The “External” Shears In Strong Lens Models

The distribution of mass in galaxy-scale strong gravitational lenses is often modelled as an elliptical power law plus ‘external shear’, which notionally accounts for line-of-sight galaxies and cosmic shear. We argue that it does not, using three lines of evidence from the analysis of 54 galaxy-scale strong lenses: (i) strong lensing external shears do not correlate with weak lensing; (ii) the measured shear magnitudes in strong lenses (which are field galaxies) are too large (exceeding 0.05) for their environment and; (iii) the external shear position angle preferentially aligns or anti-aligns with the mass model position angle, indicating an internal origin. We argue the measured strong lensing shears are therefore systematically accounting for missing complexity in the canonical elliptical power-law mass model. If we can introduce this complexity into our lens models, this will further lensing studies of galaxy formation, dark matter and Cosmology

Scanning For Dark Matter Subhalos in Hubble Space Telescope Imaging of 54 Strong Lenses

The cold dark matter (DM) model predicts that every galaxy contains thousands of DM subhalos; almost all other DM models include a physical process that smooths away the subhalos. The subhalos are invisible, but could be detected via strong gravitational lensing, if they lie on the line of sight to a multiply-imaged background source, and perturb its apparent shape. We present a predominantly automated strong lens analysis framework, and scan for DM subhalos in Hubble Space Telescope imaging of 54 strong lenses. We identify two compelling DM subhalo candidates (including one previously found in SLACS0946+1006), where a subhalo is favoured after every systematic test we perform. We find that the detectability of subhalos depends upon the assumed parametric form for the lens galaxy's mass distribution. Comparing fits which assume several more complex mass models reveals $8$ additional (generally lower mass) DM subhalo candidates worthy of further study, and the removal of 7 false positives. We identify 38 non-detections, which are vital to building up enough statistical power to test DM models. Future work will apply even more flexible models to the results of this study, to constrain different DM models. Our full analysis results are available at https://github.com/Jammy2211/autolens_subhalo.Comment: 25 Pages, 15 Figure

Beyond the bulge–halo conspiracy? Density profiles of early-type galaxies from extended-source strong lensing

Observations suggest that the dark matter and stars in early-type galaxies ‘conspire’ to produce a surprisingly simple distribution of total mass, ρ(r) ∝ ρ−γ, with γ ≈ 2. We measure the distribution of mass in 48 early-type galaxies that gravitationally lens a resolved background source. By fitting the source light in every pixel of images from the Hubble Space Telescope, we find a mean ⟨γ⟩=2.075+0.023−0.024 with an intrinsic scatter between galaxies of σγ=0.172+0.022−0.032 for the overall sample. This is consistent with and has similar precision to traditional techniques that employ spectroscopic observations to supplement lensing with mass estimates from stellar dynamics. Comparing measurements of γ for individual lenses using both techniques, we find a statistically insignificant correlation of −0.150+0.223−0.217 between the two, indicating a lack of statistical power or deviations from a power-law density in certain lenses. At fixed surface mass density, we measure a redshift dependence, ∂⟨γ⟩/z=0.345+0.322−0.296⁠, that is consistent with traditional techniques for the same sample of Sloan Lens ACS and GALaxy-Lyα EmitteR sYstems (GALLERY) lenses. Interestingly, the consistency breaks down when we measure the dependence of γ on the surface mass density of a lens galaxy. We argue that this is tentative evidence for an inflection point in the total mass-density profile at a few times the galaxy effective radius – breaking the conspiracy

Discovery of a radio lobe in the Cloverleaf Quasar at z = 2.56

The fast growth of supermassive black holes and their feedback to the host galaxies play an important role in regulating the evolution of galaxies, especially in the early Universe. However, due to cosmological dimming and the limited angular resolution of most observations, it is difficult to resolve the feedback from the active galactic nuclei (AGN) to their host galaxies. Gravitational lensing, for its magnification, provides a powerful tool to spatially differentiate emission originated from AGN and host galaxy at high redshifts. Here we report a discovery of a radio lobe in a strongly lensed starburst quasar, H1413+117 or Cloverleaf at redshift $z= 2.56$, based on observational data at optical, sub-millimetre, and radio wavelengths. With both parametric and non-parametric lens models and with reconstructed images on the source plane, we find a differentially lensed, kpc scaled, single-sided radio lobe, located at ${\sim}1.2\,\mathrm{kpc}$ to the north west of the host galaxy on the source plane. From the spectral energy distribution in radio bands, we find that the radio lobe has an energy turning point residing between 1.5 GHz and 8 GHz, indicating an age of 20--50 Myr. This could indicate a feedback switching of Cloverleaf quasar from the jet mode to the quasar mode

Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses.

CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs). Further, challenge of peripheral blood mononuclear cells ex vivo with HCMV∆UL148 increased both CTL and natural killer (NK) cell degranulation against HCMV-infected cells, including NK-driven antibody-dependent cellular cytotoxicity, showing that UL148 is a modulator of the function of multiple effector cell subsets. Our data stress the effect of HCMV immune evasion functions on shaping the immune response, highlighting the capacity for their potential use in modulating immunity during the development of anti-HCMV vaccines and HCMV-based vaccine vectors

Histone Modifications at Human Enhancers Reflect Global Cell-Type-Specific Gene Expression

The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA sequences for each gene1, 2, 3, the relative roles of these regulatory elements in this process are not clear. We have previously developed a chromatin-immunoprecipitation-based microarray method (ChIP-chip) to locate promoters, enhancers and insulators in the human genome4, 5, 6. Here we use the same approach to identify these elements in multiple cell types and investigate their roles in cell-type-specific gene expression. We observed that the chromatin state at promoters and CTCF-binding at insulators is largely invariant across diverse cell types. In contrast, enhancers are marked with highly cell-type-specific histone modification patterns, strongly correlate to cell-type-specific gene expression programs on a global scale, and are functionally active in a cell-type-specific manner. Our results define over 55,000 potential transcriptional enhancers in the human genome, significantly expanding the current catalogue of human enhancers and highlighting the role of these elements in cell-type-specific gene expression

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. Funding: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research

Air-sea CO2 exchange in the equatorial Pacific

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C08S02, doi:10.1029/2003JC002256.GasEx-2001, a 15-day air-sea carbon dioxide (CO2) exchange study conducted in the equatorial Pacific, used a combination of ships, buoys, and drifters equipped with ocean and atmospheric sensors to assess variability and surface mechanisms controlling air-sea CO2 fluxes. Direct covariance and profile method air-sea CO2 fluxes were measured together with the surface ocean and marine boundary layer processes. The study took place in February 2001 near 125°W, 3°S in a region of high CO2. The diurnal variation in the air-sea CO2 difference was 2.5%, driven predominantly by temperature effects on surface solubility. The wind speed was 6.0 ± 1.3 m s−1, and the atmospheric boundary layer was unstable with conditions over the range −1 < z/L < 0. Diurnal heat fluxes generated daytime surface ocean stratification and subsequent large nighttime buoyancy fluxes. The average CO2 flux from the ocean to the atmosphere was determined to be 3.9 mol m−2 yr−1, with nighttime CO2 fluxes increasing by 40% over daytime values because of a strong nighttime increase in (vertical) convective velocities. The 15 days of air-sea flux measurements taken during GasEx-2001 demonstrate some of the systematic environmental trends of the eastern equatorial Pacific Ocean. The fact that other physical processes, in addition to wind, were observed to control the rate of CO2 transfer from the ocean to the atmosphere indicates that these processes need to be taken into account in local and global biogeochemical models. These local processes can vary on regional and global scales. The GasEx-2001 results show a weak wind dependence but a strong variability in processes governed by the diurnal heating cycle. This implies that any changes in the incident radiation, including atmospheric cloud dynamics, phytoplankton biomass, and surface ocean stratification may have significant feedbacks on the amount and variability of air-sea gas exchange. This is in sharp contrast with previous field studies of air-sea gas exchange, which showed that wind was the dominating forcing function. The results suggest that gas transfer parameterizations that rely solely on wind will be insufficient for regions with low to intermediate winds and strong insolation.This work was performed with the support of the National Science Foundation Grant OCE-9986724 and the NOAA Global Carbon Cycle Program Grants NA06GP048, NA17RJ1223, and NA87RJ0445 in the Office of Global Programs

Renal artery sympathetic denervation:observations from the UK experience

Background: Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response—particularly in those prescribed aldosterone antagonists at the time of RDN. Methods: We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres. Results: Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p &lt; 0.001 for trend). Use of aldosterone antagonist did not predict response (p &lt; 0.2). Conclusion: In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy