Analysis of imatinib in bone marrow and plasma samples of chronic myeloid leukaemia patients using solid phase extraction LC-ESI-MS

The LC-ESI-MS was developed and validated for the analysis of imatinib in plasma and bone marrow samples using deuterated imatinib (D(8)-IM) as an internal standard. The biological samples were extracted using Strata-X-C SPE cartridges and separated on C<sub>8</sub> column (50 x 3 mm, 3 µm), and methanol: 0.1% formic acid (70:30) was delivered at the rate of 0.7 ml/min as a mobile phase. Imatinib was quantified in samples by monitoring the ions m/z 494.3 for imatinib and 502.3 for D<sub>8</sub>-imatinib on mass spectrometer. The method was linear in the concentration range of 1-1500 ng/250 µl in spiked human plasma samples and limit of quantification was 5 ng/mL. Inter-day and intra-day variations in spiked human plasma spiked with 50, 250 and 500 ng /mL were less than 3.16%. The repeatability and reproducibility and other parameters of the methods were also validated. The method was employed for the analysis of the imatinib in human plasma and bone marrow samples. The drug levels in bone marrow and plasma samples were correlated to the degree of cytogenetic response. No significant difference of imatinib level between blood and bone marrow in IM-treated patients dosed to steady state was observed

W-026, acceptance test report manipulator system

The purpose of the WRAP Manipulator System Acceptance Test Plan (ATP) is to verify that the 4 glovebox sets of WRAP manipulator components, including rail/carriage, slave arm, master controller and auxiliary equipment, meets the requirements of the functional segments of 14590 specification. The demonstration of performance elements of the ATP are performed as a part of the Assembly specifications. Manipulator integration is integrated in the performance testing of the gloveboxes. Each requirement of the Assembly specification will be carried out in conjunction with glovebox performance tests

First Report of Soybean Vein Necrosis Disease Caused by Soybean vein necrosis-associated virus in Wisconsin and Iowa

Several viral diseases of soybean (Glycine max) have been identified in the north-central U.S. soybean production area, which includes Wisconsin and Iowa (2). Previously, Soybean vein necrosis disease (SVND) caused by Soybean vein necrosis-associated virus was reported in Arkansas, Tennessee, and other southern states (4). In September 2012, soybean plants with symptoms similar to those reported for SVND (4) were observed in fields across Wisconsin and Iowa. Symptoms included leaf-vein and leaf chlorosis, followed by necrosis of the leaf veins and eventually necrosis of the entire leaf. Six samples with symptoms indicative of SVNaV were collected from research plots located at the West Madison Agricultural Research Station located in Madison, WI. An additional three samples were collected from three locations in central Iowa. Total RNA extracted from each sample using the Trizol Plus RNA purification kit (Invitrogen, Carlsbad, CA) was used to generate complementary DNA (cDNA) using the iScript cDNA synthesis kit (Bio-Rad Laboratories, Hercules, CA) following the manufacturers\u27 suggested protocols. The resulting cDNA was used as template in a PCR with SVNaV-specific primers, SVNaV-f1 and SVNaV-r1 (3). PCRs of two of the six Wisconsin samples and two Iowa samples were positive. Amplification products were not detected in the other five samples. The amplification products from the four strongly positive samples were purified using the Wizard SV Gel and PCR Purification Kit (Promega, Madison, WI) following the manufacturer\u27s suggested protocol and were subjected to automated sequencing (University of Wisconsin Biotechnology Center or Iowa State University, DNA Sequencing Facilities). BLASTn (1) alignments of the 915-bp consensus sequence revealed 98% and \u3e99% identity of the Wisconsin and Iowa samples, respectively, with the ‘S’ segment of the SVNaV ‘TN’ isolate (GenBank Accession No. GU722319.1). Samples from the same leaf tissue used above, were subjected to serological tests for SVNaV using antigen coated-indirect ELISA (3). Asymptomatic soybeans grown in the greenhouse were used as a source of leaves for negative controls. These tests confirmed the presence of SVNaV in eight symptomatic soybean leaflets collected in Wisconsin and Iowa. The asymptomatic control and one Iowa sample, which was also PCR-negative, were also negative by serological testing. Six additional samples from soybean fields in as many Wisconsin counties (Fond Du Lac, Grant, Green, Juneau, Richland, Rock) tested positive for SVNaV using specific primers that amplify the ‘L’ segment (4). The sequenced amplification products (297-bp) showed 99 to 100% homology to the L segment of the TN isolate (GU722317.1). To our knowledge, this is the first report of SVNaV associated with soybean and the first report of SVND in Wisconsin and Iowa. Considering that little is known about SVNaV, it is assumed that it is like other Tospoviruses and can cause significant yield loss (4). Soybean is a major cash crop for Wisconsin and Iowa, and infection by SVNaV could result in potential yield loss in years where epidemics begin early and at a high initial inoculum level

Exploring morphological correlations among H2CO, 12CO, MSX and continuum mappings

There are relatively few H2CO mappings of large-area giant molecular cloud (GMCs). H2CO absorption lines are good tracers for low-temperature molecular clouds towards star formation regions. Thus, the aim of the study was to identify H2CO distributions in ambient molecular clouds. We investigated morphologic relations among 6-cm continuum brightness temperature (CBT) data and H2CO (111-110; Nanshan 25-m radio telescope), 12CO (1--0; 1.2-m CfA telescope) and midcourse space experiment (MSX) data, and considered the impact of background components on foreground clouds. We report simultaneous 6-cm H2CO absorption lines and H110\alpha radio recombination line observations and give several large-area mappings at 4.8 GHz toward W49 (50'\times50'), W3 (70'\times90'), DR21/W75 (60'\times90') and NGC2024/NGC2023 (50'\times100') GMCs. By superimposing H2CO and 12CO contours onto the MSX color map, we can compare correlations. The resolution for H2CO, 12CO and MSX data was about 10', 8' and 18.3", respectively. Comparison of H2CO and 12CO contours, 8.28-\mu m MSX colorscale and CBT data revealed great morphological correlation in the large area, although there are some discrepancies between 12CO and H2CO peaks in small areas. The NGC2024/NGC2023 GMC is a large area of HII regions with a high CBT, but a H2CO cloud to the north is possible against the cosmic microwave background. A statistical diagram shows that 85.21% of H2CO absorption lines are distributed in the intensity range from -1.0 to 0 Jy and the \Delta V range from 1.206 to 5 km/s.Comment: 18 pages, 22 figures, 5 tables. Accepted to be published in Astrophysics and Space Scienc

Density-functional embedding using a plane-wave basis

The constrained electron density method of embedding a Kohn-Sham system in a substrate system (first described by P. Cortona, Phys. Rev. B {\bf 44}, 8454 (1991) and T.A. Wesolowski and A. Warshel, J. Phys. Chem {\bf 97}, 8050 (1993)) is applied with a plane-wave basis and both local and non-local pseudopotentials. This method divides the electron density of the system into substrate and embedded electron densities, the sum of which is the electron density of the system of interest. Coupling between the substrate and embedded systems is achieved via approximate kinetic energy functionals. Bulk aluminium is examined as a test case for which there is a strong interaction between the substrate and embedded systems. A number of approximations to the kinetic-energy functional, both semi-local and non-local, are investigated. It is found that Kohn-Sham results can be well reproduced using a non-local kinetic energy functional, with the total energy accurate to better than 0.1 eV per atom and good agreement between the electron densities.Comment: 11 pages, 4 figure

Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter