Efficient XAI Techniques: A Taxonomic Survey

Recently, there has been a growing demand for the deployment of Explainable Artificial Intelligence (XAI) algorithms in real-world applications. However, traditional XAI methods typically suffer from a high computational complexity problem, which discourages the deployment of real-time systems to meet the time-demanding requirements of real-world scenarios. Although many approaches have been proposed to improve the efficiency of XAI methods, a comprehensive understanding of the achievements and challenges is still needed. To this end, in this paper we provide a review of efficient XAI. Specifically, we categorize existing techniques of XAI acceleration into efficient non-amortized and efficient amortized methods. The efficient non-amortized methods focus on data-centric or model-centric acceleration upon each individual instance. In contrast, amortized methods focus on learning a unified distribution of model explanations, following the predictive, generative, or reinforcement frameworks, to rapidly derive multiple model explanations. We also analyze the limitations of an efficient XAI pipeline from the perspectives of the training phase, the deployment phase, and the use scenarios. Finally, we summarize the challenges of deploying XAI acceleration methods to real-world scenarios, overcoming the trade-off between faithfulness and efficiency, and the selection of different acceleration methods.Comment: 15 pages, 3 figure

Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies

Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system

Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

<i>In vitro</i> antiviral activity of the anti-HCV drugs daclatasvir and sofosbuvir against SARS-CoV-2, the aetiological agent of COVID-19

BackgroundCurrent approaches of drug repurposing against COVID-19 have not proven overwhelmingly successful and the SARS-CoV-2 pandemic continues to cause major global mortality. SARS-CoV-2 nsp12, its RNA polymerase, shares homology in the nucleotide uptake channel with the HCV orthologue enzyme NS5B. Besides, HCV enzyme NS5A has pleiotropic activities, such as RNA binding, that are shared with various SARS-CoV-2 proteins. Thus, anti-HCV NS5B and NS5A inhibitors, like sofosbuvir and daclatasvir, respectively, could be endowed with anti-SARS-CoV-2 activity.MethodsSARS-CoV-2-infected Vero cells, HuH-7 cells, Calu-3 cells, neural stem cells and monocytes were used to investigate the effects of daclatasvir and sofosbuvir. In silico and cell-free based assays were performed with SARS-CoV-2 RNA and nsp12 to better comprehend the mechanism of inhibition of the investigated compounds. A physiologically based pharmacokinetic model was generated to estimate daclatasvir's dose and schedule to maximize the probability of success for COVID-19.ResultsDaclatasvir inhibited SARS-CoV-2 replication in Vero, HuH-7 and Calu-3 cells, with potencies of 0.8, 0.6 and 1.1 μM, respectively. Although less potent than daclatasvir, sofosbuvir alone and combined with daclatasvir inhibited replication in Calu-3 cells. Sofosbuvir and daclatasvir prevented virus-induced neuronal apoptosis and release of cytokine storm-related inflammatory mediators, respectively. Sofosbuvir inhibited RNA synthesis by chain termination and daclatasvir targeted the folding of secondary RNA structures in the SARS-CoV-2 genome. Concentrations required for partial daclatasvir in vitro activity are achieved in plasma at Cmax after administration of the approved dose to humans.ConclusionsDaclatasvir, alone or in combination with sofosbuvir, at higher doses than used against HCV, may be further fostered as an anti-COVID-19 therapy

Identification of SARS-CoV-2 Polymerase and Exonuclease Inhibitors and Novel Methods for Single-Color Fluorescent DNA Sequencing by Synthesis

This dissertation is divided into two main sections describing major portions of my Ph.D. research: (1) development of two enzymatic assays for identifying inhibitors of SARS-CoV-2 RNA dependent RNA polymerase (RdRp) and the associated proofreading exonuclease complexes, two key enzymatic activities of SARS-CoV-2, the virus responsible for the COVID-19 pandemic and (2) the design and implementation of four novel single-color fluorescent DNA sequencing by synthesis (SBS) methods, including the synthesis of many of the key nucleotide analogues required for these studies. In response to the COVID-19 pandemic, the first part of my research is focused on the discovery of potential therapeutics for combating coronavirus infections. Chapter 1 describes the identification of several polymerase and exonuclease inhibitors for SARS-CoV-2 using novel mass spectrometry-based molecular assays. SARS-CoV-2 has an exonuclease complex, which removes nucleotide inhibitors such as Remdesivir that are incorporated into the viral RNA during replication, reducing the efficacy of these drugs for treating COVID-19. Combinations of inhibitors of both the viral RdRp and the exonuclease could overcome this deficiency. Chapter 1 reports the identification of hepatitis C virus NS5A inhibitors Pibrentasvir and Ombitasvir as SARS-CoV-2 exonuclease inhibitors. In the presence of identified exonuclease inhibitors, RNAs terminated with the active forms of the prodrugs like Sofosbuvir, Remdesivir and Favipiravir were largely protected from excision by the exonuclease, while in the absence of exonuclease inhibitors, there was rapid excision. Viral cell culture studies also demonstrate significant synergy using this combination strategy. This study supports the use of combination drugs that inhibit both the SARS-CoV-2 polymerase and exonuclease for effective COVID-19 treatment. Chapters 2-6 describe the single-color DNA SBS studies. Chapter 2 provides essential background on the structure of DNA, the DNA polymerase reaction, and several key DNA sequencing technologies, with an emphasis on the design of nucleotide analogues for the DNA SBS approach. Chapter 3 delineates a one-color fluorescent DNA SBS method based on a set of nucleotide reversible terminators (NRTs) comprising two orthogonal cleavable linkers, one fluorescent dye and one anchor. Chapter 4 describes a one-color hybrid DNA sequencing approach using a set of dideoxynucleotide analogues bearing two orthogonal cleavable linkers, one fluorophore and one anchor as well as a set of unlabeled NRTs. By introducing a pH responsive fluorophore into the design of nucleotide analogues, Chapter 5 demonstrates a novel type of single-color DNA SBS method using a set of NRTs comprising one pH-responsive fluorescent dye or one non-responsive fluorescent dye tethered with one cleavable linker. Chapter 6 presents another option for the single-color DNA sequencing technique using a set of deoxynucleotide analogues comprising the above pH responsive or non-responsive dyes tethered with a cleavable linker, along with a set of unlabeled NRTs. The one-color SBS approaches have the potential for higher sensitivity, miniaturization and cost effectiveness compared with four-color SBS methods. Finally, Chapter 7 summarizes the SARS-CoV-2 antiviral drug discovery and one-color sequencing techniques and discusses potential follow-up research on these projects

Impacts of Urban Spatial Development Patterns on Carbon Emissions: Evidence from Chinese Cities

A rational urban spatial development pattern is necessary for China to optimize urban resource allocation and promote low-carbon urban development. Although research on carbon emission reduction has increased, few studies examine the impact of urban spatial development patterns from a spatial–structural perspective. This study uses static and dynamic spatial Durbin models to analyze the dynamic impact of urban spatial development patterns on carbon emissions based on municipal-level statistical data and LandScan high-resolution global population distribution data from 2004 to 2019. The empirical results show that (1) urban spatial development patterns characterized by coefficients of variation have an inverted U-shaped relationship with carbon emissions; (2) direct spatial spillover effects have a long-term U-shaped relationship, while indirect effects have an inverted U-shaped relationship; (3) by analyzing the heterogeneity of city sizes and geographical area, the smaller the city is, the more effectively the compact urban spatial development pattern reduces carbon emissions; and (4) compact urban spatial development patterns in the west suppress carbon emissions compared to the east and central regions. The findings of this paper have policy implications for optimizing spatial development patterns and achieving low-carbon development in Chinese cities

Impacts of Urban Spatial Development Patterns on Carbon Emissions: Evidence from Chinese Cities

A rational urban spatial development pattern is necessary for China to optimize urban resource allocation and promote low-carbon urban development. Although research on carbon emission reduction has increased, few studies examine the impact of urban spatial development patterns from a spatial&ndash;structural perspective. This study uses static and dynamic spatial Durbin models to analyze the dynamic impact of urban spatial development patterns on carbon emissions based on municipal-level statistical data and LandScan high-resolution global population distribution data from 2004 to 2019. The empirical results show that (1) urban spatial development patterns characterized by coefficients of variation have an inverted U-shaped relationship with carbon emissions; (2) direct spatial spillover effects have a long-term U-shaped relationship, while indirect effects have an inverted U-shaped relationship; (3) by analyzing the heterogeneity of city sizes and geographical area, the smaller the city is, the more effectively the compact urban spatial development pattern reduces carbon emissions; and (4) compact urban spatial development patterns in the west suppress carbon emissions compared to the east and central regions. The findings of this paper have policy implications for optimizing spatial development patterns and achieving low-carbon development in Chinese cities

Investigation of the Deformation Failure Occurring When Extracting Minerals via Underground Mining: A Case Study

Metal mines mined using the sublevel caving method often exhibit various environmental problems on the ground surface. This can affect the safety of the production process in the mining area. A numerical model using Universal Distinct Element Code has been established to investigate deformation failure giving rise to this underground mining. The calculations are combined with in-situ monitoring data collected over a period of 10 years. The results indicate that the strata movement in the footwall can be divided into two stages: an arch caving development stage and post arch caving development stage. Mining disturbance is the main cause of caving in the arch caving development stage. The overlying strata experience &lsquo;caving&ndash;stability&ndash;caving&rsquo;, leading to the formation of an &lsquo;arch-shaped&rsquo; caving pattern. In the post arch caving development stage, flexural-toppling deformation occurs in the strata in the direction of the collapse pit due to the tectonic stress present and high dip angles of the discontinuities. Through-going failure surface has been analyzed by studying the plastic state and displacement of elements. The formation of through-going failure surface is related to the flexural-toppling deformation and stress concentration caused by mining activities. Based on the different failure mechanisms, an efficient partition has been proposed such that the footwall can be divided into a stable zone, flexural-toppling failure zone, compression and slipping-toppling failure zone, and shear-slipping failure zone. The results are a useful reference when applied to the Chengchao Iron Mine and other similar metal mines