Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS)

Genetics plays a crucial role in human aging with up to 30% of those living to the mid-80s being determined by genetic variation. Survival to older ages likely entails an even greater genetic contribution. There is increasing evidence that genes implicated in age-related diseases, such as cancer and neuronal disease, play a role in affecting human life span. We have selected the 10 most promising late-onset Alzheimer's disease (LOAD) susceptibility genes identified through several recent large genome-wide association studies (GWAS). These 10 LOAD genes (APOE, CLU, PICALM, CR1, BIN1, ABCA7, MS4A6A, CD33, CD2AP, and EPHA1) have been tested for association with human aging in our dataset (1385 samples with documented age at death [AAD], age range: 58-108 years; mean age at death: 80.2) using the most significant single nucleotide polymorphisms (SNPs) found in the previous studies. Apart from the APOE locus (rs2075650) which showed compelling evidence of association with risk on human life span (p = 5.27 × 10(-4)), none of the other LOAD gene loci demonstrated significant evidence of association. In addition to examining the known LOAD genes, we carried out analyses using age at death as a quantitative trait. No genome-wide significant SNPs were discovered. Increasing sample size and statistical power will be imperative to detect genuine aging-associated variants in the future. In this report, we also discuss issues relating to the analysis of genome-wide association studies data from different centers and the bioinformatic approach required to distinguish spurious genome-wide significant signals from real SNP associations.

Delamination threshold load for dynamic impact on plates

A criterion is derived for delamination onset in transversely isotropic laminated plates under small mass, high velocity impact. The resulting delamination threshold load is about 21% higher than the corresponding quasi-static threshold load. A closed form approximation for the peak impact load is then used to predict the delamination threshold velocity. The theory is validated for a range of test cases by comparison with 3D finite element simulation using LS-DYNA and a newly developed interface element to model delamination onset and growth. The predicted delamination threshold loads and velocities are in very good agreement with the finite element simulations. Good agreement is also shown in a comparison with published experimental results. In contrast to quasi-static impacts, delamination growth occurs under a rapidly decreasing load. Inclusion of finite thickness effects and a proper description of the contact stiffness are found to be vital for accurate prediction of the delamination threshold velocity

Predicting the ultimate load of a CFRP wingbox

The finite element method in conjunction with the Soutis-Fleck model is used to predict the residual strength after impact of a carbon-fibre reinforced plastic wingbox subjected to a cantilever type loading. The maximum stress failure criterion further validates the Soutis-Fleck model predictions. The Soutis-Fleck model predicts that the wingbox fails at a tip load of 99.2 kN, approximately 5.5% less than the experimental observation

Design technique for mm-wave IC realization of the load network of switched-mode class-EF power amplifier

Analysis and synthesis of the new Class-EF power amplifier (PA) are presented in this paper. The proposed circuit offers means to alleviate some of the major issues faced by existing Class-EF and Class-EF PAs, such as (1) substantial power losses due to parasitic resistance of the large inductor in the Class-EF load network, (2) unpredictable behaviour of practical lumped inductors and capacitors at harmonic frequencies, and (3) deviation from ideal Class-EF operation mode due to detrimental effects of device output inductance at high frequencies. The transmission-line load network of the Class-EF PA topology elaborated in this paper simultaneously satisfies the Class-EF optimum impedance requirements at fundamental frequency, second, and third harmonics as well as simultaneously providing matching to the circuit optimum load resistance for any prescribed system load resistance. Furthermore, an elegant solution using an open and short-circuit stub arrangement is suggested to overcome the problem encountered in the mm-wave IC realizations of the Class-EF PA load network due to lossy quarter-wave line. © 2010 IEICE Institute of Electronics Informati.

In Demand: Therapeutic Services for Children and Young People Who Have Experienced Sexual Abuse

This paper describes the key findings of an NSPCC study estimating need, in the UK, for therapeutic services for children who have experienced sexual abuse. This is based upon current estimates of the prevalence and impact of sexual abuse towards children and young people against the availability of therapeutic services in the UK. Data were collected on service location, availability, scope and coverage across England, Wales, Northern Ireland and Scotland. Researchers: (1) mapped 508 services; (2) collected data from 195 services via a structured questionnaire; (3) followed up 21 service managers and 11 service commissioners with a semi-structured interview; and (4) carried out two focus groups with young people. Data were collected on service location, availability, scope and coverage The overall level of specialist provision is low, with less than one service available per 10 000 children and young people in the UK. Calculations of need indicate that 57 156 children across the UK in the last year may have been unable to access a service. Findings from services support the view that need outstrips availability; that referral routes are limited, leaving few options for young people who have been raped or seriously sexually assaulted to directly access support; that significant waiting lists mean services must focus on reactive, rather than preventive, work; and that services are less accessible for certain groups, especially sexually abused teenagers, children with disabilities and those from Black, Asian, Minority Ethnic and Refugee backgrounds. Copyright (c) 2012 John Wiley & Sons, Ltd. Key Practitioner Messages Relevant professionals must be adequately trained to talk to children about sexual abuse and to identify those vulnerable in order to identify need. Expert specialist services are well placed to share learning on early help and identification with broader children's service providers. Active steps need to be taken by commissioners in consultation with young people, voluntary sector and adult sexual violence service providers to meet the shortfall at the level of local authorities.

Examining the presence of Arching-Action in Edge Stiffened Bridge Deck Cantilever Overhangs Subjected to a Wheel Load

Engineers have proposed the idea that there may be some arching action present in bridge deck cantilever overhangs stiffened along their longitudinal free edge, via a traffic barrier, subjected to a wheel load. This paper includes the details of a full-scale corrosion-free bridge deck with cantilever overhangs stiffened along their longitudinal free edge by a traffic barrier wall that has been constructed and tested under static and fatigue wheel loads at the University of Manitoba. It also reviews experimental test results and postulates various discussions that suggest the presence of arching-action in cantilever slab overhangs. Test results indicated static ultimate load capacities significantly greater than the ultimate capacity if the mode of failure and behavior of the cantilever overhang was completely flexural. These early results confirm and indicate the presence of arching-action resulting in a significant break-through in cantilever behavior when subjected to a wheel load. The theory to account for this arching-action is not yet developed and further research should be conducted.

Improving the Fuel Economy of a Tuned 600cc FSAE Engine

To maintain its relevance, motorsport cannot be exempt from
the trend of increasing fuel economy. This bears obvious
competitive benefits as well, either in decreasing the
frequency of pit stops or the mass of fuel carried. Given the
increased points weighting of fuel economy for the Formula
Student (FS) competition, a complete analysis was performed
on the Queen's Formula Racing 600cc motorcycle engine in
preparation for the 2011 competition.
The criteria for such high performance fuel economy differ to
a degree from most mass transportation counterparts and were
divided into three distinct regimes; full load, part load and no
load conditions.
Full load positions naturally demand maximum torque for
performance but that does not imply that fuel savings cannot
be made whilst preserving this. The point at which maximum
torque is produced with minimum air -fuel ratio, Leanest
mixture for Best Torque (LBT), was therefore sought and
mapped for full load.
At part load, torque is less of a concern, and maintaining a
sustainable engine temperature and transient response become
more important. With decreasing AFR, engine temperatures
can rise dramatically so temperatures were measured close to
the exhaust port for a wide range of air-fuel ratios.
Competition track data was analysed to highlight key part load
operating regions and these were mapped according to
measured safe temperature limits. Torque response to a step
throttle change was also measured to ensure suitable engine
transient performance was maintained.
At no load conditions, with low engine speed only idle
conditions need to be satisfied. In the situation where the
engine is still at high speed without load, the engine is being
motored and no fuel is required. An overrun fuel cut was
employed to reflect this giving significant fuel savings. The
effect on torque and engine pickup was measured.
Modifications were also made to the fuel injector location to
improve fuel mixing and evaporation at this lower air flow
condition.
These mapping regimes were implemented and tested using
fully transient lap simulations using competition track data
and a four quadrant AC engine dynamometer. The experiment
indicated a reduction in fuel consumption for 22 laps of the FS
track from 5.08litres to 3.67litres, around 27% in total. The
actual fuel used at the 2011 competition was 3.6 litres while
placing 8th in the endurance event, further validating the
benefits of these mapping regimes.

Algorithmic method for scraper load-time optimization

Scrapers have established an important position in the earthmoving field as they are independently capable of accomplishing an earthmoving operation. Given that loading a scraper to its capacity does not entail its maximum production, optimizing the scraper’s loading time is an essential prerequisite for successful operations management. The relevant literature addresses the loading time optimization through a graphical method that is founded on the invalid assumption that the hauling time is independent of the load time. To correct this, a new algorithmic optimization method that incorporates the golden section search and the bisection algorithm is proposed. Comparison of the results derived from the proposed and the existing method demonstrates that the latter entails the systematic needless prolongation of the loading stage thus resulting in reduced hourly production and increased cost. Therefore, the proposed method achieves an improved modeling of scraper earthmoving operations and contributes toward a more efficient cost management.