386 research outputs found

    Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids.

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    During gastrulation, the pluripotent epiblast self-organizes into the 3 germ layers-endoderm, mesoderm and ectoderm, which eventually form the entire embryo. Decades of research in the mouse embryo have revealed that a signaling cascade involving the Bone Morphogenic Protein (BMP), WNT, and NODAL pathways is necessary for gastrulation. In vivo, WNT and NODAL ligands are expressed near the site of gastrulation in the posterior of the embryo, and knockout of these ligands leads to a failure to gastrulate. These data have led to the prevailing view that a signaling gradient in WNT and NODAL underlies patterning during gastrulation; however, the activities of these pathways in space and time have never been directly observed. In this study, we quantify BMP, WNT, and NODAL signaling dynamics in an in vitro model of human gastrulation. Our data suggest that BMP signaling initiates waves of WNT and NODAL signaling activity that move toward the colony center at a constant rate. Using a simple mathematical model, we show that this wave-like behavior is inconsistent with a reaction-diffusion-based Turing system, indicating that there is no stable signaling gradient of WNT/NODAL. Instead, the final signaling state is homogeneous, and spatial differences arise only from boundary effects. We further show that the durations of WNT and NODAL signaling control mesoderm differentiation, while the duration of BMP signaling controls differentiation of CDX2-positive extra-embryonic cells. The identity of these extra-embryonic cells has been controversial, and we use RNA sequencing (RNA-seq) to obtain their transcriptomes and show that they closely resemble human trophoblast cells in vivo. The domain of BMP signaling is identical to the domain of differentiation of these trophoblast-like cells; however, neither WNT nor NODAL forms a spatial pattern that maps directly to the mesodermal region, suggesting that mesoderm differentiation is controlled dynamically by the combinatorial effect of multiple signals. We synthesize our data into a mathematical model that accurately recapitulates signaling dynamics and predicts cell fate patterning upon chemical and physical perturbations. Taken together, our study shows that the dynamics of signaling events in the BMP, WNT, and NODAL cascade in the absence of a stable signaling gradient control fate patterning of human gastruloids.R01 GM126122 - NIGMS NIH HHSPublished versio

    Four field coupled dynamics for a micro resonant gas sensor

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    In a micro resonant gas sensor, the electrostatic excitation is used widely. For a micro resonant gas sensor with electrostatic excitation, four physical fields are involved. In this paper, for the micro resonant gas sensor, the four-field coupled dynamics equation is proposed. It includes mechanical force field, chemical density field, electrostatic force field, and the van der Waals force field. Using the method of multiple scales, the coupled dynamics equation is resolved. The effects of the four physical fields on the natural frequencies for the micro resonant gas sensor are investigated. Results show that the effects of the Van der Waals force on the natural frequencies of the micro resonant gas sensor depend on the mechanical parameters and the bias voltages; the sensitivity of the natural frequencies to the gas adsorption depends on the mechanical parameters, the bias voltages, and the Van der Waals force

    IP Management System

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    This study involves systematic analysis of an existing IP Management System used by the UNC School of Medicine and UNC hospital to manage their network devices. The data structure and user interface in the current system were examined in this study. The data structure was evaluated on a set of criteria such as database normalization, data integrity, and indexing, and the user interface was studied through on-site interviews with its users, designers and systems administrators. Based on these analyses, a new system was designed and implemented. This process involved system design and implementation, data cleanup and migration, testing, and application deployment in the Web environment

    Detect to Learn: Structure Learning with Attention and Decision Feedback for MIMO-OFDM Receive Processing

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    The limited over-the-air (OTA) pilot symbols in multiple-input-multiple-output orthogonal-frequency-division-multiplexing (MIMO-OFDM) systems presents a major challenge for detecting transmitted data symbols at the receiver, especially for machine learning-based approaches. While it is crucial to explore effective ways to exploit pilots, one can also take advantage of the data symbols to improve detection performance. Thus, this paper introduces an online attention-based approach, namely RC-AttStructNet-DF, that can efficiently utilize pilot symbols and be dynamically updated with the detected payload data using the decision feedback (DF) mechanism. Reservoir computing (RC) is employed in the time domain network to facilitate efficient online training. The frequency domain network adopts the novel 2D multi-head attention (MHA) module to capture the time and frequency correlations, and the structural-based StructNet to facilitate the DF mechanism. The attention loss is designed to learn the frequency domain network. The DF mechanism further enhances detection performance by dynamically tracking the channel changes through detected data symbols. The effectiveness of the RC-AttStructNet-DF approach is demonstrated through extensive experiments in MIMO-OFDM and massive MIMO-OFDM systems with different modulation orders and under various scenarios.Comment: Accepted to IEEE Transactions on Communication

    Universal Approximation of Linear Time-Invariant (LTI) Systems through RNNs: Power of Randomness in Reservoir Computing

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    Recurrent neural networks (RNNs) are known to be universal approximators of dynamic systems under fairly mild and general assumptions, making them good tools to process temporal information. However, RNNs usually suffer from the issues of vanishing and exploding gradients in the standard RNN training. Reservoir computing (RC), a special RNN where the recurrent weights are randomized and left untrained, has been introduced to overcome these issues and has demonstrated superior empirical performance in fields as diverse as natural language processing and wireless communications especially in scenarios where training samples are extremely limited. On the contrary, the theoretical grounding to support this observed performance has not been fully developed at the same pace. In this work, we show that RNNs can provide universal approximation of linear time-invariant (LTI) systems. Specifically, we show that RC can universally approximate a general LTI system. We present a clear signal processing interpretation of RC and utilize this understanding in the problem of simulating a generic LTI system through RC. Under this setup, we analytically characterize the optimal probability distribution function for generating the recurrent weights of the underlying RNN of the RC. We provide extensive numerical evaluations to validate the optimality of the derived optimum distribution of the recurrent weights of the RC for the LTI system simulation problem. Our work results in clear signal processing-based model interpretability of RC and provides theoretical explanation for the power of randomness in setting instead of training RC's recurrent weights. It further provides a complete optimum analytical characterization for the untrained recurrent weights, marking an important step towards explainable machine learning (XML) which is extremely important for applications where training samples are limited.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

    Differentially Private ERM Based on Data Perturbation

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    In this paper, after observing that different training data instances affect the machine learning model to different extents, we attempt to improve the performance of differentially private empirical risk minimization (DP-ERM) from a new perspective. Specifically, we measure the contributions of various training data instances on the final machine learning model, and select some of them to add random noise. Considering that the key of our method is to measure each data instance separately, we propose a new `Data perturbation' based (DB) paradigm for DP-ERM: adding random noise to the original training data and achieving (ϵ,δ\epsilon,\delta)-differential privacy on the final machine learning model, along with the preservation on the original data. By introducing the Influence Function (IF), we quantitatively measure the impact of the training data on the final model. Theoretical and experimental results show that our proposed DBDP-ERM paradigm enhances the model performance significantly
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