4,275 research outputs found

    On the Calibration of a Size-Structured Population Model from Experimental Data

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    The aim of this work is twofold. First, we survey the techniques developed in (Perthame, Zubelli, 2007) and (Doumic, Perthame, Zubelli, 2008) to reconstruct the division (birth) rate from the cell volume distribution data in certain structured population models. Secondly, we implement such techniques on experimental cell volume distributions available in the literature so as to validate the theoretical and numerical results. As a proof of concept, we use the data reported in the classical work of Kubitschek [3] concerning Escherichia coli in vitro experiments measured by means of a Coulter transducer-multichannel analyzer system (Coulter Electronics, Inc., Hialeah, Fla, USA.) Despite the rather old measurement technology, the reconstructed division rates still display potentially useful biological features

    Imaging the Phase Transformation in Single Particles of the Lithium Titanate Anode for Lithium-Ion Batteries

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    Lithium uptake and release in lithium titanate (LTO) anode materials during a discharge and charge cycle is one of the fundamental processes of a lithium-ion battery (LIB), still not fully understood at the microscopic level. During the discharge cycle, LTO undergoes a phase transformation between Li4Ti5O12 and Li7Ti5O12 states within a cubic crystal lattice. To reveal the details of the microscopic mechanism, it is necessary to track the sequence of phase transformations at different discharge/charge states under operating conditions. Here, we use in situ Bragg coherent diffraction imaging (BCDI) and in situ X-ray diffraction (XRD) experiments to examine the lithium insertion-induced materials phase transformation within a single LTO particle and a bulk battery analogue, respectively. BCDI analysis from (111) Bragg peak shows the two-phase transformation manifesting as a distinct image phase modulation within a single LTO nanoparticle occurring in the middle of the discharge region then subsiding toward the end of the discharge cycle. We observe the biggest phase variation at the two-phase stage, indicating the formation of phase domains of 200 nm in size during the discharge process. We also observe a lattice contraction of >0.2% in a single LTO nanoparticle at the (400) Bragg peak measurement, larger than that in the corresponding bulk material. Our observation of this phase transformation at a single-particle level has implications for the understanding of the microscopic/mesoscale picture of the phase transformation in anode and cathode LIBs materials

    Nonlinear response of the vacuum Rabi resonance

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    On the level of single atoms and photons, the coupling between atoms and the electromagnetic field is typically very weak. By employing a cavity to confine the field, the strength of this interaction can be increased many orders of magnitude to a point where it dominates over any dissipative process. This strong-coupling regime of cavity quantum electrodynamics has been reached for real atoms in optical cavities, and for artificial atoms in circuit QED and quantum-dot systems. A signature of strong coupling is the splitting of the cavity transmission peak into a pair of resolvable peaks when a single resonant atom is placed inside the cavity - an effect known as vacuum Rabi splitting. The circuit QED architecture is ideally suited for going beyond this linear response effect. Here, we show that increasing the drive power results in two unique nonlinear features in the transmitted heterodyne signal: the supersplitting of each vacuum Rabi peak into a doublet, and the appearance of additional peaks with the characteristic sqrt(n) spacing of the Jaynes-Cummings ladder. These constitute direct evidence for the coupling between the quantized microwave field and the anharmonic spectrum of a superconducting qubit acting as an artificial atom.Comment: 6 pages, 4 figures. Supplementary Material and Supplementary Movies are available at http://www.eng.yale.edu/rslab/publications.htm

    Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice.

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    Heart failure is accompanied by severely impaired beta-adrenergic receptor (betaAR) function, which includes loss of betaAR density and functional uncoupling of remaining receptors. An important mechanism for the rapid desensitization of betaAR function is agonist-stimulated receptor phosphorylation by the betaAR kinase (betaARK1), an enzyme known to be elevated in failing human heart tissue. To investigate whether alterations in betaAR function contribute to the development of myocardial failure, transgenic mice with cardiac-restricted overexpression of either a peptide inhibitor of betaARK1 or the beta2AR were mated into a genetic model of murine heart failure (MLP-/-). In vivo cardiac function was assessed by echocardiography and cardiac catheterization. Both MLP-/- and MLP-/-/beta2AR mice had enlarged left ventricular (LV) chambers with significantly reduced fractional shortening and mean velocity of circumferential fiber shortening. In contrast, MLP-/-/betaARKct mice had normal LV chamber size and function. Basal LV contractility in the MLP-/-/betaARKct mice, as measured by LV dP/dtmax, was increased significantly compared with the MLP-/- mice but less than controls. Importantly, heightened betaAR desensitization in the MLP-/- mice, measured in vivo (responsiveness to isoproterenol) and in vitro (isoproterenol-stimulated membrane adenylyl cyclase activity), was completely reversed with overexpression of the betaARK1 inhibitor. We report here the striking finding that overexpression of this inhibitor prevents the development of cardiomyopathy in this murine model of heart failure. These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy

    Noiseless nonreciprocity in a parametric active device

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    Nonreciprocal devices such as circulators and isolators belong to an important class of microwave components employed in applications like the measurement of mesoscopic circuits at cryogenic temperatures. The measurement protocols usually involve an amplification chain which relies on circulators to separate input and output channels and to suppress backaction from different stages on the sample under test. In these devices the usual reciprocal symmetry of circuits is broken by the phenomenon of Faraday rotation based on magnetic materials and fields. However, magnets are averse to on-chip integration, and magnetic fields are deleterious to delicate superconducting devices. Here we present a new proposal combining two stages of parametric modulation emulating the action of a circulator. It is devoid of magnetic components and suitable for on-chip integration. As the design is free of any dissipative elements and based on reversible operation, the device operates noiselessly, giving it an important advantage over other nonreciprocal active devices for quantum information processing applications.Comment: 17 pages, 4 figures + 12 pages Supplementary Informatio

    Is thirty-seven years sufficient for full return of the ant biota following restoration?

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    Introduction: An assessment of whether rehabilitated mine sites have resulted in natural or novel ecosystems requires monitoring over considerable periods of time or the use of space-for-time substitution (chronosequence) approaches. Methods: To provide an assessment of ecosystem recovery in areas mined for bauxite in 1975, the ant fauna of one area planted with Eucalyptus resinifera, one seeded with mixed native species, one topsoiled but unrestored, and a forest reference was subjected to a ‘long-term’ study by sampling monthly and latterly annually between 1976 and 1989 using pitfall traps. These plots were resampled in 2012. A companion ‘short-term’ chronosequence study was performed in 1979 in 28 bauxite mines of various ages and restored by a range of different methods, plus three forest references. In order to examine the assertion that the observed differences between restored areas and forest references will lessen with time, sampling using comparable methods was repeated in 2012 in seven of the original plots, representing progressive advances in rehabilitation technology: planted pines; planted eastern states eucalypts; planted native eucalypts; planted eucalypts over seeded understorey; and planted eucalypts on fresh, double-stripped topsoil, plus two forest reference sites. Results: Ant and other invertebrate richness in the long-term study was initially superior in the seeded plot, with little difference between the planted and unplanted plots. It was concluded that although composition of the ant fauna had converged on that of the forest over the 14-year period, differences still persisted.The 2012 resampling revealed that ant species richness and composition had deteriorated in the seeded plot, while values in the unplanted plot, which now supported naturally colonised trees and an understorey, had increased. Differences between all rehabilitated plots and forest still persisted. As with the long-term study, the rate of fauna return and the type of ants present in the short-term study plots differed with the method of rehabilitation used, and, in 1979, no plots had converged on the forest in terms of the ant assemblage. By 2012 ant richness increased, and more so with each advance in rehabilitation technology, except for seeding, in which the understorey had collapsed. Double-stripping of topsoil resulted in the greatest improvements in ant species richness, although none of the areas had converged on the forest reference areas in terms of assemblage composition or ant functional group profiles. Furthermore, assemblage composition in the forest had changed over time, possibly due to reductions in rainfall, which further complicates rehabilitation objectives. Conclusions: It is concluded that although rehabilitation can achieve its objective of restoring diversity, the original assemblage has still not been achieved after 37 years, suggesting that a degree of novelty has been introduced into these older-style rehabilitated areas. The company’s current rehabilitation practices reflect multiple advances in their approach, lending optimism that current restoration may achieve something close to the original ecosystem, an outcome that can only be verified by extended studies like the one described here

    Climbing the Jaynes-Cummings Ladder and Observing its Sqrt(n) Nonlinearity in a Cavity QED System

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    The already very active field of cavity quantum electrodynamics (QED), traditionally studied in atomic systems, has recently gained additional momentum by the advent of experiments with semiconducting and superconducting systems. In these solid state implementations, novel quantum optics experiments are enabled by the possibility to engineer many of the characteristic parameters at will. In cavity QED, the observation of the vacuum Rabi mode splitting is a hallmark experiment aimed at probing the nature of matter-light interaction on the level of a single quantum. However, this effect can, at least in principle, be explained classically as the normal mode splitting of two coupled linear oscillators. It has been suggested that an observation of the scaling of the resonant atom-photon coupling strength in the Jaynes-Cummings energy ladder with the square root of photon number n is sufficient to prove that the system is quantum mechanical in nature. Here we report a direct spectroscopic observation of this characteristic quantum nonlinearity. Measuring the photonic degree of freedom of the coupled system, our measurements provide unambiguous, long sought for spectroscopic evidence for the quantum nature of the resonant atom-field interaction in cavity QED. We explore atom-photon superposition states involving up to two photons, using a spectroscopic pump and probe technique. The experiments have been performed in a circuit QED setup, in which ultra strong coupling is realized by the large dipole coupling strength and the long coherence time of a superconducting qubit embedded in a high quality on-chip microwave cavity.Comment: ArXiv version of manuscript published in Nature in July 2008, 5 pages, 5 figures, hi-res version at http://www.finkjohannes.com/SqrtNArxivPreprint.pd

    Restoration of beta-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer.

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    Cardiovascular gene therapy is a novel approach to the treatment of diseases such as congestive heart failure (CHF). Gene transfer to the heart would allow for the replacement of defective or missing cellular proteins that may improve cardiac performance. Our laboratory has been focusing on the feasibility of restoring beta-adrenergic signaling deficiencies that are a characteristic of chronic CHF. We have now studied isolated ventricular myocytes from rabbits that have been chronically paced to produce hemodynamic failure. We document molecular beta-adrenergic signaling defects including down-regulation of myocardial beta-adrenergic receptors (beta-ARs), functional beta-AR uncoupling, and an up-regulation of the beta-AR kinase (betaARK1). Adenoviral-mediated gene transfer of the human beta2-AR or an inhibitor of betaARK1 to these failing myocytes led to the restoration of beta-AR signaling. These results demonstrate that defects present in this critical myocardial signaling pathway can be corrected in vitro using genetic modification and raise the possibility of novel inotropic therapies for CHF including the inhibition of betaARK1 activity in the heart

    Flow cytometry method for absolute counting and single-cell phenotyping of mycobacteria

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    Detection and accurate quantitation of viable Mycobacterium tuberculosis is fundamental to understanding mycobacterial pathogenicity, tuberculosis (TB) disease progression and outcomes; TB transmission; drug action, efficacy and drug resistance. Despite this importance, methods for determining numbers of viable bacilli are limited in accuracy and precision owing to inherent characteristics of mycobacterial cell biology – including the tendency to clump, and “differential” culturability – and technical challenges consequent on handling an infectious pathogen under biosafe conditions. We developed an absolute counting method for mycobacteria in liquid cultures using a bench-top flow cytometer, and the low-cost fluorescent dyes Calcein-AM (CA) and SYBR-gold (SG). During exponential growth CA+ cell counts are highly correlated with CFU counts and can be used as a real-time alternative to simplify the accurate standardisation of inocula for experiments. In contrast to CFU counting, this method can detect and enumerate cell aggregates in samples, which we show are a potential source of variance and bias when using established methods. We show that CFUs comprise a sub-population of intact, metabolically active mycobacterial cells in liquid cultures, with CFU proportion varying by growth conditions. A pharmacodynamic application of the flow cytometry method, exploring kinetics of fluorescent probe defined subpopulations compared to CFU is demonstrated. Flow cytometry derived Mycobacterium bovis bacillus Calmette-Guérin (BCG) time-kill curves differ for rifampicin and kanamycin versus isoniazid and ethambutol, as do the relative dynamics of discrete morphologically-distinct subpopulations of bacilli revealed by this high-throughput single-cell technique
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