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Renal medullary carcinoma (RMC) is an aggressive desmoplastic tumour driven by bi-allelic loss of SMARCB1, however the cell-of-origin, the oncogenic mechanism and the features of its microenvironment remain poorly understood. Using single-cell and multi-region sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into at least three RMC cell states along an epithelial-mesenchymal gradient through a transcriptional switch involving loss of renal transcription factor TFCP2L1 and gain of a NFE2L2-associated ferroptosis resistance program. SMARCB1 re-expression in cultured RMC cells reactivates TFCP2L1 that relocates SWI/SNF from the promoters of the MYC-driven oncogenic program to the enhancers of TAL identity genes followed by ferroptotic cell death. We further show that RMC is associated with abundant M2-type macrophages and cancer-associated fibroblasts (CAFs) and we identify key regulatory cross-talks that shape this immunosuppressive microenvironment. Together our data describe the molecular events of RMC transformation and identify novel therapeutically targetable vulnerabilities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=64 SRC="FIGDIR/small/462391v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@3cb5c2org.highwire.dtl.DTLVardef@1c0fec2org.highwire.dtl.DTLVardef@195a2a4org.highwire.dtl.DTLVardef@e8d250_HPS_FORMAT_FIGEXP M_FIG C_FIG

We consider the approximation of Reissner-Mindlin plates with curved boundaries, using a p-version MITC finite element method. We describe in detail the formulation and implementation of the method, and emphasize the need for a Piola-type map in order to handle the curved geometry of the elements. The results of our numerical computations demonstrate the robustness of the method and suggest that it gives near exponential convergence when the error is measured in the energy norm. For the robust computation of quantities of engineering interest, such as the shear force, the proposed method yields very satisfactory results without the need for any additional post-processing. Comparisons are made with the standard finite element formulation, with and without post-processing. © 2005 Elsevier B.V. All rights reserved. 192 2 374 395 Cited By :4

We consider the approximation of the Reissner-Mindlin plate model by the standard Galerkin p version finite element method. Under the assumption of sufficient smoothness on the solution, we illustrate that the method is asymptotically free of locking even when certain curvilinear elements are used. The amount of preasymptotic locking is also identified and is shown to depend on the element mappings. We identify which mappings will result in asymptotically locking free methods and through numerical computations we verify the results for various mappings used in practice. © 2003 IMACS. Published by Elsevier B.V. All rights reserved. 46 2 231 246 Cited By :3

C1 - Journal Articles Refereed

In early 1976 a literature review of low temperature fog was carried out so that the potential for this fog type in the vicinity of the Syncrude synthetic crude oil complex could be assessed. Moreover, a site visit under suitable synoptic meteorological conditions was made in early March 1976 to determine the local controls on fog at low temperatures. The incidence of winter fogs at Mildred Lake is expected to increase due to the water vapour emitted by plant operations. However, evaporation from the large tailings pond is not expected to make a significant contribution, because during winter the pond should be frozen over except where the hot tailings enter. Additional dust and smoke particles may be associated with industrial operations and human activities. The presence of additional condensation or freezing nuclei will alter the temperatures at which fogs occur. However, the concentration and types of nuclei that may be present in the vicinity of the Syncrude plant have yet to be determined. Fogs are often accompanied by increased pollution levels in urban or industrialized areas because of the light winds and stable atmospheric conditions which accompany the fog. The depth of the layer through which the pollutants are mixed is shallow, only 10 to 100 metres, when low temperature fog occurs. Mixing of the elevated plant plumes with fog is unlikely to occur, because under the very stable atmospheric conditions associated with fog, the plumes diffuse slowly and remain above the fog layer.

Contains fulltext : 283536.pdf (Publisher’s version ) (Closed access) The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.

Herbicide application for pest control can negatively affect soil biodiversity, mainly acting on species that are involved in ecosystem service. In this study, field and laboratory trials were designed to assay herbicide exposure effects on the constitutive immunity of Harpalus (Pseudoophonus) rufipes (De Geer, 1774), a beneficial carabid species that inhabits croplands. The circulating hemocytes (THCs) and plasmatic levels of basal and total phenoloxidase (PO), as well as lysozyme-like enzyme activities, were measured as markers of exposure. In laboratory tests, the exposure to realistic field doses of pendimethalin-based herbicides for two, seven and 21 days caused a reduction in enzyme activities in beetles from organic crops. In beetles from conventional fields, the THCs and total PO activity decreased significantly at two and seven days after the initial exposure, though no effects were recorded on basal PO and lysozyme like-enzyme activities. These differences in enzyme activities and THCs indicate that the interference of pendimethalin with immune parameters clearly depends on both the different field conditions from which the population comes and the cumulative effects of repeated applications over the time.

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion.