What do we learn from HER2-positive breast cancer genomic profiles?

Patients with a tumor presenting amplification of the HER2 gene are currently proposed trastuzumab (herceptin) and this has greatly changed their outcome. However, a number of HER2-positive cancers show intrinsic or acquired resistance to trastuzumab and there are clear indications that they form a heterogeneous group of tumors. A paper in this issue of Breast Cancer Research addresses this heterogeneity at the genomic level

Exploring 4D Quantum Hall Physics with a 2D Topological Charge Pump

The discovery of topological states of matter has profoundly augmented our understanding of phase transitions in physical systems. Instead of local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example thereof is the two-dimensional integer quantum Hall effect. It is characterized by the first Chern number which manifests in the quantized Hall response induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional systems leads to the appearance of a novel non-linear Hall response that is quantized as well, but described by a 4D topological invariant - the second Chern number. Here, we report on the first observation of a bulk response with intrinsic 4D topology and the measurement of the associated second Chern number. By implementing a 2D topological charge pump with ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small atom cloud as a local probe, we fully characterize the non-linear response of the system by in-situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probe higher-dimensional quantum Hall systems, where new topological phases with exotic excitations are predicted

Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)

Experimental Measurement of the Berry Curvature from Anomalous Transport

Geometrical properties of energy bands underlie fascinating phenomena in a wide-range of systems, including solid-state materials, ultracold gases and photonics. Most famously, local geometrical characteristics like the Berry curvature can be related to global topological invariants such as those classifying quantum Hall states or topological insulators. Regardless of the band topology, however, any non-zero Berry curvature can have important consequences, such as in the semi-classical evolution of a wave packet. Here, we experimentally demonstrate for the first time that wave packet dynamics can be used to directly map out the Berry curvature. To this end, we use optical pulses in two coupled fibre loops to study the discrete time-evolution of a wave packet in a 1D geometrical "charge" pump, where the Berry curvature leads to an anomalous displacement of the wave packet under pumping. This is both the first direct observation of Berry curvature effects in an optical system, and, more generally, the proof-of-principle demonstration that semi-classical dynamics can serve as a high-resolution tool for mapping out geometrical properties

Positive approximations of the inverse of fractional powers of SPD M-matrices

This study is motivated by the recent development in the fractional calculus and its applications. During last few years, several different techniques are proposed to localize the nonlocal fractional diffusion operator. They are based on transformation of the original problem to a local elliptic or pseudoparabolic problem, or to an integral representation of the solution, thus increasing the dimension of the computational domain. More recently, an alternative approach aimed at reducing the computational complexity was developed. The linear algebraic system $\cal A^\alpha \bf u=\bf f$, $0< \alpha <1$ is considered, where $\cal A$ is a properly normalized (scalded) symmetric and positive definite matrix obtained from finite element or finite difference approximation of second order elliptic problems in $\Omega\subset\mathbb{R}^d$, $d=1,2,3$. The method is based on best uniform rational approximations (BURA) of the function $t^{\beta-\alpha}$ for $0 < t \le 1$ and natural $\beta$. The maximum principles are among the major qualitative properties of linear elliptic operators/PDEs. In many studies and applications, it is important that such properties are preserved by the selected numerical solution method. In this paper we present and analyze the properties of positive approximations of $\cal A^{-\alpha}$ obtained by the BURA technique. Sufficient conditions for positiveness are proven, complemented by sharp error estimates. The theoretical results are supported by representative numerical tests

Sparse aperture masking interferometry survey of transitional discs: Search for substellar-mass companions and asymmetries in their parent discs

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Context. Transitional discs are a class of circumstellar discs around young stars with extensive clearing of dusty material within their inner regions on 10s of au scales. One of the primary candidates for this kind of clearing is the formation of planet(s) within the disc that then accrete or clear their immediate area as they migrate through the disc. Aims. The goal of this survey was to search for asymmetries in the brightness distribution around a selection of transitional disc targets. We then aimed to determine whether these asymmetries trace dynamically-induced structures in the disc or the gap-opening planets themselves. Methods. Our sample included eight transitional discs. Using the Keck/NIRC2 instrument we utilised the Sparse Aperture Masking (SAM) interferometry technique to search for asymmetries indicative of ongoing planet formation. We searched for close-in companions using both model fitting and interferometric image reconstruction techniques. Using simulated data, we derived diagnostics that helped us to distinguish between point sources and extended asymmetric disc emission. In addition, we investigated the degeneracy between the contrast and separation that appear for marginally resolved companions. Results. We found FP Tau to contain a previously unseen disc wall, and DM Tau, LkHα330, and TW Hya to contain an asymmetric signal indicative of point source-like emission. We placed upper limits on the contrast of a companion in RXJ1842.9-3532 and V2246 Oph. We ruled the asymmetry signal in RXJ1615.3-3255 and V2062 Oph to be false positives. In the cases where our data indicated a potential companion we computed estimates for the value of McM˙ c and found values in the range of 10−5 − 10−3M2 J yr−1 . Conclusions. We found significant asymmetries in four targets. Of these, three were consistent with companions. We resolved a previously unseen gap in the disc of FP Tau extending inwards from approximately 10 au.We acknowledge support from a STFC Rutherford Fellowship and Grant (ST/J004030/1, ST/K003445/1), Marie Sklodowska-Curie CIG grant (Ref. 618910), and Philip Leverhulme Prize (PLP-2013-110). We additionally acknowledge support from NASA KPDA grants (JPL-1452321, 1474717, 1485953, 1496788). The authors wish to recognise and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundatio

Sparse aperture masking interferometry survey of transitional discs. Search for substellar-mass companions and asymmetries in their parent discs

This is the author accepted manuscript. The final version is available from EDP Sciences via the DOI in this record.Context. Transitional discs are a class of circumstellar discs around young stars with extensive clearing of dusty material within their inner regions on 10s of au scales. One of the primary candidates for this kind of clearing is the formation of planet(s) within the disc that then accrete or clear their immediate area as they migrate through the disc. Aims. The goal of this survey was to search for asymmetries in the brightness distribution around a selection of transitional disc targets. We then aimed to determine whether these asymmetries trace dynamically-induced structures in the disc or the gap-opening planets themselves. Methods. Our sample included eight transitional discs. Using the Keck/NIRC2 instrument we utilised the Sparse Aperture Masking (SAM) interferometry technique to search for asymmetries indicative of ongoing planet formation. We searched for close-in companions using both model fitting and interferometric image reconstruction techniques. Using simulated data, we derived diagnostics that helped us to distinguish between point sources and extended asymmetric disc emission. In addition, we investigated the degeneracy between the contrast and separation that appear for marginally resolved companions. Results. We found FP Tau to contain a previously unseen disc wall, and DM Tau, LkHα330, and TW Hya to contain an asymmetric signal indicative of point source-like emission. We placed upper limits on the contrast of a companion in RXJ 1842.9-3532 and V2246 Oph. We ruled the asymmetry signal in RXJ 1615.3-3255 and V2062 Oph to be false positives. In the cases where our data indicated a potential companion we computed estimates for the value of McṀc and found values in the range of 10−5−10−3 M2J yr−1. Conclusions. We found significant asymmetries in four targets. Of these, three were consistent with companions. We resolved a previously unseen gap in the disc of FP Tau extending inwards from approximately 10 au.We acknowledge support from a STFC Rutherford Fellowship and Grant (ST/J004030/1, ST/K003445/1), Marie Sklodowska-Curie CIG grant (Ref. 618910), and Philip Leverhulme Prize (PLP-2013-110). We additionally acknowledge support from NASA KPDA grants (JPL-1452321, 1474717, 1485953, 1496788). The authors wish to recognise and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation

Resolving the Gap and AU-scale Asymmetries in the Pre-transitional Disk of V1247 Orionis

archiveprefix: arXiv primaryclass: astro-ph.SR keywords: accretion, accretion disks, protoplanetary disks, stars: pre-main sequence, techniques: interferometric eid: 80 adsurl: http://adsabs.harvard.edu/abs/2013ApJ...768...80K adsnote: Provided by the SAO/NASA Astrophysics Data SystemarticlePre-transitional disks are protoplanetary disks with a gapped disk structure, potentially indicating the presence of young planets in these systems. In order to explore the structure of these objects and their gap-opening mechanism, we observed the pre-transitional disk V1247 Orionis using the Very Large Telescope Interferometer, the Keck Interferometer, Keck-II, Gemini South, and IRTF. This allows us to spatially resolve the AU-scale disk structure from near- to mid-infrared wavelengths (1.5-13 μm), tracing material at different temperatures and over a wide range of stellocentric radii. Our observations reveal a narrow, optically thick inner-disk component (located at 0.18 AU from the star) that is separated from the optically thick outer disk (radii gsim 46 AU), providing unambiguous evidence for the existence of a gap in this pre-transitional disk. Surprisingly, we find that the gap region is filled with significant amounts of optically thin material with a carbon-dominated dust mineralogy. The presence of this optically thin gap material cannot be deduced solely from the spectral energy distribution, yet it is the dominant contributor at mid-infrared wavelengths. Furthermore, using Keck/NIRC2 aperture masking observations in the H, K', and L' bands, we detect asymmetries in the brightness distribution on scales of ~15-40 AU, i.e., within the gap region. The detected asymmetries are highly significant, yet their amplitude and direction changes with wavelength, which is not consistent with a companion interpretation but indicates an inhomogeneous distribution of the gap material. We interpret this as strong evidence for the presence of complex density structures, possibly reflecting the dynamical interaction of the disk material with sub-stellar mass bodies that are responsible for the gap clearing.This work was done in part under contract with the California Institute of Technology (Caltech), funded by NASA through the Sagan Fellowship Program (S.K. and C.E. are Sagan Fellows). Data presented herein were obtained at the W. M. Keck Observatory from telescope time allocated to the National Aeronautics and Space Administration through the agency's scientific partnership with the California Institute of Technology and the University of California. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation. The authors wish to recognize and acknowledge the very significant cultural role and reverence that the summit of Mauna Kea has always had within the indigenous Hawaiian community. We are most fortunate to have the opportunity to conduct observations from this mountain. This work was supported in part by the Aerospace Corporation's Independent Research and Development (IR&D) program. This work was supported by NASA ADP grant NNX09AC73G

Holographic View on Quantum Correlations and Mutual Information between Disjoint Blocks of a Quantum Critical System

In (d+1) dimensional Multiscale Entanglement Renormalization Ansatz (MERA) networks, tensors are connected so as to reproduce the discrete, (d + 2) holographic geometry of Anti de Sitter space (AdSd+2) with the original system lying at the boundary. We analyze the MERA renormalization flow that arises when computing the quantum correlations between two disjoint blocks of a quantum critical system, to show that the structure of the causal cones characteristic of MERA, requires a transition between two different regimes attainable by changing the ratio between the size and the separation of the two disjoint blocks. We argue that this transition in the MERA causal developments of the blocks may be easily accounted by an AdSd+2 black hole geometry when the mutual information is computed using the Ryu-Takayanagi formula. As an explicit example, we use a BTZ AdS3 black hole to compute the MI and the quantum correlations between two disjoint intervals of a one dimensional boundary critical system. Our results for this low dimensional system not only show the existence of a phase transition emerging when the conformal four point ratio reaches a critical value but also provide an intuitive entropic argument accounting for the source of this instability. We discuss the robustness of this transition when finite temperature and finite size effects are taken into account.Comment: 21 pages, 5 figures. Abstract and Figure 1 has been modified. Minor modifications in Section 1 and Section

Realisation of a programmable two-qubit quantum processor

The universal quantum computer is a device capable of simulating any physical system and represents a major goal for the field of quantum information science. Algorithms performed on such a device are predicted to offer significant gains for some important computational tasks. In the context of quantum information, "universal" refers to the ability to perform arbitrary unitary transformations in the system's computational space. The combination of arbitrary single-quantum-bit (qubit) gates with an entangling two-qubit gate is a gate set capable of achieving universal control of any number of qubits, provided that these gates can be performed repeatedly and between arbitrary pairs of qubits. Although gate sets have been demonstrated in several technologies, they have as yet been tailored toward specific tasks, forming a small subset of all unitary operators. Here we demonstrate a programmable quantum processor that realises arbitrary unitary transformations on two qubits, which are stored in trapped atomic ions. Using quantum state and process tomography, we characterise the fidelity of our implementation for 160 randomly chosen operations. This universal control is equivalent to simulating any pairwise interaction between spin-1/2 systems. A programmable multi-qubit register could form a core component of a large-scale quantum processor, and the methods used here are suitable for such a device.Comment: 7 pages, 4 figure