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Quantitative assessment of single cell fluxome is critical for understanding the metabolic heterogeneity in diseases. Unfortunately, laboratory-based single cell fluxomics is currently impractical, and the current computational tools for flux estimation are not designed for single cell-level prediction. Given the well-established link between transcriptomic and metabolomic profiles, leveraging single cell transcriptomics data to predict single cell fluxome is not only feasible but also an urgent task. In this study, we present FLUXestimator, an online platform for predicting metabolic fluxome and variations using single cell or general transcriptomics data of large sample-size. The FLUXestimator webserver implements a recently developed unsupervised approach called single cell flux estimation analysis (scFEA), which uses a new neural network architecture to estimate reaction rates from transcriptomics data. To the best of our knowledge, FLUXestimator is the first web-based tool dedicated to predicting cell-/sample-wise metabolic flux and metabolite variations using transcriptomics data of human, mouse and 15 other common experimental organisms. The FLUXestimator webserver is available at http://scFLUX.org/, and stand-alone tools for local use are available at https://github.com/changwn/scFEA. Our tool provides a new avenue for studying metabolic heterogeneity in diseases and has the potential to facilitate the development of new therapeutic strategies.

Many recent efforts in the diagnostic field address the accessibility of cancer diagnosis. Typical histological staining methods identify cancer cells visually by a larger nucleus with more condensed chromatin. Machine learning (ML) has been incorporated into image analysis for improving this process. Recently, impedance spectrometers have been shown to generate all-inclusive lab-on-a-chip platforms to detect nucleus abnormities. In this paper, a wideband electrical sensor and data analysis paradigm that can identify nuclear changes shows the realization of a single-cell microfluidic device to detect nuclei of altered sizes. To model cells of altered nucleus, Jurkat cells were treated to enlarge or shrink their nucleus followed by broadband sensing to obtain the S-parameters of single cells. The ability to deduce important frequencies associated with nucleus size is demonstrated and used to improve classification models in both binary and multiclass scenarios, despite a heterogeneous and overlapping cell population. The important frequency features match those predicted in a double-shell circuit model published in prior work, demonstrating a coherent new analytical technique for electrical data analysis. The electrical sensing platform assisted by ML with impressive accuracy of cell classification looks forward to a label-free and flexible approach to cancer diagnosis.

Flooding of low-lying Arctic regions has the potential to warm and thaw permafrost by changing the surface reflectance of solar insolation, increasing subsurface soil moisture, and increasing soil thermal conductivity. However, the impact of flooding on permafrost in the continuous permafrost environment remains poorly understood. To address this knowledge gap, we used a combination of available flooding data on the Ikpikpuk delta and a numerical model to simulate the hydro-thermal processes under coastal floodplain flooding. We first constructed the three most common flood events based on water level data on the Ikpikpuk: snowmelt floods in the late spring and early summer, middle and late summer floods, and floods throughout the whole spring and summer. Then the impact of these flooding events on the permafrost was simulated for one-dimensional permafrost columns using the Advanced Terrestrial Simulator (ATSv1.0), a fully coupled permafrost-hydrology and thermal dynamic model. Our results show that coastal floods have an important impact on coastal permafrost dynamics with a cooling effect on the surficial soil and a warming effect on the deeper soil. Cumulative flooding events over several years can cause continuous warming of the deep subsurface but cool down the surficial layer. Flood timing is a primarymore »control of the vertical extent of the permafrost thaw and the active layer deepening.

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Abstract During development, neural progenitors are temporally patterned to sequentially generate a variety of neural types. In Drosophila neural progenitors called neuroblasts, temporal patterning is regulated by cascades of Temporal Transcription Factors (TTFs). However, known TTFs were mostly identified through candidate approaches and may not be complete. In addition, many fundamental questions remain concerning the TTF cascade initiation, progression, and termination. In this work, we use single-cell RNA sequencing of Drosophila medulla neuroblasts of all ages to identify a list of previously unknown TTFs, and experimentally characterize their roles in temporal patterning and neuronal specification. Our study reveals a comprehensive temporal gene network that patterns medulla neuroblasts from start to end. Furthermore, the speed of the cascade progression is regulated by Lola transcription factors expressed in all medulla neuroblasts. Our comprehensive study of the medulla neuroblast temporal cascade illustrates mechanisms that may be conserved in the temporal patterning of neural progenitors.

The existence of quantum tricriticality and exotic phases are found in a tricritical Dicke triangle (TDT) where three cavities, each one containing an ensemble of three-level atoms, are connected to each other through the action of an artificial magnetic field. The conventional superradiant phase (SR) is connected to the normal phase through first- and second-order boundaries, with tricritical points located at the intersection of such boundaries. Apart from the SR phase, a chiral superradiant (CSR) phase is found by tuning the artificial magnetic field. This phase is characterized by a nonzero photon current and its boundary presents chiral tricritical points (CTCPs). Through the study of different critical exponents, we are able to differentiate the universality class of the CTCP and TCP from that of second-order critical points, as well as find distinctive critical behavior among the two different superradiant phases. The TDT can be implemented in various systems, including atoms in optical cavities as well as the circuit QED system, allowing the exploration of a great variety of critical manifolds.