179 research outputs found

    High-Resolution Convolutional Neural Networks on Homomorphically Encrypted Data via Sharding Ciphertexts

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    Recently, Deep Convolutional Neural Networks (DCNNs) including the ResNet-20 architecture have been privately evaluated on encrypted, low-resolution data with the Residue-Number-System Cheon-Kim-Kim-Song (RNS-CKKS) homomorphic encryption scheme. We extend methods for evaluating DCNNs on images with larger dimensions and many channels, beyond what can be stored in single ciphertexts. Additionally, we simplify and improve the efficiency of the recently introduced multiplexed image format, demonstrating that homomorphic evaluation can work with standard, row-major matrix packing and results in encrypted inference time speedups by 4.66.5×4.6-6.5\times. We also show how existing DCNN models can be regularized during the training process to further improve efficiency and accuracy. These techniques are applied to homomorphically evaluate a DCNN with high accuracy on the high-resolution ImageNet dataset, achieving 80.2%80.2\% top-1 accuracy. We also achieve an accuracy of homomorphically evaluated CNNs on the CIFAR-10 dataset of 98.3%98.3\%.Comment: 14 pages, 9 figure

    Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons

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    CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying 3D chromatin structure. Human mutations inCTCFcause intellectual disability and autistic features. Knocking outCtcfin mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked outCtcfpostnatally in glutamatergic forebrain neurons under the control ofCamk2a-Cre. CtcfloxP/loxP;Camk2a-Cre+(CtcfCKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor coordination, and decreased sociability by 4 months of age.CtcfCKO mice also had reduced dendritic spine density in the hippocampus and cerebral cortex. Microarray analysis of mRNA fromCtcfCKO mouse hippocampus identified increased transcription of inflammation-related genes linked to microglia. Separate microarray analysis of mRNA isolated specifically fromCtcfCKO mouse hippocampal neurons by ribosomal affinity purification identified upregulation of chemokine signaling genes, suggesting crosstalk between neurons and microglia inCtcfCKO hippocampus. Finally, we found that microglia inCtcfCKO mouse hippocampus had abnormal morphology by Sholl analysis and increased immunostaining for CD68, a marker of microglial activation. Our findings confirm thatCtcfKO in postnatal neurons causes a neurobehavioral phenotype in mice and provide novel evidence that CTCF depletion leads to overexpression of inflammation-related genes and microglial dysfunction.SIGNIFICANCE STATEMENTCCCTC-binding factor (CTCF) is a DNA-binding protein that organizes nuclear chromatin topology. Mutations inCTCFcause intellectual disability and autistic features in humans. CTCF deficiency in embryonic neurons is lethal in mice, but mice with postnatal CTCF depletion are less well studied. We find that mice lackingCtcfinCamk2a-expressing neurons (CtcfCKO mice) have spatial learning/memory deficits, impaired fine motor skills, subtly altered social interactions, and decreased dendritic spine density. We demonstrate thatCtcfCKO mice overexpress inflammation-related genes in the brain and have microglia with abnormal morphology that label positive for CD68, a marker of microglial activation. Our findings suggest that inflammation and dysfunctional neuron–microglia interactions are factors in the pathology of CTCF deficiency.</jats:p

    Space Propulsion Research Facility (B-2): An Innovative, Multi-Purpose Test Facility

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    The Space Propulsion Research Facility, commonly referred to as B-2, is designed to hot fire rocket engines or upper stage launch vehicles with up to 890,000 N force (200,000 lb force), after environmental conditioning of the test article in simulated thermal vacuum space environment. As NASA s third largest thermal vacuum facility, and the largest designed to store and transfer large quantities of propellant, it is uniquely suited to support developmental testing associated with large lightweight structures and Cryogenic Fluid Management (CFM) systems, as well as non-traditional propulsion test programs such as Electric and In-Space propulsion. B-2 has undergone refurbishment of key subsystems to support the NASA s future test needs, including data acquisition and controls, vacuum, and propellant systems. This paper details the modernization efforts at B-2 to support the Nation s thermal vacuum/propellant test capabilities, the unique design considerations implemented for efficient operations and maintenance, and ultimately to reduce test costs

    Reference Genomes from Distantly Related Species Can Be Used for Discovery of Single Nucleotide Polymorphisms to Inform Conservation Management

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    Threatened species recovery programmes benefit from incorporating genomic data into conservation management strategies to enhance species recovery. However, a lack of readily available genomic resources, including conspecific reference genomes, often limits the inclusion of genomic data. Here, we investigate the utility of closely related high-quality reference genomes for single nucleotide polymorphism (SNP) discovery using the critically endangered kakī/black stilt (Himantopus novaezelandiae) and four Charadriiform reference genomes as proof of concept. We compare diversity estimates (i.e., nucleotide diversity, individual heterozygosity, and relatedness) based on kakī SNPs discovered from genotyping-by-sequencing and whole genome resequencing reads mapped to conordinal (killdeer, Charadrius vociferus), confamilial (pied avocet, Recurvirostra avosetta), congeneric (pied stilt, Himantopus himantopus) and conspecific reference genomes. Results indicate that diversity estimates calculated from SNPs discovered using closely related reference genomes correlate significantly with estimates calculated from SNPs discovered using a conspecific genome. Congeneric and confamilial references provide higher correlations and more similar measures of nucleotide diversity, individual heterozygosity, and relatedness. While conspecific genomes may be necessary to address other questions in conservation, SNP discovery using high-quality reference genomes of closely related species is a cost-effective approach for estimating diversity measures in threatened species

    APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016

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    Historically, mpox has been characterized as an endemic zoonotic disease that transmits through contact with the reservoir rodent host in West and Central Africa. However, in May 2022, human cases of mpox were detected spreading internationally beyond countries with known endemic reservoirs. When the first cases from 2022 were sequenced, they shared 42 nucleotide differences from the closest mpox virus (MPXV) previously sampled. Nearly all these mutations are characteristic of the action of APOBEC3 deaminases, host enzymes with antiviral function. Assuming APOBEC3 editing is characteristic of human MPXV infection, we developed a dual-process phylogenetic molecular clock that-inferring a rate of ~6 APOBEC3 mutations per year-estimates that MPXV has been circulating in humans since 2016. These observations of sustained MPXV transmission present a fundamental shift to the perceived paradigm of MPXV epidemiology as a zoonosis and highlight the need for revising public health messaging around MPXV as well as outbreak management and control.Editor’s summary: In March 2022, an international epidemic of human Mpox was detected, showing that it was not solely a zoonotic infection. A hallmark of the approximately 88,000 cases that have been reported were TC>TT and GA>AA mutations in Mpox viruses, which were acquired at a surprisingly high evolutionary rate for a pox virus. Knowing that these types of mutation are a sign of activity by a host antiviral enzyme called APOBEC3, O’Toole et al. investigated whether the mutations reflected human-to-human transmission rather than repeated zoonotic spillover. Bayesian evolutionary analysis showed that Mpox virus recently diversified into several lineages in humans that display elevated numbers of mutations, signaling APOBEC exposure and sustained human-to-human transmission rather than zoonosis as the source of new cases. —Caroline AshWellcome Trust ARTIC (Collaborators Award 206298/Z/17/Z, ARTIC network) (Á.O.T., P.L., M.A.S., A.R.); European Research Council (grant agreement no. 725422 – ReservoirDOCS) (P.L., M.A.S., A.R.); National Institutes of Health (R01 AI153044) (P.L., M.A.S., A.R.); David and Lucile Packard Foundation (M.W.); Research Foundation, Flanders– Fonds voor Wetenschappelijk Onderzoek–Vlaanderen, G066215N, G0D5117N and G0B9317N (P.L.); HORIZON 2020 EU grant 874850 MOOD (P.L.); HERA project (grant/2021/PHF/23776) supported by the European Commission through the European Centre for Disease Control and Prevention (V.B. and J.P.G.). The Nigeria Centre for Disease Control and Prevention receives core funding from the Nigerian government.info:eu-repo/semantics/publishedVersio

    Rabies-Related Knowledge and Practices Among Persons At Risk of Bat Exposures in Thailand

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    Rabies is a fatal encephalitis caused by lyssaviruses. Evidence of lyssavirus circulation has recently emerged in Southeast Asian bats. We surveyed persons regularly exposed to bats and bat habitats in Thailand to assess rabies‐related knowledge and practices. Targeted groups included guano miners, bat hunters, game wardens, and residents/personnel at Buddhist temples where mass bat roosting occurs. Of the 106 people interviewed, 11 (10%) identified bats as a source of rabies. History of a bat bite/scratch was reported by 29 (27%), and 38 (36%) expressed either that they would do nothing or that they did not know what they would do in response to a bat bite. Guano miners were less likely than other groups to indicate animal bites as a mechanism of transmission (68% vs. 90%, p=0.03) and were less likely to say they would respond appropriately to a bat bite or scratch (61% vs. 27%, p=0.003). These findings indicate a need for educational outreach in Thailand to raise awareness of bat rabies, promote exposure prevention, and ensure health‐seeking behaviors for bat‐inflicted wounds, particularly among at‐risk groups

    Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity

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    <p>Abstract</p> <p>Background</p> <p>Originating from Africa, India, and the Middle East, frankincense oil has been important both socially and economically as an ingredient in incense and perfumes for thousands of years. Frankincense oil is prepared from aromatic hardened gum resins obtained by tapping <it>Boswellia </it>trees. One of the main components of frankincense oil is boswellic acid, a component known to have anti-neoplastic properties. The goal of this study was to evaluate frankincense oil for its anti-tumor activity and signaling pathways in bladder cancer cells.</p> <p>Methods</p> <p>Frankincense oil-induced cell viability was investigated in human bladder cancer J82 cells and immortalized normal bladder urothelial UROtsa cells. Temporal regulation of frankincense oil-activated gene expression in bladder cancer cells was identified by microarray and bioinformatics analysis.</p> <p>Results</p> <p>Within a range of concentration, frankincense oil suppressed cell viability in bladder transitional carcinoma J82 cells but not in UROtsa cells. Comprehensive gene expression analysis confirmed that frankincense oil activates genes that are responsible for cell cycle arrest, cell growth suppression, and apoptosis in J82 cells. However, frankincense oil-induced cell death in J82 cells did not result in DNA fragmentation, a hallmark of apoptosis.</p> <p>Conclusion</p> <p>Frankincense oil appears to distinguish cancerous from normal bladder cells and suppress cancer cell viability. Microarray and bioinformatics analysis proposed multiple pathways that can be activated by frankincense oil to induce bladder cancer cell death. Frankincense oil might represent an alternative intravesical agent for bladder cancer treatment.</p
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