The Cochlear Tuning Curve

The tuning curve of the cochlea measures how large an input is required to elicit a given output level as a function of the frequency. It is a fundamental object of auditory theory, for it summarizes how to infer what a sound was on the basis of the cochlear output. A simple model is presented showing that only two elements are sufficient for establishing the cochlear tuning curve: a broadly tuned traveling wave, moving unidirectionally from high to low frequencies, and a set of mechanosensors poised at the threshold of an oscillatory (Hopf) instability. These two components suffice to generate the various frequency-response regimes which are needed for a cochlear tuning curve with a high slope

Modified Profile Likelihood for Fixed-Effects Panel Data Models

We show how modified profile likelihood methods, developed in the statistical literature, may be effectively applied to estimate the structural parameters of econometric models for panel data, with a remarkable reduction of bias with respect to ordinary likelihood methods. Initially, the implementation of these methods is illustrated for general models for panel data including individual-specific fixed effects and then, in more detail, for the truncated linear regression model and dynamic regression models for binary data formulated along with different specifications. Simulation studies show the good behavior of the inference based on the modified profile likelihood, even when compared to an ideal, although infeasible, procedure (in which the fixed effects are known) and also to alternative estimators existing in the econometric literature. The proposed estimation methods are implemented in an R package that we make available to the reader

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 ..

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

Dexamethasone nano-embedded sodium hyaluronate microparticles for treatment of COVID-19 acute respiratory distress syndrome

Dexamethasone (DX) is a synthetic glucocorticoid employed in a wide range of diseases asimmunosuppressant. Recent studies reported that DX could be administered orally or intravenouslyfor the treatment of acute respiratory distress syndrome in patients with COVID-19 phase-3infection caused by an overreaction of their immune system, reducing 28-day mortality in patientsmechanically ventilated or receiving oxygen [1]. Nevertheless, the long-term systemicadministration of dexamethasone led to severe side effects, highlighting the urgent need of newstrategies for its delivery [2][3]. The aim of this work was to develop a new formulation for inhalationbased on DX-nanoparticles. High molecular weight sodium hyaluronate (HA, 750 kDa) was employedto coat DX nanoparticles to exploit HA targeting to CD44 receptors on pulmonary macrophages andits anti-inflammatory effects[4]. DX-nanoparticles were obtained by anti-solvent precipitation usingwater as anti-solvent dripped into an alcoholic solution of drug. The suspension was spray-dried toobtain a dry powder. Size distribution and morphology of microparticles were investigated by laserdiffraction and scanning electron microscopy. Nanoparticle characteristics and composition wereassessed after powder redispersion in physiological medium by dynamic light scattering and X-rayscattering techniques. Results revealed the release of quite polydisperse nanoparticles (PdI = 0.3-0.4) with size around 290 nm in water and 180 nm in phosphate buffer. SAXS results showednanoparticles with a DX-rich crystalline core stabilized in solution by the presence of a shell of HAchains partially embedded in the core. After particle redispersion in water the aerodynamicbehavior of the obtained suspension was assessed in vitro using a device for aerosol therapyobtaining a Fine Particle Fraction of 87.5 +- 0.7% while the Emitted Fraction was 26.4 +-2.9%. Thelatter figure represents a limit that may be overcome by nebulizing directly the nanosuspension inthe pipe of a ventilator.Fil: Laura Bertocchi. Università di Parma; Italia. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;Fil: Cámara, Candelaria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Laura F. Cantú. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Elena Del Favero. Universita Degli Studi Di Milano. Dipartimento Di Beitecnologe Mediche E Medicina Traslazionale.; ItaliaFil: Ruggero Bettini. Departamento de Alimentos y Drogas ; Universita Degli Studi Di Parma;20th Advanced Course in Pharmaceutical TechnologyItaliaAssociazione Docenti e Ricercatori Italiani di Tecnologie e Legislazione Farmaceutich

Проблемы формирования государственной экологической политики в условиях ограниченности ресурсов

Проблема ограниченности ресурсов является основой развития экономики. Однако также ограниченность оказывает влияние и на экологическую политику в стране. В статье рассмотрены ключевые механизмы формирования государственной экологической политики, экологического менеджмента; предложены пути повышения эффективности экологической политики.The problem of limited resources is the basis for economic development. However, the limited nature also influences the environmental policy in the country. The article considers the key mechanisms for the formation of state environmental policy, environmental management; ways to improve the effectiveness of environmental policy