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Nuclear morphology plays a critical role in regulating gene expression and cell functions. While most research has focused on the direct effects of nuclear morphology on cell fate, its impact on the cell secretome and surrounding cells remains largely unexplored. In this study, we fabricate implants with a micropillar topography using methacrylated poly(octamethylene citrate)/hydroxyapatite (mPOC/HA) composites to investigate how micropillar-induced nuclear deformation influences cell secretome for osteogenesis and cranial bone regeneration. In vitro, cells with deformed nuclei show enhanced secretion of proteins that support extracellular matrix (ECM) organization, which promotes osteogenic differentiation in neighboring mesenchymal stromal cells (MSCs). In a female mouse model with critical-size cranial defects, nuclear-deformed MSCs on micropillar mPOC/HA implants elevate Col1a2 expression, contributing to bone matrix formation, and drive cell differentiation toward osteogenic progenitor cells. These findings indicate that micropillars modulate the secretome of hMSCs, thereby influencing the fate of surrounding cells through matricrine effects. 

Abstract A 25‐year (1996–2020) hindcast from a coupled physical‐biogeochemical model is evaluated with nutrients, phytoplankton and zooplankton field data and is analyzed to identify mechanisms controlling seasonal and interannual variability of the northern Gulf of Alaska (NGA) planktonic food web. Characterized by a mosaic of processes, the NGA is a biologically complex and productive marine ecosystem. Empirical Orthogonal Function (EOF) analysis combining abiotic and biotic variables averaged over the continental shelf reveals that light intensity is a main driver for nanophytoplankton variability during spring, and that nitrate availability is a main driver for diatoms during spring and for both phytoplankton during summer. Zooplankton variability is a combination of carry‐over effects from the previous year and bottom‐up controls from the current year, with copepods and euphausiids responding to diatoms and microzooplankton responding to nanophytoplankton. The results also demonstrate the effect of nitrate availability and phytoplankton community structure on changes in biomass and energy transfers across the planktonic food web over the entire growing season. In particular, the biomass of large copepods and euphausiids increases more significantly during years of higher relative diatom abundance, as opposed to years with higher nitrate availability. Large microzooplankton was identified as the planktonic group most sensitive to perturbations, presumably due to its central position in the food web. By quantifying the combined variability of several key planktonic functional groups over a 25‐year period, this work lays the foundation for an improved understanding of the long‐term impacts of climate change on the NGA shelf. 

Discrete-event simulation models generate random variates from input distributions and compute outputs according to the simulation logic. The input distributions are typically fitted to finite real-world data and thus are subject to estimation errors that can propagate to the simulation outputs: an issue commonly known as input uncertainty (IU). This paper investigates quantifying IU using the output confidence intervals (CIs) computed from bootstrap quantile estimators. The standard direct bootstrap method has overcoverage due to convolution of the simulation error and IU; however, the brute-force way of washing away the former is computationally demanding. We present two new bootstrap methods to enhance direct resampling in both statistical and computational efficiencies using shrinkage strategies to down-scale the variabilities encapsulated in the CIs. Our asymptotic analysis shows how both approaches produce tight CIs accounting for IU under limited input data and simulation effort along with the simulation sample-size requirements relative to the input data size. We demonstrate performances of the shrinkage strategies with several numerical experiments and investigate the conditions under which each method performs well. We also show advantages of nonparametric approaches over parametric bootstrap when the distribution family is misspecified and over metamodel approaches when the dimension of the distribution parameters is high. History: Accepted by Bruno Tuffin, Area Editor for Simulation. Funding: This work was supported by the National Science Foundation [CAREER CMMI-1834710, CAREER CMMI-2045400, DMS-1854659, and IIS-1849280]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0044 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0044 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ . 

Lewis acid catalyzed condensation of pyrrole and 4-fluoro-2,6-dimethylbenzaldehyde followed by chemical oxidation afforded the corresponding chlorin along with the parent porphyrin. The subsequent metalation of the porphyrin-chlorin mixture in the presence of Zn(OAc)₂•2H₂O afforded Zn monoand di-hydroxychlorins in addition to the Zn porphyrin in a one-flask synthesis. This new direct hydroxylation reaction eliminates the need for highly toxic OsO₄and H₂S that are traditionally used for the generation of hydroxy chlorins. In addition to the full characterization of the zinc chlorins, we present cyclic voltammograms, steady-state absorption, and emission profiles of this rarely available class of compounds. Our findings show that Zn mono- and di-hydroxychlorins are stable compounds that possess exceptionally long triplet excited states in solution, making them promising candidates for photodynamic therapy. 

Abstract Abundance, biomass, size and distribution of macro-jellyfish were measured in the Northern Gulf of Alaska (NGA). Nearly 1000 kg dispersed among ~13 800 jellyfish were collected using a 5-m2 Methot net. We present length-weight regressions for seven most-common taxa. Catches were dominated by the hydrozoan Aequorea victoria and the scyphozoan Chrysaora melanaster. During 2018, epipelagic macro-jellyfish biomass averaged 1.46 ± 0.36 g WW m−3 for July and 1.14 ± 0.23 g WW m−3 for September, while during 2019 they averaged 0.86 ± 0.19 g WW m−3 for July and 0.72 ± 0.21 g WW m−3 by September. Despite similar biomass among seasons within a year, July abundances were fivefold greater than abundances in September, with July catches dominated by smaller-sized jellyfish over the inner shelf, while during September larger jellyfish were more prominent and most predominant at offshore stations. Comparison to 20 years of data from standard towed nets allowed determination of the relative magnitude of the dominant carnivorous zooplankton components: scyphozoans, hydrozoans and chaetognaths in the NGA. The biomass of these smaller epipelagic predators (5.4 mg WW m−3 for hydrozoans and 10.5 mg WW m−3 for chaetognaths) is a low percentage of the macro-jellyfish, despite their much higher numerical abundance.