Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan

The Benefits of the Passive and Active Aeroelastic Design of Aircraft Structures

Increasing performance requirements and the economical pressure to reduce the Direct Operational Costs of new aircraft designs can no longer be met by traditional and sequential design strategies. Especially in the field of aeroelasticity, multidisciplinary design concepts must be applied during the early design stage to develop flutter-free structures and to guarantee excellent multi-point design characteristics, e.g. for wing flight shape, control efficiencies, etc. This paper describes aeroelastic design methods like stiffness optimization, mass balance, and the aeroelastic tailoring of the composite structures of primary structures in order to maximize aeroelastic performance and to minimize weight penalties

The Benefits of the Passive and Active Design of Aircraft Structures

Increasing performance requirements and the economical pressure to reduce the Direct Operational Costs of new aircraft designs can no longer be met by traditional and sequential design strategies. Especially in the field of aeroelasticity, multidisciplinary design concepts must be applied during the early design stage to develop flutter-free structures and to guarantee excellent multi-point design characteristics, e.g. for wing flight shape, control efficiencies, etc. This paper describes aeroelastic design methods like stiffness optimization, mass balance, and the aeroelastic tailoring of the composite structures of primary structures in order to maximize aeroelastic performance and to minimize weight penalties

Hedonic travel cost and random utility models of recreation

Micro-economic theory began as an attempt to describe, predict and value the demand and supply of consumption goods. Quality was largely ignored at first, but economists have started to address quality within the theory of demand and specifically the question of site quality, which is an important component of land management. This paper demonstrates that hedonic and random utility models emanate from the same utility theoretical foundation, although they make different estimation assumptions. Using a theoretically consistent comparison, both approaches are applied to examine the quality of wilderness areas in the Southeastern US. Data were collected on 4778 visits to 46 trails in 20 different forest areas near the Smoky Mountains. Visitor data came from permits and an independent survey. The authors limited the data set to visitors from within 300 miles of the North Carolina and Tennessee border in order to focus the analysis on single purpose trips. When consistently applied, both models lead to results with similar signs but different magnitudes. Because the two models are equally valid, recreation studies should continue to use both models to value site quality. Further, practitioners should be careful not to make simplifying a priori assumptions which limit the effectiveness of both techniques

Identification of Novel Cyclic Lipopeptides from a Positional Scanning Combinatorial Library with Enhanced Antibacterial and Antibiofilm Activities

Treating bacterial infections can be difficult due to innate or acquired resistance mechanisms, and the formation of biofilms. Cyclic lipopeptides derived from fusaricidin/LI-F natural products represent particularly attractive candidates for the development of new antibacterial and antibiofilm agents, with the potential to meet the challenge of bacterial resistance to antibiotics. A positional-scanning combinatorial approach was used to identify the amino acid residues responsible for driving antibacterial activity, and increase the potency of these cyclic lipopeptides. Screening against the antibiotic resistant ESKAPE pathogens revealed the importance of hydrophobic as well as positively charged amino acid residues for activity of this class of peptides. The improvement in potency was especially evident against bacterial biofilms, since the lead cyclic lipopeptide showed promising in vitro and in vivo anti-biofilm activity at the concentration far below its respective MICs. Importantly, structural changes resulting in a more hydrophobic and positively charged analog did not lead to an increase in toxicity toward human cells