From Frank Miller to Zack Snyder, and Return: Contemporary Superhero Comics and Post-Classical Hollywood

Film adaptations of superhero comic-books offer a particularly rich case study to analyse narrative strategies of contemporary Hollywood cinema. The serial structures adopted by the comics they are based on, as well as their use of the spectacular potential of the image, provide a successful model for current audiovisual productions. Without completely abandoning classical techniques, these adaptations try to find a new balance between narrative and digital phantasmagoria. This paper discusses some significant examples of this genre, including adaptations of classical DC and Marvel franchises and more recent series, as well as other comic-book influenced films such as The Matrix and Unbreakable.

Nile blue-based nano-sized pH sensors for simultaneous far-red and near-infrared live bioimaging

Diblock copolymer vesicles are tagged with pH-responsive Nile Blue-based labels and used as a new type of pH-responsive colorimetric/fluorescent biosensor for far-red and near-infrared imaging of live cells. The diblock copolymer vesicles described herein are based on poly(2-(methacryloyloxy)ethyl phosphorylcholine-block-2-(diisopropylamino)ethyl methacrylate) [PMPC-PDPA]: the biomimetic PMPC block is known to facilitate rapid cell uptake for a wide range of cell lines, while the PDPA block constitutes the pH-responsive component that enables facile vesicle self-assembly in aqueous solution. These biocompatible vesicles can be utilized to detect interstitial hypoxic/acidic regions in a tumor model via a pH-dependent colorimetric shift. In addition, they are also useful for selective intracellular staining of lysosomes and early endosomes via subtle changes in fluorescence emission. Such nanoparticles combine efficient cellular uptake with a pH-responsive Nile Blue dye label to produce a highly versatile dual capability probe. This is in marked contrast to small molecule dyes, which are usually poorly uptaken by cells, frequently exhibit cytotoxicity, and are characterized by intracellular distributions invariably dictated by their hydrophilic/hydrophobic balance.

The sustainability and assessment of drystone retaining walls

The art of drystone walling is a highly sustainable traditional practice which uses local materials and craftsmen. As no<br/>mortar is used they have low embodied carbon, and much repair work or rebuilding can be carried out using very little if any new<br/>materials. However local practices developed to suit local materials, leading to a range of construction styles, making them difficult to<br/>assess. This paper examines a range of construction styles of drystone retaining walls in use across the United Kingdom.<br/>Understanding of the substantial variations of construction style is essential to enable proper assessment of these structures. Different<br/>frictional and weathering characteristics, and the naturally occurring shapes of stone found in an area, all affect the ways in which the<br/>stones have traditionally been assembled into walls. Ease of construction also plays a part, as the craftsman will naturally wish to<br/>achieve a robust construction in a way that is economical of time and effort. Aesthetics may be very important, for both client and<br/>craftsman. It is also shown that construction style is influenced by the location and function of the structures, with harbour walls<br/>particularly likely to have unique characteristics, and the reasons for this are explored.

IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0-50,000 Years Cal BP

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

Aims/hypothesis: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD. Methods: We exploited a novel algorithm, ���Bag of Naive Bayes���, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK���Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US). Results: Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2-rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the RGMA and MCTP2 genes, was replicated in independent case���control cohorts. rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under the genotypic model (p���&lt;���0.05), and rs12137135 upstream of WNT4 was associated with ESRD in Steno. Conclusions/interpretation: This study supports the previously identified findings on the RGMA/MCTP2 region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.

Spitzer Space Telescope spectra of post-AGB stars in the large magellanic Cloud-polycyclic aromatic hydrocarbons at low metallicities

<p>This paper reports variations of polycyclic aromatic hydrocarbons (PAHs) features that were found in Spitzer Space Telescope spectra of carbon-rich post-asymptotic giant branch (post-AGB) stars in the Large Magellanic Cloud (LMC). The paper consists of two parts. The first part describes our Spitzer spectral observing programme of 24 stars including post-AGB candidates. The latter half of this paper presents the analysis of PAH features in 20 carbon-rich post-AGB stars in the LMC, assembled from the Spitzer archive as well as from our own programme.We found that five post-AGB stars showed a broad feature with a peak at 7.7 ��m, that had not been classified before. Further, the 10-13 ��m PAH spectra were classified into four classes, one of which has three broad peaks at 11.3, 12.3 and 13.3 ��m rather than two distinct sharp peaks at 11.3 and 12.7 ��m, as commonly found in HII regions. Our studies suggest that PAHs are gradually processed while the central stars evolve from post-AGB phase to planetary nebulae, changing their composition before PAHs are incorporated into the interstellar medium. Although some metallicity dependence of PAH spectra exists, the evolutionary state of an object is more significant than its metallicity in determining the spectral characteristics of PAHs for LMC and Galactic post-AGB stars. �� 2014 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.</p>

SORBS1 gene, a new candidate for diabetic nephropathy: results from a multi-stage genome-wide association study in patients with type 1 diabetes

Aims/hypothesis<p class="a-plus-plus">The genetic determinants of diabetic nephropathy remain poorly understood. We aimed to identify novel susceptibility genes for diabetic nephropathy.</p>Methods<p class="a-plus-plus">We performed a genome-wide association study using 1000 Genomes-based imputation to compare type 1 diabetic nephropathy cases with proteinuria and with or without renal failure with control patients who have had diabetes for more than 15��years and no evidence of renal disease.</p>Results<p class="a-plus-plus">None of the single nucleotide polymorphisms (SNPs) tested in a discovery cohort composed of 683 cases and 779 controls reached genome-wide statistical significance. The 46 top hits (<em class="a-plus-plus">p</em>���&lt;���10<sup class="a-plus-plus">���5</sup>) were then sought for first-stage analysis in the Genetics of Kidneys in Diabetes US (US-GoKinD) study, an independent population of 820 cases and 885 controls. Two SNPs in strong linkage disequilibrium with each other and located in the <em class="a-plus-plus">SORBS1</em> gene were consistently and significantly (<em class="a-plus-plus">p</em>���&lt;���10<sup class="a-plus-plus">���4</sup>) associated with diabetic nephropathy. The minor rs1326934-C allele was less frequent in cases than in controls (0.34 vs 0.43) and was associated with a decreased risk for diabetic nephropathy (OR 0.70; 95% CI 0.60, 0.82). However, this association was not observed in a second stage with two additional diabetic nephropathy cohorts, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK and Republic of Ireland (UK-ROI; <em class="a-plus-plus">p</em>���=���0.15) and the Finnish Diabetic Nephropathy (FinnDiane; <em class="a-plus-plus">p</em>���=���0.44) studies, totalling 2,142 cases and 2,494 controls. Altogether, the random-effect meta-analysed rs1326934-C allele OR for diabetic nephropathy was 0.83 (95% CI 0.72, 0.96; <em class="a-plus-plus">p</em>���=���0.009).</p>Conclusions/interpretation<p class="a-plus-plus">These data suggest that <em class="a-plus-plus">SORBS1</em> might be a gene involved in diabetic nephropathy.</p>

Prediction of surface roughness during hard turning of AISI 4340 steel (69 HRC)

In this study, 39 sets of hard turning (HT) experimental trials were performed on a Mori-Seiki SL-25Y (4-axis) computer numerical controlled (CNC) lathe to study the effect of cutting parameters in influencing the machined surface roughness. In all the trials, AISI 4340 steel workpiece (hardened up to 69 HRC) was machined with a commercially available CBN insert (Warren Tooling Limited, UK) under dry conditions. The surface topography of the machined samples was examined by using a white light interferometer and a reconfirmation of measurement was done using a Form Talysurf. The machining outcome was used as an input to develop various regression models to predict the average machined surface roughness on this material. Three regression models - Multiple regression, Random Forest, and Quantile regression were applied to the experimental outcomes. To the best of the authors��� knowledge, this paper is the first to apply Random Forest or Quantile regression techniques to the machining domain. The performance of these models was compared to each other to ascertain how feed, depth of cut, and spindle speed affect surface roughness and finally to obtain a mathematical equation correlating these variables. It was concluded that the random forest regression model is a superior choice over multiple regression models for prediction of surface roughness during machining of AISI 4340 steel (69 HRC).

Genetic studies of body mass index yield new insights for obesity biology

<p>Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P &lt; 5 �� 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ���2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for &gt;20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p>

Convergence of products from Povarov and von Miller reactions: approaches to helquinoline

<p>Yttrium triflate or triflic acid catalysed Povarov reaction of methyl anthranilate with ethyl vinyl ether, both as aldehyde surrogate and as alkene, gave the desired 2-methyl-4-ethoxytetrahydroquinoline diastereoisomers as the major products along with four component coupling von Miller adducts. A proton NMR-study, using yttrium triflate as catalyst, revealed that the cis-diastereoisomers were the initial major products in both the Povarov and von Miller reactions but that these isomerised to the trans-diastereoisomers under the reaction conditions. Two distinct pathways for forming von Miller adducts were uncovered with the initial Povarov products being converted to von Miller adducts under the reaction conditions. Replacement of the 4-ethoxy with a 4-methoxy group under acidic conditions gave predominantly the trans-diastereoisomer, which was subsequently converted to a cis/trans mixture of the tetrahydroquinoline antibiotic helquinoline. It was also possible to convert the von Miller products to Povarov products under acidic conditions</p>

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

<p>To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.</p>