Gene amplifications associated with the development of hormone- resistant prostate cancer

Purpose: Hormone resistance remains a significant clinical problem in prostate cancer with few therapeutic options. Research into mechanisms of hormone resistance is essential. Experimental Design: We analyzed 38 paired (prehormone/posthormone resistance) prostate cancer samples using the Vysis GenoSensor. Archival microdissected tumor DNA was extracted, amplified, labeled, and hybridized to Amplione I DNA microarrays containing 57 oncogenes. Results: Genetic instability increased during progression from hormone-sensitive to hormone-resistant cancer (P = 0.008). Amplification frequencies of 15 genes (TERC, MYBL3, HRAS, PI3KCA, JUNB, LAMC2, RAF1, MYC, GARP, SAS, FGFR1, PGY1, MYCL1, MYB, FGR) increased by greater than 10% during hormone escape. Receptor tyrosine kinases were amplified in 73% of cases; this was unrelated to development of hormone resistance. However, downstream receptor tyrosine kinase signaling pathways showed increased amplification rates in resistant tumors for the mitogen-activated protein kinase (FGR/Src-2, HRAS, and RAF1; P = 0.005) and phosphatidylinositol 3'-kinase pathways (FGR/ Src-2, PI3K, and Akt; P = 0.046). Transcription factors regulated by these pathways were also more frequently amplified after escape (MYC family: 21% before versus 63% after, P = 0.027; MYB family: 26 % before versus 53 % after, P = 0.18). Conclusions: Development of clinical hormone escape is linked to phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways. These pathways may function independently of the androgen receptor or via androgen receptor activation by phosphorylation, providing novel therapeutic targets

Convergence improvement for coupled cluster calculations

Convergence problems in coupled-cluster iterations are discussed, and a new iteration scheme is proposed. Whereas the Jacobi method inverts only the diagonal part of the large matrix of equation coefficients, we invert a matrix which also includes a relatively small number of off-diagonal coefficients, selected according to the excitation amplitudes undergoing the largest change in the coupled cluster iteration. A test case shows that the new IPM (inversion of partial matrix) method gives much better convergence than the straightforward Jacobi-type scheme or such well-known convergence aids as the reduced linear equations or direct inversion in iterative subspace methods.Comment: 7 pages, IOPP styl

Contextuality under weak assumptions

The presence of contextuality in quantum theory was first highlighted by Bell, Kochen and Specker, who discovered that for quantum systems of three or more dimensions, measurements could not be viewed as deterministically revealing pre-existing properties of the system. More precisely, no model can assign deterministic outcomes to the projectors of a quantum measurement in a way that depends only on the projector and not the context (the full set of projectors) in which it appeared, despite the fact that the Born rule probabilities associated with projectors are independent of the context. A more general, operational definition of contextuality introduced by Spekkens, which we will term "probabilistic contextuality", drops the assumption of determinism and allows for operations other than measurements to be considered contextual. Even two-dimensional quantum mechanics can be shown to be contextual under this generalised notion. Probabilistic noncontextuality represents the postulate that elements of an operational theory that cannot be distinguished from each other based on the statistics of arbitrarily many repeated experiments (they give rise to the same operational probabilities) are ontologically identical. In this paper, we introduce a framework that enables us to distinguish between different noncontextuality assumptions in terms of the relationships between the ontological representations of objects in the theory given a certain relation between their operational representations. This framework can be used to motivate and define a "possibilistic" analogue, encapsulating the idea that elements of an operational theory that cannot be unambiguously distinguished operationally can also not be unambiguously distinguished ontologically. We then prove that possibilistic noncontextuality is equivalent to an alternative notion of noncontextuality proposed by Hardy. Finally, we demonstrate that these weaker noncontextuality assumptions are sufficient to prove alternative versions of known "no-go" theorems that constrain ψ-epistemic models for quantum mechanics

Observers can always generate nonlocal correlations without aligning measurements by covering all their bases

Quantum theory allows for correlations between the outcomes of distant measurements that are inconsistent with any locally causal theory, as demonstrated by the violation of a Bell inequality. Typical demonstrations of these correlations require careful alignment between the measurements, which requires distant parties to share a reference frame. Here, we prove, following a numerical observation by Shadbolt et al., that if two parties share a Bell state and each party randomly chooses three orthogonal measurements, then the parties will always violate a Bell inequality. Furthermore, we prove that this probability is highly robust against local depolarizing noise, in that small levels of noise only decrease the probability of violating a Bell inequality by a small amount. We also show that generalizing to N parties increases the robustness against noise. These results improve on previous ones that only allowed a high probability of violating a Bell inequality for large numbers of parties.Comment: 4 pages, 2 figures. v2: updated reference. v3: published versio

The unitary-model-operator approach to nuclear many-body problems

Microscopic nuclear structure calculations have been performed within the framework of the unitary-model-operator approach. Ground-state and single-particle energies are calculated for nuclei around ^{14}C, ^{16}O and ^{40}Ca with modern nucleon-nucleon interactions.Comment: 6 pages, 4 figures, Talk presented at the International Symposium on Correlation Dynamics in Nuclei (CDN05), Jan. 1 - Feb. 4, 2005, Tokyo, Japa

SXP 7.92: A Recently Rediscovered Be/X-ray Binary in the Small Magellanic Cloud, Viewed Edge On

We present a detailed optical and X-ray study of the 2013 outburst of the Small Magellanic Cloud Be/X-ray binary SXP 7.92, as well as an overview of the last 18 years of observations from OGLE (Optical Gravitational Lensing Experiment), RXTE, Chandra and XMM-Newton. We revise the position of this source to RA(J2000) = 00:57:58.4, Dec(J2000) = −72:22:29.5 with a 1σ uncertainty of 1.5 arcsec, correcting the previously reported position by Coe et al. by more than 20 arcmin. We identify and spectrally classify the correct counterpart as a B1Ve star. The optical spectrum is distinguished by an uncharacteristically deep narrow Balmer series, with the Hα line in particular having a distinctive shell profile, i.e. a deep absorption core embedded in an emission line. We interpret this as evidence that we are viewing the system edge on and are seeing self-obscuration of the circumstellar disc. We derive an optical period for the system of 40.0 ± 0.3 d, which we interpret as the orbital period, and present several mechanisms to describe the X-ray/optical behaviour in the recent outburst, in particular the ‘flares'and ‘dips’ seen in the optical light curve, including a transient accretion disc and an elongated precessing disc

Dynamics of a Quantum Reference Frame

We analyze a quantum mechanical gyroscope which is modeled as a large spin and used as a reference against which to measure the angular momenta of spin-1/2 particles. These measurements induce a back-action on the reference which is the central focus of our study. We begin by deriving explicit expressions for the quantum channel representing the back-action. Then, we analyze the dynamics incurred by the reference when it is used to sequentially measure particles drawn from a fixed ensemble. We prove that the reference thermalizes with the measured particles and find that generically, the thermal state is reached in time which scales linearly with the size of the reference. This contrasts a recent conclusion of Bartlett et al. that this takes a quadratic amount of time when the particles are completely unpolarized. We now understand their result in terms of a simple physical principle based on symmetries and conservation laws. Finally, we initiate the study of the non-equilibrium dynamics of the reference. Here we find that a reference in a coherent state will essentially remain in one when measuring polarized particles, while rotating itself to ultimately align with the polarization of the particles