p130Cas, a substrate associated with v-Src and v-Crk, localizes to focal adhesions and binds to focal adhesion kinase

p130(Cas) (crk associated substrate) has the structural characteristics of an adapter protein, containing multiple consensus SH2 binding sites, an SH3 domain, and a proline-rich domain. The structure of p130(Cas) suggests that it may act to provide a framework for protein-protein interactions; however, as yet, its functional role in cells is unknown. In this report we show that p130(Cas) is localized to focal adhesions. We demonstrate that p130(Cas) associates both in vitro and in vivo with pp125(FAK) (focal adhesion kinase), a kinase implicated in signaling by the integrin family of cell adhesion receptors. p130(Cas) also associates with pp41/43(FRNK) (pp125(FAK)-related, non-kinase), an autonomously expressed form of pp125(FAK) composed of only the C-terminal noncatalytic domain. We show that the association of p130(Cas) with pp125(Fak) and pp41/43(FRNK) is direct, and is mediated by the binding of the SH3 domain of p130(Cas) to a proline-rich sequence present in both the C terminus of pp125(FAK) and in pp41/43(FRNK). In agreement with recent studies we show that p130(Cas) is tyrosine-phosphorylated upon integrin mediated cell adhesion. The association of p130(Cas) with pp125(FAK), a kinase which is activated upon cell adhesion, is likely to be functionally important in integrin mediated signal transduction.

Implementation of phantom-less IMRT delivery verification using Varian DynaLog files and R/V output

This study aims to evaluate the use of Varian radiotherapy dynamic treatment log (DynaLog) files to verify IMRT plan delivery as part of a routine quality assurance procedure. Delivery accuracy in terms of machine performance was quantified by multileaf collimator (MLC) position errors and fluence delivery accuracy for patients receiving intensity modulated radiation therapy (IMRT) treatment. The relationship between machine performance and plan complexity, quantified by the modulation complexity score (MCS) was also investigated. Actual MLC positions and delivered fraction of monitor units (MU), recorded every 50 ms during IMRT delivery, were extracted from the DynaLog files. The planned MLC positions and fractional MU were taken from the record and verify system MLC control file. Planned and delivered beam data were compared to determine leaf position errors with and without the overshoot effect. Analysis was also performed on planned and actual fluence maps reconstructed from the MLC control file and delivered treatment log files respectively. This analysis was performed for all treatment fractions for 5 prostate, 5 prostate and pelvic node (PPN) and 5 head and neck (H&N) IMRT plans, totalling 82 IMRT fields in ∼5500 DynaLog files. The root mean square (RMS) leaf position errors without the overshoot effect were 0.09, 0.26, 0.19 mm for the prostate, PPN and H&N plans respectively, which increased to 0.30, 0.39 and 0.30 mm when the overshoot effect was considered. Average errors were not affected by the overshoot effect and were 0.05, 0.13 and 0.17 mm for prostate, PPN and H&N plans respectively. The percentage of pixels passing fluence map gamma analysis at 3%/3 mm was 99.94 ± 0.25%, which reduced to 91.62 ± 11.39% at 1%/1 mm criterion. Leaf position errors, but not gamma passing rate, were directly related to plan complexity as determined by the MCS. Site specific confidence intervals for average leaf position errors were set at -0.03-0.12 mm for prostate and -0.02-0.28 mm for more complex PPN and H&N plans. For all treatment sites confidence intervals for RMS errors with the overshoot was set at 0-0.50 mm and for the percentage of pixels passing a gamma analysis at 1%/1 mm a confidence interval of 68.83% was set also for all treatment sites. This work demonstrates the successful implementation of treatment log files to validate IMRT deliveries and how dynamic log files can diagnose delivery errors not possible with phantom based QC. Machine performance was found to be directly related to plan complexity but this is not the dominant determinant of delivery accuracy.

Güler and Öngel v Turkey: Article 3 of the European Convention on Human Rights and Strasbourg’s discourse on the justified use of force

This article discusses the discourse on the justified use of force in the Strasbourg Court’s analysis of Article 3. With particular focus on the judgment in Güler and Öngel v Turkey, a case concerning the use of force by State agents against demonstrators, it addresses the question of the implications of such discourse, found in this and other cases, on the absolute nature of Article 3. It offers a perspective which suggests that the discourse on the justified use of force can be reconciled with Article 3’s absolute nature.

Relatively Absolute? The Undermining of Article 3 ECHR in Ahmad v UK

The recent decision of the European Court of Human Rights in Ahmad v UK dangerously undermines the well-established case law of the Court on counter-terrorism and non-refoulement towards torture, inhuman and degrading treatment or punishment. Although ostensibly rejecting the ‘relativist’ approach to Article 3 ECHR adopted by the House of Lords in Wellington v Secretary of State for the Home Department, the Court appeared to accept that what is a breach of Article 3 in a domestic context may not be a breach in an extradition or expulsion context. This statement is difficult to reconcile with the jurisprudence constante of the Court in the last fifteen years, according to which Article 3 ECHR is an absolute right in all its applications, including non-refoulement, regardless of who the potential victim of torture, inhuman or degrading treatment is, what she may have done, or where the treatment at issue would occur.

Optical quantum memory for polarization qubits with V-type three-level atoms

We investigate an optical quantum memory scheme with V-type three-level atoms based on the controlled reversible inhomogeneous broadening (CRIB) technique. We theoretically show the possibility to store and retrieve a weak light pulse interacting with the two optical transitions of the system. This scheme implements a quantum memory for a polarization qubit - a single photon in an arbitrary polarization state - without the need of two spatially separated two-level media, thus offering the advantage of experimental compactness overcoming the limitations due to mismatching and unequal efficiencies that can arise in spatially separated memories. The effects of a relative phase change between the atomic levels, as well as of phase noise due to, for example, the presence of spurious electric and magnetic fields are analyzed.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Adsorption Study using Optimised 3D Organised Mesoporous Silica Coated with Fe and Al Oxides for Specific As(III) and As(V) Removal from Contaminated Synthetic Groundwater

This work presents the possibility of optimising 3D Organised Mesoporous Silica (OMS) coated with both iron and aluminium oxides for the optimal removal of As(III) and As(V) from synthetic contaminated water. The materials developed were fully characterised and were tested for removing arsenic in batch experiments. The effect of total Al to Fe oxides coating on the selective removal of As(III) and As(V) was studied. It was shown that 8% metal coating was the optimal configuration for the coated OMS materials in removing arsenic. The effect of arsenic initial concentration and pH, kinetics and diffusion mechanisms was studied, modelled and discussed. It was shown that the advantage of an organised material over an un-structured sorbent was very limited in terms of kinetic and diffusion under the experimental conditions. It was shown that physisorption was the main adsorption process involved in As removal by the coated OMS. Maximum adsorption capacity of 55 mg As(V).g-1 was noticed at pH 5 for material coated with 8% Al oxides while 35 mg As(V).g-1 was removed at pH 4 for equivalent material coated with Fe oxides.

Physical and dynamical characterisation of low ΔV NEA (190491) 2000 FJ10

Aims: We investigated the physical properties and dynamical evolution of near-Earth asteroid (NEA) (190491) 2000 FJ10 in order to assess the suitability of this accessible NEA as a space mission target. Methods: Photometry and colour determination were carried out with the 1.54 m Kuiper Telescope (Mt Bigelow, USA) and the 10 m Southern African Large Telescope (SALT; Sutherland, South Africa) during the object's recent favourable apparition in 2011-12. During the earlier 2008 apparition, a spectrum of the object in the 6000-9000 Angstrom region was obtained with the 4.2 m William Herschel Telescope (WHT; Canary Islands, Spain). Interpretation of the observational results was aided by numerical simulations of 1000 dynamical clones of 2000 FJ10 up to 106 yr in the past and in the future. Results: The asteroid's spectrum and colours determined by our observations suggest a taxonomic classification within the S-complex although other classifications (V, D, E, M, P) cannot be ruled out. On this evidence, it is unlikely to be a primitive, relatively unaltered remnant from the early history of the solar system and thus a low priority target for robotic sample return. Our photometry placed a lower bound of 2 h to the asteroid's rotation period. Its absolute magnitude was estimated to be 21.54 ± 0.1 which, for a typical S-complex albedo, translates into a diameter of 130 ± 20 m. Our dynamical simulations show that it has likely been an Amor for the past 105 yr. Although currently not Earth-crossing, it will likely become so during the period 50-100 kyr in the future. It may have arrived from the inner or central main belt >1 Myr ago as a former member of a low-inclination S-class asteroid family. Its relatively slow rotation and large size make it a suitable destination for a human mission. We show that ballistic Earth-190491-Earth transfer trajectories with ΔV <2 km s-1 at the asteroid exist between 2052 and 2061. Based on observations made with the Southern African Large Telescope (SALT).

Instructional Methods For Optimal Learning For An Aerospace Assembly Task: digital animation v pictogram-based instructions

Previous studies on work instruction delivery for complex assembly tasks have shown that the mode and delivery method for the instructions in an engineering context can influence both build time and product quality. The benefits of digital, animated instructional formats when compared to static pictures and text only formats have already been demonstrated. Although pictograms have found applications for relatively straight forward operations and activities, their applicability to relatively complex assembly tasks has yet to be demonstrated. This study compares animated instructions and pictograms for the assembly of an aircraft panel. Based around a series of build experiments, the work records build time as well as the number of media references to measure and compare build efficiency. The number of build errors and the time required to correct them is also recorded. The experiments included five participants completing five builds over five consecutive days for each media type. Results showed that on average the total build time was 13.1% lower for the group using animated instructions. The benefit of animated instructions on build time was most prominent in the first three builds, by build four this benefit had disappeared. There were a similar number of instructional references for the two groups over the five builds but the pictogram users required a lot more references during build 1. There were more errors among the group using pictograms requiring more time for corrections during the build.

A genome-wide association study of anorexia nervosa

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(^-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Barrier characteristics of PtSi/p-Si schottky diodes as determined from I-V-T measurements

The current-voltage-temperature characteristics of PtSi/p-Si Schottky barrier diodes were measured in the temperature range 60-115 K. Deviation of the ideality factor from unity below 80 K may be modelled using the so-called T-0 parameter with T-0 = 18 K. It is also shown that the curvature in the Richardson plots may be remedied by using the flatband rather than the zero-bias saturation current density. Physically, the departure from ideality is interpreted in terms of an inhomogeneous Schottky contact. Here we determine a mean barrier height at T = 0 K, phi(b)(-0) = 223 mV, with an (assumed) Gaussian distribution of standard deviation sigma(phi) = 12.5 mV. These data are correlated with the zero-bias barrier height, phi(j)(0) = 192 mV (at T = 90 K), the photoresponse barrier height, phi(ph) = 205 mV, and the flatband barrier height, phi(fb) = 214 mV. Finally, the temperature coefficient of the flatband barrier was found to be -0.121 mV K-1, which is approximately equal to 1/2(dE(g)(i)/dT), thus suggesting that the Fermi level at the interface is pinned to the middle of the band gap.

Analysis of deformation behavior and workability of advanced 9Cr-Nb-V ferritic heat resistant steels

Hot compression tests were carried out on 9Cr–Nb–V heat resistant steels in the temperature range of 600–1200 °C and the strain rate range of 10−2–100 s−1 to study their deformation characteristics. The full recrystallization temperature and the carbon-free bainite phase transformation temperature were determined by the slope-change points in the curve of mean flow stress versus the inverse of temperature. The parameters of the constitutive equation for the experimental steels were calculated, including the stress exponent and the activation energy. The lower carbon content in steel would increase the fraction of precipitates by increasing the volume of dynamic strain-induced (DSIT) ferrite during deformation. The ln(εc) versus ln(Z) and the ln(σc) versus ln(Z) plots for both steels have similar trends. The efficiency of power dissipation maps with instability maps merged together show excellent workability from the strain of 0.05 to 0.6. The microstructure of the experimental steels was fully recrystallized upon deformation at low Z value owing to the dynamic recrystallization (DRX), and exhibited a necklace structure under the condition of 1050 °C/0.1 s−1 due to the suppression of the secondary flow of DRX. However, there were barely any DRX grains but elongated pancake grains under the condition of 1000 °C/1 s−1 because of the suppression of the metadynamic recrystallization (MDRX).

The Double Life of Duke of Somerset v Cookson, or a Legal Excavation of the Corbridge Lanx

Duke of Somerset v Cookson (1735) occupies an important place in English legal history as a leading authority for Chancery jurisdiction to order specific delivery of movable property where an award of damages would be inadequate. The property at issue was the Corbridge lanx, now in the British Museum, but then claimed as treasure trove by the duke of Somerset as lord of the manor of Corbridge. This paper re-examines Cookson as the first reported English decision relating to treasure trove, and uses later treasure trove claims by the duke of Somerset's successors to the manor of Corbridge, the dukes of Northumberland, to shed fresh light on the 1735 decision and on the development of treasure trove practice from the eighteenth century onwards.

Arsenic(III,V) adsorption onto charred dolomite: charring optimization and batch studies

In this work, the removal of arsenic from aqueous solutions onto thermally processed dolomite is investigated. The dolomite was thermally processed (charred) at temperatures of 600, 700 and 800 degrees C for 1, 2, 4 and 8 h. Isotherm experiments were carried out on these samples over a wide pH range. A complete arsenic removal was achieved over the pH range studied when using the 800 degrees C charred dolomite. However, at this temperature, thermal degradation of the dolomite weakens its structure due to the decomposition of the magnesium carbonate, leading to a partial dissolution. For this reason, the dolomitic sorbent chosen for further investigations was the 8 h at 700 degrees C material. Isotherm studies indicated that the Langmuir model was successful in describing the process to a better extent than the Freundlich model for the As(V) adsorption on the selected charred dolomite. However, for the As(III) adsorption, the Freundlich model was more successful in describing the process. The maximum adsorption capacities of charred dolomite for arsenite and arsenate ions are 1.846 and 2.157 mg/g, respectively. It was found that both the pseudo first- and second-order kinetic models are able to describe the experimental data (R-2 > 0.980). The data suggest the charring process allows dissociation of the dolomite to calcium carbonate and magnesium oxide, which accelerates the process of arsenic oxide and arsenic carbonate precipitation. (C) 2014 Elsevier B.V. All rights reserved.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.