High-order harmonic generation from polyatomic molecules including nuclear motion and a nuclear modes analysis

We present a generic approach for treating the effect of nuclear motion in the high-order harmonic generation from polyatomic molecules. Our procedure relies on a separation of nuclear and electron dynamics where we account for the electronic part using the Lewenstein model and nuclear motion enters as a nuclear correlation function. We express the nuclear correlation function in terms of Franck-Condon factors which allows us to decompose nuclear motion into modes and identify the modes that are dominant in the high-order harmonic generation process. We show results for the isotopes CH$_4$ and CD$_4$ and thereby provide direct theoretical support for a recent experiment [Baker {\it et al.}, Science {\bf 312}, 424 (2006)] that uses high-order harmonic generation to probe the ultra-fast structural nuclear rearrangement of ionized methane.Comment: 6 pages, 6 figure

The Multi-Fungicide Resistance Status of Aspergillus fumigatus Populations in Arable Soils and the Wider European Environment

The evolution and spread of pan-azole resistance alleles in clinical and environmental isolates of Aspergillus fumigatus is a global human health concern. The identification of hotspots for azole resistance development in the wider environment can inform optimal measures to counteract further spread by minimizing exposure to azole fungicides and reducing inoculum build-up and pathogen dispersal. We investigated the fungicide sensitivity status of soil populations sampled from arable crops and the wider environment and compared these with urban airborne populations. Low levels of azole resistance were observed for isolates carrying the CYP51A variant F46Y/M172V/E427K, all belonging to a cluster of related cell surface protein (CSP) types which included t07, t08, t13, t15, t19, and t02B, a new allele. High levels of resistance were found in soil isolates carrying CYP51A variants TR34/L98H and TR46/Y121F/T289A, all belonging to CSP types t01, t02, t04B, or t11. TR46/Y121F/M172V/T289A/G448S (CSP t01) and TR46/Y121F/T289A/S363P/I364V/G448S (CSP t01), a new haplotype associated with high levels of resistance, were isolated from Dutch urban air samples, indicating azole resistance evolution is ongoing. Based on low numbers of pan-azole resistant isolates and lack of new genotypes in soils of fungicide-treated commercial and experimental wheat crops, we consider arable crop production as a coldspot for azole resistance development, in contrast to previously reported flower bulb waste heaps. This study also shows that, in addition to azole resistance, several lineages of A. fumigatus carrying TR-based CYP51A variants have also developed acquired resistance to methyl benzimidazole carbamate, quinone outside inhibitor and succinate dehydrogenase (Sdh) inhibitor fungicides through target-site alterations in the corresponding fungicide target proteins; beta-tubulin (F200Y), cytochrome b (G143A), and Sdh subunit B (H270Y and H270R), respectively. Molecular typing showed that several multi-fungicide resistant strains found in agricultural soils in this study were clonal as identical isolates have been found earlier in the environment and/or in patients. Further research on the spread of different fungicide-resistant alleles from the wider environment to patients and vice versa can inform optimal practices to tackle the further spread of antifungal resistance in A. fumigatus populations and to safeguard the efficacy of azoles for future treatment of invasive aspergillosis

Homogenisation of carnivorous mammal ensembles caused by global range reductions of large-bodied hypercarnivores during the late Quaternary

Carnivorous mammals play crucial roles in ecosystems by influencing prey densities and behaviour, and recycling carrion. Yet, the influence of carnivores on global ecosystems has been affected by extinctions and range contractions throughout the Late Pleistocene and Holocene (~130 000 years ago to the current). Large-bodied mammals were particularly affected, but how dietary strategies influenced species’ susceptibility to geographic range reductions remains unknown. We investigated 1) the importance of dietary strategies in explaining range reductions of carnivorous mammals (≥5% vertebrate meat consumption), and 2) differences in functional diversity of continental carnivore ensembles by comparing current, known ranges to current, expected ranges under a present-natural counterfactual scenario. The present-natural counterfactual estimates current mammal ranges had modern humans not expanded out of Africa during the Late Pleistocene and were not a main driver of extinctions and range contractions, alongside changing climates. Ranges of large-bodied hypercarnivorous mammals are currently smaller than expected, compared to smaller-bodied carnivorous mammals that consume less vertebrate meat. This resulted in consistent differences in continental functional diversity, whereby current ensembles of carnivorous mammals have undergone homogenisation through structural shifts towards smaller-bodied insectivorous and herbivorous species. The magnitude of ensemble structural shift varied among continents, with Australia experiencing the greatest difference. Weighting functional diversity by species’ geographic range sizes caused a three-fold greater shift in ensemble centroids than when using presence-absence alone. Conservation efforts should acknowledge current reductions in the potential geographic ranges of large-bodied hypercarnivores and aim to restore functional roles in carnivore ensembles, where possible, across continents

Study of Small-Scale Anisotropy of Ultrahigh Energy Cosmic Rays Observed in Stereo by HiRes

The High Resolution Fly's Eye (HiRes) experiment is an air fluorescence detector which, operating in stereo mode, has a typical angular resolution of 0.6 degrees and is sensitive to cosmic rays with energies above 10^18 eV. HiRes is thus an excellent instrument for the study of the arrival directions of ultrahigh energy cosmic rays. We present the results of a search for anisotropies in the distribution of arrival directions on small scales (<5 degrees) and at the highest energies (>10^19 eV). The search is based on data recorded between 1999 December and 2004 January, with a total of 271 events above 10^19 eV. No small-scale anisotropy is found, and the strongest clustering found in the HiRes stereo data is consistent at the 52% level with the null hypothesis of isotropically distributed arrival directions.Comment: 4 pages, 3 figures. Matches accepted ApJL versio

The cytoplasm of living cells: A functional mixture of thousands of components

Inside every living cell is the cytoplasm: a fluid mixture of thousands of different macromolecules, predominantly proteins. This mixture is where most of the biochemistry occurs that enables living cells to function, and it is perhaps the most complex liquid on earth. Here we take an inventory of what is actually in this mixture. Recent genome-sequencing work has given us for the first time at least some information on all of these thousands of components. Having done so we consider two physical phenomena in the cytoplasm: diffusion and possible phase separation. Diffusion is slower in the highly crowded cytoplasm than in dilute solution. Reasonable estimates of this slowdown can be obtained and their consequences explored, for example, monomer-dimer equilibria are established approximately twenty times slower than in a dilute solution. Phase separation in all except exceptional cells appears not to be a problem, despite the high density and so strong protein-protein interactions present. We suggest that this may be partially a byproduct of the evolution of other properties, and partially a result of the huge number of components present.Comment: 11 pages, 1 figure, 1 tabl

Epidemiological studies of pan-azole resistant Aspergillus fumigatus populations sampled during tulip cultivation show clonal expansion with acquisition of multi-fungicide resistance as potential driver

Pan-azole resistant isolates are found in clinical and environmental Aspergillus fumigatus (Af) populations. Azole resistance can evolve in both settings, with Af directly targeted by antifungals in patients and, in the environment, Af unintendedly exposed to fungicides used for material preservation and plant disease control. Resistance to non-azole fungi-cides, including methyl benzimidazole carbamates (MBCs), quinone outside inhibitors (QoIs) and succinate dehydrogenase inhibitors (SDHIs), have recently been reported. These fungicide groups are not used in medicine but can play an important role in further spread of pan-azole resistant genotypes. We investigated the multi-fungicide resistance status and genetic diversity of Af populations sampled from tulip field soils, tulip peel waste and flower compost heaps using fungicide sensitivity testing and a range of genotyping tools, including STRAf typing and sequencing of fungicide resistant alleles. Two major clones were present in the tulip bulb population. Comparisons with clinical isolates and literature data revealed that several common clonal lineages of TR34/L98H and TR46/Y121F/T289A strains that have expanded successfully in the environment have also acquired resistance to MBC, QoI and/or SDHI fungicides. Strains carrying multiple fungicide resistant alleles have an advantage in environments where residues of multiple fungicides belonging to different modes of action are presen

Could humans recognize odor by phonon assisted tunneling?

Our sense of smell relies on sensitive, selective atomic-scale processes that are initiated when a scent molecule meets specific receptors in the nose. However, the physical mechanisms of detection are not clear. While odorant shape and size are important, experiment indicates these are insufficient. One novel proposal suggests inelastic electron tunneling from a donor to an acceptor mediated by the odorant actuates a receptor, and provides critical discrimination. We test the physical viability of this mechanism using a simple but general model. Using values of key parameters in line with those for other biomolecular systems, we find the proposed mechanism is consistent both with the underlying physics and with observed features of smell, provided the receptor has certain general properties. This mechanism suggests a distinct paradigm for selective molecular interactions at receptors (the swipe card model): recognition and actuation involve size and shape, but also exploit other processes.Comment: 10 pages, 1 figur

Maintenance of GLUT4 expression in smooth muscle prevents hypertension‐induced changes in vascular reactivity

Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth‐muscle‐specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild‐type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F2α was significantly increased in endothelium‐intact aortic rings from hypertensive wild‐type mice but not in aortae of SMG4 mice. Inhibition of Rho‐kinase equally reduced serotonin‐stimulated contractility in aortae of hypertensive wild‐type and SMG4‐mice. In addition, acetylcholine‐stimulated relaxation was significantly decreased in aortic rings of hypertensive wild‐type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase‐2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase‐2 had no effect on relaxation in rings of hypertensive wild‐type mice. Cyclooxygenase‐2 protein expression was decreased in hypertensive wild‐type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium‐dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses.e12299In the smooth muscle of aortae of hypertensive mice, expression of GLUT4 is decreased. Maintenance of aortic smooth muscle GLUT4 expression prevents hypertension‐mediated changes in vasomotor response. These effects include decreasing/preventing endothelial dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110755/1/phy212299.pd