Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. © 2011 Duncan et al.

Channel selection in the short-time modulation domain for distant speech recognition

Automatic speech recognition from multiple distant micro- phones poses significant challenges because of noise and reverberations. The quality of speech acquisition may vary between microphones because of movements of speakers and channel distortions. This paper proposes a channel selection approach for selecting reliable channels based on selection criterion operating in the short-term modulation spectrum domain. The proposed approach quantifies the relative strength of speech from each microphone and speech obtained from beamforming modulations. The new technique is compared experimentally in the real reverb conditions in terms of perceptual evaluation of speech quality (PESQ) measures and word error rate (WER). Overall improvement in recognition rate is observed using delay-sum and superdirective beamformers compared to the case when the channel is selected randomly using circular microphone arrays.

IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection

Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases. The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset. A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.

Simultaneous voltammetric determination of four triazine herbicides in water samples with the aid of chemometrics

A novel differential pulse voltammetry (DPV) method was developed for the simultaneous analysis of herbicides in water. A mixture of four herbicides, atrazine, simazine, propazine and terbuthylazine was analyzed simultaneously and the complex, overlapping DPV voltammograms were resolved by several chemometrics methods such as partial least squares (PLS), principal component regression (PCR) and principal component–artificial networks (PC–ANN). The complex profiles of the voltammograms collected from a synthetic set of samples were best resolved with the use of the PC–ANN method, and the best predictions of the concentrations of the analytes were obtained with the PC-ANN model (%RPET = 6.1 and average %Recovery = 99.0). The new method was also used for analysis of real samples, and the obtained results were compared well with those from the GC-MS technique. Such conclusions suggest that the novel method is a viable alternative to the other commonly used methods such as GC, HPLC and GC-MS.

Separate or simultaneous removal of radioactive cations and anions from water by layered sodium vanadate-based sorbents

Nanofibers of sodium vanadate, consisting of very thin negatively charged layers and exchangeable sodium ions between the layers, are efficient sorbents for the removal of radioactive 137Cs+ and 85Sr2+ cations from water. The exchange of 137Cs+ or 85Sr2+ ions with the interlayer Na+ ions eventually triggered structural deformation of the thin layers, trapping the 137Cs+ and 85Sr2+ ions in the nanofibers. Furthermore, when the nanofibers were dispersed in a AgNO3 solution at pH >7, well-dispersed Ag2O nanocrystals formed by firmly anchoring themselves on the fiber surfaces along planes of crystallographic similarity with those of Ag2O. These nanocrystals can efficiently capture I– anions by forming a AgI precipitate, which was firmly attached to the substrates. We also designed sorbents that can remove 137Cs+ and 125I– ions simultaneously for safe disposal by optimizing the Ag2O loading and sodium content of the vanadate. This study confirms that sorbent features such as fibril morphology, negatively charged thin layers and readily exchangeable Na+ ions between the layers, and the crystal planes for the formation of a coherent interface with Ag2O nanocrystals on the fiber surface are very important for the simultaneous uptake of cations and anions.

Simultaneous kinetic spectrometric determination of three flavonoid antioxidants in fruit with the aid of chemometrics

A simple, inexpensive and sensitive kinetic spectrophotometric method was developed for the simultaneous determination of three anti-carcinogenic flavonoids: catechin, quercetin and naringenin, in fruit samples. A yellow chelate product was produced in the presence neocuproine and Cu(I) – a reduction product of the reaction between the flavonoids with Cu(II), and this enabled the quantitative measurements with UV–vis spectrophotometry. The overlapping spectra obtained, were resolved with chemometrics calibration models, and the best performing method was the fast independent component analysis (fast-ICA/PCR (Principal component regression)); the limits of detection were 0.075, 0.057 and 0.063 mg L−1 for catechin, quercetin and naringenin, respectively. The novel method was found to outperform significantly the common HPLC procedure.

Polymorphisms in a desaturase 2 ortholog associate with cuticular hydrocarbon and male mating success variation in a natural population of Drosophila serrata

Elucidating the nature of genetic variation underlying both sexually selected traits and the fitness components of sexual selection is essential to understanding the broader consequences of sexual selection as an evolutionary process. To date, there have been relatively few attempts to connect the genetic variance in sexually selected traits with segregating DNA sequence polymorphisms. We set out to address this in a well-characterized sexual selection system - the cuticular hydrocarbons (CHCs) of Drosophila serrata - using an indirect association study design that allowed simultaneous estimation of the genetic variance in CHCs, sexual fitness and single nucleotide polymorphism (SNP) effects in an outbred population. We cloned and sequenced an ortholog of the D. melanogaster desaturase 2 gene, previously shown to affect CHC biosynthesis in D. melanogaster, and associated 36 SNPs with minor allele frequencies > 0.02 with variance in CHCs and sexual fitness. Three SNPs had significant multivariate associations with CHC phenotype (q-value < 0.05). At these loci, minor alleles had multivariate effects on CHCs that were weakly associated with the multivariate direction of sexual selection operating on these traits. Two of these SNPs had pleiotropic associations with male mating success, suggesting these variants may underlie responses to sexual selection due to this locus. There were 15 significant male mating success associations (q-value < 0.1), and interestingly, we detected a nonrandom pattern in the relationship between allele frequency and direction of effect on male mating success. The minor-frequency allele usually reduced male mating success, suggesting a positive association between male mating success and total fitness at this locus.

Electronic Control of Facial Selection in Additions to Sterically Unbiased Ketones and Olefins

By definition, the two faces of a pi bond are equivalent.1 However, they are rendered nonequivalent in most molecules because of the absence of a plane of symmetry encompassing the double bond and the adjacent substituents. As a result, additions to trigonal centers from the two faces need not be equally facile. Exploiting this stereodifferentiation in a controlled manner represents one of the core problems in organic synthesis. Evidently, the factors which determine such diastereoselection need to be delineated in as much detail as possible.

Artificial Neural Network Based Automatic Emergency Landing Site Selection for UAVs and Highly Automated Aircraft

In this report an artificial neural network (ANN) based automated emergency landing site selection system for unmanned aerial vehicle (UAV) and general aviation (GA) is described. The system aims increase safety of UAV operation by emulating pilot decision making in emergency landing scenarios using an ANN to select a safe landing site from available candidates. The strength of an ANN to model complex input relationships makes it a perfect system to handle the multicriteria decision making (MCDM) process of emergency landing site selection. The ANN operates by identifying the more favorable of two landing sites when provided with an input vector derived from both landing site's parameters, the aircraft's current state and wind measurements. The system consists of a feed forward ANN, a pre-processor class which produces ANN input vectors and a class in charge of creating a ranking of landing site candidates using the ANN. The system was successfully implemented in C++ using the FANN C++ library and ROS. Results obtained from ANN training and simulations using randomly generated landing sites by a site detection simulator data verify the feasibility of an ANN based automated emergency landing site selection system.

Influence of road traffic environment and mobile phone distraction on the speed selection behaviour of young drivers

Travel speed is one of the most critical parameters for road safety; the evidence suggests that increased vehicle speed is associated with higher crash risk and injury severity. Both naturalistic and simulator studies have reported that drivers distracted by a mobile phone select a lower driving speed. Speed decrements have been argued to be a risk compensatory behaviour of distracted drivers. Nonetheless, the extent and circumstances of the speed change among distracted drivers are still not known very well. As such, the primary objective of this study was to investigate patterns of speed variation in relation to contextual factors and distraction. Using the CARRS-Q high-fidelity Advanced Driving Simulator, the speed selection behaviour of 32 drivers aged 18-26 years was examined in two phone conditions: baseline (no phone conversation) and handheld phone operation. The simulator driving route contained five different types of road traffic complexities, including one road section with a horizontal S curve, one horizontal S curve with adjacent traffic, one straight segment of suburban road without traffic, one straight segment of suburban road with traffic interactions, and one road segment in a city environment. Speed deviations from the posted speed limit were analysed using Ward’s Hierarchical Clustering method to identify the effects of road traffic environment and cognitive distraction. The speed deviations along curved road sections formed two different clusters for the two phone conditions, implying that distracted drivers adopt a different strategy for selecting driving speed in a complex driving situation. In particular, distracted drivers selected a lower speed while driving along a horizontal curve. The speed deviation along the city road segment and other straight road segments grouped into a different cluster, and the deviations were not significantly different across phone conditions, suggesting a negligible effect of distraction on speed selection along these road sections. Future research should focus on developing a risk compensation model to explain the relationship between road traffic complexity and distraction.

Perception of ultraviolet light by crab spiders and its role in selection of hunting sites

The perception of ultraviolet (UV) light by spiders has so far been only demonstrated in salticids. Crab spiders (Thomisidae) hunt mostly on flowers and need to find appropriate hunting sites. Previous studies have shown that some crab spiders that reflect UV light use UV contrast to enhance prey capture. The high UV contrast can be obtained either by modulation of body colouration or active selection of appropriate backgrounds for foraging. We show that crab spiders (Thomisus sp.)hunting on Spathiphyllum plants use chromatic contrast, especially UV contrast, to make themselves attractive to hymenopteran prey. Apart from that, they are able to achieve high UV contrast by active selection of non-UV reflecting surfaces when given a choice of UV-reflecting and non-UV reflecting surfaces in the absence of odour cues. Honeybees (Apis cerana) approached Spathiphyllum plants bearing crab spiders on which the spiders were high UV-contrast targets with greater frequency than those plants on which the UV-contrast of the spiders was low. Thus, crab spiders can perceive UV and may use it to choose appropriate backgrounds to enhance prey capture, by exploiting the attraction of prey such as honeybees to UV.

Synthesis and characterisation of heterometallic molecular triangles using ambidentate linker: self-selection of a single linkage isomer

The coordination driven self-assembly of discrete molecular triangles from a non-symmetric ambidentate linker 5-pyrimidinecarboxylate (5-pmc) and Pd(II)/Pt(II) based 90◦ acceptors is presented. Despite the possibility of formation of a mixture of isomeric macrocycles (linkage isomers) due to different connectivity of the ambidentate linker, formation of a single and symmetrical linkage somer in both the cases is an interesting observation. Moreover, the reported macrocycles represent the first example of discrete metallamacrocycles of bridging 5-pmc. While solution composition in both the cases was characterised by multinuclear NMR study and electrospray ionization mass spectrometry (ESI-MS), the identity of the assemblies in the solid state was established by X-ray single crystals structure analysis. Variable temperature NMR study clearly ruled out the formation of any other macrocycles by [4 + 4] or [2 + 2] self-assembly of the reacting components.

Simultaneous Electrodeposition of MnO2 and Mn(OH)(2) for Supercapacitor Studies

Among the various Mn compounds, both MnO2 and Mn(OH)2 are electrochemically active in supercapacitor studies. MnO2 and Mn(OH)2 are simultaneously deposited, through a one-pot method, on the anode and cathode, respectively, of a galvanostatic electrolysis cell consisting of aqueous Mn(NO3)2 electrolyte. MnO2 and Mn(OH)2 coated stainless steel (SS) electrodes are found to exhibit a capacitive behavior with a high specific capacitance. MnO2/SS and Mn(OH)2/SS electrodes are used as the negative and positive electrodes, respectively, in assembling nonsymmetrical capacitors and testing. The results indicate that both Mn-based electrodes prepared simultaneously in a single electrolysis possess interesting electrochemical properties for supercapacitor application.

Fast Multiple Access Selection through variable power transmissions

Many wireless applications demand a fast mechanism to detect the packet from a node with the highest priority ("best node") only, while packets from nodes with lower priority are irrelevant. In this paper, we introduce an extremely fast contention-based multiple access algorithm that selects the best node and requires only local information of the priorities of the nodes. The algorithm, which we call Variable Power Multiple Access Selection (VP-MAS), uses the local channel state information from the accessing nodes to the receiver, and maps the priorities onto the receive power. It is based on a key result that shows that mapping onto a set of discrete receive power levels is optimal, when the power levels are chosen to exploit packet capture that inherently occurs in a wireless physical layer. The VP-MAS algorithm adjusts the expected number of users that contend in each step and their respective transmission powers, depending on whether previous transmission attempts resulted in capture, idle channel, or collision. We also show how reliable information regarding the total received power at the receiver can be used to improve the algorithm by enhancing the feedback mechanism. The algorithm detects the packet from the best node in 1.5 to 2.1 slots, which is considerably lower than the 2.43 slot average achieved by the best algorithm known to date.

Non-invasive MR imaging of inflammation in a patient with both asymptomatic carotid atheroma and an abdominal aortic aneurysm: A case report

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. USPIO-enhanced MRI imaging is a promising non-i nvasive method to identify high-risk atheromatous plaque inflammation in vivo in humans, in which areas of focal signal loss on MR images have been shown to correspond to the location of activated macrophages, typically at the shoulder regions of the plaque. This is the first report in humans describing simultaneous USPIO uptake within atheroma in two different arterial territories and again emphasises that atherosclerosis is a truly systemic disease. With further work, USPIO-enhanced MR imaging may be useful in identifying inflamed vulnerable atheromatous plaques in vivo, so refining patient selection for intervention and allowing appropriate early aggressive pharmacotherapy to prevent plaque rupture.