Syntactic vs Semantic Linear Abstraction and Refinement of Neural Networks

Abstraction is a key verification technique to improve scalability. However, its use for neural networks is so far extremely limited. Previous approaches for abstracting classification networks replace several neurons with one of them that is similar enough. We can classify the similarity as defined either syntactically (using quantities on the connections between neurons) or semantically (on the activation values of neurons for various inputs). Unfortunately, the previous approaches only achieve moderate reductions, when implemented at all. In this work, we provide a more flexible framework where a neuron can be replaced with a linear combination of other neurons, improving the reduction. We apply this approach both on syntactic and semantic abstractions, and implement and evaluate them experimentally. Further, we introduce a refinement method for our abstractions, allowing for finding a better balance between reduction and precision.Comment: Accepted at ATVA 202

A Two-Hit Trigger for siRNA Biogenesis in Plants

SummaryIn Arabidopsis, microRNA-directed cleavage can define one end of RNAs that then generate phased siRNAs. However, most miRNA-targeted RNAs do not spawn siRNAs, suggesting the existence of additional determinants within those that do. We find that in moss, phased siRNAs arise from regions flanked by dual miR390 cleavage sites. AtTAS3, an siRNA locus important for development and conserved among higher plants, also has dual miR390 complementary sites. Both sites bind miR390 in vitro and are functionally required in Arabidopsis, but cleavage is undetectable at the 5′ site—demonstrating that noncleavable sites can be functional in plants. Phased siRNAs also emanate from the bounded regions of every Arabidopsis gene with two known microRNA/siRNA complementary sites, but only rarely from genes with single sites. Therefore, two “hits,”—often, but not always, two cleavage events—constitute a conserved trigger for siRNA biogenesis, a finding with implications for recognition and silencing of aberrant RNA

Formation, regulation and evolution of Caenorhabditis elegans 3'UTRs

Post-transcriptional gene regulation frequently occurs through elements in mRNA 3′ untranslated regions (UTRs)1, 2. Although crucial roles for 3′UTR-mediated gene regulation have been found in Caenorhabditis elegans3, 4, 5, most C. elegans genes have lacked annotated 3′UTRs6, 7. Here we describe a high-throughput method for reliable identification of polyadenylated RNA termini, and we apply this method, called poly(A)-position profiling by sequencing (3P-Seq), to determine C. elegans 3′UTRs. Compared to standard methods also recently applied to C. elegans UTRs8, 3P-Seq identified 8,580 additional UTRs while excluding thousands of shorter UTR isoforms that do not seem to be authentic. Analysis of this expanded and corrected data set suggested that the high A/U content of C. elegans 3′UTRs facilitated genome compaction, because the elements specifying cleavage and polyadenylation, which are A/U rich, can more readily emerge in A/U-rich regions. Indeed, 30% of the protein-coding genes have mRNAs with alternative, partially overlapping end regions that generate another 10,480 cleavage and polyadenylation sites that had gone largely unnoticed and represent potential evolutionary intermediates of progressive UTR shortening. Moreover, a third of the convergently transcribed genes use palindromic arrangements of bidirectional elements to specify UTRs with convergent overlap, which also contributes to genome compaction by eliminating regions between genes. Although nematode 3′UTRs have median length only one-sixth that of mammalian 3′UTRs, they have twice the density of conserved microRNA sites, in part because additional types of seed-complementary sites are preferentially conserved. These findings reveal the influence of cleavage and polyadenylation on the evolution of genome architecture and provide resources for studying post-transcriptional gene regulation.National Institutes of Health (U.S.) (Grant number GM067031)National Science Foundation (U.S.). Predoctural FellowshipUnited States. Dept. of Energy. Computational Science Graduate Fellowship (Krell Institute

Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting

MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3′ UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3′ UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3′ UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3′ UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.Korea (South). Ministry of Education, Science and Technology (MEST) (National Research Foundation of Korea. NRF-2013R1A1A1010185)National Institutes of Health (U.S.) (Grant RO1 GM067031)National Institutes of Health (U.S.) (Grant K99 GM102319)National Science Foundation (U.S.). Graduate Research Fellowship Progra

A Memetic Analysis of a Phrase by Beethoven: Calvinian Perspectives on Similarity and Lexicon-Abstraction

This article discusses some general issues arising from the study of similarity in music, both human-conducted and computer-aided, and then progresses to a consideration of similarity relationships between patterns in a phrase by Beethoven, from the first movement of the Piano Sonata in A flat major op. 110 (1821), and various potential memetic precursors. This analysis is followed by a consideration of how the kinds of similarity identified in the Beethoven phrase might be understood in psychological/conceptual and then neurobiological terms, the latter by means of William Calvin’s Hexagonal Cloning Theory. This theory offers a mechanism for the operation of David Cope’s concept of the lexicon, conceived here as a museme allele-class. I conclude by attempting to correlate and map the various spaces within which memetic replication occurs

From holism to compositionality: memes and the evolution of segmentation, syntax, and signification in music and language

Steven Mithen argues that language evolved from an antecedent he terms “Hmmmmm, [meaning it was] Holistic, manipulative, multi-modal, musical and mimetic”. Owing to certain innate and learned factors, a capacity for segmentation and cross-stream mapping in early Homo sapiens broke the continuous line of Hmmmmm, creating discrete replicated units which, with the initial support of Hmmmmm, eventually became the semantically freighted words of modern language. That which remained after what was a bifurcation of Hmmmmm arguably survived as music, existing as a sound stream segmented into discrete units, although one without the explicit and relatively fixed semantic content of language. All three types of utterance – the parent Hmmmmm, language, and music – are amenable to a memetic interpretation which applies Universal Darwinism to what are understood as language and musical memes. On the basis of Peter Carruthers’ distinction between ‘cognitivism’ and ‘communicativism’ in language, and William Calvin’s theories of cortical information encoding, a framework is hypothesized for the semantic and syntactic associations between, on the one hand, the sonic patterns of language memes (‘lexemes’) and of musical memes (‘musemes’) and, on the other hand, ‘mentalese’ conceptual structures, in Chomsky’s ‘Logical Form’ (LF)

Impacts of climate variability on the tuna economy of Seychelles

Many small island states have developed economies that are strongly dependent on tuna fisheries. Consequently, they are vulnerable to the socio-economic effects of climate change and variability, processes that are known to impact upon tuna fisheries distribution and productivity. The aim of this study was to assess the impacts of climate oscillations on the tuna-dependent economy of Seychelles. Using a multiplier approach, the direct, indirect and induced economic effects of the tuna industry declined by 58%, 34% and 60%, respectively, in 1998, the year of a strong warming event in the western Indian Ocean. Patterns in tuna purse seine vessel expenditures in port were substantially modified by strong climate oscillations. A cointegration time-series model predicted that a 40% decline in tuna landings and transhipment in Port Victoria, a value commensurate with that observed in 1998, would result in a 34% loss for the local economy. Of several indices tested, the Indian Oscillation Index was the best at predicting the probability of entering a regime of low landings and transhipment. In 2007, a moderate climate anomaly was compounded by prior overfishing to produce a stronger that expected impact on the fishery and economy of Seychelles. The effects of fishing and climate variability on tuna stocks are complex and pose significant challenges for fisheries management and the economic development of countries in the Indian Ocean

Impacts of climate variability on the tuna economy of Seychelles

Many small island states have developed economies that are strongly dependent on tuna fisheries. Consequently, they are vulnerable to the socio-economic effects of climate change and variability, processes that are known to impact upon tuna fisheries distribution and productivity. The aim of this study was to assess the impacts of climate oscillations on the tuna-dependent economy of Seychelles. Using a multiplier approach, the direct, indirect and induced economic effects of the tuna industry declined by 58%, 34% and 60%, respectively, in 1998, the year of a strong warming event in the western Indian Ocean. Patterns in tuna purse seine vessel expenditures in port were substantially modified by strong climate oscillations. A cointegration time-series model predicted that a 40% decline in tuna landings and transhipment in Port Victoria, a value commensurate with that observed in 1998, would result in a 34% loss for the local economy. Of several indices tested, the Indian Oscillation Index was the best at predicting the probability of entering a regime of low landings and transhipment. In 2007, a moderate climate anomaly was compounded by prior overfishing to produce a stronger that expected impact on the fishery and economy of Seychelles. The effects of fishing and climate variability on tuna stocks are complex and pose significant challenges for fisheries management and the economic development of countries in the Indian Ocean.

Cremations, Dental Amalgams, and You

Introduction: In Vermont, cremation has increasingly become an alternative to interment of an intact body. Many of the bodies being cremated contain dental amalgams, which are commonly used by dentists to repair dental erosion and caries (cavities). They are an economical option for caries repair, and remain popular. Roughly one third of all caries fillings done in 2002 in the U.S. utilized amalgam. Amalgam is a metal alloy containing as much as 50% mercury by volume, a metal that is a known toxicant. Dental amalgams, may constitute a source of low level, continual exposure for those with these dental devices in situ and may be released to the atmosphere upon cremation. The goal of this project was to investigate: 1. The status of the scientific opinion on potential health effects that may be associated with having dental amalgams. 2. To help refine State estimates of potential mercury emissions from Vermont crematoria.https://scholarworks.uvm.edu/comphp_gallery/1075/thumbnail.jp

Extensive alternative polyadenylation during zebrafish development

The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3′ untranslated regions (3′ UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-seq reads substantially increased and improved existing 3′ UTR annotations, resulting in confidently identified 3′ UTRs for >79% of the annotated protein-coding genes in zebrafish. mRNAs from most zebrafish genes undergo alternative CPA, with those from more than a thousand genes using different dominant 3′ UTRs at different stages. These included one of the poly(A) polymerase genes, for which alternative CPA reinforces its repression in the ovary. 3′ UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3′ UTRs are highly expressed in the ovary, yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3′ UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3′ UTRs provide a resource for studying gene regulation during vertebrate development.National Institutes of Health (U.S.) (Grant GM067031)