Dual contribution to amplification in the mammalian inner ear

The inner ear achieves a wide dynamic range of responsiveness by mechanically amplifying weak sounds. The enormous mechanical gain reported for the mammalian cochlea, which exceeds a factor of 4,000, poses a challenge for theory. Here we show how such a large gain can result from an interaction between amplification by low-gain hair bundles and a pressure wave: hair bundles can amplify both their displacement per locally applied pressure and the pressure wave itself. A recently proposed ratchet mechanism, in which hair-bundle forces do not feed back on the pressure wave, delineates the two effects. Our analytical calculations with a WKB approximation agree with numerical solutions.Comment: 4 pages, 4 figure

IsotopicLabelling: an R package for the analysis of MS isotopic patterns of labelled analytes.

Abstract Motivation Labelling experiments in biology usually make use of isotopically enriched substrates, with the two most commonly employed isotopes for metabolism being 2H and 13C. At the end of the experiment some metabolites will have incorporated the labelling isotope, to a degree that depends on the metabolic turnover. In order to propose a meaningful biological interpretation, it is necessary to estimate the amount of labelling, and one possible route is to exploit the fact that MS isotopic patterns reflect the isotopic distributions. Results We developed the IsotopicLabelling R package, a tool able to extract and analyze isotopic patterns from liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-MS (GC-MS) data relative to labelling experiments. This package estimates the isotopic abundance of the employed stable isotope (either 2H or 13C) within a specified list of analytes. Availability and Implementation The IsotopicLabelling R package is freely available at https://github.com/RuggeroFerrazza/IsotopicLabelling. Supplementary information Supplementary data are available at Bioinformatics online

Reentrant behavior of the phase stiffness in Josephson junction arrays

The phase diagram of a 2D Josephson junction array with large substrate resistance, described by a quantum XY model, is studied by means of Fourier path-integral Monte Carlo. A genuine Berezinskii-Kosterlitz-Thouless transition is found up to a threshold value g* of the quantum coupling, beyond which no phase coherence is established. Slightly below g* the phase stiffness shows a reentrant behavior with temperature, in connection with a low-temperature disappearance of the superconducting phase, driven by strong nonlinear quantum fluctuations.Comment: 4 pages, 7 figures, to appear in Phys.Rev.Let

Essential nonlinearities in hearing

Our hearing organ, the cochlea, evidently poises itself at a Hopf bifurcation to maximize tuning and amplification. We show that in this condition several effects are expected to be generic: compression of the dynamic range, infinitely shrap tuning at zero input, and generation of combination tones. These effects are "essentially" nonlinear in that they become more marked the smaller the forcing: there is no audible sound soft enough not to evoke them. All the well-documented nonlinear aspects of hearing therefore appear to be consequences of the same underlying mechanism.Comment: 4 pages, 3 figure

BAFF Index and CXCL13 levels in the cerebrospinal fluid associate respectively with intrathecal IgG synthesis and cortical atrophy in multiple sclerosis at clinical onset

Abstract Background B lymphocytes are thought to play a relevant role in multiple sclerosis (MS) pathology. The in vivo analysis of intrathecally produced B cell-related cytokines may help to clarify the mechanisms of B cell recruitment and immunoglobulin production within the central nervous system (CNS) in MS. Methods Paired cerebrospinal fluid (CSF) and serum specimens from 40 clinically isolated syndrome suggestive of MS or early-onset relapsing-remitting MS patients (CIS/eRRMS) and 17 healthy controls (HC) were analyzed for the intrathecal synthesis of IgG (quantitative formulae and IgG oligoclonal bands, IgGOB), CXCL13, BAFF, and IL-21. 3D-FLAIR, 3D-DIR, and 3D-T1 MRI sequences were applied to evaluate white matter (WM) and gray matter (GM) lesions and global cortical thickness (gCTh). Results Compared to HC, CIS/eRRMS having IgGOB (IgGOB+, 26 patients) had higher intrathecal IgG indexes ( p \u2009<\u20090.01), lower values of BAFF Index (11.9\u2009\ub1\u20096.1 vs 17.5\u2009\ub1\u20095.2, p \u2009<\u20090.01), and higher CSF CXCL13 levels (27.7\u2009\ub1\u200933.5 vs 0.9\u2009\ub1\u20091.5, p \u2009<\u20090.005). In these patients, BAFF Index but not CSF CXCL13 levels inversely correlated with the intrathecal IgG synthesis ( r \u2009>\u20090.5 and p \u2009<\u20090.05 for all correlations). CSF leukocyte counts were significantly higher in IgGOB+ compared to IgGOB\u2212 ( p \u2009<\u20090.05) and HC ( p \u2009<\u20090.01), and correlated to CSF CXCL13 concentrations ( r 0.77, p \u2009<\u20090.001). The gCTh was significantly lower in patients with higher CSF CXCL13 levels (2.41\u2009\ub1\u20090.1 vs 2.49\u2009\ub1\u20090.1\ua0mm, p \u2009<\u20090.05), while no difference in MRI parameters of WM and GM pathology was observed between IgGOB+ and IgGOB\u2212. Conclusions The intrathecal IgG synthesis inversely correlated with BAFF Index and showed no correlation with CSF CXCL13. These findings seem to indicate that intrathecally synthesized IgG are produced by long-term PCs that have entered the CNS from the peripheral blood, rather than produced by PCs developed in the meningeal follicle-like structures (FLS). In this study, CXCL13 identifies a subgroup of MS patients characterized by ..

Revealing nascent proteomics in signaling pathways and cell differentiation.

Regulation of gene expression at the level of protein synthesis is a crucial element in driving how the genetic landscape is expressed. However, we are still limited in technologies that can quantitatively capture the immediate proteomic changes that allow cells to respond to specific stimuli. Here, we present a method to capture and identify nascent proteomes in situ across different cell types without disturbing normal growth conditions, using O-propargyl-puromycin (OPP). Cell-permeable OPP rapidly labels nascent elongating polypeptides, which are subsequently conjugated to biotin-azide, using click chemistry, and captured with streptavidin beads, followed by digestion and analysis, using liquid chromatography-tandem mass spectrometry. Our technique of OPP-mediated identification (OPP-ID) allows detection of widespread proteomic changes within a short 2-hour pulse of OPP. We illustrate our technique by recapitulating alterations of proteomic networks induced by a potent mammalian target of rapamycin inhibitor, MLN128. In addition, by employing OPP-ID, we identify more than 2,100 proteins and uncover distinct protein networks underlying early erythroid progenitor and differentiation states not amenable to alternative approaches such as amino acid analog labeling. We present OPP-ID as a method to quantitatively identify nascent proteomes across an array of biological contexts while preserving the subtleties directing signaling in the native cellular environment

The Aladin2 experiment: status and perspectives

Aladin2 is an experiment devoted to the first measurement of variations of Casimir energy in a rigid cavity. The main scientific motivation relies on the possibility of the first demonstration of a phase transition influenced by vacuum fluctuations. The guiding principle of the measurement, based on the behaviour of the critical field for an in-cavity superconducting film, will be only briefly recalled. In this paper, after an introduction to the long term motivations, the experimental apparatus and the results of the first measurement of sensitivity will be presented in detail, particularly in comparison with the expected signal. Last, the most important steps towards the final measurement will be discussed.Comment: Talk given by Calloni at QFEXT05 Conference in Barcelona: Quantum Field Theory Under the Influence of External Condition

Critical currents of MgB2 thin films depositedin situby sputtering

We have measured the temperature and magnetic field dependencies of the critical current density J(c)(H,T) in MgB2 thin films, in situ deposited by sputtering. Three-dimensional point like normal core pinning was evidenced by measurements of the magnetic dependence of the pinning forces independently from the superconducting and structural quality of the investigated films. The analysis of the experimental data in terms of the collective pinning model has pointed out the presence of a crossover magnetic field from a single vortex to a small vortex bundle pinning regime. A DeltaT(c) pinning mechanism, i.e., a pinning associated with spatial fluctuations of the transition temperature, has been evidenced by the temperature dependence of this crossover field, in agreement with previous observations performed on MgB2 bulk materials

Circular dichroism mode splitting and bounds to its enhancement with cavity-plasmon-polaritons

Geometrical chirality is a widespread phenomenon that has fundamental implications for discriminating enantiomers of biomolecules. In order to enhance the chiral response of the medium, it has been suggested to couple chiral molecules to resonant optical cavities in order to enhance the circular dichroism (CD) signal at the resonant frequency of the cavity. Here, we studied a distinctly different regime of chiral light-matter interaction, wherein the CD signal of a chiral medium splits into polaritonic modes by reaching the strong coupling regime with an optical microcavity. Specifically, we show that by strongly coupling chiral plasmonic nanoparticles to a non-chiral Fabry-P\ue9rot microcavity one can imprint the mode splitting on the CD spectrum of the coupled system and thereby effectively shift the initial chiral resonance to a different energy. We first examined the effect with the use of analytical transfer-matrix method as well as numerical finite-difference time-domain (FDTD) simulations. Furthermore, we confirmed the validity of theoretical predictions in a proof-of-principle experiment involving chiral plasmonic nanoparticles coupled to a Fabry-P\ue9rot microcavity