62 research outputs found

    An Alternative to Regulation: The Case for Public AI

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    Can governments build AI? In this paper, we describe an ongoing effort to develop ``public AI'' -- publicly accessible AI models funded, provisioned, and governed by governments or other public bodies. Public AI presents both an alternative and a complement to standard regulatory approaches to AI, but it also suggests new technical and policy challenges. We present a roadmap for how the ML research community can help shape this initiative and support its implementation, and how public AI can complement other responsible AI initiatives.Comment: To be presented at Regulatable ML @ NeurIPS2023 worksho

    FIND: A Function Description Benchmark for Evaluating Interpretability Methods

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    Labeling neural network submodules with human-legible descriptions is useful for many downstream tasks: such descriptions can surface failures, guide interventions, and perhaps even explain important model behaviors. To date, most mechanistic descriptions of trained networks have involved small models, narrowly delimited phenomena, and large amounts of human labor. Labeling all human-interpretable sub-computations in models of increasing size and complexity will almost certainly require tools that can generate and validate descriptions automatically. Recently, techniques that use learned models in-the-loop for labeling have begun to gain traction, but methods for evaluating their efficacy are limited and ad-hoc. How should we validate and compare open-ended labeling tools? This paper introduces FIND (Function INterpretation and Description), a benchmark suite for evaluating the building blocks of automated interpretability methods. FIND contains functions that resemble components of trained neural networks, and accompanying descriptions of the kind we seek to generate. The functions span textual and numeric domains, and involve a range of real-world complexities. We evaluate methods that use pretrained language models (LMs) to produce descriptions of function behavior in natural language and code. Additionally, we introduce a new interactive method in which an Automated Interpretability Agent (AIA) generates function descriptions. We find that an AIA, built from an LM with black-box access to functions, can infer function structure, acting as a scientist by forming hypotheses, proposing experiments, and updating descriptions in light of new data. However, AIA descriptions tend to capture global function behavior and miss local details. These results suggest that FIND will be useful for evaluating more sophisticated interpretability methods before they are applied to real-world models.Comment: 28 pages, 10 figure

    Phylogenetic Analysis of the MS4A and TMEM176 Gene Families

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    The MS4A gene family in humans includes CD20 (MS4A1), FcRbeta (MS4A2), Htm4 (MS4A3), and at least 13 other syntenic genes encoding membrane proteins, most having characteristic tetraspanning topology. Expression of MS4A genes is variable in tissues throughout the body; however, several are limited to cells in the hematopoietic system where they have known roles in immune cell functions. Genes in the small TMEM176 group share significant sequence similarity with MS4A genes and there is evidence of immune function of at least one of the encoded proteins. In this study, we examined the evolutionary history of the MS4A/TMEM176 families as well as tissue expression of the phylogenetically earliest members, in order to investigate their possible origins in immune cells.Orthologs of human MS4A genes were found only in mammals; however, MS4A gene homologs were found in most jawed vertebrates. TMEM176 genes were found only in mammals and bony fish. Several unusual MS4A genes having 2 or more tandem MS4A sequences were identified in the chicken (Gallus gallus) and early mammals (opossum, Monodelphis domestica and platypus, Ornithorhyncus anatinus). A large number of highly conserved MS4A and TMEM176 genes was found in zebrafish (Danio rerio). The most primitive organism identified to have MS4A genes was spiny dogfish (Squalus acanthus). Tissue expression of MS4A genes in S. acanthias and D. rerio showed no evidence of expression restricted to the hematopoietic system.Our findings suggest that MS4A genes first appeared in cartilaginous fish with expression outside of the immune system, and have since diversified in many species into their modern forms with expression and function in both immune and nonimmune cells

    Exome chip analyses in adult attention deficit hyperactivity disorder

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    Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)o1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E − 06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P = 4.46E − 08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P = 6.47E − 07); the PSD locus (P = 7.58E − 08) and ZCCHC4 locus (P = 1.79E − 06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio = 0.81, P = 1.61E − 05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD

    Exome-wide DNA capture and next generation sequencing in domestic and wild species

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    <p>Abstract</p> <p>Background</p> <p>Gene-targeted and genome-wide markers are crucial to advance evolutionary biology, agriculture, and biodiversity conservation by improving our understanding of genetic processes underlying adaptation and speciation. Unfortunately, for eukaryotic species with large genomes it remains costly to obtain genome sequences and to develop genome resources such as genome-wide SNPs. A method is needed to allow gene-targeted, next-generation sequencing that is flexible enough to include any gene or number of genes, unlike transcriptome sequencing. Such a method would allow sequencing of many individuals, avoiding ascertainment bias in subsequent population genetic analyses.</p> <p>We demonstrate the usefulness of a recent technology, exon capture, for genome-wide, gene-targeted marker discovery in species with no genome resources. We use coding gene sequences from the domestic cow genome sequence (<it>Bos taurus</it>) to capture (enrich for), and subsequently sequence, thousands of exons of <it>B. taurus</it>, <it>B. indicus</it>, and <it>Bison bison </it>(wild bison). Our capture array has probes for 16,131 exons in 2,570 genes, including 203 candidate genes with known function and of interest for their association with disease and other fitness traits.</p> <p>Results</p> <p>We successfully sequenced and mapped exon sequences from across the 29 autosomes and X chromosome in the <it>B. taurus </it>genome sequence. Exon capture and high-throughput sequencing identified thousands of putative SNPs spread evenly across all reference chromosomes, in all three individuals, including hundreds of SNPs in our targeted candidate genes.</p> <p>Conclusions</p> <p>This study shows exon capture can be customized for SNP discovery in many individuals and for non-model species without genomic resources. Our captured exome subset was small enough for affordable next-generation sequencing, and successfully captured exons from a divergent wild species using the domestic cow genome as reference.</p

    Oxide chemistry and fluid inclusion constraints on the formation of itabirite-hosted iron ore deposits at the eastern border of the southern Espinhaço Range, Brazil

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    The Piçarrão and Liberdade deposits contain high-grade iron orebodies (>65% Fe) hosted in the Guanhães Group itabirite, that are associated with pegmatite veins and bodies. Fluid inclusion studies in quartz veins associated with the high-grade orebodies show that medium to high salinities (25–28 wt% NaCl eq.) and temperatures (275–375 °C) fluids are associated with the silica leaching that led to the iron enrichment. Mineral chemistry studies by LA-ICP-MS in the iron oxides demonstrate that metasomatic processes were responsible for the mineralogical transformations of magnetite to hematite and for subsequent hematite recrystallization. These processes are related to the iron upgrade in the itabirite and the formation of high-grade orebodies. The oxidation of the magnetite to martite is associated with an enrichment in P and As, and depletion in Mg, Ti and Co; as observed in martite crystals compared to their matching kenomagnetite rims. On the other hand Ti and Mo are enriched in hematite crystals that recrystallized from martite. In this case Ti behaved as an immobile element, and its enrichment is accompanied by the depletion of most of the trace elements. A second stage of magnetite formation precipitated with quartz in discordant veins and is oxidized to martite-II. These quartz-martite-II veins contain low salinity and temperature fluid inclusions that record an episode of meteoric fluid influx. The results of the LA-ICP-MS analyses on the fluid inclusions from pegmatite and quartz veins associated with the high-grade iron bodies indicate the contribution of anatectic fluids in the evolution of the metasomatic events

    Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder:The ENIGMA adventure

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    International audienc

    The solute carrier SLC7A1 may act as a protein transporter at the blood-brain barrier

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    Despite extensive research, targeted delivery of substances to the brain still poses a great challenge due to the selectivity of the blood-brain barrier (BBB). Most molecules require either carrier- or receptor-mediated transport systems to reach the central nervous system (CNS). These transport systems form attractive routes for the delivery of therapeutics into the CNS, yet the number of known brain endothelium-enriched receptors allowing the transport of large molecules into the brain is scarce. Therefore, to identify novel BBB targets, we combined transcriptomic analysis of human and murine brain endothelium and performed a complex screening of BBB-enriched genes according to established selection criteria. As a result, we propose the high-affinity cationic amino acid transporter 1 (SLC7A1) as a novel candidate for transport of large molecules across the BBB. Using RNA sequencing and in situ hybridization assays, we demonstrated elevated SLC7A1 gene expression in both human and mouse brain endothelium. Moreover, we confirmed SLC7A1 protein expression in brain vasculature of both young and aged mice. To assess the potential of SLC7A1 as a transporter for larger proteins, we performed internalization and transcytosis studies using a radiolabelled or fluorophore-labelled anti-SLC7A1 antibody. Our results showed that SLC7A1 internalised a SLC7A1-specific antibody in human colorectal carcinoma (HCT116) cells. Moreover, transcytosis studies in both immortalised human brain endothelial (hCMEC/D3) cells and primary mouse brain endothelial cells clearly demonstrated that SLC7A1 effectively transported the SLC7A1-specific antibody from luminal to abluminal side. Therefore, here in this study, we present for the first time the SLC7A1 as a novel candidate for transport of larger molecules across the BBB

    The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

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    This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17)
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