Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

The main-belt comets: The Pan-STARRS1 perspective

We analyze a set of 760 475 observations of 333 026 unique main-belt objects obtained by the Pan-STARRS1(PS1) survey telescope between 2012 May 20 and 2013 November 9, a period during which PS1 discoveredtwo main-belt comets, P/2012 T1 (PANSTARRS) and P/2013 R3 (Catalina-PANSTARRS). PS1 cometdetection procedures currently consist of the comparison of the point spread functions (PSFs) of movingobjects to those of reference stars, and the flagging of objects that show anomalously large radial PSFwidths for human evaluation and possible observational follow-up. Based on the number of missed discoveryopportunities among comets discovered by other observers, we estimate an upper limit comet discoveryefficiency rate of 70% for PS1. Additional analyses that could improve comet discovery yields infuture surveys include linear PSF analysis, modeling of trailed stellar PSFs for comparison to trailed movingobject PSFs, searches for azimuthally localized activity, comparison of point-source-optimized photometryto extended-source-optimized photometry, searches for photometric excesses in objects withknown absolute magnitudes, and crowd-sourcing. Analysis of the discovery statistics of the PS1 surveyindicates an expected fraction of 59 MBCs per 106 outer main-belt asteroids (corresponding to a totalexpected population of 140 MBCs among the outer main-belt asteroid population with absolute magnitudesof 12 < HV < 19:5), and a 95% confidence upper limit of 96 MBCs per 106 outer main-belt asteroids(corresponding to a total of 230 MBCs), assuming a detection efficiency of 50%. We note howeverthat significantly more sensitive future surveys (particularly those utilizing larger aperture telescopes)could detect many more MBCs than estimated here. Examination of the orbital element distribution ofall known MBCs reveals an excess of high eccentricities (0:1 < e < 0:3) relative to the background asteroidpopulation. Theoretical calculations show that, given these eccentricities, the sublimation rate for atypical MBC is orders of magnitude larger at perihelion than at aphelion, providing a plausible physicalexplanation for the observed behavior of MBCs peaking in observed activity strength near perihelion.These results indicate that the overall rate of mantle growth should be slow, consistent with observationalevidence that MBC activity can be sustained over multiple orbit passages.

BUCKLED LAYER STRUCTURE FOR ATOMIC ADSORPTION ON W(100) - THE (ROOT-2X-ROOT-2)R45-DEGREES NITROGEN STRUCTURE FROM ATLEED

Adsorption of 0.5 monolayer of N adatoms on W{100} results in a sharp (root 2 X root 2)R45 degrees LEED pattern. The only previous quantitative LEED study of this system gave a simple overlayer model with a Pendry R-factor of 0.55. An exhaustive search has been made of possible structures, including a novel vacancy reconstruction, displacive reconstructions and underlayer adsorption. From this work a new overlayer structure is derived with an R(p) value of 0.22, displaying a considerable buckling of 0.27 +/- 0.05 Angstrom within the second W layer and consequently involving large changes in the interlayer spacings of the surface. The N adatom is pseudo-five-fold coordinated to the W surface, bonding to a second-layer W atom with a nearest-neighbour bond length of 2.13 Angstrom and with the four next-nearest-neighbour W atoms in the surface plane at 2.27 Angstrom. The structure does not resolve the work function anomaly observed on this surface.

AN ADSORBATE-STABILIZED VACANCY STRUCTURE FOR CU ON W(100) - A SURFACE ALLOY

Deposition of 0.5 ML of Cu on W(100) leads to the formation of a sharp c(2 x 2) structure when the surface is annealed at 800 K. A LEED intensity analysis reveals that the Cu atoms are adsorbed displacively into W sites, forming an ordered 2D surface alloy. Due to the lattice mismatch between copper and tungsten, a substantial buckling of the first layer of the alloy is also observed. The clean, bulk terminated W(100) surface is only just stable relative to the c(2 x 2) vacancy covered W(100) surface. This relative stability of the vacancy structure explains the driving force behind the formation of this alloy.

Energy levels, radiative rates, and lifetimes for transitions in W LVIII

Energy levels and radiative rates are reported for transitions in Cl-like W LVIII. Configuration interaction (CI) has been included among 44 configurations (generating 4978 levels) over a wide energy range up to 363 Ryd, and the general-purpose relativistic atomic structure package (grasp) adopted for the calculations. Since no other results of comparable complexity are available, calculations have also been performed with the flexible atomic code (fac), which help in assessing the accuracy of our results. Energies are listed for the lowest 400 levels (with energies up to ~98 Ryd), which mainly belong to the 3s²3p⁵, 3s3p⁶, 3s²3p⁴3d, 3s²3p³3d², 3s3p⁴3d², 3s²3p²3d³, and 3p⁶3d configurations, and radiative rates are provided for four types of transitions, i.e.E1, E2, M1, and M2. Our energy levels are assessed to be accurate to better than 0.5%, whereas radiative rates (and lifetimes) should be accurate to better than 20% for a majority of the strong transitions.

Energy levels, radiative rates, and lifetimes for transitions in W XL

Energy levels and radiative rates are reported for transitions in Br-like tungsten, W XL, calculated with the general-purpose relativistic atomic structure package (grasp). Configuration interaction (CI) has been included among 46 configurations (generating 4215 levels) over a wide energy range up to 213 Ryd. However, for conciseness results are only listed for the lowest 360 levels (with energies up to ~43 Ryd), which mainly belong to the 4s²4p⁵,4s²4p⁴4d,4s²4p⁴4f,4s4p⁶,4p⁶4d,4s4p⁵4d,4s²4p³4d², and 4s²4p³4d4f configurations, and provided for four types of transitions, E1, E2, M1, and M2. Comparisons are made with existing (but limited) results. However, to fully assess the accuracy of our data, analogous calculations have been performed with the flexible atomic code, including an even larger CI than in grasp. Our energy levels are estimated to be accurate to better than 0.02 Ryd, whereas results for radiative rates (and lifetimes) should be accurate to better than 20% for a majority of the strong transitions.

Radiative rates for E1, E2, M1, and M2 transitions among the 3s23p5, 3s3p6, and 3s23p43d configurations of Cl-like W LVIII

We report calculations of energy levels, radiative decay rates, and lifetimes for transitions among the 3s²3p⁵, 3s3p⁶, and 3s²3p⁴3d configurations of Cl-like W LVIII. The general-purpose relativistic atomic structure package (GRASP) has been adopted for our calculations. Comparisons are made with the most recent results of Mohan et al. (Can. J. Phys. 92, 177 (2014). doi:10.1139/cjp-2013-0348) and discrepancies in lifetimes are noted, up to four orders of magnitude in some instances. Our energy levels are estimated to be accurate to better than 0.5%, whereas results for radiative rates and lifetimes should be accurate to better than 20%.

John Birks: Pioneer in quantitative palaeoecology

We describe the career of John Birks as a pioneering scientist who has, over a career spanning five decades, transformed palaeoecology from a largely descriptive to a rigorous quantitative science relevant to contemporary questions in ecology and environmental change. We review his influence on students and colleagues not only at Cambridge and Bergen Universities, his places of primary employment, but also on individuals and research groups in Europe and North America. We also introduce the collection of papers that we have assembled in his honour. The papers are written by his former students and close colleagues and span many of the areas of palaeoecology to which John himself has made major contributions. These include the relationship between ecology and palaeoecology, late-glacial and Holocene palaeoecology, ecological succession, climate change and vegetation history, the role of palaeoecological techniques in reconstructing and understanding the impact of human activity on terrestrial and freshwater ecosystems and numerical analysis of multivariate palaeoecological data.

Gamma-ray emission in near critical density plasmas at laser intensities of 1021 W/cm2

We study synchrotron radiation emission from laser interaction with near critical density (NCD) plasmas at intensities of 1021 W∕cm2 using three-dimensional particle-in-cell simulations. It is found that the electron dynamics depend on the laser shaping process in NCD plasmas, and thus the angular distribution of the emitted photons changes as the laser pulse evolves in space and time. The final properties of the resulting synchrotron radiation, such as its overall energy, the critical photon energy, and the radiation angular distribution, are strongly affected by the laser polarization and plasma density. By using a 420 TW∕50 fs laser pulse at the optimal plasma density (∼1nc ), about 108 photons/0.1% bandwidth are produced at multi-MeV photon energies, providing a route to ultraintense, femtosecond gamma ray pulses.

The determination of optimal processing conditions for PLA and PLA/CaCO3 in twin screw extrusion using DoE and multivariate analysis

Biodegradable polymers, such as PLA (Polylactide), come from renewable resources like corn starch and if disposed of correctly, degrade and become harmless to the ecosystem making them attractive alternatives to petroleum based polymers. PLA in particular is used in a variety of applications including medical devices, food packaging and waste disposal packaging. However, the industry faces challenges in melt processing of PLA due to its poor thermal stability which is influenced by processing temperatures and shearing.
Identification and control of suitable processing conditions is extremely challenging, usually relying on trial and error, and often sensitive to batch to batch variations. Off-line assessment in a lab environment can result in high scrap rates, long lead times and lengthy and expensive process development. Scrap rates are typically in the region of 25-30% for medical grade PLA costing between €2000-€5000/kg.
Additives are used to enhance material properties such as mechanical properties and may also have a therapeutic role in the case of bioresorbable medical devices, for example the release of calcium from orthopaedic implants such as fixation screws promotes healing. Additives can also reduce the costs involved as less of the polymer resin is required.
This study investigates the scope for monitoring, modelling and optimising processing conditions for twin screw extrusion of PLA and PLA w/calcium carbonate to achieve desired material properties. A DAQ system has been constructed to gather data from a bespoke measurement die comprising melt temperature; pressure drop along the length of the die; and UV-Vis spectral data which is shown to correlate to filler dispersion. Trials were carried out under a range of processing conditions using a Design of Experiments approach and samples were tested for mechanical properties, degradation rate and the release rate of calcium. Relationships between recorded process data and material characterisation results are explored.