A new sensitive method for the simultaneous chromatographic separation and tandem mass spectrometry detection of anticoccidials, including highly polar compounds, in environmental waters

peer-reviewedA sensitive and selective method was developed and validated for the determination of 26 anticoccidial compounds (six ionophores and twenty chemical coccidiostats) in surface and groundwater samples at parts-per-quadrillion (pg L−1) to parts-per-trillion (ng L−1) levels by ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC–MS/MS). A range of different analytical columns and mobile phase compositions were evaluated to enhance selectivity and retention of a number of highly polar and basic anticoccidials along with other non-polar coccidiostats. A combined separation, including these problematic polar compounds, was achieved on a phenyl-hexyl column, by binary gradient elution with water/acetonitrile using ammonium formate and formic acid as additives. The anticoccidial residues were extracted from raw, unfiltered, water samples (250 mL) using polymeric divinylbenzene solid phase extraction (SPE) cartridges, with subsequent elution (methanol:acetonitrile:ethyl acetate, 40:40:20, v/v) and concentration prior to determination. The method recovery (at a concentration representative of realistic expected environmental water concentrations based on literature review) ranged from 81% to 105%. The method was successfully validated for 26 anticoccidials, at four concentration levels, in accordance to Commission Decision 2002/657/EC and SANTE/11813/2017 guidelines. Trueness and precision, under within-laboratory reproducibility conditions, ranged from 88% to 111% and 0.9% to 10.3% respectively

Verifying Different-modality Properties for Concepts Produces Switching Costs

According to perceptual symbol systems (Barsalou, 1999), sensory-motor simulations underlie the representation of concepts. It follows that sensory-motor phenomena should arise in conceptual processing. Previous studies have shown that switching from one modality to another during perceptual processing incurs a processing cost. If perceptual simulation underlies conceptual processing, then verifying the properties of concepts should exhibit a switching cost as well. For example, verifying a property in the auditory modality (e.g., BLENDER-loud) should be slower after verifying a property in a different modality (e.g., CRANBERRIES-tart) than in the same modality (e.g., LEAVES-rustling). Only words were presented to subjects, and there were no instructions to use imagery. Nevertheless switching modalities incurred a cost, analogous to switching modalities in perception. A second experiment showed that this effect was not due to associative priming between properties in the same modality. These results support the hypothesis that perceptual simulation underlies conceptual processing

The association between distal findings and proximal colorectal neoplasia: a systematic review and meta-analysis

Objectives: Whether screening participants with distal hyperplastic polyps (HPs) detected by flexible sigmoidoscopy (FS) should be followed by subsequent colonoscopy is controversial. We evaluated the association between distal HPs and proximal neoplasia (PN)/advanced proximal neoplasia (APN) in asymptomatic, average-risk patients. Methods: We searched Ovid Medline, EMBASE, and the Cochrane Library from inception to 30 June 2016 and included all screening studies that examined the relationship between different distal findings and PN/APN. Data were independently extracted by two reviewers with disagreements resolved by a third reviewer. We pooled absolute risks and odds ratios (ORs) with a random effects meta-analysis. Seven subgroup analyses were performed according to study characteristics. Heterogeneity was characterized with theI2 statistics. Results: We analyzed 28 studies (104,961 subjects). When compared with normal distal findings, distal HP was not associated with PN (OR=1.16, 95% confidence interval (CI)=0.89–1.51,P=0.14,I2=40%) or APN (OR=1.09, 95% CI=0.87–1.36,P=0.39,I2=5%), while subjects with distal non-advanced or advanced adenoma had higher odds of PN/APN. Higher odds of PN/APN were observed for more severe distal lesions. Weaker association between distal and proximal findings was noticed in studies with higher quality, larger sample size, population-based design, and more stringent endoscopy quality-control measures. The Egger’s regression tests showed allP>0.05. Conclusions: Distal HP is not associated with PN/APN in asymptomatic screening population when compared with normal distal findings. Hence, the presence of distal HP alone detected by FS does not automatically indicate colonoscopy referral for all screening participants, as other risk factors of PN/APN should be considered

Heavy-quark mass dependence in global PDF analyses and 3- and 4-flavour parton distributions

We study the sensitivity of our recent MSTW 2008 NLO and NNLO PDF analyses to the values of the charm- and bottom-quark masses, and we provide additional public PDF sets for a wide range of these heavy-quark masses. We quantify the impact of varying m_c and m_b on the cross sections for W, Z and Higgs production at the Tevatron and the LHC. We generate 3- and 4-flavour versions of the (5-flavour) MSTW 2008 PDFs by evolving the input PDFs and alpha_S determined from fits in the 5-flavour scheme, including the eigenvector PDF sets necessary for calculation of PDF uncertainties. As an example of their use, we study the difference in the Z total cross sections at the Tevatron and LHC in the 4- and 5-flavour schemes. Significant differences are found, illustrating the need to resum large logarithms in Q^2/m_b^2 by using the 5-flavour scheme. The 4-flavour scheme is still necessary, however, if cuts are imposed on associated (massive) b-quarks, as is the case for the experimental measurement of Z b bbar production and similar processes.Comment: 40 pages, 11 figures. Grids can be found at http://projects.hepforge.org/mstwpdf/ and in LHAPDF V5.8.4. v2: version published in EPJ

Parton-Hadron Duality in Unpolarised and Polarised Structure Functions

We study the phenomenon of parton-hadron duality in both polarised and unpolarised electron proton scattering using the HERMES and the Jefferson Lab data, respectively. In both cases we extend a systematic perturbative QCD based analysis to the integrals of the structure functions in the resonance region. After subtracting target mass corrections and large x resummation effects, we extract the remaining power corrections up to order 1/Q^2. We find a sizeable suppression of these terms with respect to analyses using deep inelastic scattering data. The suppression appears consistently in both polarised and unpolarised data, except for the low Q^2 polarised data, where a large negative higher twist contribution remains. Possible scenarios generating this behavior are discussed.Comment: 17 pages, 9 figure

A DNA-binding bromodomain-containing protein interacts with and reduces Rx1-mediated immune response to Potato Virus X

Plant NLR proteins enable the immune system to recognise and respond to pathogen attack. An early consequence of immune activation is transcriptional reprogramming. Some NLRs have been shown to act in the nucleus and interact with transcription factors. The Rx1 NLR protein of potato binds and distorts double-stranded DNA. However, the components of the chromatin localized Rx1-complex are largely unknown. Here we report a physical and functional interaction between Rx1 and NbDBCP, a bromodomain-containing chromatin-interacting protein. NbDBCP accumulates in the nucleolus, interacts with chromatin and redistributes Rx1 to the nucleolus in a subpopulation of imaged cells. Rx1 over-expression reduces NbDBCP interactions with chromatin. NbDBCP is a negative regulator of Rx1-mediated immune responses to potato virus X (PVX) and this activity requires an intact bromodomain. Previously, Rx1 has been shown to regulate the DNA-binding activity of a Golden2-like transcription factor, NbGlk1. Rx1 and NbDBCP act synergistically to reduce NbGlk1 DNA-binding suggesting a mode of action for NbDBCP’s inhibitory effect on immunity. This study provides new mechanistic insight into how a chromatin localised NLR complex co-ordinates immune signalling following pathogen perception

Mechanistic insights into the C₅₅-P targeting lipopeptide antibiotics revealed by structure-activity studies and high-resolution crystal structures

AbstractThe continued rise of antibiotic resistance is a global concern that threatens to undermine many aspects of modern medical practice. Key to addressing this threat is the discovery and development of new antibiotics that operate by unexploited modes of action. The so-called calcium-dependent lipopeptide antibiotics (CDAs) are an important emerging class of natural products that provides a source of new antibiotic agents rich in structural and mechanistic diversity. Notable in this regard is the subset of CDAs comprising the laspartomycins and amphomycins/friulimicins that specifically target the bacterial cell wall precursor undecaprenyl phosphate (C55-P). In this study we describe the design and synthesis of new C55-P-targeting CDAs with structural features drawn from both the laspartomycin and amphomycin/friulimicin classes. Assessment of these lipopeptides revealed previously unknown and surprisingly subtle structural features that are required for antibacterial activity. High-resolution crystal structures further indicate that the amphomycin/friulimicin-like lipopeptides adopt a unique crystal packing that governs their interaction with C55-P and provides an explanation for their antibacterial effect. In addition, live-cell microscopy studies provide further insights into the biological activity of the C55-P targeting CDAs highlighting their unique mechanism of action relative to the clinically used CDA daptomycin.Microbial Biotechnolog

Third-order relativistic many-body calculations of energies and lifetimes of levels along the silver isoelectronic sequence

Energies of 5l_j (l= s, p, d, f, g) and 4f_j states in neutral Ag and Ag-like ions with nuclear charges Z = 48 - 100 are calculated using relativistic many-body perturbation theory. Reduced matrix elements, oscillator strengths, transition rates and lifetimes are calculated for the 17 possible 5l_j-5l'_{j'} and 4f_j-5l_{j'} electric-dipole transitions. Third-order corrections to energies and dipole matrix elements are included for neutral Ag and for ions with Z60. Comparisons are made with available experimental data for transition energies and lifetimes. Correlation energies and transition rates are shown graphically as functions of nuclear charge Z for selected cases. These calculations provide a theoretical benchmark for comparison with experiment and theory.Comment: 8 page

Two-Loop Helicity Amplitudes for Quark-Gluon Scattering in QCD and Gluino-Gluon Scattering in Supersymmetric Yang-Mills Theory

We present the two-loop QCD helicity amplitudes for quark-gluon scattering, and for quark-antiquark annihilation into two gluons. These amplitudes are relevant for next-to-next-to-leading order corrections to (polarized) jet production at hadron colliders. We give the results in the `t Hooft-Veltman and four-dimensional helicity (FDH) variants of dimensional regularization. The transition rules for converting the amplitudes between the different variants are much more intricate than for the previously discussed case of gluon-gluon scattering. Summing our two-loop expressions over helicities and colors, and converting to conventional dimensional regularization, gives results in complete agreement with those of Anastasiou, Glover, Oleari and Tejeda-Yeomans. We describe the amplitudes for 2 to 2 scattering in pure N=1 supersymmetric Yang-Mills theory, obtained from the QCD amplitudes by modifying the color representation and multiplicities, and verify supersymmetry Ward identities in the FDH scheme.Comment: 77 pages. v2: corrected errors in eqs. (3.7) and (3.8) for one-loop assembly; remaining results unaffecte

Spin Transport in Two Dimensional Hopping Systems

A two dimensional hopping system with Rashba spin-orbit interaction is considered. Our main interest is concerned with the evolution of the spin degree of freedom of the electrons. We derive the rate equations governing the evolution of the charge density and spin polarization of this system in the Markovian limit in one-particle approximation. If only two-site hopping events are taken into account, the evolution of the charge density and of the spin polarization is found to be decoupled. A critical electric field is found, above which oscillations are superimposed on the temporal decay of the total polarization. A coupling between charge density and spin polarization occurs on the level of three-site hopping events. The coupling terms are identified as the anomalous Hall effect and the recently proposed spin Hall effect. Thus, an unpolarized charge current through a sheet of finite width leads to a transversal spin accumulation in our model system.Comment: 15 pages, 3 figure