Interpreting Multivariate Shapley Interactions in DNNs

This paper aims to explain deep neural networks (DNNs) from the perspective of multivariate interactions. In this paper, we define and quantify the significance of interactions among multiple input variables of the DNN. Input variables with strong interactions usually form a coalition and reflect prototype features, which are memorized and used by the DNN for inference. We define the significance of interactions based on the Shapley value, which is designed to assign the attribution value of each input variable to the inference. We have conducted experiments with various DNNs. Experimental results have demonstrated the effectiveness of the proposed method

Single dose of morphine produced a prolonged effect on dopamine neuron activities

<p>Abstract</p> <p>Background</p> <p>Clinical observation and experimental studies have indicated that a single exposure to morphine could induce tolerance and dependence. It has become a concern in clinical antinociceptive practice. However, the underling mechanism remains unknown. This study was designed to explore the changes of dopamine (DA) neuron activities in the ventral tegmental area (VTA) by employing a spectral analysis followed single morphine treatment.</p> <p>Results</p> <p>Acute morphine treatment significantly increased not only the firing rate and firing population but also the power of slow oscillation of DA neurons in naïve rats. These changes lasted at least for 3 days following the morphine treatment. During this period of time, responses of the DA neurons to subsequent morphine challenge were diminished. We further demonstrated a transient desensitization of opiate receptors as monitored by GTPγS binding to G-proteins. The present study provided first direct evidence for the temporal changes in the VTA DA neuron activities and opiate receptors desensitization.</p> <p>Conclusion</p> <p>Prolonged VTA DA neuron activation and opiate receptors desensitization followed single morphine exposure may underlie the development of dependence and tolerance that may associate with the acute analgesic tolerance and acute addiction of morphine.</p

High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis

Objective: To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). Methods: The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. Results: P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p &lt; 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p&nbsp;=&nbsp;0.002). P4HA2 expression was significantly higher in female cases than in male cases (p&nbsp;=&nbsp;0.049) and was related to lymph node metastasis (p&nbsp;=&nbsp;0.019) and a higher TNM stage (p&nbsp;=&nbsp;0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand&nbsp;1 and cytotoxic T-lymphocyte-associated protein&nbsp;4. Conclusion: P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target

Building Interpretable Interaction Trees for Deep NLP Models

This paper proposes a method to disentangle and quantify interactions among words that are encoded inside a DNN for natural language processing. We construct a tree to encode salient interactions extracted by the DNN. Six metrics are proposed to analyze properties of interactions between constituents in a sentence. The interaction is defined based on Shapley values of words, which are considered as an unbiased estimation of word contributions to the network prediction. Our method is used to quantify word interactions encoded inside the BERT, ELMo, LSTM, CNN, and Transformer networks. Experimental results have provided a new perspective to understand these DNNs, and have demonstrated the effectiveness of our method

Investigating the influence of PFC transection and nicotine on dynamics of AMPA and NMDA receptors of VTA dopaminergic neurons

<p>Abstract</p> <p>Background</p> <p>All drugs of abuse, including nicotine, activate the mesocorticolimbic system that plays critical roles in nicotine reward and reinforcement development and triggers glutamatergic synaptic plasticity on the dopamine (DA) neurons in the ventral tegmental area (VTA). The addictive behavior and firing pattern of the VTA DA neurons are thought to be controlled by the glutamatergic synaptic input from prefrontal cortex (PFC). Interrupted functional input from PFC to VTA was shown to decrease the effects of the drug on the addiction process. Nicotine treatment could enhance the AMPA/NMDA ratio in VTA DA neurons, which is thought as a common addiction mechanism. In this study, we investigate whether or not the lack of glutamate transmission from PFC to VTA could make any change in the effects of nicotine.</p> <p>Methods</p> <p>We used the traditional AMPA/NMDA peak ratio, AMPA/NMDA area ratio, and KL (Kullback-Leibler) divergence analysis method for the present study.</p> <p>Results</p> <p>Our results using AMPA/NMDA peak ratio showed insignificant difference between PFC intact and transected and treated with saline. However, using AMPA/NMDA area ratio and KL divergence method, we observed a significant difference when PFC is interrupted with saline treatment. One possible reason for the significant effect that the PFC transection has on the synaptic responses (as indicated by the AMPA/NMDA area ratio and KL divergence) may be the loss of glutamatergic inputs. The glutamatergic input is one of the most important factors that contribute to the peak ratio level.</p> <p>Conclusions</p> <p>Our results suggested that even within one hour after a single nicotine injection, the peak ratio of AMPA/NMDA on VTA DA neurons could be enhanced.</p

Possible Generation Mechanism for Compressional Alfv\'enic Spikes as Observed by Parker Solar Probe

The solar wind is found by Parker Solar Probe (PSP) to be abundant with Alfv\'enic velocity spikes and magnetic field kinks. Temperature enhancement is another remarkable feature associated with the Alfv\'enic spikes. How the prototype of these coincident phenomena is generated intermittently in the source region becomes a hot topic of wide concerns. Here we propose a new model introducing guide-field discontinuity into the interchange magnetic reconnection between open funnels and closed loops with different magnetic helicities. The modified interchange reconnection model not only can accelerate jet flows from the newly opening closed loop but also excite and launch Alfv\'enic wave pulses along the newly-reconnected and post-reconnected open flux tubes. We find that the modeling results can reproduce the following observational features: (1) Alfv\'en disturbance is pulsive in time and asymmetric in space; (2) Alfv\'enic pulse is compressible with temperature enhancement and density variation inside the pulse. We point out that three physical processes co-happening with Alfv\'en wave propagation can be responsible for the temperature enhancement: (a) convection of heated jet flow plasmas (decrease in density), (b) propagation of compressed slow-mode waves (increase in density), and (c) conduction of heat flux (weak change in density). We also suggest that the radial nonlinear evolution of the Alfv\'enic pulses should be taken into account to explain the formation of magnetic switchback geometry