Anisotropic seismic inversion using a multigrid Monte Carlo approach

We propose a new approach for the inversion of anisotropic P-wave data based on Monte Carlo methods combined with a multigrid approach. Simulated annealing facilitates objective minimization of the functional characterizing the misfit between observed and predicted traveltimes, as controlled by the Thomsen anisotropy parameters (epsilon, delta). Cycling between finer and coarser grids enhances the computational efficiency of the inversion process, thus accelerating the convergence of the solution while acting as a regularization technique of the inverse problem. Multigrid perturbation samples the probability density function without the requirements for the user to adjust tuning parameters. This increases the probability that the preferred global, rather than a poor local, minimum is attained. Undertaking multigrid refinement and Monte Carlo search in parallel produces more robust convergence than does the initially more intuitive approach of completing them sequentially. We demonstrate the usefulness of the new multigrid Monte Carlo (MGMC) scheme by applying it to (a) synthetic, noise-contaminated data reflecting an isotropic subsurface of constant slowness, horizontally layered geologic media and discrete subsurface anomalies; and (b) a crosshole seismic data set acquired by previous authors at the Reskajeage test site in Cornwall, UK. Inverted distributions of slowness (s) and the Thomson anisotropy parameters (epsilon, delta) compare favourably with those obtained previously using a popular matrix-based method. Reconstruction of the Thomsen epsilon parameter is particularly robust compared to that of slowness and the Thomsen delta parameter, even in the face of complex subsurface anomalies. The Thomsen epsilon and delta parameters have enhanced sensitivities to bulk-fabric and fracture-based anisotropies in the TI medium at Reskajeage. Because reconstruction of slowness (s) is intimately linked to that epsilon and delta in the MGMC scheme, inverted images of phase velocity reflect the integrated effects of these two modes of anisotropy. The new MGMC technique thus promises to facilitate rapid inversion of crosshole P-wave data for seismic slownesses and the Thomsen anisotropy parameters, with minimal user input in the inversion process.

3D Analysis of Heat Transfer Intensification by Re-Entrance Flow Pin-Fins Microstructures with a Highly Thermal-Conductive Plate

Joule heat-induced hot-spot formation sets severe limits in the operation of continuous annular electrochromatography (CAEC), a new concept for preparative separation as an analog to analytical capillary electrochromatography (CEC). This may lead to eluent flow perturbance, even to boiling, which would massively weaken separation efficiency and may even hamper the stationary phase used for separation. For reasons of system integration and high-efficiency heat transfer, micro flow heat exchangers are considered with a separate coolant flow. A 3D numerical analysis of the heat transfer of water single-phase laminar flow in a square microchannel and different arrays of micro pin-fins was carried out using COMSOL Multiphysics. Several advanced materials with low electric conductivity and at the same time with high heat conductivity were put forward to be used in the CAEC system. As essential design point, it is proposed to constitute the micro heat exchanger from two different parts of the CAEC system, namely a microstructured pin-fins plate and a so-called conductive plate.

Debates over Palaeolithic chronology - the reliability of C-14 is confirmed

The debate about the complex issues of human development during the Middle to Upper Palaeolithic transition period (45-35 ka BP) has been hampered by concerns about the reliability of the radiocarbon dating method. Large C-14 anomalies were postulated and radiocarbon dating was considered flawed. We show here that these issues are no longer relevant, because the large anomalies are artefacts beyond plausible physical limits for their magnitude. Previous inconsistencies between C-14 radiocarbon datasets have been resolved, and a new radiocarbon calibration curve, IntCal09 (Reimer et al., 2009), was created. Improved procedures for bone collagen extraction and charcoal pre-treatment generally result in older ages, consistent with independently dated time markers. (C) 2012 Elsevier Ltd. All rights reserved.

Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli

The steps involved in the biosynthesis of the ADP-L-glycero-beta-D-manno-heptose (ADP-L-beta-D-heptose) precursor of the inner core lipopolysaccharide (LPS) have not been completely elucidated. In this work, we have purified the enzymes involved in catalyzing the intermediate steps leading to the synthesis of ADP-D-beta-D-heptose and have biochemically characterized the reaction products by high-performance anion-exchange chromatography. We have also constructed a deletion in a novel gene, gmhB (formerly yaeD), which results in the formation of an altered LPS core. This mutation confirms that the GmhB protein is required for the formation of ADP-D-beta-D-heptose. Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate. A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-L-beta-D-heptose precursor utilized in the assembly of inner core LPS.

Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure

The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.

Translation suppression promotes stress granule formation and cell survival in response to cold shock

Cells respond to different types of stress by inhibition of protein synthesis and subsequent assembly of stress granules (SGs), cytoplasmic aggregates that contain stalled translation preinitiation complexes. Global translation is regulated through the translation initiation factor eukaryotic initiation factor 2a (eIF2a) and the mTOR pathway. Here we identify cold shock as a novel trigger of SG assembly in yeast and mammals. Whereas cold shock-induced SGs take hours to form, they dissolve within minutes when cells are returned to optimal growth temperatures. Cold shock causes eIF2a phosphorylation through the kinase PERK in mammalian cells, yet this pathway is not alone responsible for translation arrest and SG formation. In addition, cold shock leads to reduced mitochondrial function, energy depletion, concomitant activation of AMP-activated protein kinase (AMPK), and inhibition of mTOR signaling. Compound C, a pharmacological inhibitor of AMPK, prevents the formation of SGs and strongly reduces cellular survival in a translation-dependent manner. Our results demonstrate that cells actively suppress protein synthesis by parallel pathways, which induce SG formation and ensure cellular survival during hypothermia.

D3.1 Benefits Analysis of the Initial Operational Cruiser-Feeder Concept

The REsearch on a CRuiser Enabled Air Transport Environment (RECREATE) project is considers the introduction and airworthiness of cruiser-feeder operations for civil aircraft. Cruiser-feeder operations are investigated as a promising pioneering idea for the air transport of the future. The soundness of the concept of cruiser-feeder operations for civil aircraft can be understood, taking air-to-air refueling operations as an example. For this example, a comprehensive estimate of the benefits can be made, which shows a fuel burn reduction potential and a CO2 emission reduction of 31% for a typical 6000 nautical miles flight with a payload of 250 passengers. This reduction potential is known to be large by any standard. The top level objective of the RECREATE project is to demonstrate on a preliminary design level that cruiser-feeder operations (as a concept to reduce fuel burn and CO2 emission levels) can be shown to comply with the airworthiness requirements for civil aircraft. The underlying Scientific and Technological (S&T) objectives are to determine and study airworthy operational concepts for cruiser-feeder operations, and to derive and quantify benefits in terms of CO2 emission reduction but also other benefits.

Work Package (WP) 3 has the objective to substantiate the assumed benefits of the cruiser/feeder operations through refined analysis and simulation. In this report, initial benefits evaluation of the initial RECREATE cruiser/feeder concepts is presented. The benefits analysis is conducted in delta mode, i.e. comparison is made with a baseline system. Since comparing different aircraft and air transport systems is never a trivial task, appropriate measures and metrics are defined and selected first. Non-dimensional parameters are defined and values for the baseline system derived.

The impact of cruiser/feeder operations such as air-to-air refueling are studied with respect to fuel-burn (or carbon-dioxide), noise and congestion. For this purpose, traffic simulations have been conducted.
Cruiser/feeder operations will have an impact on dispatch reliability as well. An initial assessment of the effect on dispatch reliability has been made and is reported.

Finally, a considerable effort has been made to create the infrastructure for economic delta analysis of the cruiser/feeder concept of operation. First results of the cost analysis have been obtained.

Development of a genotyping microarray for Usher syndrome

Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons.

Selection and Treatment of Data for Radiocarbon Calibration: An Update to the International Calibration (IntCal) Criteria

High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.

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/.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7–43·4] to 55·4% [54·6–56·2], p<0·0001), follicular lymphoma (58·9% [57·3–60·6] to 74·3% [72·9–75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6–33·9] to 54·4% [52·5–56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7–56·2] to 61·9% [57·0–66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1–76·0] to 79·3% [78·4–80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1–67·1] to 69·0% [68·1–69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0–30·6] to 39·6% [38·8–40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7–32·0] to 41·1% [39·0–43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9–13·3] to 14·8% [14·2–15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7–71·8] to 74·9% [73·8–75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.