33 research outputs found
Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations
Somatic insertions/deletions in the calreticulin gene have recently been discovered to be causative alterations in myeloproliferative neoplasms. A combination of qualitative and quantitative allele-specific polymerase chain reaction, fragment-sizing, high resolution melting and Sanger-sequencing was applied for the detection of three driver mutations (in Janus kinase 2, calreticulin and myeloproliferative leukemia virus oncogene genes) in 289 cases of essential thrombocythemia and 99 cases of primary myelofibrosis. In essential thrombocythemia, 154 (53%) Janus kinase 2 V617F, 96 (33%) calreticulin, 9 (3%) myeloproliferative leukemia virus oncogene gene mutation-positive and 30 triple-negative (11%) cases were identified, while in primary myelofibrosis 56 (57%) Janus kinase 2 V617F, 25 (25%) calreticulin, 7 (7%) myeloproliferative leukemia virus oncogene gene mutation-positive and 11 (11%) triple-negative cases were identified. Patients positive for the calreticulin mutation were younger and had higher platelet counts compared to Janus kinase 2 mutation-positive counterparts. Calreticulin mutation-positive patients with essential thrombocythemia showed a lower risk of developing venous thrombosis, but no difference in overall survival. Calreticulin mutation-positive patients with primary myelofibrosis had a better overall survival compared to that of the Janus kinase 2 mutation-positive (P=0.04) or triple-negative cases (P=0.01). Type 2 calreticulin mutation occurred more frequently in essential thrombocythemia than in primary myelofibrosis (P=0.049). In essential thrombocythemia, the calreticulin mutational load was higher than the Janus kinase 2 mutational load (P<0.001), and increased gradually in advanced stages. Calreticulin mutational load influenced blood counts even at the time point of diagnosis in essential thrombocythemia. We confirm that calreticulin mutation is associated with distinct clinical characteristics and explored relationships between mutation type, load and clinical outcome
Direct observation of the vortex core magnetization and its dynamics
Square-shaped thin film structures with a single magnetic vortex were investigated using a scanning transmission x-ray microscope. The authors report on the direct observation of the vortex core in 500x500 nm(2), 40 nm thick soft magnetic Ni-Fe samples. The static configuration of the vortex core was imaged as well as the gyrotropic motion of the core under excitation with an in-plane alternating magnetic field. This enabled them to directly visualize the direction of the out-of-plane magnetization in the vortex core (up or down). The reversal of the core was effected by short bursts of an alternating magnetic field. An asymmetry appears in the core's trajectory for its orientation pointing up and down, respectively
In situ measurements of angular-dependent light scattering by aerosols over the contiguous United States
This work provides a synopsis of aerosol phase function (F11) and
polarized phase function (F12) measurements made by the Polarized
Imaging Nephelometer (PI-Neph) during the Studies of Emissions,
Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys
(SEAC4RS) and the Deep Convection Clouds and Chemistry (DC3) field
campaigns. In order to more easily explore this extensive dataset, an aerosol
classification scheme is developed that identifies the different aerosol
types measured during the deployments. This scheme makes use of ancillary
data that include trace gases, chemical composition, aerodynamic particle
size and geographic location, all independent of PI-Neph measurements. The
PI-Neph measurements are then grouped according to their ancillary data
classifications and the resulting scattering patterns are examined in detail.
These results represent the first published airborne measurements of F11
and −F12∕F11 for many common aerosol types. We then explore whether
PI-Neph light-scattering measurements alone are sufficient to reconstruct the
results of this ancillary data classification algorithm. Principal component
analysis (PCA) is used to reduce the dimensionality of the multi-angle
PI-Neph scattering data and the individual measurements are examined as a
function of ancillary data classification. Clear clustering is observed in
the PCA score space, corresponding to the ancillary classification results,
suggesting that, indeed, a strong link exists between the angular-scattering
measurements and the aerosol type or composition. Two techniques are used to
quantify the degree of clustering and it is found that in most cases the
results of the ancillary data classification can be predicted from PI-Neph
measurements alone with better than 85 % recall. This result both
emphasizes the validity of the ancillary data classification as well as the
PI-Neph's ability to distinguish common aerosol types without additional
information
P1658: DELAYED REVERSAL OF FACTOR V INHIBITOR ACTIVITY POST-IMMUNOSUPPRESSIVE THERAPY, FOLLOWED BY A SUCCESSFUL PREGNANCY: A CASE REPORT
Species differences in the response of liver drug-metabolizing enzymes to (S)-4-O-tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric acid (EMD 392949) in vivo and in vitro.
Induction of drug-metabolizing enzymes (DMEs) is highly species-specific and can lead to drug-drug interaction and toxicities. In this series of studies we tested the species specificity of the antidiabetic drug development candidate and mixed peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist (S)-4-O-tolylsulfanyl-2-(4-trifluormethyl-phenoxy)-butyric acid (EMD 392949, EMD) with regard to the induction of gene expression and activities of DMEs, their regulators, and typical PPAR target genes. EMD clearly induced PPARalpha target genes in rats in vivo and in rat hepatocytes but lacked significant induction of DMEs, except for cytochrome P450 (P450) 4A. CYP2C and CYP3A were consistently induced in livers of EMD-treated monkeys. Interestingly, classic rodent peroxisomal proliferation markers were induced in monkeys after 17 weeks but not after a 4-week treatment, a fact also observed in human hepatocytes after 72 h but not 24 h of EMD treatment. In human hepatocyte cultures, EMD showed similar gene expression profiles and induction of P450 activities as in monkeys, indicating that the monkey is predictive for human P450 induction by EMD. In addition, EMD induced a similar gene expression pattern as the PPARalpha agonist fenofibrate in primary rat and human hepatocyte cultures. In conclusion, these data showed an excellent correlation of in vivo data on DME gene expression and activity levels with results generated in hepatocyte monolayer cultures, enabling a solid estimation of human P450 induction. This study also clearly highlighted major differences between primates and rodents in the regulation of major inducible P450s, with evidence of CYP3A and CYP2C inducibility by PPARalpha agonists in monkeys and humans
Electric arcing at high voltage during methane-air explosions inside explosion-proof enclosures /
"February 1982."Prepared for Bureau of Mines Coal Mine Health and Safety Program.Mode of access: Internet
Vortex dynamics in Permalloy disks with artificial defects: Suppression of the gyrotropic mode
The dynamics of magnetic vortices in thin Permalloy disks having artificial defects in the form of small holes at different locations
within the disk has been investigated by means of frequency-domain
spatially resolved ferromagnetic resonance. It is found that the vortex
can be effectively captured by such a defect. Consequently the commonly
observed gyrotropic vortex motion in an applied microwave field of 1 mT
is suppressed. However, if in addition a static magnetic field of at
least 4.3 mT is applied, the vortex core is nucleated from the
artificial defect and a modified gyrotropic motion starts again. (c)
2007 American Institute of Physics