Recent experiments on the National Ignition Facility M. J. Edwards et al., Phys. Plasmas 20, 070501 (2013) demonstrate that utilizing a near-vacuum hohlraum (low pressure gas-filled) is a viable ...option for high convergence cryogenic deuterium-tritium (DT) layered capsule implosions. This is made possible by using a dense ablator (high-density carbon), which shortens the drive duration needed to achieve high convergence: a measured 40% higher hohlraum efficiency than typical gas-filled hohlraums, which requires less laser energy going into the hohlraum, and an observed better symmetry control than anticipated by standard hydrodynamics simulations. The first series of near-vacuum hohlraum experiments culminated in a 6.8 ns, 1.2 MJ laser pulse driving a 2-shock, high adiabat (α∼3.5) cryogenic DT layered high density carbon capsule. This resulted in one of the best performances so far on the NIF relative to laser energy, with a measured primary neutron yield of 1.8×10(15) neutrons, with 20% calculated alpha heating at convergence ∼27×.
Neutron spectra from secondary H3(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in ...statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal H2(d,p)H3 reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models. This analysis represents the first test of stopping models under inertial confinement fusion conditions, covering plasma temperatures of kBT≈1–4 keV and particle densities of n≈(12–2)×1024 cm−3. Under these conditions, we find significant deviations of our data from a theory employing classical collisions whereas the theory including quantum diffraction agrees with our data.
MET
is altered by skipping exon 14 or gene amplification in 1 to 2% of patients with non–small-cell lung cancer. Capmatinib, a
MET
-specific tyrosine kinase inhibitor, led to a response in 40% of ...previously treated patients and in 67% of previously untreated patients whose tumors had
MET
alterations, with a median response duration of 9 months and 12 months, respectively.
Two apolipoprotein E (apoE) receptors, the very low density lipoprotein (VLDL) receptor and apoE receptor 2 (apoER2), are
also receptors for Reelin, a signaling protein that regulates neuronal ...migration during brain development. In the adult brain,
Reelin is expressed by GABA-ergic interneurons, suggesting a potential function as a modulator of neurotransmission. ApoE
receptors have been indirectly implicated in memory and neurodegenerative disorders because their ligand, apoE, is genetically
associated with Alzheimer disease. We have used knockout mice to investigate the role of Reelin and its receptors in cognition
and synaptic plasticity. Mice lacking either the VLDL receptor or the apoER2 show contextual fear conditioning deficits. VLDL
receptor-deficient mice also have a moderate defect in long term potentiation (LTP), and apoER2 knockouts have a pronounced
one. The perfusion of mouse hippocampal slices with Reelin has no effect on baseline synaptic transmission but significantly
enhances LTP in area CA1. This Reelin-dependent augmentation of LTP is abolished in VLDL receptor and apoER2 knockout mice.
Our results reveal a role for Reelin in controlling synaptic plasticity in the adult brain and suggest that both of its receptors
are necessary for Reelin-dependent enhancement of synaptic transmission in the hippocampus. Thus, the impairment of apoE receptor-dependent
neuromodulation may contribute to cognitive impairment and synaptic loss in Alzheimer disease.
In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the ...safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML.
Starting in 2012, we began an unprecedented observational program focused on the supermassive black hole in the center of our Galaxy, Sgr A*, utilizing the High Energy Transmission Grating ...Spectrometer (HETGS) instrument on the Chandra X-Ray Observatory. Here we report an observation performed on 2012 February 9 wherein we detected what are the highest peak flux and fluence flare ever observed from Sgr A*. The flare, which lasted for 5.6 ks and had a decidedly asymmetric profile with a faster decline than rise, achieved a mean absorbed 2-8 keV flux of (8.5 + or - 0.9) x 10 super(-12) erg cm super(-2) s super(-1). We find good agreement among the fitted spectral slopes (Gamma ~ 2) and X-ray absorbing columns (N sub(H) ~ 15 x 10 super(22) cm super(-2)) for all three of these events, resolving prior differences (which are most likely due to the combined effects of pileup and spectral modeling) among Chandra and XMM-Newton observations of Sgr A* flares.
A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net ...classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with ⩾4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.
Biallelic mutations of the CEBPA gene (CEBPAbi) define a distinct entity associated with favorable prognosis; however, the role of monoallelic mutations (CEBPAsm) is poorly understood. We ...retrospectively analyzed 4708 adults with acute myeloid leukemia (AML) who had been recruited into the Study Alliance Leukemia trials, to investigate the prognostic impact of CEBPAsm. CEBPA mutations were identified in 240 patients (5.1%): 131 CEBPAbi and 109 CEBPAsm (60 affecting the N-terminal transactivation domains CEBPAsmTAD and 49 the C-terminal DNA-binding or basic leucine zipper region CEBPAsmbZIP). Interestingly, patients carrying CEBPAbi or CEBPAsmbZIP shared several clinical factors: they were significantly younger (median, 46 and 50 years, respectively) and had higher white blood cell (WBC) counts at diagnosis (median, 23.7 × 109/L and 35.7 × 109/L) than patients with CEBPAsmTAD (median age, 63 years, median WBC 13.1 × 109/L; P < .001). Co-mutations were similar in both groups: GATA2 mutations (35.1% CEBPAbi; 36.7% CEBPAsmbZIP vs 6.7% CEBPAsmTAD; P < .001) or NPM1 mutations (3.1% CEBPAbi; 8.2% CEBPAsmbZIP vs 38.3% CEBPAsmTAD; P < .001). CEBPAbi and CEBPAsmbZIP, but not CEBPAsmTAD were associated with significantly improved overall (OS; median 103 and 63 vs 13 months) and event-free survival (EFS; median, 20.7 and 17.1 months vs 5.7 months), in univariate and multivariable analyses. Additional analyses revealed that the clinical and molecular features as well as the favorable survival were confined to patients with in-frame mutations in bZIP (CEBPAbZIP-inf). When patients were classified according to CEBPAbZIP-inf and CEBPAother (including CEBPAsmTAD and non-CEBPAbZIP-inf), only patients bearing CEBPAbZIP-inf showed superior complete remission rates and the longest median OS and EFS, arguing for a previously undefined prognostic role of this type of mutation.
•CEBPAsmbZIP- and CEBPAbi-mutant AML share clinical and mutational characteristics and are distinct from CEBPAsmTAD-mutant AML.•Only in-frame mutations in CEBPA-bZIP are associated with favorable clinical response in monoallelic and biallelic constellations.
Display omitted
Many galaxies are thought to have supermassive black holes at their centres-more than a million times the mass of the Sun. Measurements of stellar velocities and the discovery of variable X-ray ...emission have provided strong evidence in favour of such a black hole at the centre of the Milky Way, but have hitherto been unable to rule out conclusively the presence of alternative concentrations of mass. Here we report ten years of high-resolution astrometric imaging that allows us to trace two-thirds of the orbit of the star currently closest to the compact radio source (and massive black-hole candidate) Sagittarius A*. The observations, which include both pericentre and apocentre passages, show that the star is on a bound, highly elliptical keplerian orbit around Sgr A*, with an orbital period of 15.2 years and a pericentre distance of only 17 light hours. The orbit with the best fit to the observations requires a central point mass of (3.7 ± 1.5) × 106 solar masses (M ). The data no longer allow for a central mass composed of a dense cluster of dark stellar objects or a ball of massive, degenerate fermions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
