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Unlabelled: Highly multiplexed imaging assays allow simultaneous quantification of multiple protein and phosphorylation markers, providing a static snapshots of cell types and states. Pseudo-time techniques can transform these static snapshots of unsynchronized cells into dynamic trajectories, enabling the study of dynamic processes such as development trajectories and the cell cycle. Such ordering also enables training of mathematical models on these data, but technical challenges have hitherto made it difficult to integrate multiple experimental conditions, limiting the predictive power and insights these models can generate.
View Article and Find Full Text PDFNumerous computational approaches have been developed to infer cell state transition trajectories from snapshot single-cell data. Most approaches first require projecting high-dimensional data onto a low-dimensional representation, raising the question of whether the dynamics of the system become distorted. Using epithelial-to-mesenchymal transition (EMT) as a test system, we show that both biology-guided low-dimensional representations and stochastic trajectory simulations in high-dimensional state space, not representations obtained with dimension-reduction methods, reveal multiple distinct paths of TGF-β-induced EMT.
View Article and Find Full Text PDFK-RAS mutations drive oncogenesis in multiple cancers, yet the lack of druggable sites has long hindered therapeutic development. Here, we use multi-temperature X-ray crystallography (MT-XRC) to capture functionally relevant K-RAS conformations across a temperature gradient, spanning cryogenic to physiological and even "fever" conditions, and show how cryogenic conditions may obscure key dynamic states as targets for new drug development. This approach revealed a temperature-dependent conformational landscape of K-RAS, shedding light on the dynamic nature of key regions.
View Article and Find Full Text PDFSimulated millennial-scale climate variability driven by a convection-advection oscillator.
Clim Dyn
March 2025
Department of Mathematics and Statistics, University of Reading, Whiteknights House, Reading, RG6 6UR UK.
Unlabelled: The last glacial period, between around 115 and 12 thousand years before present, exhibited strong millennial-scale climate variability. This includes abrupt transitions between cold and warm climates, known as Dansgaard-Oeschger (D-O) cycles. D-O cycles have been linked to switches in dynamical regimes of the Atlantic Overturning Meridional Circulation (AMOC), but the exact mechanisms behind abrupt climate changes and AMOC regime shifts remain poorly understood.
View Article and Find Full Text PDFShort-term outcomes of extracorporeal versus intracorporeal side-to-side anastomosis after laparoscopic right hemicolectomy for colon cancer: an affiliated study of a multicenter snapshot study.
Surg Endosc
March 2025
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, No.95 Yongan Road, Xicheng District, Beijing, 100050, China.
Background: Laparoscopic right hemicolectomy (RHC) is the primary surgical approach for right-sided colon cancer. Different ileo-colonic anastomosis techniques may lead to varied postoperative outcomes. This study aims to compare intracorporeal versus extracorporeal side-to-side anastomosis post laparoscopic RHC for short-term outcomes in right-sided colon cancer patients.
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