Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro

SummaryThe driving force in the progression of COPD is the development of exacerbations which are mostly the result of excessive inflammation. Bronchodilatators play an important role in the treatment of COPD. The reported reduction in exacerbation rates in COPD is due to the inhibition of vagal-mediated bronchoconstriction and mucus secretion. However, recent studies have highlighted the existence of muscarinic receptors on inflammatory cells and we have explored the possibility that tiotropium bromide might also inhibit neutrophil migration. We analysed the influence of tiotropium on the release of neutrophil chemotactic activity in response to acetylcholine (ACh) and the expression of muscarinic receptors on human alveolar macrophages (AM), A549 cells, MonoMac6 cells, and human lung fibroblasts. We found significant levels of all muscarinic receptor subtypes on all analysed cells except the fibroblasts. Fibroblasts expressed predominantly M2, receptors and did not release chemotactic activity. AM, A549 cells, and MonoMac6 cells released chemotactic active mediators after incubation with ACh. The secretion could be suppressed by more than 70% after coincubation with tiotropium. Tiotropium alone did not influence the granulocyte migration. Most of the chemotactic activity could be attributed to leukotriene B4 (LTB4). The release of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) was not induced by ACh. From this, we suggest that the suppression of the Ach-mediated release of chemotactic substances like LTB4 modulates the inflammatory reaction. This may contribute to the decreased rate of exacerbations in COPD, which was observed in clinical trials

Rotational Bands and Electromagnetic Transitions of some even-even Neodymium Nuclei in J-Projected Hartree-Fock Model

Rotational structures of even-even $^{148-160}$Nd nuclei are studied with the self-consistent deformed Hartree-Fock (HF) and angular momentum (J) projection model. Spectra of ground band, recently observed $K=4^{-}$, $K=5^{-}$ and a few more excited, positive and negative parity bands have been studied upto high spin values. Apart from these detailed electromagnetic properties (like E2, M1 matrix elements) of all the bands have been obtained. There is substantial agreement between our model calculations and available experimental data. Predictions are made about the band structures and electromagnetic properties of these nuclei. Some 4-qasiparticle K-isomeric bands and their electromagnetic properties are predicted.Comment: 20 page

DSAM lifetime measurements for the chiral pair in 194Tl

Most important for the identification of chiral symmetry in atomic nuclei is to establish a pair of bands that are near-degenerate in energy, but also in B(M1) and B(E2) transition probabilities. Dedicated lifetime measurements were performed for four bands of 194Tl, including the pair of four-quasiparticle chiral bands with close near-degeneracy, considered as a prime candidate for best chiral symmetry pair. The lifetime measurements confirm the excellent near-degeneracy in this pair and indicate that a third band may be involved in the chiral symmetry scenario

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

Stable triaxiality at the highest spins in 138 Nd and 139 Nd

The nuclei ${}^{138}\mathrm{Nd}$ and ${}^{139}\mathrm{Nd}$ have been studied at very high spins via the ${}^{48}\mathrm{Ca}{+}^{94}\mathrm{Zr}$ reaction. Several new rotational bands were observed, four in ${}^{138}\mathrm{Nd}$ and two in ${}^{139}\mathrm{Nd}.$ The ${J}^{(2)}$ moments of inertia calculated from the observed \ensuremath{\gamma}-ray energies are very small and almost constant, indicating that these bands are triaxial. Cranked Nilsson-Strutinsky calculations reproduce the general behavior of the bands, supporting this interpretation and suggesting an approximately constant \ensuremath{\gamma} value of \ensuremath{\sim}+35\ifmmode^\circ\else\textdegree\fi{} over a large spin range up to the highest observed spins. These bands and a few similar bands in other nuclei of the N\ensuremath{\approx}80 region are a unique example of almost undisturbed triaxial bands

Reduced prediction error responses in high-as compared to low-uncertainty musical contexts

Abstract Theories of predictive processing propose that prediction error responses are modulated by the certainty of the predictive model or precision . While there is some evidence for this phenomenon in the visual and, to a lesser extent, the auditory modality, little is known about whether it operates in the complex auditory contexts of daily life. Here, we examined how prediction error responses behave in a more complex and ecologically valid auditory context than those typically studied. We created musical tone sequences with different degrees of pitch uncertainty to manipulate the precision of participants’ auditory expectations. Magnetoencephalography was used to measure the magnetic counterpart of the mismatch negativity (MMNm) as a neural marker of prediction error in a multi-feature paradigm. Pitch, slide, intensity and timbre deviants were included. We compared high-entropy stimuli, consisting of a set of non-repetitive melodies, with low-entropy stimuli consisting of a simple, repetitive pitch pattern. Pitch entropy was quantitatively assessed with an information-theoretic model of auditory expectation. We found a reduction in pitch and slide MMNm amplitudes in the high-entropy as compared to the low-entropy context. No significant differences were found for intensity and timbre MMNm amplitudes. Furthermore, in a separate behavioral experiment investigating the detection of pitch deviants, similar decreases were found for accuracy measures in response to more fine-grained increases in pitch entropy. Our results are consistent with a precision modulation of auditory prediction error in a musical context, and suggest that this effect is specific to features that depend on the manipulated dimension—pitch information, in this case. Highlights The mismatch negativity (MMNm) is reduced in musical contexts with high pitch uncertainty The MMNm reduction is restricted to pitch-related features Accuracy during deviance detection is reduced in contexts with higher uncertainty The results suggest a feature-selective precision modulation of prediction error Materials, data and scripts can be found in the Open Science Framework repository: http://bit.ly/music_entropy_MMN DOI: 10.17605/OSF.IO/MY6T

Relating industrial symbiosis and circular economy to the sustainable development debate

Industrial Symbiosis (IS) is a business-focused collaborative approach oriented towards resource efficiency that has been theorised and studied mainly over the last twenty-five years. Recently, IS seems to have found a renewed impetus in the framework of the Circular Economy (CE), a novel approach to sustainability and Sustainable Development (SD) that has been rapidly gaining momentum world-wide. This opening chapter of the book provides an introduction to the concepts of IS, CE and SD, and summarizes their complex evolutionary paths, recalling the rel-evant developments and implementation challenges. In addition, the authors point out the divergences and interrelations of these concepts, both among themselves and with other related concepts and research fields, such as industrial ecology, eco-logical modernization and the green economy. Furthermore, the potential contribu-tion of IS and the CE to SD is briefly discussed, also highlighting critical issues and trade-offs, as well as gaps in research and application, especially relating to the so-cial component of sustainability. Particular attention is given to the potential role of IS in the achievement of targets connected to the Sustainable Development Goals set in the UN Agenda 2030. The recent advances in the IS and CE discussion in the context of the SD research community are further explored, with particular empha-sis on the contribution of the International Sustainable Development Research So-ciety (ISDRS) and its 24th annual conference organised in Messina, Italy, in 2018. The programme of that conference, indeed, included specific tracks on the above-mentioned themes, the contents of which are briefly commented on here, after an overview on the whole conference and the main cross-cutting concepts emerged. In the last part of the chapter, a brief description of the chapters collected in the book is presented. These contributions describe and discuss theoretical frameworks, methodological approaches and/or experiences and case studies where IS and the principles of CE are applied in different geographical context and at different scales to ultimately improve the sustainability of the current production patterns

Coexisting Cyclic Parthenogens Comprise a Holocene Species Flock in Eubosmina

Background: Mixed breeding systems with extended clonal phases and weak sexual recruitment are widespread in nature but often thought to impede the formation of discrete evolutionary clusters. Thus, cyclic parthenogens, such as cladocerans and rotifers, could be predisposed to ‘‘species problems’ ’ and a lack of discrete species. However, species flocks have been proposed for one cladoceran group, Eubosmina, where putative species are sympatric, and there is a detailed paleolimnological record indicating a Holocene age. These factors make the Eubosmina system suitable for testing the hypotheses that extended clonal phases and weak sexual recruitment inhibit speciation. Although common garden experiments have revealed a genetic component to the morphotypic variation, the evolutionary significance of the morphotypes remains controversial. Methodology/Principal Findings: In the present study, we tested the hypothesis of a single polymorphic species (i.e., mixing occurs but selection maintains genes for morphology) in four northern European lakes where the morphotypes coexist. Our evidence is based on nuclear DNA sequence, mitochondrial DNA sequence, and morphometric analysis of coexisting morphotypes. We found significant genetic differentiation, genealogical exclusivity, and morphometric differentiation for coexisting morphotypes. Conclusions: We conclude that the studied morphotypes represent a group of young species undergoing speciation wit

What controls gain in gain control? Mismatch negativity (MMN), priors and system biases

Repetitious patterns enable the auditory system to form prediction models specifying the most likely characteristics of subsequent sounds. Pattern deviations elicit mismatch negativity (MMN), the amplitude of which is modulated by the size of the deviation and confidence in the model. Todd et al. (2001; 2013) demonstrated that a multi-timescale sequence reveals a bias that profoundly distorts the impact of local sound statistics on the MMN amplitude. Two sounds alternate roles as repetitious “standard” and rare “deviant” rapidly (every 0.8 minutes) or slowly (every 2.4 minutes). The bias manifests as larger MMN to the sound first encountered as deviant in slow compared to fast changing sequences, but no difference for the sound first encountered as a standard. We propose that the bias is due to how Bayesian priors shape filters of sound relevance. By examining the time-course of change in MMN amplitude we show that the bias manifests immediately after roles change but rapidly disappears thereafter. The bias was reflected in the response to deviant sounds only (not in response to standards), consistent with precision estimates extracted from second order patterns modulating gain differentially for the two sounds.. Evoked responses to deviants suggest that pattern extraction and reactivation of priors can operate over tens of minutes or longer. Both MMN and deviant responses establish that: (1) priors are defined by the most proximally encountered probability distribution when one exists but; (2) when no prior exists, one is instantiated by sequence onset characteristics; and (3) priors require context interruption to be updated