Active In-Flight Load Redistribution Utilizing Fiber-Optic Shape Sensing and Multiple Control Surfaces

Morphing wing technologies have gained research interest in recent years as technological advancements pave the way for such innovations. A key benefit of such a morphing wing concept is the ability of the wing to transition into an optimal configuration at multiple flight conditions. Such a morphing wing will have applications not only in drag reduction but also in flutter suppression and gust alleviation. By manipulating the wing geometry to match a given flight profile it is likely that the wing will yield increases in not just aerodynamic efficiency but also structural efficiency. These structurally efficient designs will likely rely on some type of structural sensing system which will ensure the wing maintains positive margins throughout its flight profile

The impact of the COVID-19 pandemic on cancer care.

The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection

Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Combs, B., Christensen, K. R., Richards, C., Kneynsberg, A., Mueller, R. L., Morris, S. L., Morfini, G., Brady, S. T., & Kanaan, N. M. Frontotemporal lobar dementia mutant tau impairs axonal transport through a protein phosphatase 1γ-dependent mechanism. Journal of Neuroscience, 41(45), (2021): 9431-9451, https://doi.org/10.1523/JNEUROSCI.1914-20.2021.Pathologic tau modifications are characteristic of Alzheimer's disease and related dementias, but mechanisms of tau toxicity continue to be debated. Inherited mutations in tau cause early onset frontotemporal lobar dementias (FTLD-tau) and are commonly used to model mechanisms of tau toxicity in tauopathies. Previous work in the isolated squid axoplasm model demonstrated that several pathogenic forms of tau inhibit axonal transport through a mechanism involving activation of protein phosphatase 1 (PP1). Here, we determined that P301L and R5L FTLD mutant tau proteins elicit a toxic effect on axonal transport as monomeric proteins. We evaluated interactions of wild-type or mutant tau with specific PP1 isoforms (α, β, and γ) to examine how the interaction contributes to this toxic effect using primary rat hippocampal neurons from both sexes. Pull-down and bioluminescence resonance energy transfer experiments revealed selective interactions of wild-type tau with PP1α and PP1γ isoforms, but not PP1β, which were significantly increased by the P301L tau mutation. The results from proximity ligation assays confirmed the interaction in primary hippocampal neurons. Moreover, expression of FTLD-linked mutant tau in these neurons enhanced levels of active PP1, also increasing the pausing frequency of fluorescently labeled vesicles in both anterograde and retrograde directions. Knockdown of PP1γ, but not PP1α, rescued the cargo-pausing effects of P301L and R5L tau, a result replicated by deleting a phosphatase-activating domain in the amino terminus of P301L tau. These findings support a model of tau toxicity involving aberrant activation of a specific PP1γ-dependent pathway that disrupts axonal transport in neurons.This work was supported by National Institutes of Health (NIH) Grants R01 NS082730 (N.M.K. and S.T.B.), R01 AG044372 (N.M.K.), and R01 AG067762 (N.M.K.); NIH/National Institute on Aging, Michigan Alzheimer's Disease Research Center Grant 5P30AG053760 (B.C.); Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Alzheimer's Research Program Award W81XWH-20-1-0174 (B.C.); Alzheimer's Association Research Grants 20-682085 (B.C.), R01 NS118177 (G.A.M.), and R21NS120126 (G.A.M.); Zenith Award from the Alzheimer's Association (S.T.B.); Tau Consortium/Rainwater Foundation (S.T.B.); Neurodegenerative Research (G.A.M.); and the Secchia Family Foundation (N.M.K.)

Impact of Powder Variability on the Microstructure and Mechanical Behavior of Selective Laser Melted Alloy 718

Powder-bed additive manufacturing processes use fine powders to build parts layer-by-layer. Alloy 718 powder feedstocks for selective laser melting (SLM) additive manufacturing are produced commercially by both gas and rotary atomization and are available typically in the 10-45 or 15-45 microns size ranges. A comprehensive investigation was conducted to understand the impact of powder variability on the microstructure and mechanical behavior of SLM 718 heat treated to Aerospace Material Specification (AMS) 5664. This study included sixteen virgin powders and three once-recycled powders within the 10-45 and 15-45 microns size ranges that were obtained from seven direct source suppliers and one reseller. Although alike as highly regular spheroids, these powders showed distinct differences in composition (especially Al, C and N contents), particle size distributions, and powder features such as degree of agglomeration, fusion and surface roughness. Compositional differences expectedly had the strongest impact on microstructure. High N and C contents formed TiN-nitrides and/or (Nb,Ti,Mo)-C carbides on the grain boundaries, prevented recrystallization during heat treatment, and resulted in retained (001)-scalloped shaped grains that ranged from 19 to 41 microns in average size. In the absence of this particle pinning, the average grain size of the heat treated SLM 718 ranged from 51 microns to 90 microns. Room temperature tensile and high cycle fatigue (HCF) testing compared as-fabricated (AF) and low stress ground (LSG) surface conditions. Tensile testing revealed consistent behavior between the two surface conditions and amongst the powder lots. The finer grained SLM 718 builds displayed the lowest tensile properties. A SLM 718 build fabricated from a powder with eight times lower C content showed statistically better tensile properties presumably due to enhanced coarsening of (delta)-Ni3Nb precipitates. The specimens from once-recycled powders had slightly higher tensile strengths and slightly higher ductility compared to their virgin equivalents; once-recycling also did not substantially degrade the mean HCF life. The LSG fatigue lives agreed with conventionally manufactured 718 data, while AF lives exhibited a knock-down due to surface roughness. The fatigue lives of AF specimens were statistically equivalent across powder lots except for one and failures typically initiated at stress concentrators associated with SLM surface asperities. Fatigue testing of low stress ground specimens result in both transgranular and within facet crack initiations. More than half of the cracks initiated from these facets for the machined condition; however, these facets appeared to be within grains that were larger-than-average in size. A nitrogen-atomized powder with fine prior particles of TiN-nitrides and M(Ti,Nb,Mo)C carbides from atomization on powder surfaces resulted in the best fatigue performance with segregation of these particles to the SLM 718 grain boundaries leading to higher resistance to early-stage crack propagation. Typically the fine-grained builds with minor phases along the grain boundaries did not perform well in fatigue, whereas a larger-grain build with lower carbon content and coarser delta-Ni3Nb precipitates showed the next best HCF response. Further details of the build microstructure and its impact on tensile and fatigue behavior was considered

Physico-chemical spectroscopic mapping of the planetary nebula NGC 40 and the 2D_NEB, a new 2D algorithm to study ionised nebulae

In this paper we present an analysis of the physical and chemical conditions of the planetary nebula NGC 40 through spatially-resolved spectroscopic maps. We also introduce a new algorithm --2D_NEB-- based on the well-established IRAF nebular package, which was developed to enable the use of the spectroscopic maps to easily estimate the astrophysical quantities of ionised nebulae. The 2D_NEB was benchmarked, and we clearly show that it works properly, since it compares nicely with the IRAF nebular software. Using this software, we derive the maps of several physical parameters of NGC 40. From these maps, we conclude that Te[NII] shows only a slight temperature variation from region to region, with its values constrained between ~8,000 K and ~9,500 K. Electron densities, on the other hand, have a much more prominent spatial variation, as Ne[SII] values vary from ~1,000 cm^(-3) to ~3,000 cm^(-3). Maps of the chemical abundances also show significant variations. From the big picture of our work, we strongly suggest that analysis with spatial resolution be mandatory for more complete study of the physical and chemical properties of planetary nebulae.Comment: 15 pages, 10 figures, 8 tables; Accepted for publication in MNRA

Genome-wide association study using family-based cohorts identifies the WLS and CCDC170/ESR1 loci as associated with bone mineral density.

BACKGROUND: Osteoporosis is a common and debilitating bone disease that is characterised by a low bone mineral density (BMD), a highly heritable trait. Genome-wide association studies (GWAS) have proven to be very successful in identifying common genetic variants associated with BMD adjusted for age, gender and weight, however a large portion of the genetic variance for this trait remains unexplained. There is evidence to suggest significant genetic correlation between body size traits and BMD. It has also recently been suggested that unintended bias can be introduced as a result of adjusting a phenotype for a correlated trait. We performed a GWAS meta-analysis in two populations (total n = 6,696) using BMD data adjusted for only age and gender, in an attempt to identify genetic variants associated with BMD including those that may have potential pleiotropic effects on BMD and body size traits. RESULTS: We observed a single variant, rs2566752, associated with spine BMD at the genome-wide significance level in the meta-analysis (P = 3.36 × 10(-09)). Logistic regression analysis also revealed an association between rs2566752 and fracture rate in one of our study cohorts (P = 0.017, n = 5,654). This is an intronic variant located in the wntless Wnt ligand secretion mediator (WLS) gene (1p31.3), a known BMD locus which encodes an integral component of the Wnt ligand secretion pathway. Bioinformatics analyses of variants in moderate LD with rs2566752 produced strong evidence for a regulatory role for the variants rs72670452, rs17130567 and rs1430738. Expression quantitative trait locus (eQTL) analysis suggested that the variants rs12568456 and rs17130567 are associated with expression of the WLS gene in whole blood, cerebellum and temporal cortex brain tissue (P = 0.034-1.19 × 10(-23)). Gene-wide association testing using the VErsatile Gene-based Association Study 2 (VEGAS2) software revealed associations between the coiled-coil domain containing 170 (CCDC170) gene, located adjacent to the oestrogen receptor 1 (ESR1) gene, and BMD at the spine, femoral neck and total hip sites (P = 1.0 × 10(-06), 2.0 × 10(-06) and 2.0 × 10(-06) respectively). CONCLUSIONS: Genetic variation at the WLS and CCDC170/ESR1 loci were found to be significantly associated with BMD adjusted for only age and gender at the genome-wide level in this meta-analysis

Solenodon genome reveals convergent evolution of venom in eulipotyphlan mammals

Venom systems are key adaptations that have evolved throughout the tree of life and typically facilitate predation or defense. Despite venoms being model systems for studying a variety of evolutionary and physiological processes, many taxonomic groups remain understudied, including venomous mammals. Within the order Eulipotyphla, multiple shrew species and solenodons have oral venom systems. Despite morphological variation of their delivery systems, it remains unclear whether venom represents the ancestral state in this group or is the result of multiple independent origins. We investigated the origin and evolution of venom in eulipotyphlans by characterizing the venom system of the endangered Hispaniolan solenodon (Solenodon paradoxus). We constructed a genome to underpin proteomic identifications of solenodon venom toxins, before undertaking evolutionary analyses of those constituents, and functional assessments of the secreted venom. Our findings show that solenodon venom consists of multiple paralogous kallikrein 1 (KLK1) serine proteases, which cause hypotensive effects in vivo, and seem likely to have evolved to facilitate vertebrate prey capture. Comparative analyses provide convincing evidence that the oral venom systems of solenodons and shrews have evolved convergently, with the 4 independent origins of venom in eulipotyphlans outnumbering all other venom origins in mammals. We find that KLK1s have been independently coopted into the venom of shrews and solenodons following their divergence during the late Cretaceous, suggesting that evolutionary constraints may be acting on these genes. Consequently, our findings represent a striking example of convergent molecular evolution and demonstrate that distinct structural backgrounds can yield equivalent functions

The New Generation Atlas of Quasar Spectral Energy Distributions from Radio to X-rays

We have produced the next generation of quasar spectral energy distributions (SEDs), essentially updating the work of Elvis et al. (1994) by using high-quality data obtained with several space and ground-based telescopes, including NASA's Great Observatories. We present an atlas of SEDs of 85 optically bright, non-blazar quasars over the electromagnetic spectrum from radio to X-rays. The heterogeneous sample includes 27 radio-quiet and 58 radio-loud quasars. Most objects have quasi-simultaneous ultraviolet-optical spectroscopic data, supplemented with some far-ultraviolet spectra, and more than half also have Spitzer mid-infrared IRS spectra. The X-ray spectral parameters are collected from the literature where available. The radio, far-infrared, and near-infrared photometric data are also obtained from either the literature or new observations. We construct composite spectral energy distributions for radio-loud and radio-quiet objects and compare these to those of Elvis et al., finding that ours have similar overall shapes, but our improved spectral resolution reveals more detailed features, especially in the mid and near-infrared.Comment: 46 pages, 10 figures, 10 tables, Accepted by ApJS. Composite SED data files for radio-loud and radio-quiet quasars (rlmsedMR.txt, rqmsedMR.txt) are included in the source (Other formats -> Source). Supplemental figures are not include

Generating a taxonomy for genetic conditions relevant to reproductive planning

As genome or exome sequencing (hereafter genome-scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome-scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be complicated. Carrier testing generally occurs in the context of reproductive decision-making and involves patient values in a way that other types of genetic testing may not. The Kaiser Permanente Clinical Sequencing Exploratory Research program is conducting a randomized clinical trial of preconception carrier testing that allows participants to select their preferences for results from among broad descriptive categories rather than selecting individual conditions. This paper describes 1) the criteria developed by the research team, the return of results committee (RORC), and stakeholders for defining the categories; 2) the process of refining the categories based on input from patient focus groups and validation through a patient survey; and, 3) how the RORC then assigned specific gene-condition pairs to taxonomy categories being piloted in the trial. The development of four categories (serious, moderate/mild, unpredictable, late onset) for sharing results allows patients to select results based on their values without separately deciding their interest in knowing their carrier status for hundreds of conditions. A fifth category, lifespan limiting, was always shared. The lessons learned may be applicable in other results disclosure situations, such as incidental findings