HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

The “Flexi-Chamber”: A Novel Cost-Effective In Situ Respirometry Chamber for Coral Physiological Measurements

Coral reefs are threatened worldwide, with environmental stressors increasingly affecting the ability of reef-building corals to sustain growth from calcification (G), photosynthesis (P) and respiration (R). These processes support the foundation of coral reefs by directly influencing biogeochemical nutrient cycles and complex ecological interactions and therefore represent key knowledge required for effective reef management. However, metabolic rates are not trivial to quantify and typically rely on the use of cumbersome in situ respirometry chambers and/or the need to remove material and examine ex situ, thereby fundamentally limiting the scale, resolution and possibly the accuracy of the rate data. Here we describe a novel low-cost in situ respirometry bag that mitigates many constraints of traditional glass and plexi-glass incubation chambers. We subsequently demonstrate the effectiveness of our novel "Flexi-Chamber" approach via two case studies: 1) the Flexi-Chamber provides values of P, R and G for the reef-building coral Siderastrea cf. stellata collected from reefs close to Salvador, Brazil, which were statistically similar to values collected from a traditional glass respirometry vessel; and 2) wide-scale application of obtaining P, R and G rates for different species across different habitats to obtain inter- and intra-species differences. Our novel cost-effective design allows us to increase sampling scale of metabolic rate measurements in situ without the need for destructive sampling and thus significantly expands on existing research potential, not only for corals as we have demonstrated here, but also other important benthic groups

Impacts of Sediments on Coral Energetics: Partitioning the Effects of Turbidity and Settling Particles

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragmentswere evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm22 day21). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3–17% respectively in the shaded control,contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18–34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients

Measurements of branching fraction ratios and CP asymmetries in B-+/- -> DCPK +/- decays in hadron collisions

9 páginas, 3 figuras, 2 tablas.-- PACS numbers: 13.25.Hw, 11.30.Er, 14.40.Nd.--CDF Collaboration: et al.We reconstruct B-+/- -> DK +/- decays in a data sample collected by the CDF II detector at the Tevatron collider corresponding to 1 fb(-1) of integrated luminosity. We select decay modes where the D meson decays to either K-pi(+) (flavor eigenstate) or K-K+, pi(-)pi(+) (CP-even eigenstates), and measure the direct CP asymmetry A(CP+) = 0.39 +/- 0.17(stat) +/- 0.04(syst), and the double ratio of CP-even to flavor eigenstate branching fractions RCP+ = 1.30 +/- 0.24(stat) +/- 0.12(syst). These measurements will improve the determination of the Cabibbo-Kobayashi-Maskawa angle gamma. They are performed here for the first time using data from hadron collisions.We thank the Fermilab staff and the technical staffs of the participating institutions for their vital contributions. This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A.P. Sloan Foundation; the Bundesministerium für Bildung und Forschung, Germany; the Korean Science and Engineering Foundation and the Korean Research Foundation; the Science and Technology Facilities Council and the Royal Society, UK; the Institut National de Physique Nucleaire et Physique des Particules/CNRS; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovación, and Programa Consolider- Ingenio 2010, Spain; the Slovak R&D Agency; and the Academy of Finland.Peer reviewe

Measurement of the transverse momentum distribution of [Z over γ*] bosons in proton-proton collisions at √s = 7 TeV with the ATLAS detector

A measurement of the [Z over γ*] transverse momentum (p[Z over T]) distribution in proton–proton collisions at √s = 7 TeV is presented using [Z over γ*] →e[superscript +]e[superscript −] and [Z over γ*] →μ[superscript +]μ[superscript −] decays collected with the ATLAS detector in data sets with integrated luminosities of 35 pb[superscript −1] and 40 pb[superscript −1], respectively. The normalized differential cross sections are measured separately for electron and muon decay channels as well as for their combination up to p[Z over T] of 350 GeV for invariant dilepton masses 66 GeV<m[subscript ℓℓ]<116 GeV. The measurement is compared to predictions of perturbative QCD and various event generators. The prediction of resummed QCD combined with fixed order perturbative QCD is found to be in good agreement with the data.United States. Dept. of EnergyNational Science Foundation (U.S.)Brookhaven National LaboratoryEuropean Organization for Nuclear Researc

Performance of the ATLAS Trigger System in 2010

Proton-proton collisions at sqrt{s} = 7 TeV and heavy ion collisions at sqrt{s_NN} = 2.76 TeV were produced by the LHC and recorded using the ATLAS experiment's trigger system in 2010. The LHC is designed with a maximum bunch crossing rate of 40 MHz and the ATLAS trigger system is designed to record approximately 200 of these per second. The trigger system selects events by rapidly identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. An overview of the ATLAS trigger system, the evolution of the system during 2010 and the performance of the trigger system components and selections based on the 2010 collision data are shown. A brief outline of plans for the trigger system in 2011 is presente

Pseudoscalar decay constants of kaon and D-mesons from NfN_f= 2 twisted mass Lattice QCD

We present the results of a lattice QCD calculation of the pseudoscalar meson decay constants fπ, fK, fD and fDs, performed with Nf = 2 dynamical fermions. The simulation is carried out with the tree-level improved Symanzik gauge action and with the twisted mass fermionic action at maximal twist. We have considered for the final analysis three values of the lattice spacing, a simeq 0.10 fm, 0.09 fm and 0.07 fm, with pion masses down to mπ simeq 270 MeV. Our results for the light meson decay constants are fK = 158.1(2.4) MeV and fK/fπ = 1.210(18). From the latter ratio, by using the experimental determination of Γ(K → μbar nuμ(γ))/Γ(π → μbar nuμ(γ)) and the average value of |Vud| from nuclear beta decays, we obtain |Vus| = 0.2222(34), in good agreement with the determination from semileptonic Kl3 decays and the unitarity constraint. For the D and Ds meson decay constants we obtain fD = 197(9) MeV, fDs = 244(8) MeV and fDs/fD = 1.24(3). Our result for fD is in good agreement with the CLEO experimental measurement. For fDs our determination is smaller than the PDG 2008 experimental average but in agreement with a recent improved measurement by CLEO at the 1.4 σ level.We thank all the members of the ETM Collaboration for fruitful discussions. D.P. thanks the Dipartimento di Fisica,Universita di Roma Tre, and C.T. thanks the Laboratoire de Physique Th´eorique , Universite de Paris XI, for the hospitality. V.L., R.F., F.M. and S.S thank MIUR (Italy) for partial financial support under the contract PRIN06. D.P. thanks MEC (Spain) for partial financial support under grant FPA2005-00711. This work has been supported in part by the EU Contract No. MRTN-CT-2006-035482, “FLAVIAnet”and by the DFG Sonderforschungsbereich/Transregio SFB/TR9-03. We also acknowledge the Consolider-Ingenio 2010 Program CPAN (CSD2007-00042).Peer reviewe