Local lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep

Chronic lipopolysaccharide (LPS) exposure may contribute to the pathogenesis of a number of lung diseases including COPD and emphysema. We sought to develop a large- animal model of emphysema using repeated LPS administration into sheep lung segments. An experimental protocol was designed to facilitate comparisons with elastase-treated and control segments within the same lung of individual sheep. Histopathologic evaluation of segments treated with LPS demonstrated low-grade inflammation characterized by an increase in the number of intra-alveolar macrophages and lymphocytes. Treated segments demonstrated a significant reduction in airspace surface area (ASA), an increase in percent disrupted alveolar attachments and the distance between normal alveolar attachments, and a reduction in the number of normal alveolar attachments surrounding nonrespiratory bronchioles. Coefficient of variation of individual ASA measurements in elastase-treated segments was indicative of a heterogeneous parenchymal response, in contrast to that associated with chronic LPS treatment. Our results demonstrate that chronic LPS treatment of individual lung segments in sheep induces microscopic emphysema qualitatively and quantitatively consistent with both accepted pathologic definitions of this condition and with that produced by airway instillation of elastolytic enzymes. Development of this phenotype is associated with evidence of downregulated activation of transforming growth factor beta

Classifying Sequences of Extreme Length with Constant Memory Applied to Malware Detection

Recent works within machine learning have been tackling inputs of ever-increasing size, with cybersecurity presenting sequence classification problems of particularly extreme lengths. In the case of Windows executable malware detection, inputs may exceed $100$ MB, which corresponds to a time series with $T=100,000,000$ steps. To date, the closest approach to handling such a task is MalConv, a convolutional neural network capable of processing up to $T=2,000,000$ steps. The $\mathcal{O}(T)$ memory of CNNs has prevented further application of CNNs to malware. In this work, we develop a new approach to temporal max pooling that makes the required memory invariant to the sequence length $T$. This makes MalConv $116\times$ more memory efficient, and up to $25.8\times$ faster to train on its original dataset, while removing the input length restrictions to MalConv. We re-invest these gains into improving the MalConv architecture by developing a new Global Channel Gating design, giving us an attention mechanism capable of learning feature interactions across 100 million time steps in an efficient manner, a capability lacked by the original MalConv CNN. Our implementation can be found at https://github.com/NeuromorphicComputationResearchProgram/MalConv2Comment: To appear in AAAI 202

Hybrid artificial neural network models for effective prediction and mitigation of urban roadside NO2 pollution

Traffic-related air pollution has been a serious concern amongst policy-makers and the public due to its physiological and environmental impacts. An early warning system based on accurate forecasting tools must therefore be implemented to circumvent the adverse effects of exposure to major air pollutants. A multilayer perceptron neural network was trained and developed using air pollution and meteorological data over a two-year period from a monitoring site in Marylebone Road, Central London to predict roadside concentration values of NO2 24 hours ahead. Several hybrid models were also developed by applying feature selection techniques such as stepwise regression, principal component analysis, and Classification and Regression Trees to the neural network model. Most roadside pollutant variables, e.g., oxides of nitrogen, were found to be significant in predicting NO2. The statistical results reveal overall prediction superiority of the hybrid models to the standalone neural network model

Synthesis and polymorphism of mixed aluminium-gallium oxides

DSC is grateful to the EPSRC for award of an industrial CASE studentship, partly funded by Johnson Matthey plc. SEA, DMD and JEH thank the ERC (EU FP7 Consolidator Grant 614290 “EXONMR”) for funding. SEA would also like to thank the Royal Society and Wolfson Foundation for a merit award.The synthesis of a new solidsolution of the oxyhydroxide Ga5–xAlxO7(OH) isinvestigated via solvothermalreaction between gallium acetylacetonate and aluminium isopropoxide in1,4-butanediol at 240 °C. A limited compositional range 0 ≤ x ≤ 1.5 is produced, with the hexagonalunit cell parameters refined from powder X-ray diffraction (XRD) showing alinear contraction in unit cell volume with increasing Al content. Solid-state 27Aland 71Ga NMR spectroscopy show a strong preference for Ga to occupythe tetrahedral sites and Al to occupy the octahedral sites. Using isopropanolas the solvent, g-Ga2–xAlxO3defect spinel solid solutions with x ≤ 1.8 can be prepared at 240 °C in24 hours. These materials are nanocrystalline, as evidenced by their broaddiffraction profiles, but the refined cubic lattice parameter shows a linearrelationship with the Ga:Al content and solid-state NMR spectroscopy again showsa preference for Al to occupy the octahedral sites. Thermal decomposition ofthe Ga5–xAlxO7(OH)occurs via poorly ordered materials that resemble e-Ga2–xAlxO3and k-Ga2–xAlxO3,but g-Ga2–xAlxO3transforms above 750 °C to monoclinic b-Ga2–xAlxO3for 0 ≤ x ≤ 1.3 and to hexagonal a-Ga2–xAlxO3for x = 1.8, with intermediate compositions 1.3 < x < 1.8 giving mixturesof the aand b polymorphs.Solid-state NMR spectroscopy shows only the expected octahedral Al for a-Ga2–xAlxO3and, for b-Ga2–xAlxO3,the ~1:2 ratio of tetrahedral:octahedral Al is in good agreement with Rietveldanalysis of the average structures against powder XRD data. Relative energiescalculated by periodic density functional theory (DFT) confirm that there is a~5.2 kJ mol–1 penalty for tetrahedral rather than octahedral Al inGa5–xAlxO7(OH), whereas this penalty is muchlower (~2.0 kJ mol–1) for b-Ga2–xAlxO3,in good qualitative agreement with the experimental NMR spectra.PostprintPeer reviewe

An authentic learner-centered planetary health assignment: A five-year evaluation of student choices to address Sustainable Development Goal 13 (Climate Action)

A Code Red has been declared for the planet and human health. Climate change (e.g., increasing temperatures, adverse weather events, rising sea levels) threatens the planet's already declining ecosystems. Without urgent action, all of Earth's inhabitants face an existential threat. Health professions education should therefore prepare learners to not only practice in a changing world, but authentic educational activities should also develop competencies for global and planetary citizenship. Planetary health has been integrated across the five-year Bond University (Australia) medical curriculum. It begins in the second week of Year 1 and ends with a session on Environmentally Sustainable Healthcare in the General Practice rotation in the final year. The purpose of this article is to describe the outcomes of the first 5 years (2018–2022) of a learner-centered planetary health assignment, underpinned by the 2030 United Nations (UN) Sustainable Development Goals (SDGs), in the second year of a five-year medical program. Using systems and/or design thinking with a focus on SDG13 (Climate Action) plus a second SDG of choice, self-selected teams of 4–6 students submit a protocol (with feedback) to develop a deliverable “product” for an intended audience. Data analysis of the first 5 years of implementation found that the most frequently selected SDGs in addition to SDG13 were: SDG12 Sustainable Production and Consumption (41% of teams), mostly relating to healthcare emissions and waste; SDG3 Health and Well-being (22%), generally involving the impact of air pollution; and SDG6 Clean Water and Sanitation (15%). A survey at the concluding conference garnered student feedback across various criteria. The planetary health assignment is authentic in that teams provide solutions to address climate change. Where appropriate, final “products” are sent to local or federal ministers for consideration (e.g., policy proposals) or integrated into the curriculum (e.g., learning modules). We believe that the competencies, attitudes, and values fostered through engagement with planetary health. Throughout the medical program, as evidenced by their evaluations, stands students in good stead to be change agents, not only in clinical practice but in society. An awareness has been created about the need for planetary citizenship in addition to global citizenship

A large geometric distortion in the first photointermediate of rhodopsin, determined by double-quantum solid-state NMR

Double-quantum magic-angle-spinning NMR experiments were performed on 11,12-C-13(2)-retinylidene-rhodopsin under illumination at low temperature, in order to characterize torsional angle changes at the C11-C12 photoisomerization site. The sample was illuminated in the NMR rotor at low temperature (similar to 120 K) in order to trap the primary photointermediate, bathorhodopsin. The NMR data are consistent with a strong torsional twist of the HCCH moiety at the isomerization site. Although the HCCH torsional twist was determined to be at least 40A degrees, it was not possible to quantify it more closely. The presence of a strong twist is in agreement with previous Raman observations. The energetic implications of this geometric distortion are discussed

Mass of the Southern Black Hole in NGC 6240 from Laser Guide Star Adaptive Optics

NGC 6240 is a pair of colliding disk galaxies, each with a black hole in its core. We have used laser guide star adaptive optics on the Keck II telescope to obtain high-resolution ($\sim 0.06$") near-infrared integral-field spectra of the region surrounding the supermassive black hole in the south nucleus of this galaxy merger. We use the K-band CO absorption bandheads to trace stellar kinematics. We obtain a spatial resolution of about 20 pc and thus directly resolve the sphere of gravitational influence of the massive black hole. We explore two different methods to measure the black hole mass. Using a Jeans Axisymmetric Multi-Gaussian mass model, we investigate the limit that a relaxed mass distribution produces all of the measured velocity dispersion, and find an upper limit on the black hole mass at 2.0 \pm 0.2 \times 10^9 M_{\sun}. When assuming the young stars whose spectra we observe remain in a thin disk, we compare Keplerian velocity fields to the measured two-dimensional velocity field measured and fit for a mass profile containing a black hole point mass plus a radially-varying spherical component, which suggests a lower limit for the black hole mass of 8.7 \pm 0.3 \times 10^8 M_{\sun}. Our measurements of the stellar velocity dispersion place this AGN within the scatter of the $M_{BH}$-$\sigma_{*}$ relation. As NGC 6240 is a merging system, this may indicate that the relation is preserved during a merger at least until the final coalescence of the two nuclei.Comment: 10 pages, 12 figures; accepted to Ap

Epitope-specific humoral responses to human cytomegalovirus glycoprotein-B vaccine with MF59: Anti-AD2 levels correlate with protection from viremia

The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase-2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB ELISA antibody levels whose titer correlated directly with protection against post-transplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients. We focussed on four key antigenic domains (AD) of gB; AD1, AD2, AD4 and AD5 measuring antibody levels in patient sera and correlating these with post-transplant HCMV viremia. Vaccination of seropositive patients significantly boosted pre-existing antibody levels against the immunodominant region AD1 as well as against AD2, AD4 and AD5. A decreased incidence of viremia correlated with higher antibody titers against AD2 but not with antibody titers against the other three ADs. Overall, these data support the hypothesis that antibodies against AD2 are a major component of the immune protection of seropositives seen following vaccination with gB/MF59 vaccine and identify a correlate of protective immunity in allograft patients