Application of arabinofuranosyl cytosine in the kinetic analysis and quantitation of DNA repair in human cells after ultraviolet irradiation

We have developed a technique whereby 3-h pulses of arabinofuranosyl cytosine (ara-C) and hydroxyurea (HU) are used to analyze the kinetics of repair with time after ultraviolet irradiation in human fibroblasts. We demonstrate that this technique offers a significant improvement over existing repair assays in its ability to visualize between 57 and 100% of all sites undergoing repair in a given period of time. In addition, kinetic analyses of repair are more easily made and yield more information than techniques such as repair replication or unscheduled DNA synthesis. We have also examined the nature of the inhibition event by ara-C and have determined that repair breaks accumulate in the presence of ara-C and HU only up to a certain time beyond which no further breaks appear. The time needed to reach this saturation point depends on the number of sites undergoing repair during the treatment time. This observation is discussed with respect to a possible mechanism of excision repair inhibition by ara-C and HU

Atomic layering at the liquid silicon surface: a first- principles simulation

We simulate the liquid silicon surface with first-principles molecular dynamics in a slab geometry. We find that the atom-density profile presents a pronounced layering, similar to those observed in low-temperature liquid metals like Ga and Hg. The depth-dependent pair correlation function shows that the effect originates from directional bonding of Si atoms at the surface, and propagates into the bulk. The layering has no major effects in the electronic and dynamical properties of the system, that are very similar to those of bulk liquid Si. To our knowledge, this is the first study of a liquid surface by first-principles molecular dynamics.Comment: 4 pages, 4 figures, submitted to PR

Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT

PURPOSEThe Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.METHODSThe TEXT/SOFT HR-positive/human epidermal growth factor receptor 2 (HER2)-negative analysis population included 4,891 women stratified by predetermined chemotherapy use. Kaplan-Meier estimates of 8-year freedom from distant recurrence were analyzed using subpopulation treatment effect pattern plot (STEPP) methodology across subpopulations defined by the continuous composite measure of recurrence risk. For each patient, the composite risk value was obtained from a Cox model that incorporated age; nodal status; tumor size; grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.RESULTSThe overall rate of 8-year freedom from distant recurrence was 91.1% and ranged from approximately 100% to 63% across lowest to highest composite risks. TEXT patients who received chemotherapy had an average absolute improvement with exemestane plus OFS versus tamoxifen plus OFS of 5.1%, and STEPP analysis showed improvements from less than 1% to more than 15% from lowest to highest composite risks. SOFT patients who remained premenopausal after chemotherapy had an average 5.2% absolute improvement with exemestane plus OFS versus tamoxifen and reached 10% across composite risks; for tamoxifen plus OFS versus tamoxifen, the maximum improvement was approximately 3.5%. Women who did not receive chemotherapy had a more than 97% rate of 8-year freedom from distant recurrence, and improvements with exemestane plus OFS ranged from 1% to 4%.CONCLUSIONPremenopausal women with HR-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone. The potential benefit of escalating endocrine therapy versus tamoxifen alone is minimal for those at low recurrence risk. (c) 2019 by American Society of Clinical Oncolog

Probing CP Violation with the Deuteron Electric Dipole Moment

We present an analysis of the electric dipole moment (EDM) of the deuteron as induced by CP-violating operators of dimension 4, 5 and 6 including theta QCD, the EDMs and color EDMs of quarks, four-quark interactions and the Weinberg operator. We demonstrate that the precision goal of the EDM Collaboration's proposal to search for the deuteron EDM, (1-3)\times 10^{-27} e cm, will provide an improvement in sensitivity to these sources of one-two orders of magnitude relative to the existing bounds. We consider in detail the level to which CP-odd phases can be probed within the MSSM.Comment: 5 pages, 4 figures; precision estimates clarified, to appear in Phys. Rev.

The Fueling and Evolution of AGN: Internal and External Triggers

In this chapter, I review the fueling and evolution of active galactic nuclei (AGN) under the influence of internal and external triggers, namely intrinsic properties of host galaxies (morphological or Hubble type, color, presence of bars and other non-axisymmetric features, etc) and external factors such as environment and interactions. The most daunting challenge in fueling AGN is arguably the angular momentum problem as even matter located at a radius of a few hundred pc must lose more than 99.99 % of its specific angular momentum before it is fit for consumption by a BH. I review mass accretion rates, angular momentum requirements, the effectiveness of different fueling mechanisms, and the growth and mass density of black BHs at different epochs. I discuss connections between the nuclear and larger-scale properties of AGN, both locally and at intermediate redshifts, outlining some recent results from the GEMS and GOODS HST surveys.Comment: Invited Review Chapter to appear in LNP Volume on "AGN Physics on All Scales", Chapter 6, in press. 40 pages, 12 figures. Typo in Eq 5 correcte

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ

Competition between Allowed and First-Forbidden β Decay: The Case of Hg 208 → Tl 208

6 pags., 4 figs., 1 tab.The β decay of Hg208 into the one-proton hole, one neutron-particle Tl81208127 nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Qβ window, only three negative parity states are populated directly in the β decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden β decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0+→0-β decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.This work was supported by the European Union under Contracts No. 262010 (ENSAR) and No. 654002 (ENSAR2), the Science and Technology Facilities Council (UK), the German BMBF under Contract No. 05P18PKCIA and “Verbundprojekt 05P2018,” the MINECO Projects No. FPA2015-65035-P, No. RTI2018- 098868-B-I00, No. FPA2015-64969-P, and No. FPA2017- 87568-P (Spain), FWO-Vlaanderen (Belgium), GOA/ 2015/010 (BOF KU Leuven), the Excellence of Science programme (EOS-FWO), the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (BriX network P7/12), the Romanian IFA project CERN-RO/ISOLDE and the Polish National Science Centre under Contracts No. UMO-2015/18/M/ST2/00523 and No. UMO-2019/33/N/ST2/03023. P. H. R. and S. M. J. acknowledge support from the UK Department for Business, Energy and Industrial Strategy via the National Measurement Office. Zs. P. acknowledges support from the ExtreMe Matter Institute EMMI at the GSI Helmholtzzentrum fr Schwerionenforschung, Darmstadt, Germa

The Value of Rare Genetic Variation in the Prediction of Common Obesity in European Ancestry Populations

Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRScommon) with a rare variant PRS (PRSrare) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant analyses (for both common and rare variants) and gene-based analyses (for rare variants) for association with BMI (kg/m2), obesity (BMI ≥ 30 kg/m2), and extreme obesity (BMI ≥ 40 kg/m2). We built PRSscommon and PRSsrare using a range of methods (Clumping+Thresholding [C+T], PRS-CS, lassosum, gene-burden test). We selected the best-performing PRSs and assessed their performance in 36,757 European-ancestry unrelated participants with whole genome sequencing (WGS) data from the Trans-Omics for Precision Medicine (TOPMed) program. The best-performing PRScommon explained 10.1% of variation in BMI, and 18.3% and 22.5% of the susceptibility to obesity and extreme obesity, respectively, whereas the best-performing PRSrare explained 1.49%, and 2.97% and 3.68%, respectively. The PRSrare was associated with an increased risk of obesity and extreme obesity (ORobesity = 1.37 per SDPRS, Pobesity = 1.7x10-85; ORextremeobesity = 1.55 per SDPRS, Pextremeobesity = 3.8x10-40), which was attenuated, after adjusting for PRScommon (ORobesity = 1.08 per SDPRS, Pobesity = 9.8x10-6; ORextremeobesity= 1.09 per SDPRS, Pextremeobesity = 0.02). When PRSrare and PRScommon are combined, the increase in explained variance attributed to PRSrare was small (incremental Nagelkerke R2 = 0.24% for obesity and 0.51% for extreme obesity). Consistently, combining PRSrare to PRScommon provided little improvement to the prediction of obesity (PRSrare AUC = 0.591; PRScommon AUC = 0.708; PRScombined AUC = 0.710). In summary, while rare variants show convincing association with BMI, obesity and extreme obesity, the PRSrare provides limited improvement over PRScommon in the prediction of obesity risk, based on these large populations

Investigation of the Δn = 0 selection rule in Gamow-Teller transitions : The β-decay of 207 Hg

Gamow-Teller β decay is forbidden if the number of nodes in the radial wave functions of the initial and final states is different. This Δn=0 requirement plays a major role in the β decay of heavy neutron-rich nuclei, affecting the nucleosynthesis through the increased half-lives of nuclei on the astrophysical r-process pathway below both Z=50 (for N>82) and Z=82 (for N>126). The level of forbiddenness of the Δn=1ν1g 9/2 →π0g 7/2 transition has been investigated from the β − decay of the ground state of 207 Hg into the single-proton-hole nucleus 207 Tl in an experiment at the ISOLDE Decay Station. From statistical observational limits on possible γ-ray transitions depopulating the π0g 7/2 −1 state in 207 Tl, an upper limit of 3.9×10 −3 % was obtained for the probability of this decay, corresponding to log⁡ft>8.8 within a 95% confidence limit. This is the most stringent test of the Δn=0 selection rule to date