Development, simulation validation, and wind tunnel testing of a digital controller system for flutter suppression

Flutter suppression (FS) is one of the active control concepts being investigated by the AFW program. The design goal for FS control laws was to increase the passive flutter dynamic pressure by 30 percent. In order to meet this goal, the FS control laws had to be capable of suppressing both symmetric and antisymmetric flutter instabilities simultaneously. In addition, the FS control laws had to be practical and low-order, robust and capable of real time execution within the 200 hz. sampling time. The purpose here is to present an overview of the development, simulation validation, and wind tunnel testing of a digital controller system for flutter suppression

Developmental toxicity study of sodium molybdate dihydrate administered in the diet to Sprague Dawley rats

AbstractMolybdenum is an essential nutrient for humans and animals and is a constituent of several important oxidase enzymes. It is normally absorbed from the diet and to a lesser extent from drinking water and the typical human intake is around 2μg/kg bodyweight per day. No developmental toxicity studies to contemporary standards have been published and regulatory decisions have been based primarily on older studies where the nature of the test material, or the actual dose levels consumed is uncertain.In the current study the developmental toxicity of sodium molybdate dihydrate as a representative of a broad class of soluble molybdenum(VI) compounds, was given in the diet to Sprague Dawley rats in accordance with OECD Test Guideline 414. Dose levels of 0, 3, 10, 20 and 40mgMo/kgbw/day were administered from GD6 to GD20. No adverse effects were observed at any dose level on the dams, or on embryofetal survival, fetal bodyweight, or development, with no increase in malformations or variations. Significant increases in serum and tissue copper levels were observed but no toxicity related to these was observed. The NOAEL observed in this study was 40mgMo/kgbw/day, the highest dose tested

Non-invasive Liver Fibrosis Screening on CT Images using Radiomics

Objectives: To develop and evaluate a radiomics machine learning model for detecting liver fibrosis on CT of the liver. Methods: For this retrospective, single-centre study, radiomic features were extracted from Regions of Interest (ROIs) on CT images of patients who underwent simultaneous liver biopsy and CT examinations. Combinations of contrast, normalization, machine learning model, and feature selection method were determined based on their mean test Area Under the Receiver Operating Characteristic curve (AUC) on randomly placed ROIs. The combination and selected features with the highest AUC were used to develop a final liver fibrosis screening model. Results: The study included 101 male and 68 female patients (mean age = 51.2 years $\pm$ 14.7 [SD]). When averaging the AUC across all combinations, non-contrast enhanced (NC) CT (AUC, 0.6100; 95% CI: 0.5897, 0.6303) outperformed contrast-enhanced CT (AUC, 0.5680; 95% CI: 0.5471, 0.5890). The combination of hyperparameters and features that yielded the highest AUC was a logistic regression model with inputs features of maximum, energy, kurtosis, skewness, and small area high gray level emphasis extracted from non-contrast enhanced NC CT normalized using Gamma correction with $\gamma$ = 1.5 (AUC, 0.7833; 95% CI: 0.7821, 0.7845), (sensitivity, 0.9091; 95% CI: 0.9091, 0.9091). Conclusions: Radiomics-based machine learning models allow for the detection of liver fibrosis with reasonable accuracy and high sensitivity on NC CT. Thus, these models can be used to non-invasively screen for liver fibrosis, contributing to earlier detection of the disease at a potentially curable stage

Assessing the threat of toxic contaminants to early marine survival of Chinook salmon in the Salish Sea

Human development of the Salish Sea has resulted in loss and modification of salmonid habitats, including reduced habitat quality due to contaminant inputs, particularly in the lower reaches of rivers and estuaries of the central Puget Sound. Chemical contaminants released into the Salish Sea from anthropogenic sources can reduce the health and productivity of salmon. Juvenile salmon are exposed to contaminants in freshwater, estuarine, and marine habitats but they are particularly vulnernable as they transition from fresh to saltwater because this life history stage is especially sensitive to stressors that may reduce their early marine survival. Reduced growth and disease resistance have been demonstrated for juvenile Chinook salmon exposed to environmentally relevant contaminant levels; however, synoptic, Puget Sound-wide surveys to assess the extent and magnitude of contaminant exposure are lacking. In this study we measured exposure of juvenile Chinook salmon to chemicals of concern that enter Puget Sound via stormwater, wastewater treatment facilities, atmospheric deposition to marine waters, and groundwater. During the spring and summer of 2013, outmigrating fish were sampled from the river mouthes and two adjacent marine shorelines at each of five Puget Sound river-estuary systems: Skagit, Snohomish, Green/Duwamish, Puyallup/Hylebos, and Nisqually. We (1) report the extent and magnitude of exposure, (2) compare exposure in outmigrants across five major river-estuary systems, and (3) evaluate potential effects on marine survival. Results will be used to establish a time series of contaminant conditions in juvenile Chinook salmon to measure the effectiveness of current toxics reductions strategies and actions, inform future pollution reduction efforts, and enhanced recovery of Chinook salmon

Elucidating Nature’s Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders

Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms that responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute (NHLBI) released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this Special Article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature’s solutions to heart, lung, blood, and sleep disorders through future research in this area

Impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery

Background: Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014–2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. Methods: Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. Results: With an economic investment of AU$3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers’ outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. Conclusion: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete

Elucidating Nature’s Solutions to Heart, Lung, and Blood Diseases and Sleep Disorders

Evolution has provided a number of animal species with extraordinary phenotypes. Several of these phenotypes allow species to survive and thrive in environmental conditions that mimic disease states in humans. The study of evolved mechanisms that responsible for these phenotypes may provide insights into the basis of human disease and guide the design of new therapeutic approaches. Examples include species that tolerate acute or chronic hypoxemia like deep-diving mammals and high-altitude inhabitants, as well as those that hibernate and interrupt their development when exposed to adverse environments. The evolved traits exhibited by these animal species involve modifications of common biological pathways that affect metabolic regulation, organ function, antioxidant defenses, and oxygen transport. In 2006, the National Heart, Lung, and Blood Institute (NHLBI) released a funding opportunity announcement to support studies that were designed to elucidate the natural molecular and cellular mechanisms of adaptation in species that tolerate extreme environmental conditions. The rationale for this funding opportunity is detailed in this Special Article, and the specific evolved mechanisms examined in the supported research are described. Also highlighted are past medical advances achieved through the study of animal species that have evolved extraordinary phenotypes as well as the expectations for new understanding of nature’s solutions to heart, lung, blood, and sleep disorders through future research in this area

The role of G protein gene GNB3 C825T Polymorphism in HIV-1 acquisition, progression and immune activation

<p>Abstract</p> <p>Background</p> <p>The <it>GNB3 C825T </it>polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The <it>GNB3 </it>825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. <it>GNB3 </it>825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. <it>Ex vivo </it>immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.</p> <p>Results</p> <p><it>GNB3 </it>genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, <it>GNB3 </it>genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25⁺FOXP3⁺) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.</p> <p>Conclusions</p> <p>In contrast to previous reports, we were unable to provide evidence to suggest that the <it>GNB3 C825T </it>polymorphism affects HIV-1 acquisition or disease progression within African populations. <it>Ex vivo </it>immune activation and plasma chemokine levels were similarly unaffected by <it>GNB3 </it>genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of <it>GNB3 </it>polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.</p

Urinary Arsenic Speciation in Children and Pregnant Women from Spain

Inorganic arsenic (i-As) is a non-threshold human carcinogen that has been associated with several adverse health outcomes. Exposure to i-As is of particular concern among pregnant women, infants and children, as they are specifically vulnerable to the adverse health effects of i-As, and in utero and early-life exposure, even low to moderate levels of i-As, may have a marked effect throughout the lifespan. Ion chromatography-mass spectrometry detection (IC-ICP-MS) was used to analyse urinary arsenic speciation, as an exposure biomarker, in samples of 4-year-old children with relatively low-level arsenic exposure living in different regions in Spain including Asturias, Gipuzkoa, Sabadell and Valencia. The profile of arsenic metabolites in urine was also determined in samples taken during pregnancy (1st trimester) and in the children from Valencia of 7 years old. The median of the main arsenic species found in the 4-year-old children was 9.71 mug/l (arsenobetaine-AsB), 3.97 mug/l (dimethylarsinic acid-DMA), 0.44 mug/l (monomethylarsonic acid-MMA) and 0.35 mug/l (i-As). Statistically significant differences were found in urinary AsB, MMA and i-As according to the study regions in the 4-year-old, and also in DMA among pregnant women and their children. Spearman's correlation coefficient among urinary arsenic metabolites was calculated, and, in general, a strong methylation capacity to methylate i-As to MMA was observed

Urinary Arsenic Speciation in Children and Pregnant Women from Spain

Inorganic arsenic (i-As) is a non-threshold human carcinogen that has been associated with several adverse health outcomes. Exposure to i-As is of particular concern among pregnant women, infants and children, as they are specifically vulnerable to the adverse health effects of i-As, and in utero and early-life exposure, even low to moderate levels of i-As, may have a marked effect throughout the lifespan. Ion chromatography-mass spectrometry detection (IC-ICP-MS) was used to analyse urinary arsenic speciation, as an exposure biomarker, in samples of 4-year-old children with relatively low-level arsenic exposure living in different regions in Spain including Asturias, Gipuzkoa, Sabadell and Valencia. The profile of arsenic metabolites in urine was also determined in samples taken during pregnancy (1st trimester) and in the children from Valencia of 7 years old. The median of the main arsenic species found in the 4-year-old children was 9.71 lg/l (arsenobetaine—AsB), 3.97 lg/l (dimethylarsinic acid—DMA), 0.44 lg/l (monomethylarsonic acid—MMA) and 0.35 lg/l (i-As). Statistically significant differences were found in urinary AsB, MMA and i-As according to the study regions in the 4-year-old, and also in DMA among pregnant women and their children. Spearman’s correlation coefficient among urinary arsenic metabolites was calculated, and, in general, a strong methylation capacity to methylate i-As to MMA was observed