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    Data Isotopes for Data Provenance in DNNs

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    Today, creators of data-hungry deep neural networks (DNNs) scour the Internet for training fodder, leaving users with little control over or knowledge of when their data, and in particular their images, are used to train models. To empower users to counteract unwanted use of their images, we design, implement and evaluate a practical system that enables users to detect if their data was used to train a DNN model for image classification. We show how users can create special images we call isotopes, which introduce ``spurious features'' into DNNs during training. With only query access to a model and no knowledge of the model-training process, nor control of the data labels, a user can apply statistical hypothesis testing to detect if the model learned these spurious features by training on the user's images. Isotopes can be viewed as an application of a particular type of data poisoning. In contrast to backdoors and other poisoning attacks, our purpose is not to cause misclassification but rather to create tell-tale changes in confidence scores output by the model that reveal the presence of isotopes in the training data. Isotopes thus turn DNNs' vulnerability to memorization and spurious correlations into a tool for data provenance. Our results confirm efficacy in multiple image classification settings, detecting and distinguishing between hundreds of isotopes with high accuracy. We further show that our system works on public ML-as-a-service platforms and larger models such as ImageNet, can use physical objects in images instead of digital marks, and remains robust against several adaptive countermeasures.</p

    Understanding Variation in Transcription Factor Binding by Modeling Transcription Factor Genome-Epigenome Interactions

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    Despite explosive growth in genomic datasets, the methods for studying epigenomic mechanisms of gene regulation remain primitive. Here we present a model-based approach to systematically analyze the epigenomic functions in modulating transcription factor-DNA binding. Based on the first principles of statistical mechanics, this model considers the interactions between epigenomic modifications and a cis-regulatory module, which contains multiple binding sites arranged in any configurations. We compiled a comprehensive epigenomic dataset in mouse embryonic stem (mES) cells, including DNA methylation (MeDIP-seq and MRE-seq), DNA hydroxymethylation (5-hmC-seq), and histone modifications (ChIP-seq). We discovered correlations of transcription factors (TFs) for specific combinations of epigenomic modifications, which we term epigenomic motifs. Epigenomic motifs explained why some TFs appeared to have different DNA binding motifs derived from in vivo (ChIP-seq) and in vitro experiments. Theoretical analyses suggested that the epigenome can modulate transcriptional noise and boost the cooperativity of weak TF binding sites. ChIP-seq data suggested that epigenomic boost of binding affinities in weak TF binding sites can function in mES cells. We showed in theory that the epigenome should suppress the TF binding differences on SNP-containing binding sites in two people. Using personal data, we identified strong associations between H3K4me2/H3K9ac and the degree of personal differences in NFκB binding in SNP-containing binding sites, which may explain why some SNPs introduce much smaller personal variations on TF binding than other SNPs. In summary, this model presents a powerful approach to analyze the functions of epigenomic modifications. This model was implemented into an open source program APEG (Affinity Prediction by Epigenome and Genome, http://systemsbio.ucsd.edu/apeg).</p

    Meiotic Transmission of an In Vitro<i>–</i>Assembled Autonomous Maize Minichromosome

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    Autonomous chromosomes are generated in yeast (yeast artificial chromosomes) and human fibrosarcoma cells (human artificial chromosomes) by introducing purified DNA fragments that nucleate a kinetochore, replicate, and segregate to daughter cells. These autonomous minichromosomes are convenient for manipulating and delivering DNA segments containing multiple genes. In contrast, commercial production of transgenic crops relies on methods that integrate one or a few genes into host chromosomes; extensive screening to identify insertions with the desired expression level, copy number, structure, and genomic location; and long breeding programs to produce varieties that carry multiple transgenes. As a step toward improving transgenic crop production, we report the development of autonomous maize minichromosomes (MMCs). We constructed circular MMCs by combining DsRed and nptII marker genes with 7–190 kb of genomic maize DNA fragments containing satellites, retroelements, and/or other repeats commonly found in centromeres and using particle bombardment to deliver these constructs into embryogenic maize tissue. We selected transformed cells, regenerated plants, and propagated their progeny for multiple generations in the absence of selection. Fluorescent in situ hybridization and segregation analysis demonstrated that autonomous MMCs can be mitotically and meiotically maintained. The MMC described here showed meiotic segregation ratios approaching Mendelian inheritance: 93% transmission as a disome (100% expected), 39% transmission as a monosome crossed to wild type (50% expected), and 59% transmission in self crosses (75% expected). The fluorescent DsRed reporter gene on the MMC was expressed through four generations, and Southern blot analysis indicated the encoded genes were intact. This novel approach for plant transformation can facilitate crop biotechnology by (i) combining several trait genes on a single DNA fragment, (ii) arranging genes in a defined sequence context for more consistent gene expression, and (iii) providing an independent linkage group that can be rapidly introgressed into various germplasms.</p

    The Role of Geography in Human Adaptation

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    Various observations argue for a role of adaptation in recent human evolution, including results from genome-wide studies and analyses of selection signals at candidate genes. Here, we use genome-wide SNP data from the HapMap and CEPH-Human Genome Diversity Panel samples to study the geographic distributions of putatively selected alleles at a range of geographic scales. We find that the average allele frequency divergence is highly predictive of the most extreme FST values across the whole genome. On a broad scale, the geographic distribution of putatively selected alleles almost invariably conforms to population clusters identified using randomly chosen genetic markers. Given this structure, there are surprisingly few fixed or nearly fixed differences between human populations. Among the nearly fixed differences that do exist, nearly all are due to fixation events that occurred outside of Africa, and most appear in East Asia. These patterns suggest that selection is often weak enough that neutral processes—especially population history, migration, and drift—exert powerful influences over the fate and geographic distribution of selected alleles.</p

    Magnon-mediated qubit coupling determined via dissipation measurements

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    Controlled interaction between localized and delocalized solid-state spin systems offers a compelling platform for on-chip quantum information processing with quantum spintronics. Hybrid quantum systems (HQSs) of localized nitrogen-vacancy (NV) centers in diamond and delocalized magnon modes in ferrimagnets—systems with naturally commensurate energies—have recently attracted significant attention, especially for interconnecting isolated spin qubits at length-scales far beyond those set by the dipolar coupling. However, despite extensive theoretical efforts, there is a lack of experimental characterization of the magnon-mediated interaction between NV centers, which is necessary to develop such hybrid quantum architectures. Here, we experimentally determine the magnon-mediated NV–NV coupling from the magnon-induced self-energy of NV centers. Our results are quantitatively consistent with a model in which the NV center is coupled to magnons by dipolar interactions. This work provides a versatile tool to characterize HQSs in the absence of strong coupling, informing future efforts to engineer entangled solid-state systems

    A Rice Gene of <i>De Novo</i> Origin Negatively Regulates Pathogen-Induced Defense Response

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    How defense genes originated with the evolution of their specific pathogen-responsive traits remains an important problem. It is generally known that a form of duplication can generate new genes, suggesting that a new gene usually evolves from an ancestral gene. However, we show that a new defense gene in plants may evolve by de novo origination, resulting in sophisticated disease-resistant functions in rice. Analyses of gene evolution showed that this new gene, OsDR10, had homologs only in the closest relative, Leersia genus, but not other subfamilies of the grass family; therefore, it is a rice tribe-specific gene that may have originated de novo in the tribe. We further show that this gene may evolve a highly conservative rice-specific function that contributes to the regulation difference between rice and other plant species in response to pathogen infections. Biologic analyses including gene silencing, pathologic analysis, and mutant characterization by transformation showed that the OsDR10-suppressed plants enhanced resistance to a broad spectrum of Xanthomonas oryzae pv. oryzae strains, which cause bacterial blight disease. This enhanced disease resistance was accompanied by increased accumulation of endogenous salicylic acid (SA) and suppressed accumulation of endogenous jasmonic acid (JA) as well as modified expression of a subset of defense-responsive genes functioning both upstream and downstream of SA and JA. These data and analyses provide fresh insights into the new biologic and evolutionary processes of a de novo gene recruited rapidly.</p

    <i>King Lear</i> and the Ethics of Brutal, Caring Faith

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    This essay engages with King Lear to perform an ethical meditation. The essay finds within the play an ethic resembling the ethics of care: health and flourishing are present not merely in individual human beings but in bonds between human beings. King Lear sets this ethic within a context characterized by finality and human finitude and frailty. Human beings must act within a ripe moment, without being able to consider every contingency and possibility; these acts can (and probably do) affect the wellbeing of those around the actor; and once these acts are completed, they are irrevocable. King Lear sets this state of affairs against a backdrop of indifferent, intractable realms of nature, the divine, and politics. Nevertheless, the essay finds in King Lear the possibility that human beings will grant one another the gift of dignity—even within all that is bleak, contingent, and absurd—a possibility that is ultimately grounded in faith

    Etiologic diagnosis of lower respiratory tract bacterial infections using Sputum samples and quantitative loop-mediated isothermal amplification

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    Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship. Trial Registration: ClinicalTrials.gov NCT00567827

    Saint Mark Preaching in Alexandria: A New Perspective

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    By the last decades of the ninth/fifteenth century an interest in representing the “real” world in religious narratives set within an authentic biblical background prompted Venetian artists to integrate the Mamluk world into their paintings. At that time, the Mamluks had control over Jerusalem, as well as Alexandria (Egypt), where Saint Mark had introduced Christianity. The Republic’s strong commercial ties and diplomatic relations with the Mamluk Sultanate provided Venetian painters with the necessary Mamluk details. The present article reflects on one of the most celebrated paintings in the San Marco cycle, St. Mark Preaching in Alexandria by Gentile Bellini. In an attempt to figure out why the artist incorporated an Ottoman wearing a sword among hoards of Mamluk male and female characters as they would have appeared at that time in Alexandria, this paper identifies Mamluk costume in some detail. The purpose of this study is to explain the allusions Gentile’s painting contained to contemporary events. In order to accomplish its purpose, the study examines the Mamluk phenomenon in Venetian painting, assesses Gentile’s Alexandrian setting and his accuracy in portraying Mamluk versus Ottoman figures, analyzes the relations between the Republic and the world of Islam, and finally discusses Venice’s interest in the Mamluk world

    Fe Kα XANES, Fe Kβ HERFD XANES and EPMA flank method determinations of the oxidation state of Fe in garnet

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    The ferric to total iron ratios (Fe3+/∑Fe) of garnets can be paired with thermodynamic mineral activity models to quantify the oxygen fugacity of garnet-bearing rocks. However, techniques with a high analytical and spatial resolution are necessary to distinguish differences in garnet Fe3+/∑Fe ratios at the percent level and to accurately measure garnets that are zoned or contain inclusions. We acquired conventional Fe Kα and high-resolution energy fluorescence detection (HERFD) Fe Kβ X-ray absorption near edge structure (XANES) spectra and electron microprobe flank method analyses on a suite of 27 peridotitic and eclogitic garnets with Fe3+/∑Fe ratios previously determined by Mössbauer spectroscopy to evaluate the precision of each technique. We examined variations in the energy and intensity of three XANES spectral features as a function of Fe3+/∑Fe ratios: 1) the intensity ratio of two-post edge features (I-ratio; Fe Kα only); 2) the energy of the Fe edge at 90% normalized intensity (E0.9; Fe Kα only) and 3) the pre-edge centroid energy (Fe Kα and HERFD Fe Kβ). In accordance with previous work, we find the energies of garnet pre-edge centroids are relatively insensitive to Fe3+/∑Fe ratios. The I-ratios of peridotitic and eclogitic garnets are offset from each other at low Fe3+/∑Fe ratios (≤0.13); I-ratio garnet XANES calibrations are composition-specific. The E0.9 feature is independent of garnet major element composition in spectra that have been corrected for the effects of self-absorption. We produce two Fe Kα garnet XANES calibrations based on variations in the E0.9 feature; one calibration with all garnet reference materials included (Fe3+/∑Fe up to 1.0; “all garnet calibration”) and another calibration specific to garnets with low Fe3+/∑Fe ratios (“low ferric calibration”). Fe3+/∑Fe ratios calculated from the mean of up to 25 flank method measurements on eight garnet reference materials fall within 4% absolute of a one-to-one correlation with Fe3+/∑Fe ratios measured by Mössbauer. The standard error of the mean Fe3+/∑Fe ratio calculated from flank method approaches the Mössbauer-determined Fe3+/∑Fe ratio within estimated error (3%) after three analyses. Flank method precision is enhanced at higher beam current; however, the precision of the flank method does not approach the precision of XANES under any microprobe analytical condition tested here. Garnet reference materials detailed here are available by request to the Smithsonian Institution

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