Characterization of Escherichia coli double-strand uracil-DNA glycosylase and analysis of uracil-initiated base excision DNA repair

Escherichia coli double-strand uracil-DNA glycosylase (Dug) was purified to apparent homogeneity from bacteria that were defective in uracil-DNA glycosylase (Ung). After cloning the dug gene, recombinant Dug was overexpressed, purified, and characterized with respect to activity, substrate specificity, product DNA binding, and mechanism of action. Purified Dug excised both uracil and ethenocytosine specifically from double-stranded DNA substrates. One distinctive characteristic of Dug was that the purified enzyme removed a near stoichiometric amount of uracil from DNA containing U/G mispairs. The observed lack of turnover was attributed to tight binding of Dug to the apyrimidinic-site (AP) contained in the DNA reaction product. Catalytic activity was stimulated in the presence of E. coli endonuclease IV that caused AP-site incision and dissociation of Dug. By using enzyme complementation experiments, Dug was shown to initiate uracil-initiated base excision repair (BER) in E. coli (ung) cell-free extracts. The relative rate of repair of uracil- and ethenocytosine-containing DNA in isogenic E. coli cells that were proficient or deficient in Ung and/or Dug was measured using a novel competition assay. Complete ethenocytosine-initiated BER displayed an absolute requirement for Dug and occurred at the same rate as uracil-initiated BER in the presence of both Ung and Dug. However, the rate of Dug-mediated ethenocytosine-DNA repair was 8-fold faster than that of uracil-DNA mediated by Dug. The distribution of BER patch sizes associated with both uracil- and ethenocytosine-containing DNA showed similar results. In both cases, DNA repair synthesis utilized predominantly a long patch BER mechanism involving the incorporation of 2-20 nucleotides. A previously unidentified "very long patch" mechanism of BER involving the incorporation of more than 200 nucleotides was identified and shown to be mediated by DNA polymerase I. The rate-limiting step associated with uracil-initiated BER was found to involve DNA ligase and the distribution of BER patch size was modulated by the ratio of DNA polymerase I and DNA ligase. The fidelity of DNA repair synthesis associated with complete uracil-DNA BER was measured using E. coli cell-free extracts that were proficient or deficient in Ung activity and determined to be 5.5 x 10⁻⁴ and 19.7 x 10⁻⁴, respectively

Quantitative and empirical demonstration of the Matthew effect in a study of career longevity

The Matthew effect refers to the adage written some two-thousand years ago in the Gospel of St. Matthew: "For to all those who have, more will be given." Even two millennia later, this idiom is used by sociologists to qualitatively describe the dynamics of individual progress and the interplay between status and reward. Quantitative studies of professional careers are traditionally limited by the difficulty in measuring progress and the lack of data on individual careers. However, in some professions, there are well-defined metrics that quantify career longevity, success, and prowess, which together contribute to the overall success rating for an individual employee. Here we demonstrate testable evidence of the age-old Matthew "rich get richer" effect, wherein the longevity and past success of an individual lead to a cumulative advantage in further developing his/her career. We develop an exactly solvable stochastic career progress model that quantitatively incorporates the Matthew effect, and validate our model predictions for several competitive professions. We test our model on the careers of 400,000 scientists using data from six high-impact journals, and further confirm our findings by testing the model on the careers of more than 20,000 athletes in four sports leagues. Our model highlights the importance of early career development, showing that many careers are stunted by the relative disadvantage associated with inexperience.Comment: 13 pages, 7 figures, 4 Tables; Revisions in response to critique and suggestions of referee

Surgical repair of descending thoracic and thoracoabdominal aortic aneurysm involving the distal arch: Open proximal anastomosis under deep hypothermia versus arch clamping technique

BackgroundSurgical repair of a descending thoracic and thoracoabdominal aortic aneurysm (DTA/TAAA) involving the distal arch is challenging and requires either deep hypothermic circulatory arrest (DHCA) or crossclamping of the distal arch. The aim of this study was to compare these 2 techniques in the treatment of DTA/TAAA involving the distal arch.MethodsFrom 1994 to 2012, 298 patients underwent open repair of DTA/TAAA through a left thoracotomy. One hundred seventy-four patients with distal arch involvement who were suitable for either DHCA (n = 81) or arch clamping (AC; n = 93), were analyzed. In-hospital outcomes were compared using propensity scores and inverse-probability-of-treatment weighting adjustment to reduce treatment selection bias.ResultsEarly mortality was 11.1% in the DHCA group and 8.6% in the AC group (P = .58). Major adverse outcomes included stroke in 16 patients (9.2%), low cardiac output syndrome in 15 (8.6%), paraplegia in 10 (5.7%), and multiorgan failure in 10 (5.7%). After adjustment, patients who underwent DHCA were at similar risk of death (odds ratio [OR], 1.14; P = .80) and permanent neurologic injury (OR, 0.95; P = .92) to those who underwent AC. Although prolonged ventilator support (>24 hours) was more frequent with DHCA than with AC (OR, 2.60; P = .003), DHCA showed a tendency to lower the risk of paraplegia (OR, 0.15; P = .057).ConclusionsCompared with AC, DHCA did not increase postoperative mortality and morbidity, except for prolonged ventilator support. However, DHCA may offer superior spinal cord protection to AC during repair of DTA/TAAA involving the distal arch

Resonance of Domain Wall in a Ferromagnetic Nanostrip: Relation Between Distortion and Velocity

The resonance of the magnetic domain wall under the applied field amplifies its velocity compared to the one-dimensional model. To quantify the amplification, we define the distortion variation rate of the domain wall that can represent how fast and severely the wall shape is variated. Introducing that rate gives a way to bring the resonance into the one-dimensional domain wall dynamics model. We obtain the dissipated energy and domain wall velocity amplification by calculating the distortion variation rate. The relationship between velocity and distortion variation rate agrees well with micromagnetic simulation.Comment: 15 pages, 4 figure

Indentations on Air Plasma Sprayed Thermal Barrier Coatings Prepared by Different Starting Granules

The effect of starting granules on the indentation properties of air plasma sprayed thermal barrier coatings (TBCs) is investigated in this paper. Various kinds of spray-dried granules are prepared from different processing conditions, especially varying solvent and dispersant, showing a deformed hollow-typed and a filled spherical-typed granule. The similar coating thicknesses are prepared by adjusting process parameters during air plasma spray. All XRD peaks in phase analysis are tetragonal and cubic phases without any monoclinic phase after the starting granules were heat-treated. A relatively porous microstructure of the coating layer could be obtained from the monodisperse granules, while a relatively dense microstructure resulted from the hollow-typed granules. The morphology and distribution of the granules crucially affect the microstructure of thermal barrier coatings and thus have influences on indentation properties such as indentation stress-strain curves, contact damage, and hardness. The implication concerning microstructure design of TBCs for gas turbine applications is considered

Characteristics of the Korean stock market correlations

In this study, we establish a network structure of the Korean stock market, one of the emerging markets, with its minimum spanning tree through the correlation matrix. Base on this analysis, it is found that the Korean stock market doesn't form the clusters of the business sectors or of the industry categories. When the MSCI (Morgan Stanley Capital International Inc.) index is exploited, we found that the clusters of the Korean stock market is formed. This finding implicates that the Korean market, in this context, is characteristically different form the mature markets.Comment: 11 pages, 3 figures, revised on June 200

Effects of Rating Training on Inter-Rater Consistency for Developing a Dental Hygiene Clinical Rater Qualification System

We tried to develop itemized evaluation criteria and a clinical rater qualification system through rating training of inter-rater consistency for experienced clinical dental hygienists and dental hygiene clinical educators. A total of 15 clinical dental hygienists with 1-year careers participated as clinical examination candidates, while 5 dental hygienists with 3-year educations and clinical careers or longer participated as clinical raters. They all took the clinical examination as examinees. The results were compared, and the consistency of competence was measured. The comparison of clinical competence between candidates and clinical raters showed that the candidate group's mean clinical competence ranged from 2.96 to 3.55 on a 5-point system in a total of 3 instruments (Probe, Explorer, Curet), while the clinical rater group's mean clinical competence ranged from 4.05 to 4.29. There was a higher inter-rater consistency after education of raters in the following 4 items: Probe, Explorer, Curet, and insertion on distal surface. The mean score distribution of clinical raters ranged from 75% to 100%, which was more uniform in the competence to detect an artificial calculus than that of candidates (25% to 100%). According to the above results, there was a necessity in the operating clinical rater qualification system for comprehensive dental hygiene clinicians. Furthermore, in order to execute the clinical rater qualification system, it will be necessary to keep conducting a series of studies on educational content, time, frequency, and educator level