11,125 research outputs found

    NOD2/RICK-dependent β-defensin 2 regulation is protective for nontypeable Haemophilus influenzae-induced middle ear infection.

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    Middle ear infection, otitis media (OM), is clinically important due to the high incidence in children and its impact on the development of language and motor coordination. Previously, we have demonstrated that the human middle ear epithelial cells up-regulate β-defensin 2, a model innate immune molecule, in response to nontypeable Haemophilus influenzae (NTHi), the most common OM pathogen, via TLR2 signaling. NTHi does internalize into the epithelial cells, but its intracellular trafficking and host responses to the internalized NTHi are poorly understood. Here we aimed to determine a role of cytoplasmic pathogen recognition receptors in NTHi-induced β-defensin 2 regulation and NTHi clearance from the middle ear. Notably, we observed that the internalized NTHi is able to exist freely in the cytoplasm of the human epithelial cells after rupturing the surrounding membrane. The human middle ear epithelial cells inhibited NTHi-induced β-defensin 2 production by NOD2 silencing but augmented it by NOD2 over-expression. NTHi-induced β-defensin 2 up-regulation was attenuated by cytochalasin D, an inhibitor of actin polymerization and was enhanced by α-hemolysin, a pore-forming toxin. NOD2 silencing was found to block α-hemolysin-mediated enhancement of NTHi-induced β-defensin 2 up-regulation. NOD2 deficiency appeared to reduce inflammatory reactions in response to intratympanic inoculation of NTHi and inhibit NTHi clearance from the middle ear. Taken together, our findings suggest that a cytoplasmic release of internalized NTHi is involved in the pathogenesis of NTHi infections, and NOD2-mediated β-defensin 2 regulation contributes to the protection against NTHi-induced otitis media

    On product-one sequences over dihedral groups

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    Let GG be a finite group. A sequence over GG means a finite sequence of terms from GG, where repetition is allowed and the order is disregarded. A product-one sequence is a sequence whose elements can be ordered such that their product equals the identity element of the group. The set of all product-one sequences over GG (with concatenation of sequences as the operation) is a finitely generated C-monoid. Product-one sequences over dihedral groups have a variety of extremal properties. This article provides a detailed investigation, with methods from arithmetic combinatorics, of the arithmetic of the monoid of product-one sequences over dihedral groups.Comment: to appear in Journal of Algebra and its Application

    The Shearing HI Spiral Pattern of NGC 1365

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    The Tremaine-Weinberg equations are solved for a pattern speed that is allowed to vary with radius. The solution method transforms an integral equation for the pattern speed to a least squares problem with well established procedures for statistical analysis. The method applied to the HI spiral pattern of the barred, grand-design galaxy NGC 1365 produced convincing evidence for a radial dependence in the pattern speed. The pattern speed behaves approximately as 1/r, and is very similar to the material speed. There are no clear indications of corotation or Lindblad resonances. Tests show that the results are not selection biased, and that the method is not measuring the material speed. Other methods of solving the Tremaine-Weinberg equations for shearing patterns were found to produce results in agreement with those obtained using the current method. Previous estimates that relied on the assumptions of the density-wave interpretation of spiral structure are inconsistent with the results obtained using the current method. The results are consistent with spiral structure theories that allow for shearing patterns, and contradict fundamental assumptions in the density-wave interpretation that are often used for finding spiral arm pattern speeds. The spiral pattern is winding on a characteristic timescale of ~ 500 Myrs.Comment: Accepted for publication in The Astrophysical Journa

    Channel Estimation via Successive Denoising in MIMO OFDM Systems: A Reinforcement Learning Approach

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    In general, reliable communication via multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) requires accurate channel estimation at the receiver. The existing literature largely focuses on denoising methods for channel estimation that depend on either (i)~channel analysis in the time-domain with prior channel knowledge or (ii)~supervised learning techniques which require large pre-labeled datasets for training. To address these limitations, we present a frequency-domain denoising method based on a reinforcement learning framework that does not need a priori channel knowledge and pre-labeled data. Our methodology includes a new successive channel denoising process based on channel curvature computation, for which we obtain a channel curvature magnitude threshold to identify unreliable channel estimates. Based on this process, we formulate the denoising mechanism as a Markov decision process, where we define the actions through a geometry-based channel estimation update, and the reward function based on a policy that reduces mean squared error (MSE). We then resort to Q-learning to update the channel estimates. Numerical results verify that our denoising algorithm can successfully mitigate noise in channel estimates. In particular, our algorithm provides a significant improvement over the practical least squares (LS) estimation method and provides performance that approaches that of the ideal linear minimum mean square error (LMMSE) estimation with perfect knowledge of channel statistics.Comment: This paper is accepted for publication in the proceedings of 2021 IEEE International Conference on Communications (ICC

    Direct and Simultaneous Observation of Ultrafast Electron and Hole Dynamics in Germanium

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    Understanding excited carrier dynamics in semiconductors is crucial for the development of photovoltaics and efficient photonic devices. However, overlapping spectral features in optical/NIR pump-probe spectroscopy often render assignments of separate electron and hole carrier dynamics ambiguous. Here, ultrafast electron and hole dynamics in germanium nanocrystalline thin films are directly and simultaneously observed by attosecond transient absorption spectroscopy (ATAS) in the extreme ultraviolet at the germanium M_{4,5}-edge (~30 eV). We decompose the ATAS spectra into contributions of electronic state blocking and photo-induced band shifts at a carrier density of 8*10^{20}cm^{-3}. Separate electron and hole relaxation times are observed as a function of hot carrier energies. A first order electron and hole decay of ~1 ps suggests a Shockley-Read-Hall recombination mechanism. The simultaneous observation of electrons and holes with ATAS paves the way for investigating few to sub-femtosecond dynamics of both holes and electrons in complex semiconductor materials and across junctions.Comment: Includes Supplementary Informatio

    Complexity Reduction in Machine Learning-Based Wireless Positioning: Minimum Description Features

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    A recent line of research has been investigating deep learning approaches to wireless positioning (WP). Although these WP algorithms have demonstrated high accuracy and robust performance against diverse channel conditions, they also have a major drawback: they require processing high-dimensional features, which can be prohibitive for mobile applications. In this work, we design a positioning neural network (P-NN) that substantially reduces the complexity of deep learning-based WP through carefully crafted minimum description features. Our feature selection is based on maximum power measurements and their temporal locations to convey information needed to conduct WP. We also develop a novel methodology for adaptively selecting the size of feature space, which optimizes over balancing the expected amount of useful information and classification capability, quantified using information-theoretic measures on the signal bin selection. Numerical results show that P-NN achieves a significant advantage in performance-complexity tradeoff over deep learning baselines that leverage the full power delay profile (PDP).Comment: This paper has been accepted in IEEE International Conference on Communications (ICC) 202

    Practical and clinical approaches using pacing to improve selfregulation in special populations such as children and people with mental health or learning disabilities

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    For special populations such as people with a mental health issue or learning disability, a disconnect between the ability to accurately monitor and regulate exercise behaviour can lead to reduced levels of physical activity, which, in turn, is associated with additional physical or mental health problems. Activity pacing is a strategy used in clinical settings to address issues of pain amelioration, while self-pacing research is now well addressed in sport and exercise science literature. It has been proposed recently that these overlapping areas of investigation collectively support the development of self-regulatory, lifestyle exercise skills across broad population groups. Activity pacing appears to have substantial application in numerous development and rehabilitation settings and, therefore, the purpose of this short communication is to articulate how an activity pacing approach could be utilized among population groups in whom self-regulatory skills may require development. This paper provides specific examples of exercise practice across 2 discrete populations: children, and people with mental health and learning difficulties. In these cases, homeostatic regulatory processes may either be altered, or the individual may require extrinsic support to appropriately self-regulate exercise performance. A support-based exercise environment or approach such as programmatic activity (lifestyle) pacing would be beneficial to facilitate supervised and education-based self-regulation until such time as fully self-regulated exercise is feasible. [Abstract copyright: Journal Compilation © 2021 Foundation of Rehabilitation Information.

    Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

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    Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH
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