We have studied by PCR and DNA sequencing the presence of the qnrA, qnrB, qnrS, aac(6')-Ib-cr, qepA, intI1, and ISCR1 genes in 200 clinical isolates of Enterobacter cloacae (n = 153) and E. aerogenes ...(n = 47) consecutively collected between January 2004 and October 2005 in two hospitals located in Santander (northern Spain) and Seville (southern Spain). Mutations in the quinolone resistance-determining region of gyrA and parC also were investigated in organisms containing plasmid-mediated quinolone resistance genes. The isolates had different resistant phenotypes, including AmpC hyperproduction, extended-spectrum β-lactamase production, resistance or decreased susceptibility to quinolones, and/or resistance to aminoglycosides. Among the 116 E. cloacae isolates from Santander, qnrS1, qnrB5, qnrB2, and aac(6')-Ib-cr were detected in 22 (19%), 1 (0.9%), 1 (0.9%), and 3 (2.6%) isolates, respectively. Twenty-one, 17, and 2 qnrS1-positive isolates also contained blaLAP₋₁, intI1, and ISCR1, respectively. A qnrB7-like gene was detected in one E. aerogenes isolate from Santander. No plasmid-mediated quinolone resistance gene was detected in the isolates from Seville. The qnrS1-containing isolates corresponded to four pulsed-field gel electrophoresis patterns and showed various levels of resistance to quinolones. Six isolates were susceptible to nalidixic acid and presented reduced susceptibility to ciprofloxacin. The qnrS1 gene was contained in a conjugative plasmid of ca. 110 kb, and when the plasmid was transferred to recipient strains that did not have a specific mechanism of quinolone resistance, the ciprofloxacin MICs ranged from 0.047 to 0.125 μg/ml.
We present results from the most comprehensive radio monitoring campaign towards the closest star to our Sun, Proxima Centauri. We report 1.1–3.1 GHz observations with the Australia Telescope Compact ...Array over 18 consecutive days in April 2017. We detected radio emission from Proxima Centauri for most of the observing sessions, which spanned ~1.6 orbital periods of the planet Proxima b. The radio emission is stronger at the low-frequency band, centered around 1.6 GHz, and is consistent with the expected electron-cyclotron frequency for the known star’s magnetic field intensity of ~600 gauss. The 1.6 GHz light curve shows an emission pattern that is consistent with the orbital period of the planet Proxima b around the star Proxima, with its maxima of emission happening near the quadratures. We also observed two short-duration flares (a few minutes) and a long-duration burst (about three days) whose peaks happened close to the quadratures. We find that the frequency, large degree of circular polarization, change in the sign of circular polarization, and intensity of the observed radio emission are all consistent with expectations from electron cyclotron-maser emission arising from sub-Alfvénic star–planet interaction. We interpret our radio observations as signatures of interaction between the planet Proxima b and its host star Proxima. We advocate for monitoring other dwarf stars with planets to eventually reveal periodic radio emission due to star–planet interaction, thus opening a new avenue for exoplanet hunting and the study of a new field of exoplanet–star plasma interaction.
The Transiting Exoplanet Survey Satellite (TESS) recently observed 18 transits of the hot Jupiter WASP-4b. The sequence of transits occurred 81.6 11.7 s earlier than had been predicted, based on data ...stretching back to 2007. This is unlikely to be the result of a clock error, because TESS observations of other hot Jupiters (WASP-6b, 18b, and 46b) are compatible with a constant period, ruling out an 81.6 s offset at the 6.4 level. The 1.3 day orbital period of WASP-4b appears to be decreasing at a rate of ms per year. The apparent period change might be caused by tidal orbital decay or apsidal precession, although both interpretations have shortcomings. The gravitational influence of a third body is another possibility, though at present there is minimal evidence for such a body. Further observations are needed to confirm and understand the timing variation.
This paper presents a study on the metal cutting simulation with a particular numerical technique, the Particle Finite Element Method (PFEM) with a new modified time integration algorithm and ...incorporating a contact algorithm capability . The goal is to reproduce the formation of continuous chip in orthogonal machining. The paper tells how metal cutting processes can be modelled with the PFEM and which new tools have been developed to provide the proper capabilities for a successful modelling. The developed method allows for the treatment of large deformations and heat conduction, workpiece-tool contact including friction effects as well as the full thermo-mechanical coupling for contact. The difficulties associated with the distortion of the mesh in areas with high deformation are solved introducing new improvements in the continuous Delaunay triangulation of the particles. The employment of adaptative insertion and removal of particles at every new updated configuration improves the mesh quality allowing for resolution of finer-scale features of the solution. The performance of the method is studied with a set of different two-dimensional tests of orthogonal machining. The examples consider, from the most simple case to the most complex case, different assumptions for the cutting conditions and different material properties. The results have been compared with experimental tests showing a good competitiveness of the PFEM in comparison with other available simulation tools.
We compared the effects of two resistance training (RT) programs only differing in the repetition velocity loss allowed in each set: 20% (VL20) vs 40% (VL40) on muscle structural and functional ...adaptations. Twenty‐two young males were randomly assigned to a VL20 (n = 12) or VL40 (n = 10) group. Subjects followed an 8‐week velocity‐based RT program using the squat exercise while monitoring repetition velocity. Pre‐ and post‐training assessments included: magnetic resonance imaging, vastus lateralis biopsies for muscle cross‐sectional area (CSA) and fiber type analyses, one‐repetition maximum strength and full load‐velocity squat profile, countermovement jump (CMJ), and 20‐m sprint running. VL20 resulted in similar squat strength gains than VL40 and greater improvements in CMJ (9.5% vs 3.5%, P < 0.05), despite VL20 performing 40% fewer repetitions. Although both groups increased mean fiber CSA and whole quadriceps muscle volume, VL40 training elicited a greater hypertrophy of vastus lateralis and intermedius than VL20. Training resulted in a reduction of myosin heavy chain IIX percentage in VL40, whereas it was preserved in VL20. In conclusion, the progressive accumulation of muscle fatigue as indicated by a more pronounced repetition velocity loss appears as an important variable in the configuration of the resistance exercise stimulus as it influences functional and structural neuromuscular adaptations.
Seventeen Middle Pleistocene crania from the Sima de los Huesos site (Atapuerca, Spain) are analyzed, including seven new specimens. This sample makes it possible to thoroughly characterize a Middle ...Pleistocene hominin paleodeme and to address hypotheses about the origin and evolution of the Neandertals. Using a variety of techniques, the hominin-bearing layer could be reassigned to a period around 430,000 years ago. The sample shows a consistent morphological pattern with derived Neandertal features present in the face and anterior vault, many of which are related to the masticatory apparatus. This suggests that facial modification was the first step in the evolution of the Neandertal lineage, pointing to a mosaic pattern of evolution, with different anatomical and functional modules evolving at different rates.
We describe Global Atmosphere 4.0 (GA4.0) and Global Land 4.0 (GL4.0): configurations of the Met Office Unified Model and JULES (Joint UK Land Environment Simulator) community land surface model ...developed for use in global and regional climate research and weather prediction activities. GA4.0 and GL4.0 are based on the previous GA3.0 and GL3.0 configurations, with the inclusion of developments made by the Met Office and its collaborators during its annual development cycle. This paper provides a comprehensive technical and scientific description of GA4.0 and GL4.0 as well as details of how these differ from their predecessors. We also present the results of some initial evaluations of their performance. Overall, performance is comparable with that of GA3.0/GL3.0; the updated configurations include improvements to the science of several parametrisation schemes, however, and will form a baseline for further ongoing development.
Complete rupture of the Padul Fault represents one of the largest plausible earthquakes in the Sierra Nevada Range, one of the most seismically active regions of Spain. We performed a regional ...assessment of earthquake-triggered slope instabilities in the western part of the range to determine the most likely types of failures from such an earthquake in the region and suggest where such failures have a higher likelihood of occurring. These results are broadly useful for management of regional life-lines and future development. First, a slope-instability inventory of the Sierra Nevada was produced to identify the most common instability types. Subsequently, the Newmark’s sliding rigid-block methodology, implemented in a geographic information system, was used to obtain the distribution of Newmark displacements in the area considering a M w 6.6 earthquake on the Padul Fault. The Newmark displacements were then compared to the distribution of the inventoried slope instabilities to identify the areas where seismicity could reactivate old slope instabilities or generate new ones, and to identify the involved landslide typology. The most likely seismically induced slope instabilities in the Sierra Nevada are rock falls and rock slides. These types of instabilities could be triggered by Newmark displacements of 2 cm or less.
Abstract Evaluation of specific antibody (Ab) response to polysaccharide antigens is essential for diagnosis of primary immunodeficiencies. We assessed the specific Ab responses to the ...pneumococcal-polysaccharide (PPV) and to Salmonella typhi-polysaccharide (TyphimVi) vaccines in a prospective study (EMPATHY) in patients with common variable immunodeficiency (CVID-Group, n = 22), hypogammaglobulinemia (HYPOG-Group; n = 27) and healthy controls (HC-Group; n = 16). Specific Ab concentrations in response to PPV and to TyphimVi vaccines were measured by ELISA (The Binding Site, UK), defining 3-fold increase as normal response (Ratio:3x). The RatioTyphimVi:3x was significantly greater in HC than in CVID-Group (p < 0.0001), but not than HYPOG-Group (p = 0.138). However, the RatioPPV:3x showed no significant differences among the three groups. By ROC analysis, TyphimVi better differentiated HC from CVID (AUC:0.893, IC95%: 0.791-0.996, p < 0.0001) than PPV. Our results suggest that the use of specific Ab response to TyphimVi could represent a complementary assay for the diagnosis of anti-polysaccharide Ab production deficiency in patients with CVID.
GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, ...schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABA
receptor-associated protein (GABARAP) to stabilize cell surface GABA
receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.
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