Integrating genealogical and dynamical modelling to infer escape and reversion rates in HIV epitopes

The rates of escape and reversion in response to selection pressure arising from the host immune system, notably the cytotoxic T-lymphocyte (CTL) response, are key factors determining the evolution of HIV. Existing methods for estimating these parameters from cross-sectional population data using ordinary differential equations (ODE) ignore information about the genealogy of sampled HIV sequences, which has the potential to cause systematic bias and over-estimate certainty. Here, we describe an integrated approach, validated through extensive simulations, which combines genealogical inference and epidemiological modelling, to estimate rates of CTL escape and reversion in HIV epitopes. We show that there is substantial uncertainty about rates of viral escape and reversion from cross-sectional data, which arises from the inherent stochasticity in the evolutionary process. By application to empirical data, we find that point estimates of rates from a previously published ODE model and the integrated approach presented here are often similar, but can also differ several-fold depending on the structure of the genealogy. The model-based approach we apply provides a framework for the statistical analysis of escape and reversion in population data and highlights the need for longitudinal and denser cross-sectional sampling to enable accurate estimate of these key parameters

Whitacre\u27s Thunderstorm: How Eric Whitacre Uses Form to Bring Words to Life

We will be discussing the form of Eric Whitacre\u27s \u27Cloudburst\u27 and how it mimics a storm brewing using musical elements and text painting, or reflecting the words sung through music. We will look at how the song progresses through the different stages of a storm, from the unsettled calm before the full outburst and the resolution back to calm. We will look at how Whitacre achieves this through his use of instrumentation, both traditional and unique, and through the increasing intensity of his intricate melodies. We will look at how he makes this clear to follow even for audiences who do not speak the language of the piece or have an extensive musical knowledge and show why the overall experience of the piece is breathtaking. Presentation Time: Wednesday, 11 a.m.-12 p.m

Filaggrin failure - from ichthyosis vulgaris to atopic eczema and beyond

The main proteinaceous component of the keratohyalin granules within the granular layer keratinocytes of the epidermis is the giant, repetitive polyprotein profilaggrin. When granular layer cells commit to terminal differentiation to form the flattened squames of the stratum corneum, profilaggrin is rapidly cleaved into multiple copies of the 37 kDa filaggrin monomer, which binds to and condenses the keratin cytoskeleton, thereby facilitating cellular compression. Within the stratum corneum, filaggrin is broken down to form natural moisturising factor, a pool of amino acids and derivatives thereof that exerts multiple effects. Filaggrin is therefore essential for normal stratum corneum biogenesis and physiology. In 2006, the McLean group identified the first loss‐of‐function mutations in the filaggrin gene (FLG) as the cause of the common monogenic genodermatosis ichthyosis vulgaris (IV). In parallel, they showed by multiple methods that these mutations, carried by up to 10% of various human populations are the major genetic predisposing factor for atopic dermatitis (eczema) and all of the associated allergic phenotypes that constitute the atopic diathesis. This paradigm‐shifting work showed that skin barrier deficiency is a major early event in the pathophysiology of eczema and allergy

Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure

Background Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema. Methods and Findings We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen(n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. Conclusions We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life

Moon Search Algorithms for NASA's Dawn Mission to Asteroid Vesta

A moon or natural satellite is a celestial body that orbits a planetary body such as a planet, dwarf planet, or an asteroid. Scientists seek understanding the origin and evolution of our solar system by studying moons of these bodies. Additionally, searches for satellites of planetary bodies can be important to protect the safety of a spacecraft as it approaches or orbits a planetary body. If a satellite of a celestial body is found, the mass of that body can also be calculated once its orbit is determined. Ensuring the Dawn spacecraft's safety on its mission to the asteroid Vesta primarily motivated the work of Dawn's Satellite Working Group (SWG) in summer of 2011. Dawn mission scientists and engineers utilized various computational tools and techniques for Vesta's satellite search. The objectives of this paper are to 1) introduce the natural satellite search problem, 2) present the computational challenges, approaches, and tools used when addressing this problem, and 3) describe applications of various image processing and computational algorithms for performing satellite searches to the electronic imaging and computer science community. Furthermore, we hope that this communication would enable Dawn mission scientists to improve their satellite search algorithms and tools and be better prepared for performing the same investigation in 2015, when the spacecraft is scheduled to approach and orbit the dwarf planet Ceres

Follow up ability for GRB observations on Swift

Swift is the first satellite to autonomously select its own targets and slew to them. To test the ability of the narrow field of view instruments (NFIs) to follow up gamma ray burst (GRB) triggers, we simulate a series of randomly positioned bursts. This allows us to explore how the follow up observations of the NFIs will proceed. Each located burst in the simulation is followed by four hours without bursts, to allow for the NFIs to follow up the GRB triggers. We simulated 50 bursts that were triggered and located by the Burst Alert Telescope (BAT) and observed by the NFIs to probe the follow up parameter space. The discovery orbit (when the burst is first observed after the trigger) has NFI observation durations that are random in duration, while the average observation per full-orbit (the orbits after the discovery orbit) is approximately 2500 seconds, which would then take four full orbits to fulfill the autonomous observation requirement. The NFI observations can only begin afterSwift has settled on the GRB’s location, which takes about a hundred seconds. This average hundred seconds limits to rapid follow up observations by the NFIs, leaving the earliest optical observations to ground-based robotic telescopes

Training Interventions for Improved Deceleration Ability in Adult Team-Based Field Sports Athletes

Background: Deceleration is a fundamental component of multidirectional speed by which athletes reduce the velocity of their centre of mass to stop or execute changes of direction following acceleration or running at a constant velocity. Enhancing deceleration abilities is crucial for athletes as successfully executing horizontal deceleration has important implications for match outcomes in sports requiring rapid multidirectional movements. However, specific training interventions targeting deceleration are scarce. The purpose of this systematic review and meta-analysis was to examine the effects of training interventions on deceleration performance in adult team-based field and court sports athletes. Methods: A systematic literature search was conducted through electronic databases, SPORTdiscus, PubMed, and Web of Science from inception to February 2022, and re-run in May 2023. The search terms were related to different training interventions and kinetic, kinematic, and performance outcomes related to deceleration performance. Studies were included if they consisted of a randomised controlled trial which investigated the effects of training on deceleration-specific outcome measures in adult team-based field and court sports athletes. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomised trials (RoB2). Post-intervention effect sizes (Hedge’s g) were calculated between the intervention and control groups and a meta-analysis was performed using a random effects model. Results: Twelve studies were included, with 29 deceleration-specific outcomes measured in a total of 381 participants. There was inconsistency in methodological designs, including control group types, length and type of interventions and in reported deceleration-specific outcome measures. Across all observations of deceleration performance measures there was a standardised mean difference of -0.04 (95% CI: -0.50, 0.42), favouring control groups, indicating little effect of training on deceleration performance. For secondary outcomes related to deceleration, for kinetics (SMD = -0.29, 95% CI = -0.83, 0.25, I2 = 55%, p < 0.01), joint kinetics (SMD = -0.20, 95% CI = -1.01, 0.61, I2 = 68%, p < 0.01) and muscle activation (SMD = -0.10, 95% CI = -0.44, 0.24, I2 = 19%, p = 0.28) had greater effects for control groups, whereas joint kinematics (SMD = 0.07, 95% CI = -0.11, 0.24, I2 = 0%, p = 0.77), favoured the intervention groups. Conclusion: For the deceleration-specific outcomes reported in the included studies, training was not likely to produce a performance improvement in participants compared to control groups. However, due to methodological inconsistencies between studies and observed high risk of bias, the results should be interpreted with caution. More rigorous research methods should be included in the future to address areas that may introduce potential biases. Future research should address the differences in the type, timing, frequency, and duration of the implemented training interventions for improving deceleration performance, and in the reported deceleration-specific outcome measures. Registration: This systematic review was registered on the Open Science Framework (https://osf.io/cmwbr) (https://doi.org/10.17605/OSF.IO/CMWBR