bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative in vitro killing of canine strains of Staphylococcus pseudintermedius and Escherichia coli by cefovecin, cefazolin, doxycycline and pradofloxacin
Authors: Blondeau Joseph M. , Shebelski Shantelle D. 
Published: June 2016

BackgroundBacterial eradication is necessary for clinical cure of infections and antimicrobial agents are important adjunctive therapies for inhibiting the growth of or killing bacteria. Pre‐existing skin diseases predispose animals to infection by Staphylococcus pseudintermedius and, more rarely, by Gram‐negative bacilli. The property of rapid killing of bacteria may influence drug selection and duration of therapy in the setting of infection.ObjectivesTo test the killing of canine isolates of S. pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin at the minimum inhibitory, mutant prevention, maximum serum and maximum tissue drug concentrations.MethodsUnder standard conditions, bacterial cells were exposed to clinically relevant drug concentrations in vitro and the log10 reduction (and % kill) of viable cells measured at 5, 10, 15, 20, 25, 30, 60, 120 and 180 min after drug exposure.ResultsStatistically significant differences were seen between killing efficiencies by pradofloxacin versus the other agents, whereby pradofloxacin killed cells more rapidly than the others. For example, against the S. pseudintermedius strains, significantly more cells were killed by pradofloxacin following 15 min of maximum tissue drug concentration exposure than for cefazolin (P = 0.0002), cefovecin (P = 0.0007) and doxycycline (P ≤ 0.0001).Conclusion and clinical importanceThe rank order of potency based on these kill experiments was pradofloxacin > cefazolin > cefovecin > doxycycline. Rapid killing of bacteria affects the speed of clinical resolution and may influence drug selection and duration of therapy for skin infections.
Agonist‐induced sensitisation of the irritant receptor ion channel TRPA1
Authors: Meents Jannis E. , Fischer Michael J. M. , McNaughton Peter A. 
Published: June 2016

Key points
The transient receptor potential ankyrin 1 (TRPA1) ion channel is expressed in nociceptive neurons and its activation causes ongoing pain and inflammation; TRPA1 is thought to play an important role in inflammation in the airways.
TRPA1 is sensitised by repeated stimulation with chemical agonists in a calcium‐free environment and this sensitisation is very long lasting following agonist removal.
We show that agonist‐induced sensitisation is independent of the agonist's binding site and is also independent of ion channel trafficking or of other typical signalling pathways.
We find that sensitisation is intrinsic to the TRPA1 protein and is accompanied by a slowly developing shift in the voltage dependence of TRPA1 towards more negative membrane potentials.
Agonist‐induced sensitisation may provide an explanation for sensitisation following long‐term exposure to harmful irritants and pollutants, particularly in the airways.
AbstractThe TRPA1 ion channel is expressed in nociceptive (pain‐sensitive) neurons and responds to a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here we show that in the absence of extracellular calcium the current passing through TRPA1 gradually increases (sensitises) during prolonged application of agonists. Activation by an agonist is essential, because activation of TRPA1 by membrane depolarisation did not cause sensitisation. Sensitisation is independent of the site of action of the agonist, because covalent and non‐covalent agonists were equally effective, and is long lasting following agonist removal. Mutating N‐terminal cysteines, the target of covalent agonists, did not affect sensitisation by the non‐covalent agonist carvacrol, which activates by binding to a different site. Sensitisation is unaffected by agents blocking ion channel trafficking or by block of signalling pathways involving ATP, protein kinase A or the formation of lipid rafts, and does not require ion flux through the channel. Examination of the voltage dependence of TRPA1 activation shows that sensitisation is accompanied by a slowly developing shift in the voltage dependence of TRPA1 towards more negative membrane potentials, and is therefore intrinsic to the TRPA1 channel. Sensitisation may play a role in exacerbating the pain caused by prolonged activation of TRPA1.
Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x‐ray fields
Authors: Livingstone Jayde , Stevenson Andrew W. , Butler Duncan J. , Häusermann Daniel , Adam Jean‐François 
Published: June 2016

Purpose:Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose‐rate, sub‐millimetric parallel kilovoltage x‐ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy.Methods:Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross‐referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30–120 keV. The dose‐rate dependence was measured in the range 1–700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters.Results:The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30–120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose‐rate in the range 1–700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data.Conclusions:The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.
Human IgG1, IgG3, and IgG3 Hinge-Truncated Mutants Show Different Protection Capabilities against Meningococci Depending on the Target Antigen and Epitope Specificity
Authors: Giuntini S. , Granoff D. M. , Beernink P. T. , Ihle O. , Bratlie D. , Michaelsen T. E. 
Published: June 2016

ABSTRACTWe compared the bactericidal activity of recombinant sets of chimeric IgG monoclonal antibodies against two important outer membrane meningococcal vaccine antigens: PorA and factor H binding protein (FHbp). The sets contained human Fc portions from IgG1, IgG3, and two IgG3 mutants (IgG3m15 and IgGm17) with hinge regions of 15 and 17 amino acids encoded by hinge exons h2 and h1, respectively (human IgG3 has a hinge region of 62 amino acids encoded by hinge exons h1, h2, h3, and h4, while human IgG1 has a hinge region of only 15 amino acids encoded by one hinge exon) and mouse V regions. IgG1 showed higher bactericidal activity than IgG3 when directed against PorA (an abundant antigen), while IgG3 was more bactericidal than IgG1 when directed against FHbp (a sparsely and variably distributed antigen). On the other hand, the IgG3 hinge-truncated antibodies IgG3m15 and IgGm17 showed higher bactericidal activity than both IgG1 and IgG3 regardless of the target antigen. Thus, the Fc region of IgG3 antibodies appears to have an enhanced complement-activating function, independent of their long hinge region, compared to IgG1 antibodies. The greater activity of the truncated IgG3 hinge mutants indicates that the long hinge of IgG3 seems to downregulate through an unknown mechanism the inherent increased complement-activating capability of IgG3 Fc when the antibody binds to a sparse antigen.
Development and Characterization of Monoclonal Antibodies to Yellow Fever Virus and Application in Antigen Detection and IgM Capture Enzyme-Linked Immunosorbent Assay
Authors: Adungo Ferdinard , Yu Fuxun , Kamau David , Inoue Shingo , Hayasaka Daisuke , Posadas-Herrera Guillermo , Sang Rosemary , Mwau Matilu , Morita Kouichi 
Published: June 2016

ABSTRACTYellow fever (YF) is an acute hemorrhagic viral infection transmitted by mosquitoes in Africa and South America. The major challenge in YF disease detection and confirmation of outbreaks in Africa is the limited availability of reference laboratories and the persistent lack of access to diagnostic tests. We used wild-type YF virus sequences to generate recombinant envelope protein in anEscherichia coliexpression system. Both the recombinant protein and sucrose gradient-purified YF vaccine virus 17D (YF-17D) were used to immunize BALB/c mice to generate monoclonal antibodies (MAbs). Eight MAbs were established and systematically characterized by indirect enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and immunofluorescence assay (IFA). The established MAbs showed strong reactivity with wild-type YF virus and recombinant protein with no detectable cross-reactivity to dengue virus or Japanese encephalitis virus. Epitope mapping showed strong binding of three MAbs to amino acid positions 1 to 51, while two MAbs mapped to amino acid positions 52 to 135 of the envelope protein. The remaining three MAbs did not show reactivity to envelope fragments. The established MAbs exert no neutralization against wild-type YF and 17D viruses (titer of <10 for both strains). The applicability of MAbs 8H3 and 3F4 was further evaluated using IgM capture ELISA. A total of 49 serum samples were analyzed, among which 12 positive patient and vaccinee samples were correctly identified. Using serum samples that were 2-fold serially diluted, the IgM capture ELISA was able to detect all YF-positive samples. Furthermore, MAb-based antigen detection ELISA enabled the detection of virus in culture supernatants containing titers of about 1,000 focus-forming units.
Virion Glycoprotein-Mediated Immune Evasion by Human Cytomegalovirus: a Sticky Virus Makes a Slick Getaway
Authors: Gardner Thomas J. , Tortorella Domenico 
Published: June 2016

SUMMARYThe prototypic herpesvirus human cytomegalovirus (CMV) exhibits the extraordinary ability to establish latency and maintain a chronic infection throughout the life of its human host. This is even more remarkable considering the robust adaptive immune response elicited by infection and reactivation from latency. In addition to the ability of CMV to exist in a quiescent latent state, its persistence is enabled by a large repertoire of viral proteins that subvert immune defense mechanisms, such as NK cell activation and major histocompatibility complex antigen presentation, within the cell. However, dissemination outside the cell presents a unique existential challenge to the CMV virion, which is studded with antigenic glycoprotein complexes targeted by a potent neutralizing antibody response. The CMV virion envelope proteins, which are critical mediators of cell attachment and entry, possess various characteristics that can mitigate the humoral immune response and prevent viral clearance. Here we review the CMV glycoprotein complexes crucial for cell attachment and entry and propose inherent properties of these proteins involved in evading the CMV humoral immune response. These include viral glycoprotein polymorphism, epitope competition, Fc receptor-mediated endocytosis, glycan shielding, and cell-to-cell spread. The consequences of CMV virion glycoprotein-mediated immune evasion have a major impact on persistence of the virus in the population, and a comprehensive understanding of these evasion strategies will assist in designing effective CMV biologics and vaccines to limit CMV-associated disease.
Variable El Niño–Southern Oscillation influence on biofacies dynamics of eastern Pacific shallow-water carbonate systems
Authors: Humphreys Alexander F. , Halfar Jochen , Rivera Fernando , Manzello Derek , Reymond Claire E. , Westphal Hildegard , Riegl Bernhard 
Published: June 2016

Abstract
The El Niño–Southern Oscillation (ENSO) is a periodic climatic and oceanic event caused by sea-surface temperature and nutrient anomalies over the eastern tropical Pacific Ocean (ETP). Recurring ENSO events have a significant impact on climate and the ecosystems of the circum-Pacific region. In the marine realm, ENSO is known for altering temperature and nutrient patterns, affecting the pelagic food chain, and causing widespread bleaching of corals due to temperature stress. The potential impacts of ENSO on shallow benthic ecosystems as a whole, however, are poorly understood. Here, we compared biogenic sedimentary facies of ETP shallow-water carbonate systems in a strongly ENSO-influenced area (Galápagos Islands, Ecuador [GAL]) with similar systems in an area less strongly influenced by ENSO (Gulf of California, Mexico [GOC]). Carbonate assemblages in both study regions range from coral-algal–dominated (photozoan) to molluscan-dominated (heterozoan) assemblages. Linear statistical models, comparing the distribution of carbonates against prominent local oceanographic parameters, show that minimum chlorophyll-a and maximum sea-surface temperature (which are both strongly influenced by ENSO) are dominant drivers shaping carbonate sediment facies in the GAL. In contrast, GOC carbonates have a distinct mean chlorophyll-a signature that is the result of an upwelling-induced north-south nutrient gradient not significantly influenced by ENSO.
Multiple episodes of hematite mineralization indicated by U-Pb dating of iron-ore deposits, Marquette Range, Michigan, USA
Authors: Rasmussen Birger , Zi Jian-Wei , Sheppard Stephen , Krapež Bryan , Muhling Janet R. 
Published: June 2016

Abstract
High-grade hematite ore (so-called “hard ore”) was first mined in the Lake Superior region of North America in A.D. 1848. The development of ore deposit models from the region has strongly influenced research on the origin of this deposit type worldwide. The inability to date high-grade hematite ores has hindered the testing of competing genetic models. In the Marquette Range, northern Michigan (USA), high-grade hematite ore is hosted by the 1.9–1.85 Ga Negaunee Iron Formation and unconformably overlying Goodrich Quartzite. Field relations and new in situ U-Pb geochronology of monazite and xenotime intergrown with hematite from six mines across the Marquette Range, Michigan, indicate that the formation of high-grade hematite ore bodies involved up to three events. The presence of pebbles of hematite ore in basal conglomerate of the Goodrich Quartzite indicates that the first episode of iron-oxide mineralization occurred after deposition and deformation of the Negaunee Iron Formation, but before the ca. 1.85 Ga Sudbury impact. Monazite in iron-ore deposits within the hinges of Penokean-aged folds yields an age of ca. 1.8 Ga, which is interpreted to record a second phase of hematite enrichment. Monazite and xenotime in iron-ore deposits along the limbs of regional folds give ages of ca. 1.77 Ga and are interpreted to record a later episode of hematite upgrading. The ca. 1.8 Ga and ca. 1.77 Ga phosphate ages coincide with the timing of regional tectonic events, suggesting hematite mineralization was coeval with the Penokean orogeny and Yavapai-interval accretion. Our results support the proposal that the formation of high-grade hematite ore bodies is a multistage process linked to discrete orogenic events.
Extending Alaska’s plate boundary: Tectonic tremor generated by Yakutat subduction
Authors: Wech Aaron G. 
Published: June 2016

Abstract
The tectonics of the eastern end of the Alaska-Aleutian subduction zone are complicated by the inclusion of the Yakutat microplate, which is colliding into and subducting beneath continental North America at near-Pacific-plate rates. The interaction among these plates at depth is not well understood, and further east, even less is known about the plate boundary or the source of Wrangell volcanism. The drop-off in Wadati-Benioff zone (WBZ) seismicity could signal the end of the plate boundary, the start of aseismic subduction, or a tear in the downgoing plate. Further compounding the issue is the possible presence of the Wrangell slab, which is faintly outlined by an anemic, eastward-dipping WBZ beneath the Wrangell volcanoes. In this study, I performed a search for tectonic tremor to map slow, plate-boundary slip in south-central Alaska. I identified ∼11,000 tremor epicenters, which continue 85 km east of the inferred Pacific plate edge marked by WBZ seismicity. The tremor zone coincides with the edges of the downgoing Yakutat terrane, and tremors transition from periodic to continuous behavior as they near the aseismic Wrangell slab. I interpret tremor to mark slow, semicontinuous slip occurring at the interface between the Yakutat and North America plates. The slow slip region lengthens the megathrust interface beyond the WBZ and may provide evidence for a connection between the Yakutat slab and the aseismic Wrangell slab.
Control of silicate weathering by interface-coupled dissolution-precipitation processes at the mineral-solution interface
Authors: Ruiz-Agudo Encarnación , King Helen E. , Patiño-López Luis D. , Putnis Christine V. , Geisler Thorsten , Rodriguez-Navarro Carlos , Putnis Andrew 
Published: June 2016

Abstract
The mechanism of surface coating formation (the so-called surface altered layers [SALs] or leached layers) during weathering of silicate minerals is controversial and hinges on understanding the saturation state of the fluid at the dissolving mineral surface. Here we present in-situ data on the evolution of the interfacial fluid composition during dissolution of wollastonite (CaSiO3), obtained using interferometry and micro pH and ion-selective electrodes. Steep concentration gradients develop at the mineral interface as soon as it makes contact with the solution. This interfacial fluid becomes supersaturated with respect to amorphous silica that forms a surface coating, limiting fluid access to the mineral surface and hence affecting the dissolution rate. The thickness of the supersaturated zone and the precipitated layer depends on the relative rates of mass transport and surface reaction in the system; this effect could contribute to the discrepancy between dissolution rates measured in the field and in the laboratory. As well, our results have implications for predictions of silicate weathering rates and hence climate evolution, as different assumptions on dissolution mechanisms affect calculations on CO2 drawdown during weathering and consequent effects on estimates of global mean temperatures.
Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football
Authors: Myer Gregory D , Yuan Weihong , Barber Foss Kim D , Thomas Staci , Smith David , Leach James , Kiefer Adam W , Dicesare Chris , Adams Janet , Gubanich Paul J , Kitchen Katie , Schneider Daniel K , Braswell Daniel , Krueger Darcy , Altaye Mekibib 
Published: June 2016

BackgroundHistorical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season.MethodsA prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome.ResultsWith similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05).DiscussionReduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts.Trial registration numberNCT02696200.
Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study
Authors: Alabas O A , Hall M , Dondo T B , Rutherford M J , Timmis A D , Batin P D , Deanfield J E , Hemingway H , Gale C P 
Published: June 2016

BackgroundThe long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments.MethodsNationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576).ResultsOver 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43).ConclusionsAt index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments.