A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

Diffraction enhanced x-ray imaging

Diffraction enhanced imaging (DEI) is a new x-ray radiographic imaging modality using synchrotron x-rays which produces images of thick absorbing objects that are almost completely free of scatter. They show dramatically improved contrast over standard imaging applied to the same phantoms. The contrast is based not only on attenuation but also the refraction and diffraction properties of the sample. The diffraction component and the apparent absorption component (absorption plus extinction contrast) can each be determined independently. This imaging method may improve the image quality for medical applications such as mammography

Diffraction enhanced X-ray imaging

Abstract. Diffraction enhanced imaging is a new x-ray radiographic imaging modality using monochromatic x-rays from a synchrotron which produces images of thick absorbing objects that are almost completely free of scatter. They show dramatically improved contrast over standard imaging applied to the same phantom. The contrast is based not only on attenuation but also the refraction and diffraction properties of the sample. This imaging method may improve image quality for medical applications, industrial radiography for non-destructive testing and x-ray computed tomography

DODO: an efficient orthologous genes assignment tool based on domain architectures. Domain based ortholog detection

<p>Abstract</p> <p>Background</p> <p>Orthologs are genes derived from the same ancestor gene loci after speciation events. Orthologous proteins usually have similar sequences and perform comparable biological functions. Therefore, ortholog identification is useful in annotations of newly sequenced genomes. With rapidly increasing number of sequenced genomes, constructing or updating ortholog relationship between all genomes requires lots of effort and computation time. In addition, elucidating ortholog relationships between distantly related genomes is challenging because of the lower sequence similarity. Therefore, an efficient ortholog detection method that can deal with large number of distantly related genomes is desired.</p> <p>Results</p> <p>An efficient ortholog detection pipeline DODO (DOmain based Detection of Orthologs) is created on the basis of domain architectures in this study. Supported by domain composition, which usually directly related with protein function, DODO could facilitate orthologs detection across distantly related genomes. DODO works in two main steps. Starting from domain information, it first assigns protein groups according to their domain architectures and further identifies orthologs within those groups with much reduced complexity. Here DODO is shown to detect orthologs between two genomes in considerably shorter period of time than traditional methods of reciprocal best hits and it is more significant when analyzed a large number of genomes. The output results of DODO are highly comparable with other known ortholog databases.</p> <p>Conclusions</p> <p>DODO provides a new efficient pipeline for detection of orthologs in a large number of genomes. In addition, a database established with DODO is also easier to maintain and could be updated relatively effortlessly. The pipeline of DODO could be downloaded from <url>http://140.109.42.19:16080/dodo_web/home.htm</url></p

Galaxy clusters discovered with a Sunyaev-Zel'dovich effect survey

The South Pole Telescope (SPT) is conducting a Sunyaev-Zel'dovich (SZ) effect survey over large areas of the southern sky, searching for massive galaxy clusters to high redshift. In this preliminary study, we focus on a 40 square-degree area targeted by the Blanco Cosmology Survey (BCS), which is centered roughly at right ascension 5h30m, declination -53 degrees. Over two seasons of observations, this entire region has been mapped by the SPT at 95 GHz, 150 GHz, and 225 GHz. We report the four most significant SPT detections of SZ clusters in this field, three of which were previously unknown and, therefore, represent the first galaxy clusters discovered with an SZ survey. The SZ clusters are detected as decrements with greater than 5-sigma significance in the high-sensitivity 150 GHz SPT map. The SZ spectrum of these sources is confirmed by detections of decrements at the corresponding locations in the 95 GHz SPT map and non-detections at those locations in the 225 GHz SPT map. Multiband optical images from the BCS survey demonstrate significant concentrations of similarly colored galaxies at the positions of the SZ detections. Photometric redshift estimates from the BCS data indicate that two of the clusters lie at moderate redshift (z ~ 0.4) and two at high redshift (z >~ 0.8). One of the SZ detections was previously identified as a galaxy cluster using X-ray data from the ROSAT All-Sky Survey (RASS). Potential RASS counterparts (not previously identified as clusters) are also found for two of the new discoveries. These first four galaxy clusters are the most significant SZ detections from a subset of the ongoing SPT survey. As such, they serve as a demonstration that SZ surveys, and the SPT in particular, can be an effective means for finding galaxy clusters.Comment: 11 pages, 3 figures, revised to match published version, uses emulateap

Exploring the sensitivity of coastal inundation modelling to DEM vertical error

© 2018 Informa UK Limited, trading as Taylor & Francis Group. As sea level is projected to rise throughout the twenty-first century due to climate change, there is a need to ensure that sea level rise (SLR) models accurately and defensibly represent future flood inundation levels to allow for effective coastal zone management. Digital elevation models (DEMs) are integral to SLR modelling, but are subject to error, including in their vertical resolution. Error in DEMs leads to uncertainty in the output of SLR inundation models, which if not considered, may result in poor coastal management decisions. However, DEM error is not usually described in detail by DEM suppliers; commonly only the RMSE is reported. This research explores the impact of stated vertical error in delineating zones of inundation in two locations along the Devon, United Kingdom, coastline (Exe and Otter Estuaries). We explore the consequences of needing to make assumptions about the distribution of error in the absence of detailed error data using a 1 m, publically available composite DEM with a maximum RMSE of 0.15 m, typical of recent LiDAR-derived DEMs. We compare uncertainty using two methods (i) the NOAA inundation uncertainty mapping method which assumes a normal distribution of error and (ii) a hydrologically correct bathtub method where the DEM is uniformly perturbed between the upper and lower bounds of a 95% linear error in 500 Monte Carlo Simulations (HBM+MCS). The NOAA method produced a broader zone of uncertainty (an increase of 134.9% on the HBM+MCS method), which is particularly evident in the flatter topography of the upper estuaries. The HBM+MCS method generates a narrower band of uncertainty for these flatter areas, but very similar extents where shorelines are steeper. The differences in inundation extents produced by the methods relate to a number of underpinning assumptions, and particularly, how the stated RMSE is interpreted and used to represent error in a practical sense. Unlike the NOAA method, the HBM+MCS model is computationally intensive, depending on the areas under consideration and the number of iterations. We therefore used the HBM+ MCS method to derive a regression relationship between elevation and inundation probability for the Exe Estuary. We then apply this to the adjacent Otter Estuary and show that it can defensibly reproduce zones of inundation uncertainty, avoiding the computationally intensive step of the HBM+MCS. The equation-derived zone of uncertainty was 112.1% larger than the HBM+MCS method, compared to the NOAA method which produced an uncertain area 423.9% larger. Each approach has advantages and disadvantages and requires value judgements to be made. Their use underscores the need for transparency in assumptions and communications of outputs. We urge DEM publishers to move beyond provision of a generalised RMSE and provide more detailed estimates of spatial error and complete metadata, including locations of ground control points and associated land cover

Measurements of Secondary Cosmic Microwave Background Anisotropies with the South Pole Telescope

We report cosmic microwave background (CMB) power spectrum measurements from the first 100 sq. deg. field observed by the South Pole Telescope (SPT) at 150 and 220 GHz. On angular scales where the primary CMB anisotropy is dominant, ell ~< 3000, the SPT power spectrum is consistent with the standard LambdaCDM cosmology. On smaller scales, we see strong evidence for a point source contribution, consistent with a population of dusty, star-forming galaxies. After we mask bright point sources, anisotropy power on angular scales of 3000 50 at both frequencies. We combine the 150 and 220 GHz data to remove the majority of the point source power, and use the point source subtracted spectrum to detect Sunyaev-Zel'dovich (SZ) power at 2.6 sigma. At ell=3000, the SZ power in the subtracted bandpowers is 4.2 +/- 1.5 uK^2, which is significantly lower than the power predicted by a fiducial model using WMAP5 cosmological parameters. This discrepancy may suggest that contemporary galaxy cluster models overestimate the thermal pressure of intracluster gas. Alternatively, this result can be interpreted as evidence for lower values of sigma8. When combined with an estimate of the kinetic SZ contribution, the measured SZ amplitude shifts sigma8 from the primary CMB anisotropy derived constraint of 0.794 +/- 0.028 down to 0.773 +/- 0.025. The uncertainty in the constraint on sigma8 from this analysis is dominated by uncertainties in the theoretical modeling required to predict the amplitude of the SZ power spectrum for a given set of cosmological parameters.Comment: 28 pages, 11 figures, submitted to Ap

Finding related sentence pairs in MEDLINE

We explore the feasibility of automatically identifying sentences in different MEDLINE abstracts that are related in meaning. We compared traditional vector space models with machine learning methods for detecting relatedness, and found that machine learning was superior. The Huber method, a variant of Support Vector Machines which minimizes the modified Huber loss function, achieves 73% precision when the score cutoff is set high enough to identify about one related sentence per abstract on average. We illustrate how an abstract viewed in PubMed might be modified to present the related sentences found in other abstracts by this automatic procedure

FRP-to-masonry bond durability assessment with infrared thermography method

The bond behavior between FRP composites and masonry substrate plays an important role in the performance of externally bonded reinforced masonry structures. Therefore, monitoring the bond quality during the application and subsequent service life of a structure is of crucial importance for execution control and structural health monitoring. The bond quality can change during the service life of the structure due to environmental conditions. Local detachments may occur at the FRP/substrate interface, affecting the bond performance to a large extent. Therefore, the use of expedite and efficient non-destructive techniques for assessment of the bond quality and monitoring FRP delamination is of much interest. Active infrared thermography (IR) technique was used in this study for assessing the bond quality in environmentally degraded FRP-strengthened masonry elements. The applicability and accuracy of the adopted method was initially validated by localization and size quantification of artificially embedded defects in FRP-strengthened brick specimens. Then, the method was used for investigating the appearance and progression of FRP delaminations due to environmental conditions. GFRP-strengthened brick specimens were exposed to accelerated hygrothermal ageing tests and inspected periodically with the IR camera. The results showed environmental exposure may produce large progressive FRP delaminations.Fundação para a Ciência e Tecnologi

Investigation of the Origin and Spread of a Mammalian Transposable Element Based on Current Sequence Diversity

Almost half the human genome consists of mobile DNA elements, and their analysis is a vital part of understanding the human genome as a whole. Many of these elements are ancient and have persisted in the genome for tens or hundreds of millions of years, providing a window into the evolution of modern mammals. The Golem family have been used as model transposons to highlight computational analyses which can be used to investigate these elements, particularly the use of molecular dating with large transposon families. Whole-genome searches found Golem sequences in 20 mammalian species. Golem A and B subsequences were only found in primates and squirrel. Interestingly, the full-length Golem, found as a few copies in many mammalian genomes, was found abundantly in horse. A phylogenetic profile suggested that Golem originated after the eutherian–metatherian divergence and that the A and B subfamilies originated at a much later date. Molecular dating based on sequence diversity suggests an early age, of 175 Mya, for the origin of the family and that the A and B lineages originated much earlier than expected from their current taxonomic distribution and have subsequently been lost in some lineages. Using publically available data, it is possible to investigate the evolutionary history of transposon families. Determining in which organisms a transposon can be found is often used to date the origin and expansion of the families. However, in this analysis, molecular dating, commonly used for determining the age of gene sequences, has been used, reducing the likelihood of errors from deleted lineages