Multiscale Superpixel Structured Difference Graph Convolutional Network for VL Representation

Within the multimodal field, the key to integrating vision and language lies in establishing a good alignment strategy. Recently, benefiting from the success of self-supervised learning, significant progress has been made in multimodal semantic representation based on pre-trained models for vision and language. However, there is still room for improvement in visual semantic representation. The lack of spatial semantic coherence and vulnerability to noise makes it challenging for current pixel or patch-based methods to accurately extract complex scene boundaries. To this end, this paper develops superpixel as a comprehensive compact representation of learnable image data, which effectively reduces the number of visual primitives for subsequent processing by clustering perceptually similar pixels. To mine more precise topological relations, we propose a Multiscale Difference Graph Convolutional Network (MDGCN). It parses the entire image as a fine-to-coarse hierarchical structure of constituent visual patterns, and captures multiscale features by progressively merging adjacent superpixels as graph nodes. Moreover, we predict the differences between adjacent nodes through the graph structure, facilitating key information aggregation of graph nodes to reason actual semantic relations. Afterward, we design a multi-level fusion rule in a bottom-up manner to avoid understanding deviation by learning complementary spatial information at different regional scales. Our proposed method can be well applied to multiple downstream task learning. Extensive experiments demonstrate that our method is competitive with other state-of-the-art methods in visual reasoning. Our code will be released upon publication

A missense mutation in Pitx2 leads to early-onset glaucoma via NRF2-YAP1 axis.

Glaucoma is a leading cause of blindness, affecting 70 million people worldwide. Owing to the similarity in anatomy and physiology between human and mouse eyes and the ability to genetically manipulate mice, mouse models are an invaluable resource for studying mechanisms underlying disease phenotypes and for developing therapeutic strategies. Here, we report the discovery of a new mouse model of early-onset glaucoma that bears a transversion substitution c. G344T, which results in a missense mutation, p. R115L in PITX2. The mutation causes an elevation in intraocular pressure (IOP) and progressive death of retinal ganglion cells (RGC). These ocular phenotypes recapitulate features of pathologies observed in human glaucoma. Increased oxidative stress was evident in the inner retina. We demonstrate that the mutant PITX2 protein was not capable of binding to Nuclear factor-like 2 (NRF2), which regulates Pitx2 expression and nuclear localization, and to YAP1, which is necessary for co-initiation of transcription of downstream targets. PITX2-mediated transcription of several antioxidant genes were also impaired. Treatment with N-Acetyl-L-cysteine exerted a profound neuroprotective effect on glaucoma-associated neuropathies, presumably through inhibition of oxidative stress. Our study demonstrates that a disruption of PITX2 leads to glaucoma optic pathogenesis and provides a novel early-onset glaucoma model that will enable elucidation of mechanisms underlying the disease as well as to serve as a resource to test new therapeutic strategies

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Understanding the effects of physical experience and information integration on consumer use of online to offline commerce

Online to Offline (O2O) commerce commands intense attention from both academic and practical fields, but the unique features of O2O commerce and how these features affect consumer use of O2O commerce remain unclear. Based on an analysis of the features of O2O commerce, we build a research model integrating perceived value theory and the technology acceptance model to examine the influence of the features of O2O commerce on consumer use intention. The research model is tested with data collected from a field survey using structural equation modelling. Two crucial features of O2O commerce, namely, “physical experience” and “integration of online and offline information”, are shown to exert significant impacts on consumer use intention via the classic core constructs of perceived benefit, perceived usefulness, and perceived value. The findings validate the two features’ impact on consumer use of O2O commerce via both technological and economic attributes. The implications for merchants’ and platforms’ operation in O2O commerce are discussed

What Drives Online-to-Offline Commerce: From a Perspective of Consumer

The online-to-offline (O2O) commerce has been one of the hottest topics nowadays, but which features of the O2O commerce drive the consumers to be involved into are still blur. To figure out the question, two important features of O2O commerce, i.e., offline experience and the integration of online and offline information, were incorporated into an empirical model to examine their influences on the technology and economics attributes of O2O commerce from the perspective of consumers. The two features were confirmed to exert significant impacts on consumer’s acceptance of O2O commerce. Finally, the implication and the direction of future study were discussed

Three-Party Password Authentication and Key Exchange Protocol Based on MLWE

With the rapid development of quantum theory, the discrete logarithm problem and significant integer factorization problem have polynomial solution algorithms under quantum computing, and their security is seriously threatened. Therefore, a three-party password-authenticated key agreement scheme based on module learning with errors problem was proposed, and its security was proved in the BPR model. Compared with other password-authenticated key agreement protocols, the proposed protocol has higher efficiency and a shorter key length, which can resist quantum attacks. Therefore, the protocol is efficient and secure and suitable for large-scale network communication

A Novel Virus Capable of Intelligent Program Infection through Software Framework Function Recognition

Viruses are one of the main threats to the security of today’s cyberspace. With the continuous development of virus and artificial intelligence technologies in recent years, the intelligentization of virus technology has become a trend. It is of urgent significance to study and combat intelligent viruses. In this paper, we design a new type of confirmatory virus from the attacker’s perspective that can intelligently infect software frameworks. We aim for structural software as the target and use BCSD (binary code similarity detection) to identify the framework. By incorporating a software framework functional structure recognition model in the virus, the virus is enabled to intelligently recognize software framework functions in executable files. This paper evaluates the BCSD model that is suitable for a virus to carry and constructs a lightweight BCSD model with a knowledge distillation technique. This research proposes a software framework functional structure recognition algorithm, which effectively reduces the recognition precision’s dependence on the BCSD model. Finally, this study discusses the next researching direction of intelligent viruses. This paper aims to provide a reference for the research of detection technology for possible intelligent viruses. Consequently, focused and effective defense strategies could be proposed and the technical system of malware detection could be reinforced

Targeted Next-Generation Sequencing Reveals Novel RP1 Mutations in Autosomal Recessive Retinitis Pigmentosa

Background: Retinitis pigmentosa (RP) is a group of rare inherited retinal dystrophies that result in a progressive loss of vision. Molecular diagnosis of RP is difficult due to its phenotypic and genetic heterogeneities. Aims: To investigate causative genetic mutations in a collection of RP cases: one Indian and two Chinese families with autosomal-recessive RP and two sporadic patients with RP. Materials and Methods: A total of 163 genes, which have previously been found to be involved in inherited retinal disorders, were selected for targeted next-generation sequencing (NGS). Stringent NGS data analyses followed by confirmation using Sanger sequencing and segregation analyses were applied to evaluate all identified pathogenic mutations. Results: Four novel frameshift mutations and two compound heterozygous mutations were identified in RP1. In addition, all mutations were found to co-segregate with the disease in the three familial cases; none of the mutations were detected in control samples. Conclusion: This study expands the mutational spectrums of RP1 for RP

Disease Mutation Study Identifies Critical Residues for Phosphatidylserine Flippase ATP11A

Phosphatidylserine flippase (P4-ATPase) transports PS from the outer to the inner leaflet of the lipid bilayer in the membrane to maintain PS asymmetry, which is important for biological activities of the cell. ATP11A is expressed in multiple tissues and plays a role in myotube formation. However, the detailed cellular function of ATP11A remains elusive. Mutation analysis revealed that I91, L308, and E897 residues in ATP8A2 are important for flippase activity. In order to investigate the roles of these corresponding amino acid residues in ATP11A protein, we assessed the expression and cellular localization of the respective ATP11A mutant proteins. ATP11A mainly localizes to the Golgi and plasma membrane when coexpressed with the β-subunit of the complex TMEM30A. Y300F mutation causes reduced ATP11A expression, and Y300F and D913K mutations affect correct localization of the Golgi and plasma membrane. In addition, Y300F and D913K mutations also affect PS flippase activity. Our data provides insight into important residues of ATP11A

Targeted Next-Generation Sequencing Reveals a Novel Frameshift Mutation in the MERTK Gene in a Chinese Family with Retinitis Pigmentosa

Background: Retinitis pigmentosa (RP) is a group of inherited retinal diseases that result in severe progressive visual impairment. Aims: The purpose of this article was to apply targeted next-generation sequencing (NGS) to identify the causative mutation in a Chinese RP family. Methods: Blood samples were collected from a Chinese proband diagnosed with RP and her family members. A total of 163 genes that have been previously found to be involved in inherited retinal diseases were selected for NGS. Rigorous NGS data analysis; Sanger sequencing validation; and segregation analysis were applied to evaluate a novel frameshift mutation. Results: Sequence analysis revealed that the proband and her affected sister both carried a novel homozygous frameshift mutation in MERTK (p.I103Nfs*4). Other family members carrying a heterozygous mutation were unaffected. This mutation was found to cosegregate with the disease phenotype in this family. This mutation was not found in 1,000 control individuals. Conclusions: The targeted NGS strategy employed provides an efficient tool for RP pathogenic gene detection. This study identified a new autosomal recessive mutation in the RP-related gene MERTK, which expands the spectrum of RP disease-causing mutations