A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion

Key Points Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data

Rapid state purification protocols for a Cooper pair box

We propose techniques for implementing two different rapid state purification schemes, within the constraints present in a superconducting charge qubit system. Both schemes use a continuous measurement of charge (z) measurements, and seek to minimize the time required to purify the conditional state. Our methods are designed to make the purification process relatively insensitive to rotations about the x-axis, due to the Josephson tunnelling Hamiltonian. The first proposed method, based on the scheme of Jacobs [Phys. Rev. A 67, 030301(R) (2003)] uses the measurement results to control bias (z) pulses so as to rotate the Bloch vector onto the x-axis of the Bloch sphere. The second proposed method, based on the scheme of Wiseman and Ralph [New J. Phys. 8, 90 (2006)] uses a simple feedback protocol which tightly rotates the Bloch vector about an axis almost parallel with the measurement axis. We compare the performance of these and other techniques by a number of different measures.Comment: 14 pages, 14 figures. v2: Revised version after referee comments. Accepted for publication by Physical Review

Interacting damage models mapped onto Ising and percolation models

We introduce a class of damage models on regular lattices with isotropic interactions, as e.g. quasistatic fiber bundles. The system starts intact with a surface-energy threshold required to break any cell sampled from an uncorrelated quenched-disorder distribution. The evolution of this heterogeneous system is ruled by Griffith's principle which states that a cell breaks when the release in elastic energy in the system exceeds the surface-energy barrier necessary to break the cell. By direct integration over all possible realizations of the quenched disorder, we obtain the probability distribution of each damage configuration at any level of the imposed external deformation. We demonstrate an isomorphism between the distributions so obtained and standard generalized Ising models, in which the coupling constants and effective temperature in the Ising model are functions of the nature of the quenched-disorder distribution and the extent of accumulated damage. In particular, we show that damage models with global load sharing are isomorphic to standard percolation theory, that damage models with local load sharing rule are isomorphic to the standard Ising model, and draw consequences thereof for the universality class and behavior of the autocorrelation length of the breakdown transitions corresponding to these models. We also treat damage models having more general power-law interactions, and classify the breakdown process as a function of the power-law interaction exponent. Last, we also show that the probability distribution over configurations is a maximum of Shannon's entropy under some specific constraints related to the energetic balance of the fracture process, which firmly relates this type of quenched-disorder based damage model to standard statistical mechanics.Comment: 16 pages, 3 figure

Generalized "Quasi-classical" Ground State for an Interacting Two Level System

We treat a system (a molecule or a solid) in which electrons are coupled linearly to any number and type of harmonic oscillators and which is further subject to external forces of arbitrary symmetry. With the treatment restricted to the lowest pair of electronic states, approximate "vibronic" (vibration-electronic) ground state wave functions are constructed having the form of simple, closed expressions. The basis of the method is to regard electronic density operators as classical variables. It extends an earlier "guessed solution", devised for the dynamical Jahn-Teller effect in cubic symmetry, to situations having lower (e.g., dihedral) symmetry or without any symmetry at all. While the proposed solution is expected to be quite close to the exact one, its formal simplicity allows straightforward calculations of several interesting quantities, like energies and vibronic reduction (or Ham) factors. We calculate for dihedral symmetry two different $q$-factors ("$q_z$" and "$q_x$") and a $p$-factor. In simplified situations we obtain $p=q_z +q_x -1$. The formalism enables quantitative estimates to be made for the dynamical narrowing of hyperfine lines in the observed ESR spectrum of the dihedral cyclobutane radical cation.Comment: 28 pages, 4 figure

Spectroscopy of a Cooper-Pair box in the Autler-Townes configuration

A theoretical spectroscopic analysis of a microwave driven superconducting charge qubit (Cooper-pair box coupled) to an RLC oscillator model is performed. By treating the oscillator as a probe through the backreaction effect of the qubit on the oscillator circuit, we extract frequency splitting features analogous to the Autler-Townes effect from quantum optics, thereby extending the analogies between superconducting and quantum optical phenomenology. These features are found in a frequency band that avoids the need for high frequency measurement systems and therefore may be of use in qubit characterization and coupling schemes. In addition we find this frequency band can be adjusted to suit an experimental frequency regime by changing the oscillator frequency.Comment: 13 pages, 7 figures. v2: Revised version after referee comments. Accepted for publication by Physical Review

Replication fork rescue in mammalian mitochondria

Replication stalling has been associated with the formation of pathological mitochondrial DNA (mtDNA) rearrangements. Yet, almost nothing is known about the fate of stalled replication intermediates in mitochondria. We show here that replication stalling in mitochondria leads to replication fork regression and mtDNA double-strand breaks. The resulting mtDNA fragments are normally degraded by a mechanism involving the mitochondrial exonuclease MGME1, and the loss of this enzyme results in accumulation of linear and recombining mtDNA species. Additionally, replication stress promotes the initiation of alternative replication origins as an apparent means of rescue by fork convergence. Besides demonstrating an interplay between two major mechanisms rescuing stalled replication forks - mtDNA degradation and homology-dependent repair - our data provide evidence that mitochondria employ similar mechanisms to cope with replication stress as known from other genetic systems.Peer reviewe

Magnetic anisotropies and general on--site Coulomb interactions in the cuprates

This paper derives the anisotropic superexchange interactions from a Hubbard model for excitations within the copper 3d band and the oxygen 2p band of the undoped insulating cuprates. We extend the recent calculation of Yildirim et al. [Phys. Rev. B {\bf VV}, pp, 1995] in order to include the most general on--site Coulomb interactions (including those which involve more than two orbitals) when two holes occupy the same site. Our general results apply when the oxygen ions surrounding the copper ions form an octahedron which has tetragonal symmetry (but may be rotated as in lanthanum cuprate). For the tetragonal cuprates we obtain an easy--plane anisotropy in good agreement with experimental values. We predict the magnitude of the small in--plane anisoComment: 25 pages, revte