ALBERT

Description: p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.

Description: Among the entire patients with AML the majority is 60 years of age or older. In present German multicenter AML Cooperative Group (AMLCG) trial the proportion of these older patients amounts to 54% of all 2734 patients enrolled and receiving intensive chemotherapy. While older age AML is increasingly recognized as a main challenge the therapeutic outcome unlike that in younger patients has remained constantly poor. Thus, the patients of ≥ 60y show an overall survival (OS) of 13% and a relapse rate (RR) of 82% at 5y versus 40% and 52% in younger patients. Age related differences in treatment and in risk profiles are commonly used to explain the differences in outcome. In the AMLCG 99 trial including 2734 patients 16 to 85 (median 61) years of age we investigated factors determining the disease biology and outcome. For induction treatment patients received standard dose TAD and high-dose AraC 3 (age 〈 60y) and 1 (≥ 60y) g/m² × 6/mitoxantrone (HAM) or randomly HAM-HAM, for consolidation TAD, and for maintenance monthly reduced TAD randomized (in patients 〈 60y) against autologous SCT. When compared with patients younger than 60y older patients had more frequent secondary AML (29% vs 17%, p〈 0.0001), unfavorable cytogenetics (29% vs 23%, p= 0.0004), less frequent favorable cytogenetics (4% vs 12%, p〈 0.0001), and NPM1mut/FLT3-ITDneg status (26% vs 34%, p〈 0.009) in those with normal karyotype, and overall even lower median WBC (7.360 vs 12.600/μl, p〈 0.0001) and LDH (340 vs 413 U/l, p〈 0.0001). A multivariate analysis identified independent risk factors determining therapeutic endpoints such as CR rate, OS, RR, and RFS. With similar results across all endpoints, risk factors for OS were age ≥ 60y (HR 1.96, 95% CI 1.75–2.17), AML secondary to MDS or cytotoxic treatment (1.28, 1.14–1.45), unfavorable karyotype (2.17, 1.92– 2.44), WBC 〉 20×10³/μl (1.15, 1.02– 1.30), LDH 〉 700U/L (1.32, 1.15– 1.52), favorable karyotype (0.49, 0.38– 0.63) and female gender (0.90, 0.81– 0.99). In the 891 patients with normal karyotype and complete mutation status risk factors for OS were age ≥ 60y (2.00, 1.64– 2.44), and NPM1mut/FLT3-ITDneg (0.39, 0.30– 0.49). Risk factors for RR overall were age ≥ 60y (2.04, 1.75– 2.38), unfavorable karyotype (2.08, 1.47– 2.13), LDH (1.41, 1.16– 1.72) and favorable karyotype (0.40, 0.29– 0.56). In patients with normal karyotype and complete mutation status risk factors for RR were age ≥ 60y (2.00, 1.56– 2.63), and NPM1mut/FLT3-ITDneg (0.32, 0.23– 0.43). Testing the role of older age in favorable subgroups, the 198 patients with CBF leukemia show an OS at 5 years of 27.5 (95% CI 12.0– 43.0) % in the older versus 69.4 (60.7– 78.2) % in the younger age group, and a RR of 56.6 (35.7– 77.3) % versus 25.0 (15.6– 34.4) %. Comparatively, the 264 patients with a normal karyotype and NPM1mut/FLT3-ITDneg show an OS of 37.1 (26.6– 47.5) % in the older versus 71.9 (63.4– 80.4) % in the younger age group, and a RR of 61.0 (47.8– 74.2) % versus 23.0 (14.0– 32.0) %. There was no influence by randomized treatment variables on any therapeutic endpoint. Conclusion: Considering the prognostic spectrum of all major historic or genetic subgroups older age maintains its dominant role not explained by age related differences in risk profiles. Even within CBF leukemias and sole NPM1 mutation as the best prognostic categories older age predicts for markedly shorter OS and higher RR. Thus, understanding older age AML requires further genetic and epigenetic work.

Description: p53 mutations are found in a wide variety of cancers, including hematologic malignancies. These alterations apparently contribute to development of the malignant phenotype. We analyzed a large series of lymphoid (330 cases) and a smaller series of myeloid (29 cases) malignancies of childhood for p53 mutations by single-strand conformational polymorphism (SSCP) following polymerase chain reaction. Samples with abnormal SSCP were reamplified and analyzed by direct sequencing method. p53 mutations were detected within the known mutational hotspots (exons 5 to 8) in 8 of 330 lymphoid malignancies, and in none of 29 myeloid malignancies, showing that the frequency of p53 mutations in childhood lymphoid malignancies was very low (8 of 330 cases [2%]). Four of these patients had very aggressive, fatal acute lymphocytic leukemia (ALL). None of 13 infants and none of 48 patients with T-lineage leukemia had detectable p53 mutations in their ALL cells. Exceptionally, p53 mutations were comparatively frequent in a small sample of B-cell non-Hodgkin's lymphomas (2 of 8 cases). Mutations were detected in samples from two patients with ALL at relapse; these were not detected in samples at initial diagnosis from the same patients, suggesting that p53 mutations may be associated with progression to a more malignant phenotype. Seven of eight alterations of p53 were missense mutations, and seven of eight samples may be heterozygous for the mutant p53, indicating that p53 protein may act in a dominant negative fashion.

Description: A quantum two-path interferometer allows for direct measurement of the transmission phase shift of an electron, providing useful information on coherent scattering problems. In mesoscopic systems, however, the two-path interference is easily smeared by contributions from other paths, and this makes it difficult to observe the true transmission phase shift. To eliminate this problem, multi-terminal Aharonov-Bohm (AB) interferometers have been used to derive the phase shift by assuming that the relative phase shift of the electrons between the two paths is simply obtained when a smooth shift of the AB oscillations is observed. Nevertheless, the phase shifts using such a criterion have sometimes been inconsistent with theory. On the other hand, we have used an AB ring contacted to tunnel-coupled wires and acquired the phase shift consistent with theory when the two output currents through the coupled wires oscillate with well-defined anti-phase. Here, we investigate thoroughly these two criteria used to ensure a reliable phase measurement, the anti-phase relation of the two output currents, and the smooth phase shift in the AB oscillation. We confirm that the well-defined anti-phase relation ensures a correct phase measurement with a quantum two-path interference. In contrast, we find that even in a situation where the anti-phase relation is less well-defined, the smooth phase shift in the AB oscillation can still occur but does not give the correct transmission phase due to contributions from multiple paths. This indicates that the phase relation of the two output currents in our interferometer gives a good criterion for the measurement of the true transmission phase, while the smooth phase shift in the AB oscillation itself does not.

Description: We demonstrate by injection seeding that the spectral emission of a terahertz (THz) quantum cascade laser (QCL) can be modified with broad-band THz pulses whose bandwidths are greater than the QCL bandwidth. Two broad-band THz pulses delayed in time imprint a modulation on the single THz pulse spectrum. The resulting spectrum is used to injection seed the THz QCL. By varying the time delay between the THz pulses, the amplitude distribution of the QCL longitudinal modes is modified. By applying this approach, the QCL emission is reversibly switched from multi-mode to single mode emission.

Description: Growth by chemical vapor deposition (CVD) leads to multilayer WS 2 of very high quality, based on high-resolution angle-resolved photoemission spectroscopy. The experimental valence band electronic structure is considered to be in good agreement with that obtained from density functional theory calculations. We find the spin-orbit splitting at the K ¯ point to be 420  ±  20 meV with a hole effective mass of −0.35  ±  0.02 m e for the upper spin-orbit component (the branch closer to the Fermi level) and −0.43  ±  0.07 m e for the lower spin-orbit component. As predicted by theory, a thickness-dependent increase of bandwidth is observed at the top of the valence band, in the region of the Brillouin zone center. The top of the valence band of the CVD-prepared films exhibits a substantial binding energy, consistent with n -type behavior, and in agreement with transistor characteristics acquired using devices incorporating the same WS 2 material.

Description: The influence of sodium on the band structure of MoS 2 (0001) and the comparison of the experimental band dispersion with density functional theory show excellent agreement for the occupied states (angle-resolved photoemission) and qualitative agreement for the unoccupied states (inverse photoemission spectroscopy). Na-adsorption leads to charge transfer to the MoS 2 surface causing an effect similar to n-type doping of a semiconductor. The MoS 2 occupied valence band structure shifts rigidly to greater binding with little change in the occupied state dispersion. Likewise, the unoccupied states shift downward, approaching the Fermi level, yet the amount of the shift for the unoccupied states is greater than that of the occupied states, effectively causing a narrowing of the MoS 2 bandgap.

Description: Quantum dot arrays provide a promising platform for quantum information processing. For universal quantum simulation and computation, one central issue is to demonstrate the exhaustive controllability of quantum states. Here, we report the addressable manipulation of three single electron spins in a triple quantum dot using a technique combining electron-spin-resonance and a micro-magnet. The micro-magnet makes the local Zeeman field difference between neighboring spins much larger than the nuclear field fluctuation, which ensures the addressable driving of electron-spin-resonance by shifting the resonance condition for each spin. We observe distinct coherent Rabi oscillations for three spins in a semiconductor triple quantum dot with up to 25 MHz spin rotation frequencies. This individual manipulation over three spins enables us to arbitrarily change the magnetic spin quantum number of the three spin system, and thus to operate a triple-dot device as a three-qubit system in combination with the existing technique of exchange operations among three spins.

Description: Titanium nitride (TiN) shows low resistivity at room temperature (27  μ Ω cm), high thermal stability and thus has the potential to serve as seed layer in magnetic tunnel junctions. High quality TiN thin films with regard to the crystallographic and electrical properties were grown and characterized by x-ray diffraction and 4-terminal transport measurements. Element specific x-ray absorption spectroscopy revealed pure TiN inside the thin films. To investigate the influence of a TiN seed layer on a ferro(i)magnetic bottom electrode in magnetic tunnel junctions, an out-of-plane magnetized Mn 2.45 Ga as well as in- and out-of-plane magnetized Co 2 FeAl thin films were deposited on a TiN buffer, respectively. The magnetic properties were investigated using a superconducting quantum interference device and anomalous Hall effect for Mn 2.45 Ga. Magneto optical Kerr effect measurements were carried out to investigate the magnetic properties of Co 2 FeAl. TiN buffered Mn 2.45 Ga thin films showed higher coercivity and squareness ratio compared to unbuffered samples. The Heusler compound Co 2 FeAl showed already good crystallinity when grown at room temperature on a TiN seed-layer.

Description: Time-resolved resonance fluorescence on a single self-assembled quantum dot (QD) is used to analyze the generation and capture of photoinduced free charge carriers. We directly observe the capture of electrons into the QD as an intensity reduction of the exciton transition. The exciton transition is quenched until the captured electron tunnels out of the dot again in the order of milliseconds. Our results demonstrate that even under resonant excitation, excited free electrons are generated and can negatively influence the optical properties of a QD.