Abstract
Gravitational lensing by clusters of galaxies offers a powerful probe of their structure and mass distribution. Several research groups have developed techniques independently to achieve ...this goal. While these methods have all provided remarkably high-precision mass maps, particularly with exquisite imaging data from the Hubble Space Telescope (HST), the reconstructions themselves have never been directly compared. In this paper, we present for the first time a detailed comparison of methodologies for fidelity, accuracy and precision. For this collaborative exercise, the lens modelling community was provided simulated cluster images that mimic the depth and resolution of the ongoing HST Frontier Fields. The results of the submitted reconstructions with the un-blinded true mass profile of these two clusters are presented here. Parametric, free-form and hybrid techniques have been deployed by the participating groups and we detail the strengths and trade-offs in accuracy and systematics that arise for each methodology. We note in conclusion that several properties of the lensing clusters are recovered equally well by most of the lensing techniques compared in this study. For example, the reconstruction of azimuthally averaged density and mass profiles by both parametric and free-form methods matches the input models at the level of ∼10 per cent. Parametric techniques are generally better at recovering the 2D maps of the convergence and of the magnification. For the best-performing algorithms, the accuracy in the magnification estimate is ∼10 per cent at μtrue = 3 and it degrades to ∼30 per cent at μtrue ∼ 10.
Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with ...long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria.
Numerous models and indices exist that attempt to characterize the effect of environmental factors on the comfort of animals and humans. Heat and cold indices have been utilized to adjust ambient ...temperature (Ta) for the effects of relative humidity (RH) or wind speed (WS) or both for the purposes of obtaining a "feels-like" or apparent temperature. However, no model has been found that incorporates adjustments for RH, WS, and radiation (RAD) over conditions that encompass hot and cold environmental conditions. The objective of this study was to develop a comprehensive climate index (CCI) that has application under a wide range of environmental conditions and provides an adjustment to Ta for RH, WS, and RAD. Environmental data were compiled from 9 separate summer periods in which heat stress events occurred and from 6 different winter periods to develop and validate the CCI. The RH adjustment is derived from an exponential relationship between Ta and RH with temperature being adjusted up or down from an RH value of 30%. At 45°C, the temperature adjustment for increasing RH from 30 to 100% equals approximately 16°C, whereas at -30°C temperature adjustments due to increasing RH from 30 to 100% equal approximately -3.0°C, with greater RH values contributing to a reduced apparent temperature under cold conditions. The relationship between WS and temperature adjustments was also determined to be exponential with a logarithmic adjustment to define appropriate declines in apparent temperature as WS increases. With this index, slower WS results in the greatest change in apparent temperature per unit of WS regardless of whether hot or cold conditions exist. As WS increases, the change in apparent temperature per unit of WS becomes less. Based on existing windchill and heat indices, the effect of WS on apparent temperature is sufficiently similar to allow one equation to be utilized under hot and cold conditions. The RAD component was separated into direct solar radiation and ground surface radiation. Both of these were found to have a linear relationship with Ta. This index will be useful for further development of biological response functions, which are associated with energy exchange, and improving decision-making processes, which are weather-dependent. In addition, the defined thresholds can serve as management and environmental mitigation guidelines to protect and ensure animal comfort.
It has been previously noted that mixed communities typically produce more power in microbial fuel cells than pure cultures. If true, this has important implications for the design of microbial fuel ...cells and for studying the process of electron transfer on anode biofilms. To further evaluate this, Geobacter sulfurreducens was grown with acetate as fuel in a continuous flow 'ministack' system in which the carbon cloth anode and cathode were positioned in close proximity, and the cation-selective membrane surface area was maximized in order to overcome some of the electrochemical limitations that were inherent in fuel cells previously employed for the study of pure cultures. Reducing the size of the anode in order to eliminate cathode limitation resulted in maximum current and power densities per m² of anode surface of 4.56 A m⁻² and 1.88 W m⁻² respectively. Electron recovery as current from acetate oxidation was c. 100% when oxygen diffusion into the system was minimized. This performance is comparable to the highest levels previously reported for mixed communities in similar microbial fuel cells and slightly higher than the power output of an anaerobic sludge inoculum in the same ministack system. Minimizing the volume of the anode chamber yielded a volumetric power density of 2.15 kW m⁻³, which is the highest power density per volume yet reported for a microbial fuel cell. Geobacter sulfurreducens formed relatively uniform biofilms 3-18 μm thick on the carbon cloth anodes. When graphite sticks served as the anode, the current density (3.10 A m⁻²) was somewhat less than with the carbon cloth anodes, but the biofilms were thicker (c. 50 μm) with a more complex pillar and channel structure. These results suggest that the previously observed disparity in power production in pure and mixed culture microbial fuel cell systems can be attributed more to differences in the fuel cell designs than to any inherent superior capability of mixed cultures to produce more power than pure cultures.
For lensed galaxy SGAS J111020.0+645950.8 at redshift z = 2.481, which is magnified by a factor of 28 8, we analyze the morphology of star formation, as traced by rest-frame ultraviolet emission, in ...both the highly magnified source plane and simulations of how this galaxy would appear without lensing magnification. Were this galaxy not lensed, but rather drawn from a Hubble Space Telescope deep field, we would conclude that almost all its star formation arises from an exponential disk (Sérsic index of 1.0 0.4) with an effective radius of measured from two-dimensional fitting to F606W using Galfit, and measured by fitting a radial profile to F606W elliptical isophotes. At the normal spatial resolution of the deep fields, there is no sign of clumpy star formation within SGAS J111020.0+645950.8. However, the enhanced spatial resolution enabled by gravitational lensing tells a very different story; much of the star formation arises in two dozen clumps with sizes of r = 30-50 pc spread across the 7 kpc length of the galaxy. The color and spatial distribution of the diffuse component suggests that still-smaller clumps are unresolved. Despite this clumpy, messy morphology, the radial profile is still well-characterized by an exponential profile. In this lensed galaxy, stars are forming in complexes with sizes well below 100 pc; such sizes are wholly unexplored by surveys of galaxy evolution at .
The Gram-negative bacterium Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTI), which can progress to secondary bacteremia. While numerous studies have ...investigated experimental infection with P. mirabilis in the urinary tract, little is known about pathogenesis in the bloodstream. This study identifies the genes that are important for survival in the bloodstream using a whole-genome transposon insertion-site sequencing (Tn-Seq) approach. A library of 50,000 transposon mutants was utilized to assess the relative contribution of each non-essential gene in the P. mirabilis HI4320 genome to fitness in the livers and spleens of mice at 24 hours following tail vein inoculation compared to growth in RPMI, heat-inactivated (HI) naïve serum, and HI acute phase serum. 138 genes were identified as ex vivo fitness factors in serum, which were primarily involved in amino acid transport and metabolism, and 143 genes were identified as infection-specific in vivo fitness factors for both spleen and liver colonization. Infection-specific fitness factors included genes involved in twin arginine translocation, ammonia incorporation, and polyamine biosynthesis. Mutants in sixteen genes were constructed to validate both the ex vivo and in vivo results of the transposon screen, and 12/16 (75%) exhibited the predicted phenotype. Our studies indicate a role for the twin arginine translocation (tatAC) system in motility, translocation of potential virulence factors, and fitness within the bloodstream. We also demonstrate the interplay between two nitrogen assimilation pathways in the bloodstream, providing evidence that the GS-GOGAT system may be preferentially utilized. Furthermore, we show that a dual-function arginine decarboxylase (speA) is important for fitness within the bloodstream due to its role in putrescine biosynthesis rather than its contribution to maintenance of membrane potential. This study therefore provides insight into pathways needed for fitness within the bloodstream, which may guide strategies to reduce bacteremia-associated mortality.
People with rare lysosomal storage diseases face challenges in their care that arise from disease complexity and heterogeneity, compounded by many healthcare professionals being unfamiliar with these ...diseases. These challenges can result in long diagnostic journeys and inadequate care. Over 30 years ago, the Rare Disease Registries for Gaucher, Fabry, Mucopolysaccharidosis type I and Pompe diseases were established to address knowledge gaps in disease natural history, clinical manifestations of disease and treatment outcomes. Evidence generated from the real-world data collected in these registries supports multiple stakeholders, including patients, healthcare providers, drug developers, researchers and regulators. To maximise the impact of real-world evidence from these registries, engagement and collaboration with the patient communities is essential. To this end, the Rare Disease Registries Patient Council was established in 2019 as a partnership between the Rare Disease Registries and global and local patient advocacy groups to share perspectives on how registry data are used and disseminated. The Patient Council has resulted in a number of patient initiatives including patient representation at Rare Disease Registries advisory boards; development of plain language summaries of registry publications to increase availability of real-world evidence to patient communities; and implementation of digital innovations such as electronic patient-reported outcomes, and patient-facing registry reports and electronic consent (in development), all to enhance patient engagement. The Patient Council is building on the foundations of industry-patient advocacy group collaboration to fully integrate patient communities in decision-making and co-create solutions for the rare disease community.
Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune ...responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.
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