8% of those with LVSI (p less then 0.001). Lymphatic metastases were identified in 1.7% of stage IA2 cases without LVSI versus 14.6% for those with LVSI (p less then 0.001). Among both stage IA1 and IA2 patients, squamous histology, grade 3 tumor differentiation, and white race were associated with LVSI (p less then 0.05 for all). In a univariable model, the hazard ratio for death associated with LVSI was 1.05 (95% CI 0.45 to 2.45) for women with stage IA1 tumors and 2.36 (95% CI 1.04 to 5.33) for those with IA2 neoplasms. CONCLUSIONS LVSI is associated with lymph node metastases in patients with stage IA cervical cancer. LVSI is associated with decreased survival for women with stage IA2 cervical cancer. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE The standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging surgery followed by platinum-based chemotherapy. However, the role of complete staging surgery and adjuvant chemotherapy remains controversial. The aim of this study was to investigate the role of complete staging surgery and adjuvant chemotherapy in patients with early-stage pure immature teratoma after fertility-sparing surgery. METHODS Patients with stage I pure immature teratoma who underwent fertility-sparing surgery between January 1986 and June 2018 were reviewed retrospectively. Fertility-sparing surgery was defined as preservation of the uterus and at least one adnexa. The inclusion criteria were age >18 years, stage I disease (confined to one ovary), and diagnosis of pure immature teratoma. Patients with distant metastasis or mixed ovarian germ cell tumor were excluded. Complete stone death. Tumor relapse occurred in patients with all grades of immature teratoma (G1 1/35; G2 2/25; G3 1/15). Univariate analysis revealed that complete staging surgery, adjuvant chemotherapy, and tumor grade were not associated with 5 year disease-free survival (p=0.69, p=0.46, p=0.7, respectively). The 5 year disease-free survival rate was 94.6% and the overall survival rate was 98.7%. CONCLUSION Adult patients with stage I pure immature teratoma had 98.7% overall survival and recurrence rates were low after fertility-sparing surgery. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.Instrumented indentation has been developed and widely utilized as one of the most versatile and practical means of extracting mechanical properties of materials. This method is particularly desirable for those applications where it is difficult to experimentally determine the mechanical properties using stress-strain data obtained from coupon specimens. Such applications include material processing and manufacturing of small and large engineering components and structures involving the following three-dimensional (3D) printing, thin-film and multilayered structures, and integrated manufacturing of materials for coupled mechanical and functional properties. Here, we utilize the latest developments in neural networks, including a multifidelity approach whereby deep-learning algorithms are trained to extract elastoplastic properties of metals and alloys from instrumented indentation results using multiple datasets for desired levels of improved accuracy. We have established algorithms for solving inverse problems by recourse to single, dual, and multiple indentation and demonstrate that these algorithms significantly outperform traditional brute force computations and function-fitting methods. Moreover, we present several multifidelity approaches specifically for solving the inverse indentation problem which 1) significantly reduce the number of high-fidelity datasets required to achieve a given level of accuracy, 2) utilize known physical and scaling laws to improve training efficiency and accuracy, and 3) integrate simulation and experimental data for training disparate datasets to learn and minimize systematic errors. The predictive capabilities and advantages of these multifidelity methods have been assessed by direct comparisons with experimental results for indentation for different commercial alloys, including two wrought aluminum alloys and several 3D printed titanium alloys. Copyright © 2020 the Author(s). Published by PNAS.The endoplasmic reticulum (ER) is the site of synthesis of secretory and membrane proteins and contacts every organelle of the cell, exchanging lipids and metabolites in a highly regulated manner. How the ER spatially segregates its numerous and diverse functions, including positioning nanoscopic contact sites with other organelles, is unclear. We demonstrate that hypotonic swelling of cells converts the ER and other membrane-bound organelles into micrometer-scale large intracellular vesicles (LICVs) that retain luminal protein content and maintain contact sites with each other through localized organelle tethers. Upon cooling, ER-derived LICVs phase-partition into microscopic domains having different lipid-ordering characteristics, which is reversible upon warming. Ordered ER lipid domains mark contact sites with ER and mitochondria, lipid droplets, endosomes, or plasma membrane, whereas disordered ER lipid domains mark contact sites with lysosomes or peroxisomes. Tethering proteins concentrate at ER-organelle contact sites, allowing time-dependent behavior of lipids and proteins to be studied at these sites. These findings demonstrate that LICVs provide a useful model system for studying the phase behavior and interactive properties of organelles in intact cells. Copyright © 2020 the Author(s). Published by PNAS.Protein mobility at solid-liquid interfaces can affect the performance of applications such as bioseparations and biosensors by facilitating reorganization of adsorbed protein, accelerating molecular recognition, and informing the fundamentals of adsorption. In the case of ion-exchange chromatographic beads with small, tortuous pores, where the existence of surface diffusion is often not recognized, slow mass transfer can result in lower resin capacity utilization. We demonstrate that accounting for and exploiting protein surface diffusion can alleviate the mass-transfer limitations on multiple significant length scales. Although the surface diffusivity has previously been shown to correlate with ionic strength (IS) and binding affinity, we show that the dependence is solely on the binding affinity, irrespective of pH, IS, and resin ligand density.  https://www.selleckchem.com/CDK.html  Different surface diffusivities give rise to different protein distributions within the resin, as characterized using confocal microscopy and small-angle neutron scattering (length scales of micrometer and nanometer, respectively).