A New Smoothing Technique for Bang-Bang Optimal Control Problems

Bang-bang control is ubiquitous for Optimal Control Problems (OCPs) where the constrained control variable appears linearly in the dynamics and cost function. Based on the Pontryagin's Minimum Principle, the indirect method is widely used to numerically solve OCPs because it enables to derive the theoretical structure of the optimal control. However, discontinuities in the bang-bang control structure may result in numerical difficulties for gradient-based indirect method. In this case, smoothing or regularization procedures are usually applied to eliminating the discontinuities of bang-bang controls. Traditional smoothing or regularization procedures generally modify the cost function by adding a term depending on a small parameter, or introducing a small error into the state equation. Those procedures may complexify the numerical algorithms or degenerate the convergence performance. To overcome these issues, we propose a bounded smooth function, called normalized L2-norm function, to approximate the sign function in terms of the switching function. The resulting optimal control is smooth and can be readily embedded into the indirect method. Then, the simplicity and improved performance of the proposed method over some existing methods are numerically demonstrated by a minimal-time oscillator problem and a minimal-fuel low-thrust trajectory optimization problem that involves many revolutions.Comment: This paper has been accpted for presentation at the 2024 AIAA Scitec

Real-time optimal control for attitude-constrained solar sailcrafts via neural networks

This work is devoted to generating optimal guidance commands in real time for attitude-constrained solar sailcrafts in coplanar circular-to-circular interplanetary transfers. Firstly, a nonlinear optimal control problem is established, and necessary conditions for optimality are derived by the Pontryagin's Minimum Principle. Under some assumptions, the attitude constraints are rewritten as control constraints, which are replaced by a saturation function so that a parameterized system is formulated to generate an optimal trajectory via solving an initial value problem. This approach allows for the efficient generation of a dataset containing optimal samples, which are essential for training Neural Networks (NNs) to achieve real-time implementation. However, the optimal guidance command may suddenly change from one extreme to another, resulting in discontinuous jumps that generally impair the NN's approximation performance. To address this issue, we use two co-states that the optimal guidance command depends on, to detect discontinuous jumps. A procedure for preprocessing these jumps is then established, thereby ensuring that the preprocessed guidance command remains smooth. Meanwhile, the sign of one co-state is found to be sufficient to revert the preprocessed guidance command back into the original optimal guidance command. Furthermore, three NNs are built and trained offline, and they cooperate together to precisely generate the optimal guidance command in real time. Finally, numerical simulations are presented to demonstrate the developments of the paper

(3E,5E)-3,5-Bis(4-hy­droxy-3,5-di­methoxy­benzyl­idene)oxan-4-one monohydrate

In the title compound, C23H24O8·H2O, the six-membered ring of the oxan-4-one (tetra­hydro­pyran-4-one) ring displays an envelope conformation with the heterocyclic O atom at the flap position. The dihedral angles between the terminal benzene rings is 37.23 (10)°. Classical intermolecular O—H⋯O and weak C—H⋯O hydrogen bonds are present in the crystal structure

Mouse SCNT ESCs Have Lower Somatic Mutation Load Than Syngeneic iPSCs

SummaryEctopic expression of reprogramming factors has been widely adopted to reprogram somatic nucleus into a pluripotent state (induced pluripotent stem cells [iPSCs]). However, genetic aberrations such as somatic gene mutation in the resulting iPSCs have raised concerns regarding their clinical utility. To test whether the increased somatic mutations are primarily the by-products of current reprogramming methods, we reprogrammed embryonic fibroblasts of inbred C57BL/6 mice into either iPSCs (8 lines, 4 previously published) or embryonic stem cells (ESCs) with somatic cell nuclear transfer (SCNT ESCs; 11 lines). Exome sequencing of these lines indicates a significantly lower mutation load in SCNT ESCs than iPSCs of syngeneic background. In addition, one SCNT-ESC line has no detectable exome mutation, and two pairs of SCNT-ESC lines only have shared preexisting mutations. In contrast, every iPSC line carries unique mutations. Our study highlights the need for improving reprogramming methods in more physiologically relevant conditions

Orthotopic and heterotopic tracheal transplantation model in studying obliterative bronchiolitis

AbstractBackgroundSeveral animal models have been established to investigate the mechanisms of obliterative bronchiolitis after lung transplantation. In this study, we compared three prevalent murine models of obliterative bronchiolitis in terms of several basic pathologic changes in a relatively short span of time after transplantation.MethodsEach of the recipient mice simultaneously received orthotopic, intra-omental and subcutaneous tracheal transplantation in both syngeneic and allogeneic settings. No immunosuppressive treatment was administered. Tracheal grafts were harvested on Day 14, 21 and 28 after transplantation for histological and immunohistochemical analyses.ResultsSyngeneic tracheal grafts from different transplant sites retained normal histologic structures, while their corresponding allografts demonstrated more occlusion of the airway lumen as well as more infiltration of CD4+/CD8+ mononuclear cells and myofibroblasts, but less regenerative epithelium and neovascularized vessels at indicated times (P<0.05). Compared with two heterotopic allografts, orthotopic allografts had less occlusion of the tracheal lumen as well as less infiltration of CD4+/CD8+ mononuclear cells and myofibroblasts, but more regenerative epithelium and neovascularized vessels (P<0.05).ConclusionsOrthotopic tracheal transplantation in mice can be considered as a model to study early stages of obliterative bronchiolitis, and heterotopic tracheal transplantation can be a model for late stages of obliterative bronchiolitis

Use of LC-MS/MS and Stable Isotopes to Differentiate Hydroxymethyl and Methyl DNA Adducts from Formaldehyde and Nitrosodimethylamine

Formaldehyde is a known human and animal carcinogen that forms DNA adducts, and causes mutations. While there is widespread exposure to formaldehyde in the environment, formaldehyde is also an essential biochemical in all living cells. The presence of both endogenous and exogenous sources of formaldehyde makes it difficult to develop exposure-specific DNA biomarkers. Furthermore, chemicals such as nitrosodimethylamine form one mole of formaldehyde for every mole of methylating agent, raising questions about potential co-carcinogenesis. Formaldehyde-induced hydroxymethyl DNA adducts are not stable and need to be reduced to stable methyl adducts for detection, which adds another layer of complexity to identifying the origins of these adducts. In this study, highly sensitive mass spectrometry methods and isotope labeled compounds were used to differentiate between endogenous and exogenous hydroxymethyl and methyl DNA adducts. We demonstrate that N2-hydroxymethyl-dG is the primary DNA adduct formed in cells following formaldehyde exposure. In addition, we show that alkylating agents induce methyl adducts at N2-dG and N6-dA positions, which are identical to the reduced forms of hydroxymethyl adducts arising from formaldehyde. The use of highly sensitive LC-MS/MS and isotope labeled compounds for exposure solves these challenges and provides mechanistic insights on the formation and role of these DNA adducts

(3E,5E)-3,5-Bis(4-hy­droxy­benzyl­idene)oxan-4-one

In the title compound, C19H16O4, there are two 4-hy­droxy­benzyl substituents on the oxan-4-one (tetra­hydro­pyran-4-one) ring, which exhibits an envelope conformation. The dihedral angles between pyran­one ring and the two benzene rings are 26.69 (9) and 36.01 (9)° while the benzene rings make a dihedral angle of 20.88 (10)°. In the crystal, mol­ecules are linked by inter­molecular O—H⋯O hydrogen bonds into a supra­molecular three-dimensional twofold inter­penetrating hydrogen-bonded network

Astragalus Inhibits Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells by Down-Regulating β-Catenin

Background/Aims: The epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a crucial event in the induction of peritoneal fibrosis (PF), in which canonical Wnt/β-catenin signaling participates. Smads signaling is reported to interact with β-catenin and synergistically regulates EMT. This study was aimed to reveal the effect of Astragalus on β-catenin in EMT of PMCs. Methods: To obtain the role of β-catenin in EMT, gene transfer into HMrSV5 cell line and rats has been achieved. After Astragalus treatment, EMT markers and signaling pathway-related indicators were detected by western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and real time-PCR. Results: β-catenin knockdown suppressed EMT of HMrSV5 cells. Astragalus alleviated EMT of PMCs characterized by increased E-cadherin and decreased α-SMA and Vimentin. In rat model of peritoneal dialysis (PD), Astragalus attenuated peritoneal thickening and fibrosis. Astragalus down-regulated β-catenin by stabilizing the Glycogen synthase kinase-3β (GSK-3β)/β-catenin complex and further inhibited the nuclear translocation of β-catenin. Meanwhile, Astragalus down-regulated β-catenin by enhancing Smad7 expression. Silencing Smad7 antagonized the EMT-inhibitory effect of Astragalus. Conclusion: Astragalus inhibits EMT of PMCs by down-regulating β-catenin. The modulation of β-catenin in peritoneum can be a novel tool to prevent PF