528 research outputs found
String Breaking in Quenched QCD
We present preliminary quenched results on a new operator for the
investigation of string-breaking within SU(2)-colour QCD. The ground-state of a
spatially-separated static-light meson-antimeson pair is a combination of a
state with two distinct mesons, expected to dominate for large separations, and
a state where the light-quarks have annihilated, which contributes for short
distances. The crossover between these two regimes provides a measure of the
string-breaking scale length.Comment: LATTICE98(confine), 3 pages, 4 figure
Controls on the location of compressional deformation on the NW European margin
The distribution of Cenozoic compressional structures along the NW European margin has been compared with maps of the thickness of the crystalline crust derived from a compilation of seismic refraction interpretations and gravity modelling, and with the distribution of high-velocity lower crust and/or partially serpentinized upper mantle detected by seismic experiments. Only a subset of the mapped compressional structures coincide with areas susceptible to lithospheric weakening as a result of crustal hyperextension and partial serpentinization of the upper mantle. Notably, partially serpentinized upper mantle is well documented beneath the central part of the southern Rockall Basin, but compressional features are sparse in that area. Where compressional structures have formed but the upper mantle is not serpentinized, simple rheological modelling suggests an alternative weakening mechanism involving ductile lower crust and lithospheric decoupling. The presence of pre-existing weak zones (associated with the properties of the gouge and overpressure in fault zones) and local stress magnitude and orientation are important contributing factors
The dual-acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53
YesTopoisomerase inhibitors are in common use as chemotherapeutic agents although they can display reduced efficacy in chemotherapy-resistant tumours, which have inactivated DNA damage response (DDR) genes, such as ATM and TP53. Here, we characterise the cellular response to the dual-acting agent, Alchemix (ALX), which is a modified anthraquinone that functions as a topoisomerase inhibitor as well as an alkylating agent. We show that ALX induces a robust DDR at nano-molar concentrations and this is mediated primarily through ATR- and DNA-PK- but not ATM-dependent pathways, despite DNA double strand breaks being generated after prolonged exposure to the drug. Interestingly, exposure of epithelial tumour cell lines to ALX in vitro resulted in potent activation of the G2/M checkpoint, which after a prolonged arrest, was bypassed allowing cells to progress into mitosis where they ultimately died by mitotic catastrophe. We also observed effective killing of lymphoid tumour cell lines in vitro following exposure to ALX, although, in contrast, this tended to occur via activation of a p53-independent apoptotic pathway. Lastly, we validate the effectiveness of ALX as a chemotherapeutic agent in vivo by demonstrating its ability to cause a significant reduction in tumour cell growth, irrespective of TP53 status, using a mouse leukaemia xenograft model. Taken together, these data demonstrate that ALX, through its dual action as an alkylating agent and topoisomerase inhibitor, represents a novel anti-cancer agent that could be potentially used clinically to treat refractory or relapsed tumours, particularly those harbouring mutations in DDR genes
A weakly stable algorithm for general Toeplitz systems
We show that a fast algorithm for the QR factorization of a Toeplitz or
Hankel matrix A is weakly stable in the sense that R^T.R is close to A^T.A.
Thus, when the algorithm is used to solve the semi-normal equations R^T.Rx =
A^Tb, we obtain a weakly stable method for the solution of a nonsingular
Toeplitz or Hankel linear system Ax = b. The algorithm also applies to the
solution of the full-rank Toeplitz or Hankel least squares problem.Comment: 17 pages. An old Technical Report with postscript added. For further
details, see http://wwwmaths.anu.edu.au/~brent/pub/pub143.htm
Local fluctuations in quantum critical metals
We show that spatially local, yet low-energy, fluctuations can play an
essential role in the physics of strongly correlated electron systems tuned to
a quantum critical point. A detailed microscopic analysis of the Kondo lattice
model is carried out within an extended dynamical mean-field approach. The
correlation functions for the lattice model are calculated through a
self-consistent Bose-Fermi Kondo problem, in which a local moment is coupled
both to a fermionic bath and to a bosonic bath (a fluctuating magnetic field).
A renormalization-group treatment of this impurity problem--perturbative in
, where is an exponent characterizing the spectrum
of the bosonic bath--shows that competition between the two couplings can drive
the local-moment fluctuations critical. As a result, two distinct types of
quantum critical point emerge in the Kondo lattice, one being of the usual
spin-density-wave type, the other ``locally critical.'' Near the locally
critical point, the dynamical spin susceptibility exhibits scaling
with a fractional exponent. While the spin-density-wave critical point is
Gaussian, the locally critical point is an interacting fixed point at which
long-wavelength and spatially local critical modes coexist. A Ginzburg-Landau
description for the locally critical point is discussed. It is argued that
these results are robust, that local criticality provides a natural description
of the quantum critical behavior seen in a number of heavy-fermion metals, and
that this picture may also be relevant to other strongly correlated metals.Comment: 20 pages, 12 figures; typos in figure 3 and in the main text
corrected, version as publishe
Quantum Griffiths effects and smeared phase transitions in metals: theory and experiment
In this paper, we review theoretical and experimental research on rare region
effects at quantum phase transitions in disordered itinerant electron systems.
After summarizing a few basic concepts about phase transitions in the presence
of quenched randomness, we introduce the idea of rare regions and discuss their
importance. We then analyze in detail the different phenomena that can arise at
magnetic quantum phase transitions in disordered metals, including quantum
Griffiths singularities, smeared phase transitions, and cluster-glass
formation. For each scenario, we discuss the resulting phase diagram and
summarize the behavior of various observables. We then review several recent
experiments that provide examples of these rare region phenomena. We conclude
by discussing limitations of current approaches and open questions.Comment: 31 pages, 7 eps figures included, v2: discussion of the dissipative
Ising chain fixed, references added, v3: final version as publishe
PKC in platelet CaÂČâș signalling
Rises in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) are central in platelet activation, yet many aspects of the underlying mechanisms are poorly understood. Most studies examine how experimental manipulations affect agonist-evoked rises in [Ca(2+)]cyt, but these only monitor the net effect of manipulations on the processes controlling [Ca(2+)]cyt (Ca(2+) buffering, sequestration, release, entry and removal), and cannot resolve the source of the Ca(2+) or the transporters or channels affected. To investigate the effects of protein kinase C (PKC) on platelet Ca(2+) signalling, we here monitor Ca(2+) flux around the platelet by measuring net Ca(2+) fluxes to or from the extracellular space and the intracellular Ca(2+) stores, which act as the major sources and sinks for Ca(2+) influx into and efflux from the cytosol, as well as monitoring the cytosolic Na(+) concentration ([Na(+)]cyt), which influences platelet Ca(2+) fluxes via Na(+)/Ca(2+) exchange. The intracellular store Ca(2+) concentration ([Ca(2+)]st) was monitored using Fluo-5N, the extracellular Ca(2+) concentration ([Ca(2+)]ext) was monitored using Fluo-4 whilst [Ca(2+)]cyt and [Na(+)]cyt were monitored using Fura-2 and SFBI, respectively. PKC inhibition using Ro-31-8220 or bisindolylmaleimide I potentiated ADP- and thrombin-evoked rises in [Ca(2+)]cyt in the absence of extracellular Ca(2+). PKC inhibition potentiated ADP-evoked but reduced thrombin-evoked intracellular Ca(2+) release and Ca(2+) removal into the extracellular medium. SERCA inhibition using thapsigargin and 2,5-di(tert-butyl) l,4-benzohydroquinone abolished the effect of PKC inhibitors on ADP-evoked changes in [Ca(2+)]cyt but only reduced the effect on thrombin-evoked responses. Thrombin evokes substantial rises in [Na(+)]cyt which would be expected to reduce Ca(2+) removal via the Na(+)/Ca(2+) exchanger (NCX). Thrombin-evoked rises in [Na(+)]cyt were potentiated by PKC inhibition, an effect which was not due to altered changes in non-selective cation permeability of the plasma membrane as assessed by Mn(2+) quench of Fura-2 fluorescence. PKC inhibition was without effect on thrombin-evoked rises in [Ca(2+)]cyt following SERCA inhibition and either removal of extracellular Na(+) or inhibition of Na(+)/K(+)-ATPase activity by removal of extracellular K(+) or treatment with digoxin. These data suggest that PKC limits ADP-evoked rises in [Ca(2+)]cyt by acceleration of SERCA activity, whilst rises in [Ca(2+)]cyt evoked by the stronger platelet activator thrombin are limited by PKC through acceleration of both SERCA and Na(+)/K(+)-ATPase activity, with the latter limiting the effect of thrombin on rises in [Na(+)]cyt and so forward mode NCX activity. The use of selective PKC inhibitors indicated that conventional and not novel PKC isoforms are responsible for the inhibition of agonist-evoked Ca(2+) signalling.This work was funded by the British Heart Foundation (PG/07/100/23759). AGSH was supported by a Research Fellowship from St Catharineâs College, University of Cambridge. RAL was supported by a Wellcome Trust Summer Studentship and BBS by a Browning Summer Bursary from Magdalene College, Cambridge.This is the author accepted manuscript. The final version is available from Cell Calcium via http://dx.doi.org/10.1016/j.ceca.2015.09.00
Warsaw Breakage Syndrome associated DDX11 helicase resolves G-quadruplex structures to support sister chromatid cohesion
Warsaw Breakage Syndrome (WABS) is a rare disorder related to cohesinopathies and Fanconi anemia, caused by bi-allelic mutations in DDX11. Here, we report multiple compound heterozygous WABS cases, each displaying destabilized DDX11 protein and residual DDX11 function at the cellular level. Patient-derived cell lines exhibit sensitivity to topoisomerase and PARP inhibitors, defective sister chromatid cohesion and reduced DNA replication fork speed. Deleting DDX11 in RPE1-TERT cells inhibits proliferation and survival in a TP53-dependent manner and causes chromosome breaks and cohesion defects, independent of the expressed pseudogene DDX12p. Importantly, G-quadruplex (G4) stabilizing compounds induce chromosome breaks and cohesion defects which are strongly aggravated by inactivation of DDX11 but not FANCJ. The DNA helicase domain of DD
Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment
This paper describes an analysis of the angular distribution of W->enu and
W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with
the ATLAS detector at the LHC in 2010, corresponding to an integrated
luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and
the missing transverse energy, the W decay angular distribution projected onto
the transverse plane is obtained and analysed in terms of helicity fractions
f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV
and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw
> 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour,
are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017
+/- 0.030, where the first uncertainties are statistical, and the second
include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables,
revised author list, matches European Journal of Physics C versio
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