Quiet engine program flight engine design study

The results are presented of a preliminary flight engine design study based on the Quiet Engine Program high-bypass, low-noise turbofan engines. Engine configurations, weight, noise characteristics, and performance over a range of flight conditions typical of a subsonic transport aircraft were considered. High and low tip speed engines in various acoustically treated nacelle configurations were included

Towards an efficient numerical simulation of complex 3D knee joint motion

We present a time-dependent finite element model of the human knee joint of full 3D geometric complexity together with advanced numerical algorithms needed for its simulation. The model comprises bones, cartilage and the major ligaments, while patella and menisci are still missing. Bones are modeled by linear elastic materials, cartilage by linear viscoelastic materials, and ligaments by one-dimensional nonlinear Cosserat rods. In order to capture the dynamical contact problems correctly, we solve the full PDEs of elasticity with strict contact inequalities. The spatio-temporal discretization follows a time layers approach (first time, then space discretization). For the time discretization of the elastic and viscoelastic parts we use a new contact-stabilized Newmark method, while for the Cosserat rods we choose an energy-momentum method. For the space discretization, we use linear finite elements for the elastic and viscoelastic parts and novel geodesic finite elements for the Cosserat rods. The coupled system is solved by a Dirichlet–Neumann method. The large algebraic systems of the bone–cartilage contact problems are solved efficiently by the truncated non-smooth Newton multigrid method

Predicting EQ-5D index scores from Promis Profile 29 in the United Kingdom, France, And Germany

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recor

Predicting EQ-5D-5L crosswalk from the PROMIS-29 profile for the United Kingdom, France, and Germany

BACKGROUND: EQ-5D health state utilities (HSU) are commonly used in health economics to compute quality-adjusted life years (QALYs). The EQ-5D, which is country-specific, can be derived directly or by mapping from self-reported health-related quality of life (HRQoL) scales such as the PROMIS-29 profile. The PROMIS-29 from the Patient Reported Outcome Measures Information System is a comprehensive assessment of self-reported health with excellent psychometric properties. We sought to find optimal models predicting the EQ-5D-5L crosswalk from the PROMIS-29 in the United Kingdom, France, and Germany and compared the prediction performances with that of a US model. METHODS: We collected EQ-5D-5L and PROMIS-29 profiles and three samples representative of the general populations in the UK (n = 1509), France (n = 1501), and Germany (n = 1502). We used stepwise regression with backward selection to find the best models to predict the EQ-5D-5L crosswalk from all seven PROMIS-29 domains. We investigated the agreement between the observed and predicted EQ-5D-5L crosswalk in all three countries using various indices for the prediction performance, including Bland-Altman plots to examine the performance along the HSU continuum. RESULTS: The EQ-5D-5L crosswalk was best predicted in France (nRMSEFRA = 0.075, nMAEFRA = 0.052), followed by the UK (nRMSEUK = 0.076, nMAEUK = 0.053) and Germany (nRMSEGER = 0.079, nMAEGER = 0.051). The Bland-Altman plots show that the inclusion of higher-order effects reduced the overprediction of low HSU scores. CONCLUSIONS: Our models provide a valid method to predict the EQ-5D-5L crosswalk from the PROMIS-29 for the UK, France, and Germany

Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts

BACKGROUND: Non-neuronal cells, including those derived from lung, are reported to express nicotinic acetylcholine receptors (nAChR). We examined nAChR subunit expression in short-term cultures of human airway cells derived from a series of never smokers, ex-smokers, and active smokers. METHODS AND RESULTS: At the mRNA level, human bronchial epithelial (HBE) cells and airway fibroblasts expressed a range of nAChR subunits. In multiple cultures of both cell types, mRNA was detected for subunits that constitute functional muscle-type and neuronal-type pentomeric receptors. Two immortalized cell lines derived from HBE cells also expressed muscle-type and neuronal-type nAChR subunits. Airway fibroblasts expressed mRNA for three muscle-type subunits (α1, δ, and ε) significantly more often than HBE cells. Immunoblotting of HBE cell and airway fibroblast extracts confirmed that mRNA for many nAChR subunits is translated into detectable levels of protein, and evidence of glycosylation of nAChRs was observed. Some minor differences in nAChR expression were found based on smoking status in fibroblasts or HBE cells. Nicotine triggered calcium influx in the immortalized HBE cell line BEAS2B, which was blocked by α-bungarotoxin and to a lesser extent by hexamethonium. Activation of PKC and MAPK p38, but not MAPK p42/44, was observed in BEAS2B cells exposed to nicotine. In contrast, nicotine could activate p42/44 in airway fibroblasts within five minutes of exposure. CONCLUSIONS: These results suggest that muscle-type and neuronal-type nAChRs are functional in airway fibroblasts and HBE cells, that prior tobacco exposure does not appear to be an important variable in nAChR expression, and that distinct signaling pathways are observed in response to nicotine

Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem.

Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1) contains a previously undetected Rap1-binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that has a propensity to form a helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical, as charge-reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1-binding site and a transient lipid-dependent helix in F1 work in tandem to enable a direct Rap1-talin1 interaction to cause integrin activation