Asymptotic W-symmetries in three-dimensional higher-spin gauge theories

We discuss how to systematically compute the asymptotic symmetry algebras of generic three-dimensional bosonic higher-spin gauge theories in backgrounds that are asymptotically AdS. We apply these techniques to a one-parameter family of higher-spin gauge theories that can be considered as large N limits of SL(N) x SL(N) Chern-Simons theories, and we provide a closed formula for the structure constants of the resulting infinite-dimensional non-linear W-algebras. Along the way we provide a closed formula for the structure constants of all classical W_N algebras. In both examples the higher-spin generators of the W-algebras are Virasoro primaries. We eventually discuss how to relate our basis to a non-primary quadratic basis that was previously discussed in literature.Comment: 61 page

RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major Abnormality in ALS Spinal Cord

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned \u3e50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG’s). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network “hub” gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF’s involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients

Symmetries of Holographic Minimal Models

It was recently proposed that a large N limit of a family of minimal model CFTs is dual to a certain higher spin gravity theory in AdS_3, where the 't Hooft coupling constant of the CFT is related to a deformation parameter of the higher spin algebra. We identify the asymptotic symmetry algebra of the higher spin theory for generic 't Hooft parameter, and show that it coincides with a family of W-algebras previously discovered in the context of the KP hierarchy. We furthermore demonstrate that this family of W-algebras controls the representation theory of the minimal model CFTs in the 't Hooft limit. This provides a non-trivial consistency check of the proposal and explains part of the underlying mechanism.Comment: 25 pages; references added and minor corrections (published version

SHH1, a Homeodomain Protein Required for DNA Methylation, As Well As RDR2, RDM4, and Chromatin Remodeling Factors, Associate with RNA Polymerase IV

DNA methylation is an evolutionarily conserved epigenetic modification that is critical for gene silencing and the maintenance of genome integrity. In Arabidopsis thaliana, the de novo DNA methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), is targeted to specific genomic loci by 24 nt small interfering RNAs (siRNAs) through a pathway termed RNA–directed DNA methylation (RdDM). Biogenesis of the targeting siRNAs is thought to be initiated by the activity of the plant-specific RNA polymerase IV (Pol-IV). However, the mechanism through which Pol-IV is targeted to specific genomic loci and whether factors other than the core Pol-IV machinery are required for Pol-IV activity remain unknown. Through the affinity purification of NUCLEAR RNA POLYMERASE D1 (NRPD1), the largest subunit of the Pol-IV polymerase, we found that several previously identified RdDM components co-purify with Pol-IV, namely RNA–DEPENDENT RNA POLYMERASE 2 (RDR2), CLASSY1 (CLSY1), and RNA–DIRECTED DNA METHYLATION 4 (RDM4), suggesting that the upstream siRNA generating portion of the RdDM pathway may be more physically coupled than previously envisioned. A homeodomain protein, SAWADEE HOMEODOMAIN HOMOLOG 1 (SHH1), was also found to co-purify with NRPD1; and we demonstrate that SHH1 is required for de novo and maintenance DNA methylation, as well as for the accumulation of siRNAs at specific loci, confirming it is a bonafide component of the RdDM pathway

Opuntia in México: Identifying Priority Areas for Conserving Biodiversity in a Multi-Use Landscape

BACKGROUND: México is one of the world's centers of species diversity (richness) for Opuntia cacti. Yet, in spite of their economic and ecological importance, Opuntia species remain poorly studied and protected in México. Many of the species are sparsely but widely distributed across the landscape and are subject to a variety of human uses, so devising implementable conservation plans for them presents formidable difficulties. Multi-criteria analysis can be used to design a spatially coherent conservation area network while permitting sustainable human usage. METHODS AND FINDINGS: Species distribution models were created for 60 Opuntia species using MaxEnt. Targets of representation within conservation area networks were assigned at 100% for the geographically rarest species and 10% for the most common ones. Three different conservation plans were developed to represent the species within these networks using total area, shape, and connectivity as relevant criteria. Multi-criteria analysis and a metaheuristic adaptive tabu search algorithm were used to search for optimal solutions. The plans were built on the existing protected areas of México and prioritized additional areas for management for the persistence of Opuntia species. All plans required around one-third of México's total area to be prioritized for attention for Opuntia conservation, underscoring the implausibility of Opuntia conservation through traditional land reservation. Tabu search turned out to be both computationally tractable and easily implementable for search problems of this kind. CONCLUSIONS: Opuntia conservation in México require the management of large areas of land for multiple uses. The multi-criteria analyses identified priority areas and organized them in large contiguous blocks that can be effectively managed. A high level of connectivity was established among the prioritized areas resulting in the enhancement of possible modes of plant dispersal as well as only a small number of blocks that would be recommended for conservation management

Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Seventeen Sustainable Development Goals (SDGs) were adopted by the global community to provide benchmark targets for global development between 2015 and 2030 and to reframe the Millennium Development Goals (MDGs) to achieve sustainable global development. This report presents data on maternal mortality in 195 countries from 1990 to 2015. Maternal mortality data were categorized in 3 formats, namely, number of deaths, cause-specific mortality rate per capita, and cause fraction. The overall maternal mortality was modeled using cause-of-death ensemble modeling (CODEm). The number of deaths, maternal mortality ratios (MMRs), and 95% uncertainty intervals were reported for all estimates. The results indicate that the overall decline in global maternal deaths from 1990 to 2015 was approximately 29% (390,185 in 1990; 374,321 in 2000; and 275,288 in 2015), and the reduction in MMR was 30% (282 in 1990, 288 in 2000, and 196 in 2015). In 1990, it was found that 60 countries had an MMR of more than 200, 40 countries had an MMR of more than 400, 15 countries had an MMR of more than 600, and 1 country had an MMR of more than 1000. By 2015, 122 countries had an MMR of less than 70, and 49 countries had an MMR of less than 15. Although MMR and Sociodemographic Index improved between 1990 and 2015 in almost all regions, it was observed that MMR did not universally track with Sociodemographic Index over the whole time period in any single region. The observed minus expected (O - E) MMR ratio was consistently found to be 1.25 or more in many regions; however, MMR reductions slowed considerably, and the O - E MMR ratio was 1.41 in 2015. The risk of maternal mortality increased greatly with age, but decreased greatly in almost all age groups from 1990 to 2015. It was observed that MMR in 10- to 14-year-old girls in 2015 was 278; it then decreased and was lowest in women aged 15 to 29 years before increasing significantly to 1832 in 50- to 54-year-old women. Direct obstetric causes accounted for 86% of all maternal deaths in 2015 due to maternal hemorrhage, maternal hypertensive disorders, and other maternal disorders in comparison to 1990 when direct complications accounted for 87% of all maternal deaths. Other maternal disorders caused approximately 74,299 deaths in 1990 and decreased to 32,734 deaths in 2015. The study authors conclude that although there is global progress in reducing maternal mortality in the past 15 years, more and better data collection systems should be put in place to devise better health care policies and to educate women about reproductive care options available to them