Podocyte Injury Associated with Mutant α-Actinin-4

Focal segmental glomerulosclerosis (FSGS) is an important cause of proteinuria and nephrotic syndrome in humans. The pathogenesis of FSGS may be associated with glomerular visceral epithelial cell (GEC; podocyte) injury, leading to apoptosis, detachment, and “podocytopenia”, followed by glomerulosclerosis. Mutations in α-actinin-4 are associated with FSGS in humans. In cultured GECs, α-actinin-4 mediates adhesion and cytoskeletal dynamics. FSGS-associated α-actinin-4 mutants show increased binding to actin filaments, compared with the wild-type protein. Expression of an α-actinin-4 mutant in mouse podocytes in vivo resulted in proteinuric FSGS. GECs that express mutant α-actinin-4 show defective spreading and motility, and such abnormalities could alter the mechanical properties of the podocyte, contribute to cytoskeletal disruption, and lead to injury. The potential for mutant α-actinin-4 to injure podocytes is also suggested by the characteristics of this mutant protein to form microaggregates, undergo ubiquitination, impair the ubiquitin-proteasome system, enhance endoplasmic reticulum stress, and exacerbate apoptosis

Target Selection for the LBTI Exozodi Key Science Program

The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ~300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.Comment: accepted to ApJ

A novel method for comparison of arterial remodeling in hypertension: Quantification of arterial trees and recognition of remodeling patterns on histological sections

Remodeling of spatially heterogeneous arterial trees is routinely quantified on tissue sections by averaging linear dimensions, with lack of comparison between different organs and models. The impact of experimental models or hypertension treatment modalities on organ-specific vascular remodeling remains undefined. A wide variety of arterial remodeling types has been demonstrated for hypertensive models, which include differences across organs. The purpose of this study was to reassess methods for measurement of arterial remodeling and to establish a morphometric algorithm for standard and comparable quantification of vascular remodeling in hypertension in different vascular beds. We performed a novel and comprehensive morphometric analysis of terminal arteries in the brain, heart, lung, liver, kidney, spleen, stomach, intestine, skin, skeletal muscle, and adrenal glands of control and Goldblatt hypertensive rats on routinely processed tissue sections. Mean dimensions were highly variable but grouping them into sequential 5 μm intervals permitted creation of reliable linear regression equations and complex profiles. Averaged arterial dimensions demonstrated seven remodeling patterns that were distinct from conventional inward-outward and hypertrophic-eutrophic definitions. Numerical modeling predicted at least nineteen variants of arterial spatial conformations. Recognition of remodeling variants was not possible using averaged dimensions, their ratios, or the remodeling and growth indices. To distinguish remodeling patterns, a three dimensional modeling was established and tested. The proposed algorithm permits quantitative analysis of arterial remodeling in different organs and may be applicable for comparative studies between animal hypertensive models and human hypertension. Arterial wall tapering is the most important factor to consider in arterial morphometry, while perfusion fixation with vessel relaxation is not necessary. Terminal arteries in organs undergo the same remodeling pattern in Goldblatt rats, except for organs with hemodynamics affected by the arterial clip. The existing remodeling nomenclature should be replaced by a numerical classification applicable to any type of arterial remodeling

Ground state parameters, finite-size scaling, and low-temperature properties of the two-dimensional S=1/2 XY model

We present high-precision quantum Monte Carlo results for the S=1/2 XY model on a two-dimensional square lattice, in the ground state as well as at finite temperature. The energy, the spin stiffness, the magnetization, and the susceptibility are calculated and extrapolated to the thermodynamic limit. For the ground state, we test a variety of finite-size scaling predictions of effective Lagrangian theory and find good agreement and consistency between the finite-size corrections for different quantities. The low-temperature behavior of the susceptibility and the internal energy is also in good agreement with theoretical predictions.Comment: 6 pages, 8 figure

Diet diversity in pastoral and agro-pastoral households in Ugandan rangeland ecosystems

We explore how diet diversity differs with agricultural seasons and between households within pastoral and agro-pastoral livelihood systems, using variety of foods consumed as a less complex proxy indicator of food insecurity than benchmark indicators like anthropometry and serum nutrients. The study was in the central part of the rangelands in Uganda. Seventy nine households were monitored for three seasons, and eight food groups consumed during a 24 hour diet recall period used to create a household diet diversity score (HDDS). Mean HDDS was 3.2, varied significantly with gender, age, livelihood system and season (p < .001, F = 15.04), but not with household size or household head’s education level. Agro-pastoralists exhibited lower mean diet diversity than pastoralists (p < .01, F = 7.84) and among agro-pastoralists, households headed by persons over 65 years were most vulnerable (mean HDDS 2.1). This exploratory study raises issues requiring further investigation to inform policies on nutrition security in the two communities

Sources and characteristics of summertime organic aerosol in the Colorado Front Range: perspective from measurements and WRF-Chem modeling

Abstract. The evolution of organic aerosols (OAs) and their precursors in the boundary layer (BL) of the Colorado Front Range during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ, July–August 2014) was analyzed by in situ measurements and chemical transport modeling. Measurements indicated significant production of secondary OA (SOA), with enhancement ratio of OA with respect to carbon monoxide (CO) reaching 0.085±0.003 µg m−3 ppbv−1. At background mixing ratios of CO, up to  ∼  1.8 µg m−3 background OA was observed, suggesting significant non-combustion contribution to OA in the Front Range. The mean concentration of OA in plumes with a high influence of oil and natural gas (O&amp;G) emissions was  ∼  40 % higher than in urban-influenced plumes. Positive matrix factorization (PMF) confirmed a dominant contribution of secondary, oxygenated OA (OOA) in the boundary layer instead of fresh, hydrocarbon-like OA (HOA). Combinations of primary OA (POA) volatility assumptions, aging of semi-volatile species, and different emission estimates from the O&amp;G sector were used in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulation scenarios. The assumption of semi-volatile POA resulted in greater than a factor of 10 lower POA concentrations compared to PMF-resolved HOA. Including top-down modified O&amp;G emissions resulted in substantially better agreements in modeled ethane, toluene, hydroxyl radical, and ozone compared to measurements in the high-O&amp;G-influenced plumes. By including emissions from the O&amp;G sector using the top-down approach, it was estimated that the O&amp;G sector contributed to  &lt;  5 % of total OA, but up to 38 % of anthropogenic SOA (aSOA) in the region. The best agreement between the measured and simulated median OA was achieved by limiting the extent of biogenic hydrocarbon aging and consequently biogenic SOA (bSOA) production. Despite a lower production of bSOA in this scenario, contribution of bSOA to total SOA remained high at 40–54 %. Future studies aiming at a better emissions characterization of POA and intermediate-volatility organic compounds (IVOCs) from the O&amp;G sector are valuable

Reef Cover, a coral reef classification for global habitat mapping from remote sensing

Coral reef management and conservation stand to benefit from improved high-resolution global mapping. Yet classifications underpinning large-scale reef mapping to date are typically poorly defined, not shared or region-specific, limiting end-users’ ability to interpret outputs. Here we present Reef Cover, a coral reef geomorphic zone classification, developed to support both producers and end-users of global-scale coral reef habitat maps, in a transparent and version-based framework. Scalable classes were created by focusing on attributes that can be observed remotely, but whose membership rules also reflect deep knowledge of reef form and functioning. Bridging the divide between earth observation data and geo-ecological knowledge of reefs, Reef Cover maximises the trade-off between applicability at global scales, and relevance and accuracy at local scales. Two case studies demonstrate application of the Reef Cover classification scheme and its scientific and conservation benefits: 1) detailed mapping of the Cairns Management Region of the Great Barrier Reef to support management and 2) mapping of the Caroline and Mariana Island chains in the Pacific for conservation purposes

School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial

Introduction This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students. Methods and analysis The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ∼720 senior school students (aged 16-18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction)

Time-efficient physical activity intervention for older adolescents with disability : rationale and study protocol for the Burn 2 Learn adapted (B2La) cluster randomised controlled trial

Introduction Physical activity declines during adolescence, with the lowest levels of activity observed among those with disability. Schools are ideal settings to address this issue; however, few school-based interventions have been specifically designed for older adolescents with disability. Our aim is to investigate the effects of a school-based physical activity programme, involving high-intensity interval training (HIIT), on physical, mental and cognitive health in older adolescents with disability. Methods and analysis We will evaluate the Burn 2 Learn adapted (B2La) intervention using a two-arm, parallel group, cluster randomised controlled trial with allocation occurring at the school level (treatment or waitlist control). Secondary schools will be recruited in two cohorts from New South Wales, Australia. We will aim to recruit 300 older adolescents (aged 15–19 years) with disability from 30 secondary schools (10 in cohort 1 and 20 in cohort 2). Schools allocated to the intervention group will deliver two HIIT sessions per week during scheduled specialist support classes. The sessions will include foundational aerobic and muscle strengthening exercises tailored to meet student needs. We will provide teachers with training, resources, and support to facilitate the delivery of the B2La programme. Study outcomes will be assessed at baseline, 6 months (primary endpoint), and 9 months. Our primary outcome is functional capacity assessed using the 6 min walk/push test. Secondary outcomes include physical activity, muscular fitness, body composition, cognitive function, quality of life, physical literacy, and on-task behaviour in the classroom. We will also conduct economic and process evaluations to determine cost-effectiveness, programme acceptability, implementation, adaptability, and sustainability in schools. Ethics and dissemination This study has received approval from the University of Newcastle (H-2021–0262) and the New South Wales Department of Education (SERAP: 2021257) human research ethics committees. Findings will be published in peer-reviewed journals, and key stakeholders will be provided with a detailed report following the study. Trial registration number Australian New Zealand Clinical Trials Registry Number: ACTRN12621000884808

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested