Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair

The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G1 but is dispensable for this process during S/G2 and consequently for cell survival following DNA alkylation. Little is known about BRCT I, but this domain has attracted considerable interest because it is the site of a genetic polymorphism that epidemiological studies have associated with altered cancer risk. We report that the BRCT I domain comprises the evolutionarily conserved core of XRCC1 and that this domain is required for efficient SSBR during both G1 and S/G2 cell cycle phases and for cell survival following treatment with methyl methanesulfonate. However, the naturally occurring human polymorphism in BRCT I supported XRCC1-dependent SSBR and cell survival after DNA alkylation equally well. We conclude that while the BRCT I domain is critical for XRCC1 to maintain genetic integrity and cell survival, the polymorphism does not impact significantly on this function and therefore is unlikely to impact significantly on susceptibility to cancer

Investigation of the influence of a step change in surface roughness on turbulent heat transfer

The use is studied of smooth heat flux gages on the otherwise very rough SSME fuel pump turbine blades. To gain insights into behavior of such installations, fluid mechanics and heat transfer data were collected and are reported for a turbulent boundary layer over a surface with a step change from a rough surface to a smooth surface. The first 0.9 m length of the flat plate test surface was roughened with 1.27 mm hemispheres in a staggered, uniform array spaced 2 base diameters apart. The remaining 1.5 m length was smooth. The effect of the alignment of the smooth surface with respect to the rough surface was also studied by conducting experiments with the smooth surface aligned with the bases or alternatively with the crests of the roughness elements. Stanton number distributions, skin friction distributions, and boundary layer profiles of temperature and velocity are reported and are compared to previous data for both all rough and all smooth wall cases. The experiments show that the step change from rough to smooth has a dramatic effect on the convective heat transfer. It is concluded that use of smooth heat flux gages on otherwise rough surfaces could cause large errors

Zero-shot visual reasoning through probabilistic analogical mapping

Human reasoning is grounded in an ability to identify highly abstract commonalities governing superficially dissimilar visual inputs. Recent efforts to develop algorithms with this capacity have largely focused on approaches that require extensive direct training on visual reasoning tasks, and yield limited generalization to problems with novel content. In contrast, a long tradition of research in cognitive science has focused on elucidating the computational principles underlying human analogical reasoning; however, this work has generally relied on manually constructed representations. Here we present visiPAM (visual Probabilistic Analogical Mapping), a model of visual reasoning that synthesizes these two approaches. VisiPAM employs learned representations derived directly from naturalistic visual inputs, coupled with a similarity-based mapping operation derived from cognitive theories of human reasoning. We show that without any direct training, visiPAM outperforms a state-of-the-art deep learning model on an analogical mapping task. In addition, visiPAM closely matches the pattern of human performance on a novel task involving mapping of 3D objects across disparate categories

Hybrid squeezing of solitonic resonant radiation in photonic crystal fibers

We report on the existence of a novel kind of squeezing in photonic crystal fibers which is conceptually intermediate between the four-wave mixing induced squeezing, in which all the participant waves are monochromatic waves, and the self-phase modulation induced squeezing for a single pulse in a coherent state. This hybrid squeezing occurs when an arbitrary short soliton emits quasi-monochromatic resonant radiation near a zero group velocity dispersion point of the fiber. Photons around the resonant frequency become strongly correlated due to the presence of the classical soliton, and a reduction of the quantum noise below the shot noise level is predicted.Comment: 5 pages, 2 figure

Involvement of XRCC1 and DNA Ligase III Gene Products in DNA Base Excision Repair

DNA ligase III and the essential protein XRCC1 are present at greatly reduced levels in the xrcc1 mutant CHO cell line EM-C11. Cell-free extracts prepared from these cells were used to examine the role of the XRCC1 gene product in DNA base excision repair in vitro. EM-C11 cell extract was partially defective in ligation of base excision repair patches, in comparison to wild type CHO-9 extracts. Of the two branches of the base excision repair pathway, only the single nucleotide insertion pathway was affected; no ligation defect was observed in the proliferating cell nuclear antigen-dependent pathway. Full complementation of the ligation defect in EM-C11 extracts was achieved by addition to the repair reaction of recombinant human DNA ligase III but not by XRCC1. This is consistent with the notion that XRCC1 acts as an important stabilizing factor of DNA ligase III. These data demonstrate for the first time that xrcc1 mutant cells are partially defective in ligation of base excision repair patches and that the defect is specific to the polymerase beta-dependent single nucleotide insertion pathway

The High Time Resolution Universe Pulsar Survey I: System configuration and initial discoveries

We have embarked on a survey for pulsars and fast transients using the 13-beam Multibeam receiver on the Parkes radio telescope. Installation of a digital backend allows us to record 400 MHz of bandwidth for each beam, split into 1024 channels and sampled every 64 us. Limits of the receiver package restrict us to a 340 MHz observing band centred at 1352 MHz. The factor of eight improvement in frequency resolution over previous multibeam surveys allows us to probe deeper into the Galactic plane for short duration signals such as the pulses from millisecond pulsars. We plan to survey the entire southern sky in 42641 pointings, split into low, mid and high Galactic latitude regions, with integration times of 4200, 540 and 270 s respectively. Simulations suggest that we will discover 400 pulsars, of which 75 will be millisecond pulsars. With ~30% of the mid-latitude survey complete, we have re-detected 223 previously known pulsars and discovered 27 pulsars, 5 of which are millisecond pulsars. The newly discovered millisecond pulsars tend to have larger dispersion measures than those discovered in previous surveys, as expected from the improved time and frequency resolution of our instrument.Comment: Updated author list. 10 pages, 7 figures. For publication in MNRA

CLOVER - A new instrument for measuring the B-mode polarization of the CMB

We describe the design and expected performance of Clover, a new instrument designed to measure the B-mode polarization of the cosmic microwave background. The proposed instrument will comprise three independent telescopes operating at 90, 150 and 220 GHz and is planned to be sited at Dome C, Antarctica. Each telescope will feed a focal plane array of 128 background-limited detectors and will measure polarized signals over angular multipoles 20 < l < 1000. The unique design of the telescope and careful control of systematics should enable the B-mode signature of gravitational waves to be measured to a lensing-confusion-limited tensor-to-scalar ratio r~0.005.Comment: 4 pages, 5 figures. To appear in the proceedings of the XXXVIXth Rencontres de Moriond "Exploring the Universe