Large-format 3D printing enabled by dual-curing urethane elastomers

Direct-ink-writing (DIW) is an Additive Manufacturing (AM) technique that provides a versatile approach to fabricating arbitrarily shaped objects by exploiting the shear-thinning properties of polymeric-based inks. One major drawback of DIW is that shear-thinning inks are limited to a maximum height before the combined weight of additionally deposited layers exceeds the yield stress of the underlying layers and causes the material to flow. Previous methods to combat this drawback have included intermittent or continuous exposure of the process to ultra-violet (UV) radiation to cure the material in place. However, these approaches require specific parameters that limit the UV-curable inks to specific applications and do not address the challenges associated with printing high-aspect-ratio objects. Here, we report a stepwise UV and heat curing process that facilitates DIW of a range of inks with varying rheological properties and that is no longer dimensionally limited by a yield stress. This stepwise curing process is enabled by small amounts of acrylates that cure to the back of the functionalized urethane prepolymers to promote rapid gelation in the object during extrusion, and a post thermal-curing step of the major urethane components once printing is complete. This method of fabrication effectively eliminates dimensional constraints of objects during fabrication, as well as expands the rheological range of printable inks. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-795840

Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

The Ongoing Need for High-Resolution Regional Climate Models: Process Understanding and Stakeholder Information

Regional climate modeling addresses our need to understand and simulate climatic processes and phenomena unresolved in global models. This paper highlights examples of current approaches to and innovative uses of regional climate modeling that deepen understanding of the climate system. High-resolution models are generally more skillful in simulating extremes, such as heavy precipitation, strong winds, and severe storms. In addition, research has shown that fine-scale features such as mountains, coastlines, lakes, irrigation, land use, and urban heat islands can substantially influence a region’s climate and its response to changing forcings. Regional climate simulations explicitly simulating convection are now being performed, providing an opportunity to illuminate new physical behavior that previously was represented by parameterizations with large uncertainties. Regional and global models are both advancing toward higher resolution, as computational capacity increases. However, the resolution and ensemble size necessary to produce a sufficient statistical sample of these processes in global models has proven too costly for contemporary supercomputing systems. Regional climate models are thus indispensable tools that complement global models for understanding physical processes governing regional climate variability and change. The deeper understanding of regional climate processes also benefits stakeholders and policymakers who need physically robust, high-resolution climate information to guide societal responses to changing climate. Key scientific questions that will continue to require regional climate models, and opportunities are emerging for addressing those questions.This article is published as Gutowski, William J., Paul Aaron Ullrich, Alex Hall, L. Ruby Leung, Travis Allen O’Brien, Christina M. Patricola, R. W. Arritt et al. "The ongoing need for high-resolution regional climate models: Process understanding and stakeholder information." Bulletin of the American Meteorological Society 101, no. 5 (2020): E664-E683. DOI: 10.1175/BAMS-D-19-0113.1. Copyright 2020 American Meteorological Society. https://www.ametsoc.org/ams/index.cfm/publications/authors/journal-and-bams-authors/author-resources/copyright-information/copyright-policy/. Posted with permission