The role of Slc7a11 in controlling extracellular and intracellular redox environments of lung fibroblasts - potential targets for intervention in aging and idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by extracellular matrix deposition by fibroblasts. Aging and oxidative stress increase the susceptibility to IPF. Redox couples, cysteine/cystine (Cys/CySS) and glutathione/glutathione disulfide (GSH/GSSG), and their redox potentials (Eh) quantify oxidative stress. Fibroblasts from old mice maintain more oxidized extracellular Eh(Cys/CySS) than young mice. Microarray shows down-regulation of Slc7a11 potentially mediates this age-related oxidation. Slc7a11 is the key component of system Xc-, an antiporter that imports CySS and exports glutamate. The first aim of this dissertation is to investigate the mechanistic link between Slc7a11 expression and extracellular Eh(Cys/CySS). The second aim is to evaluate the effects of aging on the redox states of intracellular proteins and whether Slc7a11 contributes to the age-dependent effects. The last aim is to compare SLC7A11 expression, extracellular Eh(Cys/CySS) and intracellular Eh(GSH/GSSG) between human lung fibroblasts from IPF and non-IPF donors and to explore their association with pro-fibrotic gene expression. Slc7a11 expression was manipulated by pharmacological and genetic methods. Reduced and oxidized forms of Cys residues were labelled by Iodoacetyl Tandem Mass Tags. The ratio of oxidized/reduced forms (i.e., redox state) of a Cys residue was determined by multiplexed tandem mass spectrometry. Eh(Cys/CySS) and Eh(GSH/GSSG) were more oxidized in conditioned media of old fibroblasts. Up-regulation of Slc7a11 reduced extracellular Eh(Cys/CySS) for old fibroblasts. Inhibition of GSH synthesis had no effect on the ability of cells to restore their extracellular Eh(Cys/CySS). Redox states of 151 proteins changed with aging. Slc7a11 over-expression restored redox states of 104 proteins. Ingenuity Pathway Analysis showed these 104 proteins were involved in pathways of protein translation initiation, ubiquitin-proteasome-mediated degradation and integrin-cytoskeleton-associated signaling. Slc7a11 expression was lower in IPF fibroblasts. Extracellular Eh(Cys/CySS) was more oxidized and expression of pro-fibrotic genes was higher in IPF fibroblasts. In conclusion, Slc7a11 is the key regulator of extracellular Eh(Cys/CySS). Its effects are independent of GSH synthesis. Aging results in changes of redox states of proteins involved in protein turnover and cytoskeleton dynamics. Up-regulating Slc7a11 restores changes of protein redox states due to aging. Decreased SLC7A11 might represent a susceptibility factor for developing tissue disrepair and fibrosis in IPF

DNA editing in DNA/RNA hybrids by adenosine deaminases that act on RNA.

Adenosine deaminases that act on RNA (ADARs) carry out adenosine (A) to inosine (I) editing reactions with a known requirement for duplex RNA. Here, we show that ADARs also react with DNA/RNA hybrid duplexes. Hybrid substrates are deaminated efficiently by ADAR deaminase domains at dA-C mismatches and with E to Q mutations in the base flipping loop of the enzyme. For a long, perfectly matched hybrid, deamination is more efficient with full length ADAR2 than its isolated deaminase domain. Guide RNA strands for directed DNA editing by ADAR were used to target six different 2΄-deoxyadenosines in the M13 bacteriophage ssDNA genome. DNA editing efficiencies varied depending on the sequence context of the editing site consistent with known sequence preferences for ADARs. These observations suggest the reaction within DNA/RNA hybrids may be a natural function of human ADARs. In addition, this work sets the stage for development of a new class of genome editing tools based on directed deamination of 2΄-deoxyadenosines in DNA/RNA hybrids

Cross-Cultural Emotion Recognition of Angry and Happy Face between China and Indonesia samples

Face emotion recognition have an important ability in surviving in social relations and have been a nosology of anxiety disorder The aim of this study is to test the influence of' culture between Indonesia and China sample. Participants of this study are 40 student from both countries. Two experiments have been conducted to measure the latency and the score of correct answer in recognizing of happy, neutral and angry face. This reserach found that China samples are significant more, faster andhigher score in angry face recognition

MoviePuzzle: Visual Narrative Reasoning through Multimodal Order Learning

We introduce MoviePuzzle, a novel challenge that targets visual narrative reasoning and holistic movie understanding. Despite the notable progress that has been witnessed in the realm of video understanding, most prior works fail to present tasks and models to address holistic video understanding and the innate visual narrative structures existing in long-form videos. To tackle this quandary, we put forth MoviePuzzle task that amplifies the temporal feature learning and structure learning of video models by reshuffling the shot, frame, and clip layers of movie segments in the presence of video-dialogue information. We start by establishing a carefully refined dataset based on MovieNet by dissecting movies into hierarchical layers and randomly permuting the orders. Besides benchmarking the MoviePuzzle with prior arts on movie understanding, we devise a Hierarchical Contrastive Movie Clustering (HCMC) model that considers the underlying structure and visual semantic orders for movie reordering. Specifically, through a pairwise and contrastive learning approach, we train models to predict the correct order of each layer. This equips them with the knack for deciphering the visual narrative structure of movies and handling the disorder lurking in video data. Experiments show that our approach outperforms existing state-of-the-art methods on the \MoviePuzzle benchmark, underscoring its efficacy

Tri-Modal Motion Retrieval by Learning a Joint Embedding Space

Information retrieval is an ever-evolving and crucial research domain. The substantial demand for high-quality human motion data especially in online acquirement has led to a surge in human motion research works. Prior works have mainly concentrated on dual-modality learning, such as text and motion tasks, but three-modality learning has been rarely explored. Intuitively, an extra introduced modality can enrich a model's application scenario, and more importantly, an adequate choice of the extra modality can also act as an intermediary and enhance the alignment between the other two disparate modalities. In this work, we introduce LAVIMO (LAnguage-VIdeo-MOtion alignment), a novel framework for three-modality learning integrating human-centric videos as an additional modality, thereby effectively bridging the gap between text and motion. Moreover, our approach leverages a specially designed attention mechanism to foster enhanced alignment and synergistic effects among text, video, and motion modalities. Empirically, our results on the HumanML3D and KIT-ML datasets show that LAVIMO achieves state-of-the-art performance in various motion-related cross-modal retrieval tasks, including text-to-motion, motion-to-text, video-to-motion and motion-to-video

Shuo Wen Jie Zi: Rethinking Dictionaries and Glyphs for Chinese Language Pre-training

We introduce CDBERT, a new learning paradigm that enhances the semantics understanding ability of the Chinese PLMs with dictionary knowledge and structure of Chinese characters. We name the two core modules of CDBERT as Shuowen and Jiezi, where Shuowen refers to the process of retrieving the most appropriate meaning from Chinese dictionaries and Jiezi refers to the process of enhancing characters' glyph representations with structure understanding. To facilitate dictionary understanding, we propose three pre-training tasks, i.e., Masked Entry Modeling, Contrastive Learning for Synonym and Antonym, and Example Learning. We evaluate our method on both modern Chinese understanding benchmark CLUE and ancient Chinese benchmark CCLUE. Moreover, we propose a new polysemy discrimination task PolyMRC based on the collected dictionary of ancient Chinese. Our paradigm demonstrates consistent improvements on previous Chinese PLMs across all tasks. Moreover, our approach yields significant boosting on few-shot setting of ancient Chinese understanding.Comment: To appear at ACL 2023 Finding

Towards the Transferable Audio Adversarial Attack via Ensemble Methods

In recent years, deep learning (DL) models have achieved significant progress in many domains, such as autonomous driving, facial recognition, and speech recognition. However, the vulnerability of deep learning models to adversarial attacks has raised serious concerns in the community because of their insufficient robustness and generalization. Also, transferable attacks have become a prominent method for black-box attacks. In this work, we explore the potential factors that impact adversarial examples (AEs) transferability in DL-based speech recognition. We also discuss the vulnerability of different DL systems and the irregular nature of decision boundaries. Our results show a remarkable difference in the transferability of AEs between speech and images, with the data relevance being low in images but opposite in speech recognition. Motivated by dropout-based ensemble approaches, we propose random gradient ensembles and dynamic gradient-weighted ensembles, and we evaluate the impact of ensembles on the transferability of AEs. The results show that the AEs created by both approaches are valid for transfer to the black box API.Comment: Submitted to Cybersecurity journal 202