Local coherence and deflation of the low quark modes in lattice QCD

The spontaneous breaking of chiral symmetry in QCD is known to be linked to a non-zero density of eigenvalues of the massless Dirac operator near the origin. Numerical studies of two-flavour QCD now suggest that the low quark modes are locally coherent to a certain extent. As a consequence, the modes can be simultaneously deflated, using local projectors, with a total computational effort proportional to the lattice volume (rather than its square). Deflation has potentially many uses in lattice QCD. The technique is here worked out for the case of quark propagator calculations, where large speed-up factors and a flat scaling behaviour with respect to the quark mass are achieved.Comment: Plain TeX, 23 pages, 4 figures included; minor text modifications; version published in JHE

SESAM and TXL Results for Wilson Action--A Status Report

Results from two studies of full QCD with two flavours of dynamical Wilson fermions are presented. At beta=5.6, the region 0.83 > m_pi/m_rho > 0.56 at m_pia > 0.23 L^{-1} is explored. The SESAM collaboration has generated ensembles of about 200 statistically independent configurations on a 16^3 x 32-lattice at three different kappa-values and is entering the final phase of data analysis. The TXL simulation on a 24^3 x 40-lattice at two kappa-values has reached half statistics and data analysis has started recently, hence most results presented here are preliminary. The focus of this report is fourfold: we demonstrate that algorithmic improvements like fast Krylov solvers and parallel preconditioning recently introduced can be put into practise in full QCD simulations, we present encouraging observations as to the critical dynamics of the Hybrid Monte Carlo algorithm in the approach to the chiral limit, we mention signal improvements of noisy estimator techniques for disconnected diagrams to the pi-N sigma term, and we report on SESAM's results for light hadron spectrum, light quark masses, and heavy quarkonia.Comment: 24 pages, tex + postscript figures, to appear in Proceedings of Int. Workshop "Lattice QCD on Parallel Computers", University of Tsukuba, Japa

Critical Dynamics of the Hybrid Monte Carlo Algorithm

We investigate the critical dynamics of the Hybrid Monte Carlo algorithm approaching the chiral limit of standard Wilson fermions. Our observations are based on time series of lengths O(5000) for a variety of observables. The lattice sizes are 16^3 x 32 and 24^3 x 40. We work at beta=5.6, and kappa=0.156, 0.157, 0.1575, 0.158, with 0.83 > m_pi/m_rho > 0.55. We find surprisingly small integrated autocorrelation times for local and extended observables. The dynamical critical exponent $z$ of the exponential autocorrelation time is compatible with 2. We estimate the total computational effort to scale between V^2 and V^2.25 towards the chiral limit.Comment: 3 pages, Latex with espcrc2.sty and postscript figures, Talk given at Lattice 9

Quenched chiral logarithms in lattice QCD with exact chiral symmetry

We examine quenched chiral logarithms in lattice QCD with overlap Dirac quark. For 100 gauge configurations generated with the Wilson gauge action at $\beta = 5.8$ on the $8^3 \times 24$ lattice, we compute quenched quark propagators for 12 bare quark masses. The pion decay constant is extracted from the pion propagator, and from which the lattice spacing is determined to be 0.147 fm. The presence of quenched chiral logarithm in the pion mass is confirmed, and its coefficient is determined to be $\delta = 0.203 \pm 0.014$, in agreement with the theoretical estimate in quenched chiral perturbation theory. Further, we obtain the topological susceptibility of these 100 gauge configurations by measuring the index of the overlap Dirac operator. Using a formula due to exact chiral symmetry, we obtain the $\eta'$ mass in quenched chiral perturbation theory, $m_{\eta'} = (901 \pm 64)$ Mev, and an estimate of $\delta = 0.197 \pm 0.027$, which is in good agreement with that determined from the pion mass.Comment: 24 pages, 6 EPS figures; v2: some clarifications added, to appear in Physical Review

Kaon B Parameter in Quenched QCD

I calculate the kaon B-parameter with a lattice simulation in quenched approximation. The lattice simulation uses an action possessing exact lattice chiral symmetry, an overlap action. Computations are performed at two lattice spacings, about 0.13 and 0.09 fm (parameterized by Wilson gauge action couplings beta=5.9 and 6.1) with nearly the same physical volumes and quark masses. I describe particular potential difficulties which arise due to the use of such a lattice action in finite volume. My results are consistent with other recent lattice determinations using domain-wall fermions.Comment: 23 pages, Revtex, 16 postscript figure

Low-lying fermion modes, topology and light hadrons in quenched QCD

We explore the properties of low lying eigenmodes of fermions in the quenched approximation of lattice QCD. The fermion action is a recently proposed overlap action and has exact chiral symmetry. We find that chiral zero-eigenvalue modes are localized in space and their positions correlate strongly with the locations (as defined through the density of pure gauge observables) of instantons of the appropriate charge. Nonchiral modes are also localized with peaks which are strongly correlated with the positions of both charges of instantons. These correlations slowly die away as the fermion eigenvalue rises. Correlators made of quark propagators restricted to these modes closely reproduce ordinary hadron correlators at small quark mass in many channels. Our results are in qualitative agreement with the expectations of instanton liquid models.Comment: 21 pages, Revtex, 21 postscript figures. COLO-HEP-45

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile

A variant approach to the overlap action

I describe an implementation of the overlap action, which is built from an action which is itself an approximate overlap action. It appears to be about a factor of 15-20 less expensive to use, than the usual overlap action with the Wilson fermion action as its kernel. Ingredients include a fat link to suppress coupling to dislocations and a free field action with a spectrum which resembles an overlap; much of the gain comes from the use of eigenmodes of the approximate action to begin the overlap calculation. As a physics example, I compute the quark condensate in finite volume in the quenched approximation.Comment: 15 pages, Revtex, postscript figures. COLO-HEP-44

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Placement and orientation of individual DNA shapes on lithographically patterned surfaces

Artificial DNA nanostructures show promise for the organization of functional materials to create nanoelectronic or nano-optical devices. DNA origami, in which a long single strand of DNA is folded into a shape using shorter 'staple strands', can display 6-nm-resolution patterns of binding sites, in principle allowing complex arrangements of carbon nanotubes, silicon nanowires, or quantum dots. However, DNA origami are synthesized in solution and uncontrolled deposition results in random arrangements; this makes it difficult to measure the properties of attached nanodevices or to integrate them with conventionally fabricated microcircuitry. Here we describe the use of electron-beam lithography and dry oxidative etching to create DNA origami-shaped binding sites on technologically useful materials, such as SiO_2 and diamond-like carbon. In buffer with ~ 100 mM MgCl_2, DNA origami bind with high selectivity and good orientation: 70–95% of sites have individual origami aligned with an angular dispersion (±1 s.d.) as low as ±10° (on diamond-like carbon) or ±20° (on SiO_2)