Three-dimensional fluorescent microscopy via simultaneous illumination and detection at multiple planes.

The conventional optical microscope is an inherently two-dimensional (2D) imaging tool. The objective lens, eyepiece and image sensor are all designed to capture light emitted from a 2D 'object plane'. Existing technologies, such as confocal or light sheet fluorescence microscopy have to utilize mechanical scanning, a time-multiplexing process, to capture a 3D image. In this paper, we present a 3D optical microscopy method based upon simultaneously illuminating and detecting multiple focal planes. This is implemented by adding two diffractive optical elements to modify the illumination and detection optics. We demonstrate that the image quality of this technique is comparable to conventional light sheet fluorescent microscopy with the advantage of the simultaneous imaging of multiple axial planes and reduced number of scans required to image the whole sample volume

Generalization Beyond Feature Alignment: Concept Activation-Guided Contrastive Learning

Learning invariant representations via contrastive learning has seen state-of-the-art performance in domain generalization (DG). Despite such success, in this paper, we find that its core learning strategy -- feature alignment -- could heavily hinder model generalization. Drawing insights in neuron interpretability, we characterize this problem from a neuron activation view. Specifically, by treating feature elements as neuron activation states, we show that conventional alignment methods tend to deteriorate the diversity of learned invariant features, as they indiscriminately minimize all neuron activation differences. This instead ignores rich relations among neurons -- many of them often identify the same visual concepts despite differing activation patterns. With this finding, we present a simple yet effective approach, Concept Contrast (CoCo), which relaxes element-wise feature alignments by contrasting high-level concepts encoded in neurons. Our CoCo performs in a plug-and-play fashion, thus it can be integrated into any contrastive method in DG. We evaluate CoCo over four canonical contrastive methods, showing that CoCo promotes the diversity of feature representations and consistently improves model generalization capability. By decoupling this success through neuron coverage analysis, we further find that CoCo potentially invokes more meaningful neurons during training, thereby improving model learning

Neuron Coverage-Guided Domain Generalization

This paper focuses on the domain generalization task where domain knowledge is unavailable, and even worse, only samples from a single domain can be utilized during training. Our motivation originates from the recent progresses in deep neural network (DNN) testing, which has shown that maximizing neuron coverage of DNN can help to explore possible defects of DNN (i.e., misclassification). More specifically, by treating the DNN as a program and each neuron as a functional point of the code, during the network training we aim to improve the generalization capability by maximizing the neuron coverage of DNN with the gradient similarity regularization between the original and augmented samples. As such, the decision behavior of the DNN is optimized, avoiding the arbitrary neurons that are deleterious for the unseen samples, and leading to the trained DNN that can be better generalized to out-of-distribution samples. Extensive studies on various domain generalization tasks based on both single and multiple domain(s) setting demonstrate the effectiveness of our proposed approach compared with state-of-the-art baseline methods. We also analyze our method by conducting visualization based on network dissection. The results further provide useful evidence on the rationality and effectiveness of our approach

Cross-Lingual Adaptation for Type Inference

Deep learning-based techniques have been widely applied to the program analysis tasks, in fields such as type inference, fault localization, and code summarization. Hitherto deep learning-based software engineering systems rely thoroughly on supervised learning approaches, which require laborious manual effort to collect and label a prohibitively large amount of data. However, most Turing-complete imperative languages share similar control- and data-flow structures, which make it possible to transfer knowledge learned from one language to another. In this paper, we propose cross-lingual adaptation of program analysis, which allows us to leverage prior knowledge learned from the labeled dataset of one language and transfer it to the others. Specifically, we implemented a cross-lingual adaptation framework, PLATO, to transfer a deep learning-based type inference procedure across weakly typed languages, e.g., Python to JavaScript and vice versa. PLATO incorporates a novel joint graph kernelized attention based on abstract syntax tree and control flow graph, and applies anchor word augmentation across different languages. Besides, by leveraging data from strongly typed languages, PLATO improves the perplexity of the backbone cross-programming-language model and the performance of downstream cross-lingual transfer for type inference. Experimental results illustrate that our framework significantly improves the transferability over the baseline method by a large margin

Neuron Activation Coverage: Rethinking Out-of-distribution Detection and Generalization

The out-of-distribution (OOD) problem generally arises when neural networks encounter data that significantly deviates from the training data distribution, i.e., in-distribution (InD). In this paper, we study the OOD problem from a neuron activation view. We first formulate neuron activation states by considering both the neuron output and its influence on model decisions. Then, to characterize the relationship between neurons and OOD issues, we introduce the \textit{neuron activation coverage} (NAC) -- a simple measure for neuron behaviors under InD data. Leveraging our NAC, we show that 1) InD and OOD inputs can be largely separated based on the neuron behavior, which significantly eases the OOD detection problem and beats the 21 previous methods over three benchmarks (CIFAR-10, CIFAR-100, and ImageNet-1K). 2) a positive correlation between NAC and model generalization ability consistently holds across architectures and datasets, which enables a NAC-based criterion for evaluating model robustness. Compared to prevalent InD validation criteria, we show that NAC not only can select more robust models, but also has a stronger correlation with OOD test performance.Comment: 28 pages, 9 figures, 20 table

Rethinking Sensors Modeling: Hierarchical Information Enhanced Traffic Forecasting

With the acceleration of urbanization, traffic forecasting has become an essential role in smart city construction. In the context of spatio-temporal prediction, the key lies in how to model the dependencies of sensors. However, existing works basically only consider the micro relationships between sensors, where the sensors are treated equally, and their macroscopic dependencies are neglected. In this paper, we argue to rethink the sensor's dependency modeling from two hierarchies: regional and global perspectives. Particularly, we merge original sensors with high intra-region correlation as a region node to preserve the inter-region dependency. Then, we generate representative and common spatio-temporal patterns as global nodes to reflect a global dependency between sensors and provide auxiliary information for spatio-temporal dependency learning. In pursuit of the generality and reality of node representations, we incorporate a Meta GCN to calibrate the regional and global nodes in the physical data space. Furthermore, we devise the cross-hierarchy graph convolution to propagate information from different hierarchies. In a nutshell, we propose a Hierarchical Information Enhanced Spatio-Temporal prediction method, HIEST, to create and utilize the regional dependency and common spatio-temporal patterns. Extensive experiments have verified the leading performance of our HIEST against state-of-the-art baselines. We publicize the code to ease reproducibility.Comment: 9 pages, accepted by CIKM'2

Assessing r2SCAN meta-GGA functional for structural parameters, cohesive energy, mechanical modulus and thermophysical properties of 3d, 4d and 5d transition metals

The recent development of the accurate and efficient semilocal density functionals on the third rung of Jacob's ladder of density functional theory such as the revised regularized strongly constrained and appropriately normed (r2SCAN) density functional could enable the rapid and highly reliable prediction of the elasticity and temperature dependence of thermophysical parameters of refractory elements and their intermetallic compounds using quasi-harmonic approximation (QHA). Here, we present a comparative evaluation of the equilibrium cell volumes, cohesive energy, mechanical moduli, and thermophysical properties (Debye temperature and thermal expansion coefficient) for 22 transition metals using semilocal density functionals, including local density approximation (LDA), the Perdew-Burke-Ernzerhof (PBE) and PBEsol generalized gradient approximations (GGA), and the r2SCAN meta-GGA. PBEsol and r2SCAN deliver the same level of accuracies for structural, mechanical and thermophysical properties. Otherwise, PBE and r2SCAN perform better than LDA and PBEsol for calculating cohesive energies of transition metals. Among the tested density functionals, r2SCAN provides an overall well-balanced performance for reliably computing the cell volumes, cohesive energies, mechanical properties, and thermophysical properties of various 3d, 4d, and 5d transition metals using QHA. Therefore, we recommend that r2SCAN could be employed as a workhorse method to evaluate the thermophysical properties of transition metal compounds and alloys in the high throughput workflows

In Silico Discovery of JMJD6 Inhibitors for Cancer Treatment.

The 2-oxoglutarate (2OG)-dependent oxygenase JMJD6 is emerging as a potential anticancer target, but its inhibitors have not been reported so far. In this study, we reported an in silico protocol to discover JMJD6 inhibitors targeting the druggable 2OG-binding site. Following this protocol, one compound, which we named as WL12, was found to be able to inhibit JMJD6 enzymatic activity and JMJD6-dependent cell proliferation. To our best knowledge, this is the first case in drug discovery targeting JMJD6

Atorvastatin attenuates ferroptosis-dependent myocardial injury and inflammation following coronary microembolization via the Hif1a/Ptgs2 pathway

Objectives: Coronary microembolization (CME) represents a serious periprocedural complication after percutaneous coronary intervention. Ferroptosis has been identified in multiple cardiovascular diseases. In this study, we aimed to investigate the effects of atorvastatin (ATV) on ferroptosis and inflammation following CME and elucidate the underlying mechanism.Methods: We established a rat model of CME by injecting microspheres into the left ventricle. Deferoxamine (DFO), a selective ferroptosis inhibitor, or ATV was pretreated before modeling. Cardiac function and cardiac troponin T (cTnT) levels were detected. Levels of ferroptosis-associated genes, malondialdehyde (MDA), glutathione (GSH), and ferrous iron (Fe2+) were measured to validate ferroptosis. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) were assayed to determine the inflammation. Chromatin immunoprecipitation was performed to determine the binding of hypoxia-inducible factor 1 subunit alpha (Hif1a) to the promoter of prostaglandin-endoperoxide synthase-2 (Ptgs2).Results: Ferroptosis and inflammation were induced following CME with increased levels of MDA (∼2.5 fold, p < 0.01), Fe2+ (∼1.5 fold, p < 0.01), TNF-α, and IL-1β and decreased GSH levels (∼42%, p < 0.01). Meanwhile, the level of Ptgs2 was significantly increased, while those of glutathione peroxidase 4 (Gpx4) and solute carrier family 7 member 11 (Slc7a11) were decreased. The level of cTnT was increased by 7-fold (p < 0.01). Left ventricular ejection fraction (LVEF) was significantly reduced (∼85% in the sham group versus ∼45% in the CME group, p < 0.01). DFO or Ptgs2 silencing inhibited the increase of MDA, Ptgs2, TNF-α, and IL-1β, and induced the levels of GSH and Gpx4, followed by reduction in cTnT levels by approximately 50% (p < 0.01). LVEF was improved by approximately 2 fold (p < 0.01). Mechanistically, the transcription factor Hif1a bound to the promoter of Ptgs2 and upregulated its expression. In addition, ATV inhibited the activation of the Hif1a/Ptgs2 axis and attenuated cardiac ferroptosis and inflammation, thus ameliorating CME-induced myocardial injury (LVEF, ∼34% elevation; cTnT, ∼1.8 fold decrease, p < 0.01).Conclusion: Atorvastatin ameliorates ferroptosis-mediated myocardial injury and inflammation following CME via the Hif1a/Ptgs2 pathway