A tradeoff between enterovirus A71 particle stability and cell entry.

A central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturb this equilibrium in a non-enveloped virus, enterovirus A71 to determine its structural basis. We isolate a single-point mutation variant with increased particle thermotolerance and decreased efficiency of cell entry. Using cryo-electron microscopy and molecular dynamics simulations, we determine that the thermostable native particles have acquired an expanded conformation that results in a significant increase in protein dynamics. Examining the intermediate states of the thermostable variant reveals a potential pathway for uncoating. We propose a sequential release of the lipid pocket factor, followed by internal VP4 and ultimately the viral RNA.

Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning.

Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library of CARs containing ~2300 synthetic costimulatory domains, built from combinations of 13 signaling motifs. These CARs promoted diverse human T cell fates, which were sensitive to motif combinations and configurations. Neural networks trained to decode the combinatorial grammar of CAR signaling motifs allowed extraction of key design rules. For example, non-native combinations of motifs that bind tumor necrosis factor receptor-associated factors (TRAFs) and phospholipase C gamma 1 (PLCγ1) enhanced cytotoxicity and stemness associated with effective tumor killing. Thus, libraries built from minimal building blocks of signaling, combined with machine learning, can efficiently guide engineering of receptors with desired phenotypes.

Applied artificial intelligence in healthcare: Listening to the winds of change in a post-COVID-19 world.

This editorial article aims to highlight advances in artificial intelligence (AI) technologies in five areas: Collaborative AI, Multimodal AI, Human-Centered AI, Equitable AI, and Ethical and Value-based AI in order to cope with future complex socioeconomic and public health issues.

Predicting Epitope Candidates for SARS-CoV-2.

Epitopes are short amino acid sequences that define the antigen signature to which an antibody or T cell receptor binds. In light of the current pandemic, epitope analysis and prediction are paramount to improving serological testing and developing vaccines. In this paper, known epitope sequences from SARS-CoV, SARS-CoV-2, and other Coronaviridae were leveraged to identify additional antigen regions in 62K SARS-CoV-2 genomes. Additionally, we present epitope distribution across SARS-CoV-2 genomes, locate the most commonly found epitopes, and discuss where epitopes are located on proteins and how epitopes can be grouped into classes. The mutation density of different protein regions is presented using a big data approach. It was observed that there are 112 B cell and 279 T cell conserved epitopes between SARS-CoV-2 and SARS-CoV, with more diverse sequences found in Nucleoprotein and Spike glycoprotein.

Designing an AI-Based Virtual Try-On Web Application.

In the last few years, Augmented Reality, Virtual Reality, and Artificial Intelligence (AI) have been increasingly employed in different application domains. Among them, the retail market presents the opportunity to allow people to check the appearance of accessories, makeup, hairstyle, hair color, and clothes on themselves, exploiting virtual try-on applications. In this paper, we propose an eyewear virtual try-on experience based on a framework that leverages advanced deep learning-based computer vision techniques. The virtual try-on is performed on a 3D face reconstructed from a single input image. In designing our system, we started by studying the underlying architecture, components, and their interactions. Then, we assessed and compared existing face reconstruction approaches. To this end, we performed an extensive analysis and experiments for evaluating their design, complexity, geometry reconstruction errors, and reconstructed texture quality. The experiments allowed us to select the most suitable approach for our proposed try-on framework. Our system considers actual glasses and face sizes to provide a realistic fit estimation using a markerless approach. The user interacts with the system by using a web application optimized for desktop and mobile devices. Finally, we performed a usability study that showed an above-average score of our eyewear virtual try-on application.

A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2. While eTIP1 replication following intranasal administration is limited to the nasal cavity, its antiviral action extends non-cell-autonomously to the lungs. eTIP1 broad-spectrum antiviral effects are mediated by both local and distal type I interferon responses. Importantly, while a single eTIP1 dose protects animals from SARS-CoV-2 infection, it also stimulates production of SARS-CoV-2 neutralizing antibodies that afford long-lasting protection from SARS-CoV-2 reinfection. Thus, eTIP1 is a safe and effective broad-spectrum antiviral generating short- and long-term protection against SARS-CoV-2 and other respiratory infections in animal models.

Semi-Supervised Pipeline for Autonomous Annotation of SARS-CoV-2 Genomes.

SARS-CoV-2 genomic sequencing efforts have scaled dramatically to address the current global pandemic and aid public health. However, autonomous genome annotation of SARS-CoV-2 genes, proteins, and domains is not readily accomplished by existing methods and results in missing or incorrect sequences. To overcome this limitation, we developed a novel semi-supervised pipeline for automated gene, protein, and functional domain annotation of SARS-CoV-2 genomes that differentiates itself by not relying on the use of a single reference genome and by overcoming atypical genomic traits that challenge traditional bioinformatic methods. We analyzed an initial corpus of 66,000 SARS-CoV-2 genome sequences collected from labs across the world using our method and identified the comprehensive set of known proteins with 98.5% set membership accuracy and 99.1% accuracy in length prediction, compared to proteome references, including Replicase polyprotein 1ab (with its transcriptional slippage site). Compared to other published tools, such as Prokka (base) and VAPiD, we yielded a 6.4- and 1.8-fold increase in protein annotations. Our method generated 13,000,000 gene, protein, and domain sequences-some conserved across time and geography and others representing emerging variants. We observed 3362 non-redundant sequences per protein on average within this corpus and described key D614G and N501Y variants spatiotemporally in the initial genome corpus. For spike glycoprotein domains, we achieved greater than 97.9% sequence identity to references and characterized receptor binding domain variants. We further demonstrated the robustness and extensibility of our method on an additional 4000 variant diverse genomes containing all named variants of concern and interest as of August 2021. In this cohort, we successfully identified all keystone spike glycoprotein mutations in our predicted protein sequences with greater than 99% accuracy as well as demonstrating high accuracy of the protein and domain annotations. This work comprehensively presents the molecular targets to refine biomedical interventions for SARS-CoV-2 with a scalable, high-accuracy method to analyze newly sequenced infections as they arise.

A Smart Mirror for Emotion Monitoring in Home Environments.

Smart mirrors are devices that can display any kind of information and can interact with the user using touch and voice commands. Different kinds of smart mirrors exist: general purpose, medical, fashion, and other task specific ones. General purpose smart mirrors are suitable for home environments but the exiting ones offer similar, limited functionalities. In this paper, we present a general-purpose smart mirror that integrates several functionalities, standard and advanced, to support users in their everyday life. Among the advanced functionalities are the capabilities of detecting a person's emotions, the short- and long-term monitoring and analysis of the emotions, a double authentication protocol to preserve the privacy, and the integration of Alexa Skills to extend the applications of the smart mirrors. We exploit a deep learning technique to develop most of the smart functionalities. The effectiveness of the device is demonstrated by the performances of the implemented functionalities, and the evaluation in terms of its usability with real users.

AI-driven prediction of SARS-CoV-2 variant binding trends from atomistic simulations.

We present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy non-hydrophobic mutations with low binding affinity from those with high binding affinity. Moreover, we show high accuracy in prediction using a small subset of the simulation, therefore requiring a much shorter simulation time. We apply our algorithm to the binding between several variants of the SARS-CoV-2 spike protein and the human receptor ACE2.

Globally local: Hyper-local modeling for accurate forecast of COVID-19.

IMPORTANCE: Assumption of a well-mixed population during modeling is often erroneously made without due analysis of its validity. Ignoring the importance of the geo-spatial granularity at which the data is collected could have significant implications on the quality of forecasts and the actionable clinical recommendations that are based on it. OBJECTIVE: This paper's primary objective is to test the hypothesis that the characteristic dynamics defining the trajectory of the pandemic in a region is lost when the data is aggregated and modeled at higher geo-spatial levels. DESIGN: We use publicly available confirmed SARS-CoV-2 cases and deaths from January 1st, 2020 to August 3rd, 2020 in the United States at different geo-spatial granularities to conduct our experiments. To understand the impact of this hypothesis, the output of this study was implemented in Tampa General Hospital (TGH) to provide resource demand forecast. RESULTS: The Mean Absolute Percentage Error (MAPE) in the forecast confirmed cases can be 30% higher for modeling at the state-level than aggregating model results at the scale of counties or clusters of counties. Similarly, modeling at a state-level and crafting policy decisions based on them may not be effective - county-level forecasts made by partitioning state-level forecasts are 3x worse for confirmed cases and 20x worse for deaths relative to the same model at the county level. By leveraging these results, TGH was able to accurately allocate clinical resources to tackle COVID-19 cases, continue elective surgical procedures largely uninterrupted and avoid costly construction of overflow capacity in the first two epidemic waves. CONCLUSIONS AND RELEVANCE: Accurate forecasting at the county level requires hyper-local modeling with county resolution. State-level modeling does not accurately predict community spread in smaller sub-regions because state populations are not well mixed, resulting in large prediction errors. Actionable decisions such as deciding whether to cancel planned surgeries or construct overflow capacity require models with local specificity.

Experimental and mathematical insights on the interactions between poliovirus and a defective interfering genome.

During replication, RNA viruses accumulate genome alterations, such as mutations and deletions. The interactions between individual variants can determine the fitness of the virus population and, thus, the outcome of infection. To investigate the effects of defective interfering genomes (DI) on wild-type (WT) poliovirus replication, we developed an ordinary differential equation model, which enables exploring the parameter space of the WT and DI competition. We also experimentally examined virus and DI replication kinetics during co-infection, and used these data to infer model parameters. Our model identifies, and our experimental measurements confirm, that the efficiencies of DI genome replication and encapsidation are two most critical parameters determining the outcome of WT replication. However, an equilibrium can be established which enables WT to replicate, albeit to reduced levels.

Examining the interplay between face mask usage, asymptomatic transmission, and social distancing on the spread of COVID-19.

COVID-19's high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-based model within a closed space that approximated real-life interactions. By explicitly considering different fractions of asymptomatic individuals, as well as a realistic hypothesis of face masks protection during inhaling and exhaling, our simulations demonstrate that a synergistic use of face masks and social distancing is the most effective intervention to curb the infection spread. To control the pandemic, our models suggest that high adherence to social distance is necessary to curb the spread of the disease, and that wearing face masks provides optimal protection even if only a small portion of the population comply with social distance. Finally, the face mask effectiveness in curbing the viral spread is not reduced if a large fraction of population is asymptomatic. Our findings have important implications for policies that dictate the reopening of social gatherings.

Optimal periodic closure for minimizing risk in emerging disease outbreaks.

Without vaccines and treatments, societies must rely on non-pharmaceutical intervention strategies to control the spread of emerging diseases such as COVID-19. Though complete lockdown is epidemiologically effective, because it eliminates infectious contacts, it comes with significant costs. Several recent studies have suggested that a plausible compromise strategy for minimizing epidemic risk is periodic closure, in which populations oscillate between wide-spread social restrictions and relaxation. However, no underlying theory has been proposed to predict and explain optimal closure periods as a function of epidemiological and social parameters. In this work we develop such an analytical theory for SEIR-like model diseases, showing how characteristic closure periods emerge that minimize the total outbreak, and increase predictably with the reproductive number and incubation periods of a disease- as long as both are within predictable limits. Using our approach we demonstrate a sweet-spot effect in which optimal periodic closure is maximally effective for diseases with similar incubation and recovery periods. Our results compare well to numerical simulations, including in COVID-19 models where infectivity and recovery show significant variation.

ARC: Angle-Retaining Chromaticity diagram for color constancy error analysis.

Color constancy algorithms are typically evaluated with a statistical analysis of the recovery angular error and the reproduction angular error between the estimated and ground truth illuminants. Such analysis provides information about only the magnitude of the errors, and not about their chromatic properties. We propose an Angle-Retaining Chromaticity diagram (ARC) for the visual analysis of the estimated illuminants and the corresponding errors. We provide both quantitative and qualitative proof of the superiority of ARC in preserving angular distances compared to other chromaticity diagrams, making it possible to quantify the reproduction and recovery errors in terms of Euclidean distances on a plane. We present two case studies for the application of the ARC diagram in the visualization of the ground truth illuminants of color constancy datasets, and the visual analysis of error distributions of color constancy algorithms.

Non-random distribution of vacuoles in Schizosaccharomyces pombe.

A central question in eukaryotic cell biology asks, during cell division, how is the growth and distribution of organelles regulated to ensure each daughter cell receives an appropriate amount. For vacuoles in budding yeast, there are well described organelle-to-cell size scaling trends as well as inheritance mechanisms involving highly coordinated movements. It is unclear whether such mechanisms are necessary in the symmetrically dividing fission yeast, Schizosaccharomyces pombe, in which random partitioning may be utilized to distribute vacuoles to daughter cells. To address the increasing need for high-throughput analysis, we are augmenting existing semi-automated image processing by developing fully automated machine learning methods for locating vacuoles and segmenting fission yeast cells from brightfield and fluorescence micrographs. All strains studied show qualitative correlations in vacuole-to-cell size scaling trends, i.e. vacuole volume, surface area, and number all increase with cell size. Furthermore, increasing vacuole number was found to be a consistent mechanism for the increase in total vacuole size in the cell. Vacuoles are not distributed evenly throughout the cell with respect to available cytoplasm. Rather, vacuoles show distinct peaks in distribution close to the nucleus, and this preferential localization was confirmed in mutants in which nucleus position is perturbed. Disruption of microtubules leads to quantitative changes in both vacuole size scaling trends and distribution patterns, indicating the microtubule cytoskeleton is a key mechanism for maintaining vacuole structure.

Mapping Attenuation Determinants in Enterovirus-D68.

Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis process observed in human disease. Among the EV-D68 strains tested, strain US/MO-14-18949 caused no observable disease in this mouse model, whereas the other strains caused paralysis and death. Sequence analysis revealed several conserved genetic changes among these virus strains: nucleotide positions 107 and 648 in the 5'-untranslated region (UTR); amino acid position 88 in VP3; 1, 148, 282 and 283 in VP1; 22 in 2A; 47 in 3A. A series of chimeric and point-mutated infectious clones were constructed to identify viral elements responsible for the distinct virulence. A single amino acid change from isoleucine to valine at position 88 in VP3 attenuated neurovirulence by reducing virus replication in the brain and spinal cord of infected mice.

Annotation-free learning of plankton for classification and anomaly detection.

The acquisition of increasingly large plankton digital image datasets requires automatic methods of recognition and classification. As data size and collection speed increases, manual annotation and database representation are often bottlenecks for utilization of machine learning algorithms for taxonomic classification of plankton species in field studies. In this paper we present a novel set of algorithms to perform accurate detection and classification of plankton species with minimal supervision. Our algorithms approach the performance of existing supervised machine learning algorithms when tested on a plankton dataset generated from a custom-built lensless digital device. Similar results are obtained on a larger image dataset obtained from the Woods Hole Oceanographic Institution. Additionally, we introduce a new algorithm to perform anomaly detection on unclassified samples. Here an anomaly is defined as a significant deviation from the established classification. Our algorithms are designed to provide a new way to monitor the environment with a class of rapid online intelligent detectors.

Personalized Image Enhancement Using Neural Spline Color Transforms.

In this work we present SpliNet, a novel CNNbased method that estimates a global color transform for the enhancement of raw images. The method is designed to improve the perceived quality of the images by reproducing the ability of an expert in the field of photo editing. The transformation applied to the input image is found by a convolutional neural network specifically trained for this purpose. More precisely, the network takes as input a raw image and produces as output one set of control points for each of the three color channels. Then, the control points are interpolated with natural cubic splines and the resulting functions are globally applied to the values of the input pixels to produce the output image. Experimental results compare favorably against recent methods in the state of the art on the MIT-Adobe FiveK dataset. Furthermore, we also propose an extension of the SpliNet in which a single neural network is used to model the style of multiple reference retouchers by embedding them into a user space. The style of new users can be reproduced without retraining the network, after a quick modeling stage in which they are positioned in the user space on the basis of their preferences on a very small set of retouched images.

IVL-SYNTHSFM-v2: A synthetic dataset with exact ground truth for the evaluation of 3D reconstruction pipelines.

This article presents a dataset with 4000 synthetic images portraying five 3D models from different viewpoints under varying lighting conditions. Depth of field and motion blur have also been used to generate realistic images. For each object, 8 scenes with different combinations of lighting, depth of field and motion blur are created and images are taken from 100 points of view. Data also includes information about camera intrinsic and extrinsic calibration parameters for each image as well as the ground truth geometry of the 3D models. The images were rendered using Blender. The aim of this dataset is to allow evaluation and comparison of different solutions for 3D reconstruction of objects starting from a set of images taken under different realistic acquisition setups.