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Cell-free (cf)DNA captures tumor genetics and can be used to assess disease kinetics and minimal residual disease (MRD). B Introduction: b The European MCL Network trial TRIANGLE (NCT02858258) evaluated the addition of ibrutinib to standard treatment with autologous stem cell transplantation (ASCT) (arm A+I) in comparison to ASCT alone (arm A) and ibrutinib plus chemoimmunotherapy without ASCT (arm I) demonstrating significant and clinically relevant superiority of additional ibrutinib on outcome. CELL-FREE DNA KINETICS DECIPHER POTENTIAL MECHANISMS OF ACTION OF IBRUTINIB COMBINATION THERAPY IN MANTLE CELL LYMPHOMA (MCL). [Extracted from the article]

The karstification of carbonate rocks creates 3D maze voids that are normally controlled by fracture networks and sedimentary bedding. The spatial distribution and density of karst systems are usually complex and difficult to predict, demanding multidisciplinary studies at different scales of investigation to determine the spatial distribution and density of karst features and their possible links with cave systems controlled by the regional structural setting. The present study integrates geophysical datasets (gravity, electrical resistivity tomography - ERT, and ground penetrating radar - GPR) with a digital elevation model to investigate a karst system in the Irecê basin, a semiarid region of Brazil. Morphostructural lineaments reveal a NNW-SSE- and E-W-oriented structural setting of the crystalline basement, which is imprinted on the internal basin architecture, and surface drainage network. Negative gravity anomalies and high-gradient gravity zones indicate the main karstic zone, where karst landforms are concentrated. In addition, 2.5D gravity modeling provides the internal basin geometry, demonstrating that the karst system has evolved in the thickest sector of the basin. ERT profiles delineate the underground passages that connect dolines at depth. Finally, GPR data image shallow subsurface ghost-rock karstification that spread out from the surface to depth and that took advantage of vertical fractures and slightly arched bedding planes. Our results point out the role of the fracture corridors in channelizing hydrodynamic energy at a sufficiently high level to create caves by the total removal of dissolved material, whereas in the surrounding areas under low hydrodynamic conditions, overall shallow ghost-rock karstification took place, creating residual weathered rocks (alterites).

The increasing population of defects in strained austenite not only increases the heterogeneous nucleation site density for pearlite transformation, but also increases the austenite free energy due to the strain. This fact leads to a reduction in the critical free energy for pearlite nucleation, which triggers pearlite formation compared with austenite transformation without straining. Besides, a significant refinement of the pearlite colony size due to hard impingement between neighboring colonies is achieved. [ABSTRACT FROM AUTHOR]

In this paper, we present an homogeneous analysis of photospheric abundances based on high-resolution spectroscopy of a sample of 182 barium stars and candidates. We determined atmospheric parameters, spectroscopic distances, stellar masses, ages, luminosities and scaleheight, radial velocities, abundances of the Na, Al, #945;-elements, iron-peak elements, and s-process elements Y, Zr, La, Ce, and Nd. We employed the local thermodynamic equilibrium model atmospheres of Kurucz and the spectral analysis code MOOG. We found that the metallicities, the temperatures and the surface gravities for barium stars cannot be represented by a single Gaussian distribution. The abundances of a-elements and iron peak elements are similar to those of field giants with the same metallicity. Sodium presents some degree of enrichment in more evolved stars that could be attributed to the NeNa cycle. As expected, the barium stars show overabundance of the elements created by the s-process. By measuring the mean heavy-element abundance pattern as given by the ratio [s/Fe], we found that the barium stars present several degrees of enrichment. We also obtained the [hs/ls] ratio by measuring the photospheric abundances of the Ba-peak and the Zr-peak elements. Our results indicated that the [s/Fe] and the [hs/ls] ratios are strongly anticorrelated with the metallicity. Our kinematical analysis showed that 90 per cent of the barium stars belong to the thin disc population. Based on their luminosities, none of the barium stars are luminous enough to be an asymptotic giant branch star, nor to become self-enriched in the s-process elements. Finally, we determined that the barium stars also follow an age-metallicity relation. [ABSTRACT FROM AUTHOR]

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The transform shearing between South American and African plates in the Cretaceous generated a series of sedimentary basins on both plate margins. In this study, we use gravity, aeromagnetic, and resistivity surveys to identify architecture of fault systems and to analyze the evolution of the eastern equatorial margin of Brazil. Our study area is the southern onshore termination of the Potiguar rift, which is an aborted NE-trending rift arm developed during the breakup of Pangea. The basin is located along the NNE margin of South America that faces the main transform zone that separates the North and the South Atlantic. The Potiguar rift is a Neocomian structure located at the intersection of the equatorial and western South Atlantic and is composed of a series of NE-trending horsts and grabens. This study reveals new grabens in the Potiguar rift and indicates that stretching in the southern rift termination created aWNW-trending, 10 km wide, and ~40 km long right-lateral strike-slip fault zone. This zone encompasses at least eight depocenters, which are bounded by a left-stepping, en echelon system of NW-SE- to NS-striking normal faults. These depocenters form grabens up to 1200m deep with a rhomb-shaped geometry, which are filled with rift sedimentary units and capped by postrift sedimentary sequences. The evolution of the rift termination is consistent with the right-lateral shearing of the equatorial margin in the Cretaceous and occurs not only at the rift termination but also as isolated structures away from the main rift. This study indicates that the strike-slip shearing between two plates propagated to the interior of one of these plates, where faults with similar orientation, kinematics, geometry, and timing of the major transform are observed. These faults also influence rift geometry. [ABSTRACT FROM AUTHOR]

The transform shearing between South American and African plates in the Cretaceous generated a series of sedimentary basins on both plate margins. In this study, we use gravity, aeromagnetic, and resistivity surveys to identify fault architecture and to analyse the evolution of the eastern Equatorial margin of Brazil. Our study area is the southern onshore termination of the Potiguar rift, which is an aborted NE-trending rift arm developed during the breakup of Pangea. The Potiguar rift is a Neocomian structure located in the intersection of the Equatorial and western South Atlantic and is composed of a series of NE-trending horsts and grabens. This study reveals new grabens in the Potiguar rift and indicates that stretching in the southern rift termination created a WNW-trending, 10 km wide and ∼ 40 km long right-lateral strike-slip fault zone. This zone encompasses at least eight depocenters, which are bounded by a leftstepping, en-echelon system of NW- to EW-striking normal faults. These depocenters form grabens up to 1200m deep with a rhomb-shaped geometry, which are filled with rift sedimentary units and capped by post-rift sedimentary sequences. The evolution of the rift termination is consistent with the right-lateral shearing of the Equatorial margin in the Cretaceous and occurs not only at the rift termination, but also as isolated structures away from the main rift. [ABSTRACT FROM AUTHOR]

Abstract: Background: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluourouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. Patients and methods: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. Results: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. Conclusions: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect. [Copyright &y& Elsevier]

Background:KRAS mutation testing is required to select patients with metastatic colorectal cancer (CRC) to receive anti-epidermal growth factor receptor antibodies, but the optimal KRAS mutation test method is uncertain.Methods:We conducted a two-site comparison of two commercial KRAS mutation kits - the cobas KRAS Mutation Test and the Qiagen therascreen KRAS Kit - and Sanger sequencing. A panel of 120 CRC specimens was tested with all three methods. The agreement between the cobas test and each of the other methods was assessed. Specimens with discordant results were subjected to quantitative massively parallel pyrosequencing (MPP). DNA blends were tested to determine detection rates at 5% mutant alleles.Results:Reproducibility of the cobas test between sites was 98%. Six mutations were detected by cobas that were not detected by Sanger, and five were confirmed by MPP. The cobas test detected eight mutations which were not detected by the therascreen test, and seven were confirmed by MPP. Detection rates with 5% mutant DNA blends were 100% for the cobas and therascreen tests and 19% for Sanger.Conclusion:The cobas test was reproducible between sites, and detected several mutations that were not detected by the therascreen test or Sanger. Sanger sequencing had poor sensitivity for low levels of mutation. [ABSTRACT FROM AUTHOR]

Context. High-velocity halo stars provide important information about the properties of the extreme Galactic halo. The study of unbound and bound Population II stars permits us to better estimate the mass of the halo. Aims. We carried out a detailed spectroscopic and kinematic study and have significantly refined the distance and the evolutionary state of the star. Methods. Its atmospheric parameters, chemical abundances and kinematical properties were determined using high-resolution optical spectroscopy and employing the local-thermodynamic-equilibrium model atmospheres of Kurucz and the spectral analysis code moog. Results. We found that CD-62°1346 is a metal-poor ([Fe/H] = -1.6) evolved giant star with Teff = 5300 K and log g = 1.7. The star exhibits high carbon and s-element abundances typical of CH stars. It is also a lead star. Our kinematic analysis of its 3D space motions shows that this star has a highly eccentric (e = 0.91) retrograde orbit with an apogalactic distance of ∼100 kpc, exceeding by a factor of two the distance of the Magellanic Clouds. The star travels with very high velocity relative to the Galactocentric reference frame (VGRF = 570 km s-1). Conclusions. CD-62°1346 is an evolved giant star and not a subgiant star, as was considered earlier. Whether it is bound or unbound to the Galaxy depends on the assumed mass and on the adopted Galactic potential. We also show that the star HD5223 is another example of a high-velocity CH star that exceeds the Galactic escape velocity. Possible origins of these two high-velocity stars are briefly discussed. CD-62°1346 and HD5223 are the first red giant stars to join the restricted group of hypervelocity stars. [ABSTRACT FROM AUTHOR]

Acquired resistance to selective FLT3 inhibitors is an emerging clinical problem in the treatment of FLT3-ITD+ acute myeloid leukaemia (AML). The paucity of valid pre-clinical models has restricted investigations to determine the mechanism of acquired therapeutic resistance, thereby limiting the development of effective treatments. We generated selective FLT3 inhibitor-resistant cells by treating the FLT3-ITD+ human AML cell line MOLM-13 in vitro with the FLT3-selective inhibitor MLN518, and validated the resistant phenotype in vivo and in vitro. The resistant cells, MOLM-13-RES, harboured a new D835Y tyrosine kinase domain (TKD) mutation on the FLT3-ITD+ allele. Acquired TKD mutations, including D835Y, have recently been identified in FLT3-ITD+ patients relapsing after treatment with the novel FLT3 inhibitor, AC220. Consistent with this clinical pattern of resistance, MOLM-13-RES cells displayed high relative resistance to AC220 and Sorafenib. Furthermore, treatment of MOLM-13-RES cells with AC220 lead to loss of the FLT3 wild-type allele and the duplication of the FLT3-ITD-D835Y allele. Our FLT3-Aurora kinase inhibitor, CCT137690, successfully inhibited growth of FLT3-ITD-D835Y cells in vitro and in vivo, suggesting that dual FLT3-Aurora inhibition may overcome selective FLT3 inhibitor resistance, in part due to inhibition of Aurora kinase, and may benefit patients with FLT3-mutated AML. [ABSTRACT FROM AUTHOR]

A recently developed method for pseudo-component delumping is tested for delumping the results of compositional reservoir simulation. The procedure, based on the reduction concept, is analytical and consistent and it accurately takes into account non-zero binary interaction parameters in cubic equations of state. The delumping method was implemented in a postprocessor to the commercial Eclipse reservoir simulator and successfully tested on several cases: oil and gas condensate reservoirs for depletion, lean gas re-injection, and carbon dioxide injection. The analytical delumping method based on reduction gives systematically better results than the regression-based delumping method used previously. [ABSTRACT FROM AUTHOR]

In this work, differences and similarities between bainitic and martensitic structures obtained by isothermal heat treatments such as austempering, quench and partitioning (Q&P) and quench and tempering (Q&T), are investigated by multiple techniques including X-ray diffraction, electron backscatter diffraction, scanning and transmission electron microscopy and atom probe tomography. Results reveal that analogous lath-like ferritic structures with similar austenite content can be achieved by adjusting the isothermal holding temperature. However, certain variability in hardness is recorded, which is consistent with differences on the precipitation state revealed by the nano-scale examination of the structure, and with dissimilar crystallographic size distribution of ferritic grains. Unlabelled Image • Nanoscale precipitation and crystallographic hierarchy differentiate bainite and martensite • Analogous bainitic and martensitic structures with similar austenite content can be obtained by adjusting the isothermal holding temperature of austempering, quench and partitioning (Q&P) and quench and tempering (Q&T). • Nano-scale examination of bainitic and martensitic structures discloses some differences on the precipitation state that explain detected variability in hardness. • The crystallographic hierarchy reveals significant differences between bainitic and martensitic structures, which is important for controlling crack propagation to increase fracture toughness and fatigue performance of materials. [ABSTRACT FROM AUTHOR]

This paper proposes a method for in-flight parameter estimation for Multirotor Aerial Vehicles (MAV). This task is important because it provides parameters with better accuracy for the actual vehicle operation. In order to simulate a flight it is adopted a simulation environment Software-In-the-Loop (SIL).

This work presents the modeling and control of a multirotor aerial vehicle with tethered configuration. It is considered an octocopter with a saturated proportional-plus-derivative position control. A viscoelastic model is considered for the tether, which has a tension control. Numerical simulations are carried out to compare the performance of the tethred configuration with the vehicle in free flight.

The interest for multirotor aerial vehicles (MAVs) is currently growing due to their low cost, high manoeuvrability, simplified mechanics, capability to perform vertical take-off and landing as well as hovering flight. These characteristics make them a promising technology suitable for applications such as surveillance of indoor and urban environments. The present work faces the problem of controlling the attitude of a MAV by means of a linear feedback control which guarantees asymptotic stability when controlling nonlinear dynamics. The simulations show the effectiveness of the method.

A response from the author of the article "A comparison of three methods for detecting KRAS mutations in formalin-fixed colorectal cancer specimens" in the September 25, 2012 issue which analyses Kristen Reticular Activating System (KRAS) mutation is presented.

Abstract Background Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in other solid tumours. This is a multimutational study of ctDNA over multiple timepoints, designed to test the hypothesis that ctDNA is a potential biomarker in patients with advanced thyroid cancer. Methods Mutational analysis of archival tumour tissue was performed using NGS with a targeted gene panel. Custom TaqMan assays were designed for plasma ctDNA testing using digital droplet polymerase chain reaction. Concentrations of detected ctDNA were correlated with the conventional biomarker concentration and axial imaging status defined by the Response Evaluation Criteria in Solid Tumours criteria. Results Tumour tissue from 51 patients was obtained, with the following histologies: 32 differentiated (differentiated thyroid cancer [DTC]), 15 medullary (medullary thyroid cancer [MTC]), three poorly differentiated and one anaplastic. NGS analysis detected variants in 42 (82%) of cases. Plasma was assayed for these patients in 190 samples, and ctDNA was detected in 67% of patients. Earlier detection of disease progression was noted in three patients with MTC. In two cases (PTC and ATC), where conventional biomarkers were not detectable, ctDNA was detected before disease progression. Changes in ctDNA concentration occurred earlier than conventional markers in response to disease progression in multiple patients with DTC receiving targeted therapies. Conclusion The majority of patients with advanced thyroid cancer had detectable ctDNA. ctDNA measurement may offer superiority over conventional markers in several scenarios: earlier detection of progression in MTC; as an alternative biomarker when conventional markers are not available; more rapid assessment of the disease status in response to targeted therapies, thereby potentially allowing prompter discontinuation of futile therapies. These early results support the hypothesis that ctDNA may be a clinically useful biomarker in thyroid cancer. Highlights • Circulating tumour DNA (ctDNA) is found in majority (67%) of patients with thyroid cancer. • Detection of ctDNA appears to be reflective of disease burden. • ctDNA measurement may predict disease progression earlier than conventional biomarkers in medullary cancer. • ctDNA measurement may allow more rapid assessment of response to targeted therapies in differentiated thyroid cancer. [ABSTRACT FROM AUTHOR]