Identification of a novel regulatory mechanism for the disease associated protein, uPAR

Expression quantitative trait loci (eQTLs), as determined through a series of statistical association studies collectively known as genome-wide association (GWA) studies, have provided us with a hypothesis free approach for the investigation into regulatory loci for disease and disease-associated proteins. This has led to the identification of multiple novel gene-disease interactions, especially in the field of respiratory medicine. This review describes the case study of a GWA approach in order to identify eQTLs for the soluble form of the urokinase plasminogen activator receptor (uPAR), a protein associated with obstructive respiratory disease. Molecular and cellular investigations based on the eQTLs identified for this GWA study has led to the identification of a novel regulatory mechanism with implications in the disease processes with which this protein is associated. This highlights the potential of eQTLs defined associations in the identification of novel mechanisms, with implications in disease.peer-reviewe

Symbolic Computation of Polynomial Conserved Densities, Generalized Symmetries, and Recursion Operators for Nonlinear Differential-Difference Equations

Algorithms for the symbolic computation of polynomial conserved densities, fluxes, generalized symmetries, and recursion operators for systems of nonlinear differential-difference equations are presented. In the algorithms we use discrete versions of the Fréchet and variational derivatives, as well as discrete Euler and homotopy operators. The algorithms are illustrated for prototypical nonlinear polynomial lattices, including the Kac-van Moerbeke (Volterra) and Toda lattices. Results are shown for the modified Volterra and Ablowitz-Ladik lattices

Rumen fluke in Irish sheep: prevalence, risk factors and molecular identification of two paramphistome species

peer-reviewedBackground Rumen flukes are trematode parasites found globally; in tropical and sub-tropical climates, infection can result in paramphistomosis, which can have a deleterious impact on livestock. In Europe, rumen fluke is not regarded as a clinically significant parasite, recently however, the prevalence of rumen fluke has sharply increased and several outbreaks of clinical paramphistomosis have been reported. Gaining a better understanding of rumen fluke transmission and identification of risk factors is crucial to improve the control of this parasitic disease. In this regard, a national prevalence study of rumen fluke infection and an investigation of associated risk factors were conducted in Irish sheep flocks between November 2014 and January 2015. In addition, a molecular identification of the rumen fluke species present in Ireland was carried out using an isolation method of individual eggs from faecal material coupled with a PCR. After the DNA extraction of 54 individual eggs, the nuclear fragment ITS-2 was amplified and sequenced using the same primers. Results An apparent herd prevalence of 77.3 % was determined. Several risk factors were identified including type of pasture grazed, regional variation, and sharing of the paddocks with other livestock species. A novel relationship between the Suffolk breed and higher FEC was reported for the first time. The predominant rumen fluke species found was C. daubneyi. Nevertheless, P. leydeni was unexpectedly identified infecting sheep in Ireland for the first time. Conclusions An exceptionally high prevalence of rumen fluke among Irish sheep flocks has been highlighted in this study and a more thorough investigation is necessary to analyse its economic impact. The isolation of individual eggs coupled with the PCR technique used here has proven a reliable tool for discrimination of Paramphistomum spp. This technique may facilitate forthcoming studies of the effects of paramphistomosis on livestock production. The most noteworthy finding was the identification of P. leydeni affecting sheep in Ireland, however further studies are required to clarify its implications. Also, a significant relationship between Suffolk breed and a heavier infection was found, which can be used as a starting point for future research on control strategies of rumen fluke infection.This study was funded by Irish Department of Agriculture, Food and the Marine research stimulus funding; project reference 13/ S/405

Investigation of Graded La2NiO4+ Cathodes to Improve SOFC Electrochemical Performance

Mixed ionic and electronic conducting MIEC oxides are promising materials for use as cathodes in solid oxide fuel cells SOFCs due to their enhanced electrocatalytic activity compared with electronic conducting oxides. In this paper, the MIEC oxide La2NiO4+ was prepared by the sol-gel route. Graded cathodes were deposited onto yttria-stabilized zirconia YSZ pellets by dip-coating, and electrochemical impedance spectroscopy studies were performed to characterize the symmetrical cell performance. By adapting the slurries, cathode layers with different porosities and thicknesses were obtained. A ceria gadolinium oxide CGO barrier layer was introduced, avoiding insulating La2Zr2O7 phase formation and thus reducing resistance polarization of the cathode. A systematic correlation between microstructure, composition, and electrochemical performance of these cathodes has been performed. An improvement of the electrochemical performance has been demonstrated, and a reduction in the area specific resistance ASR by a factor of 4.5 has been achieved with a compact interlayer of La2NiO4+ between the dense electrolyte and the porous La2NiO4+ cathode layer. The lowest observed ASR of 0.11 cm2 at 800°C was obtained from a symmetrical cell composed of a YSZ electrolyte, a CGO interlayer, an intermediate compact La2NiO4+ layer, a porous La2NiO4+ electrode layer, and a current collection layer of platinum paste

A Search for Cosmic Microwave Background Anisotropies on Arcminute Scales with Bolocam

We have surveyed two science fields totaling one square degree with Bolocam at 2.1 mm to search for secondary CMB anisotropies caused by the Sunyaev- Zel'dovich effect (SZE). The fields are in the Lynx and Subaru/XMM SDS1 fields. Our survey is sensitive to angular scales with an effective angular multipole of l_eff = 5700 with FWHM_l = 2800 and has an angular resolution of 60 arcseconds FWHM. Our data provide no evidence for anisotropy. We are able to constrain the level of total astronomical anisotropy, modeled as a flat bandpower in C_l, with frequentist 68%, 90%, and 95% CL upper limits of 590, 760, and 830 uKCMB^2. We statistically subtract the known contribution from primary CMB anisotropy, including cosmic variance, to obtain constraints on the SZE anisotropy contribution. Now including flux calibration uncertainty, our frequentist 68%, 90% and 95% CL upper limits on a flat bandpower in C_l are 690, 960, and 1000 uKCMB^2. When we instead employ the analytic spectrum suggested by Komatsu and Seljak (2002), and account for the non-Gaussianity of the SZE anisotropy signal, we obtain upper limits on the average amplitude of their spectrum weighted by our transfer function of 790, 1060, and 1080 uKCMB^2. We obtain a 90% CL upper limit on sigma8, which normalizes the power spectrum of density fluctuations, of 1.57. These are the first constraints on anisotropy and sigma8 from survey data at these angular scales at frequencies near 150 GHz.Comment: 68 pages, 17 figures, 2 tables, accepted for publication in Ap

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

Oxford Nanopore sequencing, hybrid error correction, and de novo assembly of a eukaryotic genome

Monitoring the progress of DNA molecules through a membrane pore has been postulated as a method for sequencing DNA for several decades. Recently, a nanopore-based sequencing instrument, the Oxford Nanopore MinION, has become available, and we used this for sequencing the Saccharomyces cerevisiae genome. To make use of these data, we developed a novel open-source hybrid error correction algorithm Nanocorr specifically for Oxford Nanopore reads, because existing packages were incapable of assembling the long read lengths (5-50 kbp) at such high error rates (between approximately 5% and 40% error). With this new method, we were able to perform a hybrid error correction of the nanopore reads using complementary MiSeq data and produce a de novo assembly that is highly contiguous and accurate: The contig N50 length is more than ten times greater than an Illumina-only assembly (678 kb versus 59.9 kbp) and has >99.88% consensus identity when compared to the reference. Furthermore, the assembly with the long nanopore reads presents a much more complete representation of the features of the genome and correctly assembles gene cassettes, rRNAs, transposable elements, and other genomic features that were almost entirely absent in the Illumina-only assembly

Voltage- and light-induced hysteresis effects at the high-k dielectric- poly(3-hexylthiophene) interface

Capacitance-voltage (C-V) measurements have been undertaken on metal-insulator-semiconductor capacitors formed from atomic-layer-deposited films of aluminium titanium oxide as the insulator and poly(3-hexylthiophene) as the insulator. Upon cycling from -30 to +30 V in the dark, the C-V plots show large, temperature-dependent, reversible shifts in the flatband voltage to more negative voltages consistent with reversible, shallow hole trapping at or near the insulator-semiconductor interface. When illuminated with photons of energy exceeding the polymer band gap, even larger shifts to positive voltages are observed accompanied by inversion layer formation. This latter effect has potential applications in optical sensing. (c) 2007 American Institute of Physics

A millimeter-wave kinetic inductance detector camera for long-range imaging through optical obscurants

Millimeter-wave imaging provides a promising option for long-range target detection through optical obscurants such as fog, which often occur in marine environments. Given this motivation, we are currently developing a 150 GHz polarization-sensitive imager using a relatively new type of superconducting pair-breaking detector, the kinetic inductance detector (KID). This imager will be paired with a 1.5 m telescope to obtain an angular resolution of 0.09° over a 3.5° field of view using 3,840 KIDs. We have fully characterized a prototype KID array, which shows excellent performance with noise strongly limited by the irreducible fluctuations from the ambient temperature background. Full-scale KID arrays are now being fabricated and characterized for a planned demonstration in a maritime environment later this year