Traditional response criteria in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are based on bone marrow morphology and may not accurately reflect clonal tumor burden in patients ...treated with non-cytotoxic chemotherapy. We used next-generation sequencing of serial bone marrow samples to monitor MDS and AML tumor burden during treatment with epigenetic therapy (decitabine and panobinostat). Serial bone marrow samples (and skin as a source of normal DNA) from 25 MDS and AML patients were sequenced (exome or 285 gene panel). We observed that responders, including those in complete remission (CR), can have persistent measurable tumor burden (that is, mutations) for at least 1 year without disease progression. Using an ultrasensitive sequencing approach, we detected extremely rare mutations (equivalent to 1 heterozygous mutant cell in 2000 non-mutant cells) months to years before their expansion at disease relapse. While patients can live with persistent clonal hematopoiesis in a CR or stable disease, ultimately we find evidence that expansion of a rare subclone occurs at relapse or progression. Here we demonstrate that sequencing of serial samples provides an alternative measure of tumor burden in MDS or AML patients and augments traditional response criteria that rely on bone marrow blast percentage.
Galactic cosmic rays consist of protons, electrons and ions, most of which are believed to be accelerated to relativistic speeds in supernova remnants. All components of the cosmic rays show an ...intensity that decreases as a power law with increasing energy (for example as E-2.7). Electrons in particular lose energy rapidly through synchrotron and inverse Compton processes, resulting in a relatively short lifetime (about 105 years) and a rapidly falling intensity, which raises the possibility of seeing the contribution from individual nearby sources (less than one kiloparsec away). Here we report an excess of galactic cosmic-ray electrons at energies of ∼300-800 GeV, which indicates a nearby source of energetic electrons. Such a source could be an unseen astrophysical object (such as a pulsar or micro-quasar) that accelerates electrons to those energies, or the electrons could arise from the annihilation of dark matter particles (such as a Kaluza-Klein particle with a mass of about 620 GeV).
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cosmic-ray proton and helium spectra have been measured with the balloon-borne Cosmic Ray Energetics And Mass experiment flown for 42 days in Antarctica in the 2004-2005 austral summer season. ...High-energy cosmic-ray data were collected at an average altitude of ~38.5 km with an average atmospheric overburden of ~3.9 g cm--2. Individual elements are clearly separated with a charge resolution of ~0.15 e (in charge units) and ~0.2 e for protons and helium nuclei, respectively. The measured spectra at the top of the atmosphere are represented by power laws with a spectral index of --2.66 ? 0.02 for protons from 2.5 TeV to 250 TeV and --2.58 ? 0.02 for helium nuclei from 630 GeV nucleon--1 to 63 TeV nucleon--1. They are harder than previous measurements at a few tens of GeV nucleon--1. The helium flux is higher than that expected from the extrapolation of the power law fitted to the lower-energy data. The relative abundance of protons to helium nuclei is 9.1 ? 0.5 for the range from 2.5 TeV nucleon--1 to 63 TeV nucleon--1. This ratio is considerably smaller than the previous measurements at a few tens of GeV nucleon--1.
Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal ...opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland. We identify 303 novel association signals, more than one third at variants rare or enriched in Finns. Many of these signals identify genes not previously implicated in metabolite genome-wide association studies and suggest mechanisms for diseases and disease-related traits.
The final results of processing the data from the balloon-born experiment ATIC-2 (Antarctica, 2002–2003) for the energy spectra of protons and He, C, O, Ne, Mg, Si, and Fe nuclei, the spectrum of all ...particles, and the mean logarithm of atomic weight of primary cosmic rays as a function of energy are presented. The final results are based on improvement of the methods used earlier, in particular, considerably increased resolution of the charge spectrum. The preliminary conclusions on the significant difference in the spectra of protons and helium nuclei (the proton spectrum is steeper) and the non-power character of the spectra of protons and heavier nuclei (flattening of carbon spectrum at energies above 10 TeV) are confirmed. A complex structure of the energy dependence of the mean logarithm of atomic weight is found.
We present new measurements of the energy spectra of cosmic-ray (CR) nuclei from the second flight of the balloon-borne experiment Cosmic-Ray Energetics And Mass (CREAM). The instrument included ...different particle detectors to provide redundant charge identification and measure the energy of CRs up to several hundred TeV. The measured individual energy spectra of C, O, Ne, Mg, Si, and Fe are presented up to ~1014 eV. The spectral shape looks nearly the same for these primary elements and it can be fitted to an E -2.66 +/- 0.04 power law in energy. Moreover, a new measurement of the absolute intensity of nitrogen in the 100-800 GeV/n energy range with smaller errors than previous observations, clearly indicates a hardening of the spectrum at high energy. The relative abundance of N/O at the top of the atmosphere is measured to be 0.080 +/- 0.025 (stat.)+/-0.025 (sys.) at ~800 GeV/n, in good agreement with a recent result from the first CREAM flight.
Canadian Institutes of Health Research Group on Action and Perception, Department of Psychology, University of Western Ontario, London, Canada
Submitted 9 November 2005;
accepted in final form 20 ...February 2006
The idea that visually guided action is independent of visual perception has been supported by neurological, neuropsychological, and behavioral studies. In healthy subjects, evidence for this distinction has come from psychophysical studies of the effects of visual illusions on perceptual judgments and object-directed grasping. This evidence is limited, however, by the fact that virtually all studies have involved right-handed subjects using their dominant hand, which is presumably controlled by the left hemisphere. There is tentative evidence from earlier neurological studies that the left hemisphere may in fact play a special role in the integration of visual and motor information during grasping. We designed two experiments to test this idea. The first experiment involved pictorial illusions, which are known to have robust effects on perceptual judgments but little influence on grasping. Right- and left-handed subjects reached out and grasped objects embedded in two different visual illusions with either their dominant or their nondominant hand. For both right- and left-handed subjects, precision grasping with the left hand, but not with the right, was affected by the illusions. In a follow-up experiment, we examined precision grasping in a more natural setting and showed that left-handed subjects use their nondominant (right) hand significantly more as compared with right-handed subjects. We conclude that visuomotor mechanisms encapsulated in the left hemisphere play a crucial role in the visual control of action and that this hemispheric specialization evolved independently of handedness.
Address for reprint requests and other correspondence: C.L.R. Gonzalez, CIHR Group on Action and Perception, Department of Psychology, University of Western Ontario, London N6A 5C2, Canada (E-mail: cgonzal6{at}uwo.ca )
Face perception, recognition and priming were examined with event-related functional magnetic resonance imaging (fMRI) and scalp event-related potentials (ERPs). Face perception was associated with ...haemodynamic increases in regions including bilateral fusiform and right superior temporal cortices, and a right posterior negativity (N170), most likely generated in the superior temporal region. Face recognition was associated with haemodynamic increases in fusiform, medial frontal and orbitofrontal cortices, and with a frontocentral positivity from 550 ms poststimulus. Face repetition was associated with a positivity from 400 to 600 ms and behavioural priming. Repetition of familiar faces was also associated with earlier onset of the ERP familiarity effect, and haemodynamic decreases in fusiform cortex. These data support a multi-component model of face-processing, with priming arising from more than one stage.
We present measurements of the relative abundances of cosmic-ray nuclei in the energy range of 500-3980 GeV/nucleon from the second flight of the Cosmic Ray Energetics And Mass balloon-borne ...experiment. Particle energy was determined using a sampling tungsten/scintillating-fiber calorimeter, while particle charge was identified precisely with a dual-layer silicon charge detector installed for this flight. The resulting element ratios C/O, N/O, Ne/O, Mg/O, Si/O, and Fe/O at the top of atmosphere are 0.919 {+-} 0.123{sup stat} {+-} 0.030{sup syst}, 0.076 {+-} 0.019{sup stat} {+-} 0.013{sup syst}, 0.115 {+-} 0.031{sup stat} {+-} 0.004{sup syst}, 0.153 {+-} 0.039{sup stat} {+-} 0.005{sup syst}, 0.180 {+-} 0.045{sup stat} {+-} 0.006{sup syst}, and 0.139 {+-} 0.043{sup stat} {+-} 0.005{sup syst}, respectively, which agree with measurements at lower energies. The source abundance of N/O is found to be 0.054 {+-} 0.013{sup stat} {+-} 0.009{sup syst+0.010esc} {sub -0.017}. The cosmic-ray source abundances are compared to local Galactic (LG) abundances as a function of first ionization potential and as a function of condensation temperature. At high energies the trend that the cosmic-ray source abundances at large ionization potential or low condensation temperature are suppressed compared to their LG abundances continues. Therefore, the injection mechanism must be the same at TeV/nucleon energies as at the lower energies measured by HEAO-3, CRN, and TRACER. Furthermore, the cosmic-ray source abundances are compared to a mixture of 80% solar system abundances and 20% massive stellar outflow (MSO) as a function of atomic mass. The good agreement with TIGER measurements at lower energies confirms the existence of a substantial fraction of MSO material required in the {approx}TeV per nucleon region.
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