Gravitational-wave astronomy with a physical calibration model

We carry out astrophysical inference for compact binary merger events in LIGO-Virgo’s first gravitational-wave transient catalog (GWTC-1) using a physically motivated calibration model. We demonstrate that importance sampling can be used to reduce the cost of what would otherwise be a computationally challenging analysis for signal-to-noise ratios of current gravitational-wave detections. We show that including the physical estimate for the calibration error distribution has negligible impact on the inference of parameters for the events in GWTC-1. Studying a simulated signal with matched filter signal-to-noise ratio SNR = 200, we project that a calibration error estimate typical of GWTC-1 is likely to be negligible for the current generation of gravitational-wave detectors. We argue that other sources of systematic error—from waveforms, prior distributions, and noise modeling—are likely to be more important. Finally, using the events in GWTC-1 as standard sirens, we infer an astrophysically informed improvement on the estimate of the calibration error in the LIGO interferometers

Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology.

Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-gamma transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1alpha and MIP-1beta mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP-1beta-driven macrophage immunopathology

Influence of Hydrodynamic Interactions on the Adsorption Process of Large Particles

We have studied the adsorption process of non-Brownian particles on a line incorporating hydrodynamic interactionsa and we have numerically analyzed their effect on typical relevant quantities. We compare our model to the ballistic deposition model (BM) and address the limitations of BM in experimental situations. The results obtained can explain some differences observed between recent experiments and BM predictions.Comment: 10 pages, LaTeX. 4 Figures upon reques

Improving regional ozone modeling through systematic evaluation of errors using the aircraft observations during the International Consortium for Atmospheric Research on Transport and Transformation

During the operational phase of the ICARTT field experiment in 2004, the regional air quality model STEM showed a strong positive surface bias and a negative upper troposphere bias (compared to observed DC-8 and WP-3 observations) with respect to ozone. After updating emissions from NEI 1999 to NEI 2001 (with a 2004 large point sources inventory update), and modifying boundary conditions, low-level model bias decreases from 11.21 to 1.45 ppbv for the NASA DC-8 observations and from 8.26 to −0.34 for the NOAA WP-3. Improvements in boundary conditions provided by global models decrease the upper troposphere negative ozone bias, while accounting for biomass burning emissions improved model performance for CO. The covariances of ozone bias were highly correlated to NOz, NOy, and HNO3 biases. Interpolation of bias information through kriging showed that decreasing emissions in SE United States would reduce regional ozone model bias and improve model correlation coefficients. The spatial distribution of forecast errors was analyzed using kriging, which identified distinct features, which when compared to errors in postanalysis simulations, helped document improvements. Changes in dry deposition to crops were shown to reduce substantially high bias in the forecasts in the Midwest, while updated emissions were shown to account for decreases in bias in the eastern United States. Observed and modeled ozone production efficiencies for the DC-8 were calculated and shown to be very similar (7.8) suggesting that recurring ozone bias is due to overestimation of NOx emissions. Sensitivity studies showed that ozone formation in the United States is most sensitive to NOx emissions, followed by VOCs and CO. PAN as a reservoir of NOx can contribute to a significant amount of surface ozone through thermal decomposition

best practices in bioassay development to support registration of biopharmaceuticals

Biological activity is a critical quality attribute for biopharmaceuticals, which is accurately measured using an appropriate relative potency bioassay. Developing a bioassay is a complex, rigorous undertaking that needs to address several challenges including modelling all of the mechanisms of action associated with the biotherapeutic. Bioassay development is also an exciting and fast evolving field, not only from a scientific, medical and technological point of view, but also in terms of statistical approaches and regulatory expectations. This has led to an industry-wide discussion on the most appropriate ways to develop, validate and control the bioassays throughout the drug lifecycle

Ecological consequences of early Late Pleistocene megadroughts in tropical Africa

Extremely arid conditions in tropical Africa occurred in several discrete episodes between 135 and 90 ka, as demonstrated by lake core and seismic records from multiple basins [Scholz CA, Johnson TC, Cohen AS, King JW, Peck J, Overpeck JT, Talbot MR, Brown ET, Kalindekafe L, Amoako PYO, et al. (2007) Proc Natl Acad Sci USA 104:16416–16421]. This resulted in extraordinarily low lake levels, even in Africa\u27s deepest lakes. On the basis of well dated paleoecological records from Lake Malawi, which reflect both local and regional conditions, we show that this aridity had severe consequences for terrestrial and aquatic ecosystems. During the most arid phase, there was extremely low pollen production and limited charred-particle deposition, indicating insufficient vegetation to maintain substantial fires, and the Lake Malawi watershed experienced cool, semidesert conditions (\u3c400 mm/yr precipitation). Fossil and sedimentological data show that Lake Malawi itself, currently 706 m deep, was reduced to an ≈125 m deep saline, alkaline, well mixed lake. This episode of aridity was far more extreme than any experienced in the Afrotropics during the Last Glacial Maximum (≈35–15 ka). Aridity diminished after 95 ka, lake levels rose erratically, and salinity/alkalinity declined, reaching near-modern conditions after 60 ka. This record of lake levels and changing limnological conditions provides a framework for interpreting the evolution of the Lake Malawi fish and invertebrate species flocks. Moreover, this record, coupled with other regional records of early Late Pleistocene aridity, places new constraints on models of Afrotropical biogeographic refugia and early modern human population expansion into and out of tropical Africa

Use of RecA fusion proteins to induce genomic modifications in zebrafish

The bacterial recombinase RecA forms a nucleic acid-protein filament on single-stranded (ss) DNA during the repair of double-strand breaks (DSBs) that efficiently undergoes a homology search and engages in pairing with the complementary DNA sequence. We utilized the pairing activity of RecA–DNA filaments to tether biochemical activities to specific chromosomal sites. Different filaments with chimeric RecA proteins were tested for the ability to induce loss of heterozygosity at the golden locus in zebrafish after injection at the one-cell stage. A fusion protein between RecA containing a nuclear localization signal (NLS) and the DNA-binding domain of Gal4 (NLS-RecA-Gal4) displayed the most activity. Our results demonstrate that complementary ssDNA filaments as short as 60 nucleotides coated with NLS-RecA-Gal4 protein are able to cause loss of heterozygosity in ∼3% of the injected embryos. We demonstrate that lesions in ∼9% of the F0 zebrafish are transmitted to subsequent generations as large chromosomal deletions. Co-injection of linear DNA with the NLS-RecA-Gal4 DNA filaments promotes the insertion of the DNA into targeted genomic locations. Our data support a model whereby NLS-RecA-Gal4 DNA filaments bind to complementary target sites on chromatin and stall DNA replication forks, resulting in a DNA DSB

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t