779 research outputs found

    Teaching Text-to-Image Models to Communicate in Dialog

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    A picture is worth a thousand words, thus, it is crucial for conversational agents to understand, perceive, and effectively respond with pictures. However, we find that directly employing conventional image generation techniques is inadequate for conversational agents to produce image responses effectively. In this paper, we focus on the innovative dialog-to-image generation task, where the model synthesizes a high-resolution image aligned with the given dialog context as a response. To tackle this problem, we design a tailored fine-tuning approach on the top of state-of-the-art text-to-image generation models to fully exploit the structural and semantic features in dialog context during image generation. Concretely, we linearize the dialog context with specific indicators to maintain the dialog structure, and employ in-domain data to alleviate the style mismatch between dialog-to-image and conventional image generation tasks. Empirical results on PhotoChat and MMDialog Corpus show that our approach brings consistent and remarkable improvement with 3 state-of-the-art pre-trained text-to-image generation backbones.Comment: Work in progres

    ROS from menadione induces astrocytic damage: protective effects of apocynin

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    Abstract only availableOxidative stress is a core cause of neurodegenerative diseases such as Alzheimer's disease. When cells are under oxidative stress, they will produce a high amount of reactive oxygen species (ROS). ROS are small and highly reactive and include compounds such as oxygen ions, free radicals, and peroxides. Understanding what triggers oxidative stress and how to ameliorate its damaging effects is a crucial step in discovering a cure for Alzheimer's disease. Menadione, a vitamin precursor of K2, is an oxidative compound that is capable of delivering ROS to the cells. Apocynin, a natural organic compound that has been isolated from Picrorhiza curroa grown in the Himalayan Mountains, is an inhibitor of NADPH oxidase, an enzyme for ROS production in cells. In this experiment, we studied whether apocynin may neutralize the effects of menadione using an immortalized astrocyte cell line DITNC. Astrocytes are glial cells that play a crucial role in the brain by providing necessary nutrient to surrounding neurons. We had three sample groups and treated each group with different drugs. The first group was the control, the second group was treated with menadione, and the third group was treated with both menadione and apocynin. After treating the cells, we recorded morphological changes of the cells by taking pictures of each sample group at three different time intervals (30 min, 1 and 2 hours). In addition to the morphological evidence, we also did a MTT assay to assess cell viability and later a data analysis based on the result from the MTT test. MTT assay measures mitochondrial activity and thus indirectly measures cell viability. Both morphological data and MTT analysis showed menadione caused DITNC cell damage with decreased mitochondrial activity. When cells are treated with menadione, they formed processes, shrink, and then round up. We also found apocynin protects against the oxidative damage caused by menadione to a certain extent. Since apocynin is an inhibitor of NADPH oxidase, this also indicates oxidative stress is generated by NADPH oxidase, suggesting apocynin may be a potential means to treat Alzheimer's disease.Alzheimer disease program project grant 2P01 AG018357 to G. Su

    Single-Shot Top-Down Proteomics with Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry for Identification of Nearly 600 Escherichia coli Proteoforms

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    Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry (CZE-ESI-MS/MS) has been recognized as an invaluable platform for top-down proteomics. However, the scale of top-down proteomics using CZE-MS/MS is still limited due to the low loading capacity and narrow separation window of CZE. In this work, for the first time we systematically evaluated the dynamic pH junction method for focusing of intact proteins during CZE-MS. The optimized dynamic pH junction-based CZE-MS/MS approached a 1 μL loading capacity, 90 min separation window, and high peak capacity (∼280) for characterization of an Escherichia coli proteome. The results represent the largest loading capacity and the highest peak capacity of CZE for top-down characterization of complex proteomes. Single-shot CZE-MS/MS identified about 2800 proteoform-spectrum matches, nearly 600 proteoforms, and 200 proteins from the Escherichia coli proteome with spectrum-level false discovery rate (FDR) less than 1%. The number of identified proteoforms in this work is over three times higher than that in previous single-shot CZE-MS/MS studies. Truncations, N-terminal methionine excision, signal peptide removal, and some post-translational modifications including oxidation and acetylation were detected

    Deep Top-Down Proteomics Using Capillary Zone Electrophoresis-Tandem Mass Spectrometry: Identification of 5700 Proteoforms from the Escherichia coli Proteome

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    Capillary zone electrophoresis (CZE)-tandem mass spectrometry (MS/MS) has been recognized as a useful tool for top-down proteomics. However, its performance for deep top-down proteomics is still dramatically lower than widely used reversed-phase liquid chromatography (RPLC)-MS/MS. We present an orthogonal multidimensional separation platform that couples size exclusion chromatography (SEC) and RPLC based protein prefractionation to CZE-MS/MS for deep top-down proteomics of Escherichia coli. The platform generated high peak capacity (∼4000) for separation of intact proteins, leading to the identification of 5700 proteoforms from the Escherichia coli proteome. The data represents a 10-fold improvement in the number of proteoform identifications compared with previous CZE-MS/MS studies and represents the largest bacterial top-down proteomics data set reported to date. The performance of the CZE-MS/MS based platform is comparable to the state-of-the-art RPLC-MS/MS based systems in terms of the number of proteoform identifications and the instrument time

    Genetic etiological analysis of auditory neuropathy spectrum disorder by next-generation sequencing

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    ObjectiveAuditory neuropathy spectrum disease (ANSD) is caused by both environmental and genetic causes and is defined by a failure in peripheral auditory neural transmission but normal outer hair cells function. To date, 13 genes identified as potentially causing ANSD have been documented. To study the etiology of ANSD, we collected 9 probands with ANSD diagnosed in the clinic and performed targeted next-generation sequencing.MethodsNine probands have been identified as ANSD based on the results of the ABR tests and DPOAE/CMs. Genomic DNA extracted from their peripheral blood was examined by next-generation sequencing (NGS) for a gene panel to identify any potential causal variations. For candidate pathogenic genes, we performed co-segregation among all family members of the pedigrees. Subsequently, using a mini-gene assay, we examined the function of a novel splice site mutant of OTOF.ResultsWe analyzed nine cases of patients with ANSD with normal CMs/DPOAE and abnormal ABR, discovered three novel mutants of the OTOF gene that are known to cause ANSD, and six cases of other gene mutations including TBC1D24, LARS2, TIMM8A, MITF, and WFS1.ConclusionOur results extend the mutation spectrum of the OTOF gene and indicate that the genetic etiology of ANSD may be related to gene mutations of TBC1D24, LARS2, TIMM8A, MITF, and WFS1
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