow conditions typical of an operating fuel cell. This hysteresis is noted when the air and water flow rates are increased and then decreased along the same path, exhibiting different pressure drops. When starting from dry conditions, the descending pressure drop tended to be higher than the ascending pressure drop at lower simulated current densities. The hysteresis effect was noted for stoichiometries of 1-4 and was eliminated at a stoichiometry of 5. It was found that the hysteresis was greater when water breakthrough occurred at higher simulated current densities, which is a function of GDL properties. The operating range had to reach a critical simulated current density (800 mA cm⁻² in this case) between the ascending and descending approach to create a pressure drop hysteresis zone. The descending step size does not change the size of the hysteresis effect, but a larger step size leads to lower fluctuations in the pressure drop signal. An initially flooded condition also showed hysteresis, but the ascending approach tended to have a higher pressure drop than the descending approach.     

Real options valuation of US federal renewable energy research,development, demonstration,and deployment

Benefits analysis of US Federal government research, development, demonstration, and deployment (RD³) programmes for renewable energy (RE) technology improvement typically employs a deterministic forecast of the cost and performance of renewable and non-renewable fuels. The benefits estimate for the programme derives from the difference between two forecasts, with and without the RD³ programme in place. Three deficiencies of this approach are that it ignores: (1) uncertainty in the cost of non-renewable energy (NRE); (2) the possibility of adjustment to the RD³ effort commensurate with the evolving state of the world; and (3) the underlying technical risk associated with RD³. In this paper, an intuitive approach to determining the option value of RE RD³ is developed. This approach seeks to tackle the first two deficiencies noted above by providing an estimate via a compound real option of an RE RD³ programme in a future with uncertain NRE costs. A binomial lattice reveals the economic intuition underlying the decision-making process, while a numerical example illustrates the option components embedded in a simplified representation of current US Federal RE RD³.