High-Resolution Measurements of the Dark Matter Halo of NGC 2976: Evidence for a Shallow Density Profile

We have obtained two-dimensional velocity fields of the dwarf spiral galaxy NGC 2976 in Halpha and CO. The high spatial (~75 pc) and spectral (13 km/s and 2 km/s, respectively) resolution of these observations, along with our multicolor optical and near-infrared imaging, allow us to measure the shape of the density profile of the dark matter halo with good precision. We find that the total (baryonic plus dark matter) mass distribution of NGC 2976 follows a rho_tot ~ r^(-0.27 +/- 0.09) power law out to a radius of 1.8 kpc, assuming that the observed radial motions provide no support. The density profile attributed to the dark halo is even shallower, consistent with a nearly constant density of dark matter over the entire observed region. A maximal disk fit yields an upper limit to the K-band stellar mass-to-light ratio (M*/L_K) of 0.09^{+0.15}_{-0.08} M_sun/L_sun,K (including systematic uncertainties), with the caveat that for M*/L_K > 0.19 M_sun/L_sun,K the dark matter density increases with radius, which is unphysical. Assuming 0.10 M_sun/L_sun,K < M*/L_K < 0.19 M_sun/L_sun,K, the dark matter density profile lies between rho_dm ~ r^-0.17 and rho_dm ~ r^-0.01. Therefore, independent of any assumptions about the stellar disk or the functional form of the density profile, NGC 2976 does not contain a cuspy dark matter halo. We also investigate some of the systematic effects that can hamper rotation curve studies, and show that 1) longslit rotation curves are far more vulnerable to systematic errors than two-dimensional velocity fields, 2) NGC 2976 contains large radial motions at small radii, and 3) the Halpha and CO velocity fields of NGC 2976 agree within their uncertainties. [slightly abridged]Comment: 30 pages, 4 tables, 13 figures (7 in color; Figures 1 and 3 are low-resolution to save space). Accepted for publication in ApJ. Version with full-resolution figures available at http://astro.berkeley.edu/~bolatto/ngc2976rotation.ps (46 MB

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Inherited biotic protection in a Neotropical pioneer plant

Chelonanthus alatus is a bat-pollinated, pioneer Gentianaceae that clusters in patches where still-standing, dried-out stems are interspersed among live individuals. Flowers bear circum-floral nectaries (CFNs) that are attractive to ants, and seed dispersal is both barochorous and anemochorous. Although, in this study, live individuals never sheltered ant colonies, dried-out hollow stems - that can remain standing for 2 years - did. Workers from species nesting in dried-out stems as well as from ground-nesting species exploited the CFNs of live C. alatus individuals in the same patches during the daytime, but were absent at night (when bat pollination occurs) on 60.5% of the plants. By visiting the CFNs, the ants indirectly protect the flowers - but not the plant foliage - from herbivorous insects. We show that this protection is provided mostly by species nesting in dried-out stems, predominantly Pseudomyrmex gracilis. That dried-out stems remain standing for years and are regularly replaced results in an opportunistic, but stable association where colonies are sheltered by one generation of dead C. alatus while the live individuals nearby, belonging to the next generation, provide them with nectar; in turn, the ants protect their flowers from herbivores. We suggest that the investment in wood by C. alatus individuals permitting stillstanding, dried-out stems to shelter ant colonies constitutes an extended phenotype because foraging workers protect the flowers of live individuals in the same patch. Also, through this process these dried-out stems indirectly favor the reproduction (and so the fitness) of the next generation including both their own offspring and that of their siblings, alladding up to a potential case of inclusive fitness in plants

Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation

Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD). In the present study, we performed yeast two-hybrid screens and protein co-purifications with HaloTag-DUX fusions or GST-DUX4 pull-down to identify protein partners of DUX4, DUX4c (which is identical to DUX4 except for the end of the carboxyl terminal domain) and DUX1 (which is limited to the double homeodomain). Unexpectedly, we identified and validated (by co-immunoprecipitation, GST pull-down, co-immunofluorescence and in situ Proximal Ligation Assay) the interaction of DUX4, DUX4c and DUX1 with type III intermediate filament protein desmin in the cytoplasm and at the nuclear periphery. Desmin filaments link adjacent sarcomere at the Z-discs, connect them to sarcolemma proteins and interact with mitochondria. These intermediate filament also contact the nuclear lamina and contribute to positioning of the nuclei. Another Z-disc protein, LMCD1 that contains a LIM domain was also validated as a DUX4 partner. The functionality of DUX4 or DUX4c interactions with cytoplasmic proteins is underscored by the cytoplasmic detection of DUX4/DUX4c upon myoblast fusion. In addition, we identified and validated (by co-immunoprecipitation, co-immunofluorescence and in situ Proximal Ligation Assay) as DUX4/4c partners several RNA-binding proteins such as C1QBP, SRSF9, RBM3, FUS/TLS and SFPQ that are involved in mRNA splicing and translation. FUS and SFPQ are nuclear proteins, however their cytoplasmic translocation was reported in neuronal cells where they associated with ribonucleoparticles (RNPs). Several other validated or identified DUX4/DUX4c partners are also contained in mRNP granules, and the co-localizations with cytoplasmic DAPI-positive spots is in keeping with such an association. Large muscle RNPs were recently shown to exit the nucleus via a novel mechanism of nuclear envelope budding. Following DUX4 or DUX4c overexpression in muscle cell cultures, we observed their association with similar nuclear buds. In conclusion, our study demonstrated unexpected interactions of DUX4/4c with cytoplasmic proteins playing major roles during muscle differentiation. Further investigations are on-going to evaluate whether these interactions play roles during muscle regeneration as previously suggested for DUX4c

Extreme Rainfall Events Alter the Trophic Structure in Bromeliad Tanks Across the Neotropics

Changes in global and regional precipitation regimes are among the most pervasive components of climate change. Intensification of rainfall cycles, ranging from frequent downpours to severe droughts, could cause widespread, but largely unknown, alterations to trophic structure and ecosystem function. We conducted multi-site coordinated experiments to show how variation in the quantity and evenness of rainfall modulates trophic structure in 210 natural freshwater microcosms (tank bromeliads) across Central and South America (18°N to 29°S). The biomass of smaller organisms (detritivores) was higher under more stable hydrological conditions. Conversely, the biomass of predators was highest when rainfall was uneven, resulting in top-heavy biomass pyramids. These results illustrate how extremes of precipitation, resulting in localized droughts or flooding, can erode the base of freshwater food webs, with negative implications for the stability of trophic dynamics

Ecological Response to Altered Rainfall Differs Across the Neotropics

There is growing recognition that ecosystems may be more impacted by infrequent extreme climatic events than by changes in mean climatic conditions. This has led to calls for experiments that explore the sensitivity of ecosystems over broad ranges of climatic parameter space. However, because such response surface experiments have so far been limited in geographic and biological scope, it is not clear if differences between studies reflect geographic location or the ecosystem component considered. In this study, we manipulated rainfall entering tank bromeliads in seven sites across the Neotropics, and characterized the response of the aquatic ecosystem in terms of invertebrate functional composition, biological stocks (total invertebrate biomass, bacterial density) and ecosystem fluxes (decomposition, carbon, nitrogen). Of these response types, invertebrate functional composition was the most sensitive, even though, in some sites, the species pool had a high proportion of drought‐tolerant families. Total invertebrate biomass was universally insensitive to rainfall change because of statistical averaging of divergent responses between functional groups. The response of invertebrate functional composition to rain differed between geographical locations because (1) the effect of rainfall on bromeliad hydrology differed between sites, and invertebrates directly experience hydrology not rainfall and (2) the taxonomic composition of some functional groups differed between sites, and families differed in their response to bromeliad hydrology. These findings suggest that it will be difficult to establish thresholds of “safe ecosystem functioning” when ecosystem components differ in their sensitivity to climatic variables, and such thresholds may not be broadly applicable over geographic space. In particular, ecological forecast horizons for climate change may be spatially restricted in systems where habitat properties mediate climatic impacts, and those, like the tropics, with high spatial turnover in species composition

Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease

BACKGROUND: 5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs). METHODS: We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5’UTRs by different whole exome sequencing (WES) kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches. RESULTS: Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe design, 3–20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels. CONCLUSIONS: This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure