Hearing the Tonality in Microtonality

In the late 1970s and 1980s, composer-pianist Easley Blackwood wrote a series of microtonal compositions exploring the tonal and modal behavior of a dozen non–twelve-tone equal temperaments, ranging from 13 to 24 tones per octave. This dissertation investigates a central paradox of Blackwood’s microtonal music: that despite being full of intervals most Western listeners have never heard before, it still seems to “make sense” in nontrivial ways. Much of this has to do with the music’s idiosyncratic approach to tonality, which I define as a regime of culturally conditioned expectations that guides one’s attentional processing of music’s gravitational qualities over time. More specifically, Blackwood configures each tuning’s unfamiliar elements in ways that correspond to certain schematic expectations Western listeners tend to have about how tonal music “works.” This is why it is still possible to hear the forest of tonality in this music, so to speak, despite the odd-sounding trees that comprise it. Because of its paradoxical blend of expectational conformance and expectational noncompliance, Blackwood’s microtonal music makes for a useful tool to snap most Western-enculturated listeners out of their ingrained modes of musical processing and reveal certain things about tonality that are often taken for granted. Accordingly, just as Blackwood writes conventional-sounding music in unconventional tunings, this dissertation rethinks several familiar music-theoretic terms and concepts through the defamiliarizing lens of microtonality. I use Blackwood’s microtonal music as a prism to shine a light on traditional theories of tonality, scale degrees, consonance and dissonance, and harmonic function, arguing that many of these theories rely on assumptions that are tacitly tied to twelve-tone equal temperament and common-practice major/minor music. By unhooking these terms and concepts from any one specific tuning or historical period, I build up a set of analytical tools that can allow one to engage more productively with the many modalities of tonality typically heard on a daily basis today. This dissertation proceeds in six chapters. The four interior chapters each center on one of the terms and concepts mentioned above: scale degrees (Chapter 2), consonance and dissonance (Chapter 3), harmonic function (Chapter 4), and tonality (Chapter 5). In Chapter 2, I propose a system for labeling scale degrees that can provide more nuance and flexibility when reckoning with music in any diatonic mode (and in any tuning). In Chapter 3, I advance an account of consonance and dissonance as expectational phenomena (rather than purely psychoacoustic ones), and I consider the ways that non-pitched elements such as meter and notation can act as “consonating” and/or “dissonating” forces. In Chapter 4, I characterize harmonic function as arising from the interaction of generic scalar position and metrical position, and I devise a system for labeling harmonic functions that is better attuned to affective differences across the diatonic modes. In Chapter 5, I synthesize these building blocks into a conception of fuzzy heptatonic diatonic tonality that links together not only all of Blackwood’s microtonal compositions but also more familiar musics that use a twelve-tone octave, from Euroclassical to popular styles. The outer chapters are less explicitly music-analytical in focus. Chapter 1 introduces readers to Blackwood’s compositional approach and notational system, considers the question of his intended audience, and discusses the ways that enculturation mediates the cognition of microtonality (and of unfamiliar music more generally). Chapter 6 draws upon archival documents to paint a more detailed picture of who Blackwood was as a person and how his idiosyncratic worldview colors his approach to composition, scholarship, and interpersonal interaction. While my nominal focus in these six chapters is Blackwood’s microtonal music, the repertorial purview of my project is far broader. One of my guiding claims throughout is that attending more closely to the paradoxes and contradictions of Blackwood’s microtonality can help one better understand the musics they are accustomed to hearing. For this reason, I frequently compare moments in Blackwood’s microtonal music to ones in more familiar styles to highlight unexpected analogies and point up common concerns. Sharing space with Blackwood in the pages that follow are Anita Baker, Ornette Coleman, Claude Debussy, and Richard Rodgers, among others—not to mention music from Curb Your Enthusiasm, Fortnite, Sesame Street, and Star Wars. Ultimately, this project is a testament to the value of stepping outside of one’s musical comfort zone. For not only can this reveal certain things about that comfort zone that would not be apparent otherwise, but it can also help one think with greater nuance, precision, and (self-)awareness when “stepping back in” to reflect upon the music they know and love

A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids

Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type

Thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate)-ran-(polyethylene glycol methacrylate) graft copolymers exhibiting temperature-dependent rheology and self-assembly

© 2021 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Graft copolymers with brush-type architectures are explored containing poly (ethylene glycol) methacrylates copolymerized with “thermoresponsive” monomers which impart lower critical solution temperatures to the polymer. Initially, the chemical structure of the thermoresponsive polymer is explored, synthesizing materials containing N-isopropyl acrylamide, N,N-diethylacrylamide and diethylene glycol methyl ether methacrylate. Thermoresponsive graftcopolymers containing di(ethylene glycol) methyl ether methacrylate (DEGMA) exhibited phase transition temperature close to physiological conditions (ca 30 °C). The effect of polymer composition was explored, including molecular weight, PEG-methacrylate (PEGMA) terminal functionality and PEGMA/DEGMA ratios. Molecular weight exhibited complex relationships with phase behavior, where lower molecular weight systems appeared more stable above lower critical solution temperatures (LCST), but a lower limit was identified. PEGMA/DEGMA feed was able to control transition temperature, with higher PEGMA ratios elevating thermal transition. It was found that PEGMA terminated with methoxy functionality formed stablecolloidal structures above LCST, whereas those the hydroxy termini generally formed two phase sedimented systems when heated. Two thermoresponsive DEGMA-based graft polymers, poly(PEGMA7-ran-DEGMA170) and poly(PEGMA1-ran-DEGMA38), gave interesting temperature-dependent rheology, transitioning to a viscous state upon heating. These materials may find application in forming thermothickening systems which modify rheology upon exposure to the body’s heatPeer reviewe

Quantum memories for fundamental science in space

Investigating and verifying the connections between the foundations of quantum mechanics and general relativity will require extremely sensitive quantum experiments. To provide ultimate insight into this fascinating area of physics, the realization of dedicated experiments in space will sooner or later become a necessity. Quantum technologies, and among them quantum memories in particular, are providing novel approaches to reach conclusive experimental results due to their advanced state of development backed by decades of progress. Storing quantum states for prolonged time will make it possible to study Bell tests on astronomical baselines, to increase measurement precision for investigations of gravitational effects on quantum systems, or enable distributed networks of quantum sensors and clocks. We here promote the case of exploiting quantum memories for fundamental physics in space, and discuss both distinct experiments as well as potential quantum memory platforms and their performance

Assessing mucoadhesion in polymer gels : The effect of method type and instrument variables

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The process of mucoadhesion has been widely studied using a wide variety of methods, which are influenced by instrumental variables and experiment design, making the comparison between the results of different studies difficult. The aim of this work was to standardize the conditions of the detachment test and the rheological methods of mucoadhesion assessment for semisolids, and introduce a texture profile analysis (TPA) method. A factorial design was developed to suggest standard conditions for performing the detachment force method. To evaluate the method, binary polymeric systems were prepared containing poloxamer 407 and Carbopol 971P®, Carbopol 974P®, or Noveon® Polycarbophil. The mucoadhesion of systems was evaluated, and the reproducibility of these measurements investigated. This detachment force method was demonstrated to be reproduceable, and gave different adhesion when mucin disk or ex vivo oral mucosa was used. The factorial design demonstrated that all evaluated parameters had an effect on measurements of mucoadhesive force, but the same was not observed for the work of adhesion. It was suggested that the work of adhesion is a more appropriate metric for evaluating mucoadhesion. Oscillatory rheology was more capable of investigating adhesive interactions than flow rheology. TPA method was demonstrated to be reproducible and can evaluate the adhesiveness interaction parameter. This investigation demonstrates the need for standardized methods to evaluate mucoadhesion and makes suggestions for a standard study design.Peer reviewedFinal Published versio

Yeast mother cell-specific ageing, genetic (in)stability, and the somatic mutation theory of ageing

Yeast mother cell-specific ageing is characterized by a limited capacity to produce daughter cells. The replicative lifespan is determined by the number of cell cycles a mother cell has undergone, not by calendar time, and in a population of cells its distribution follows the Gompertz law. Daughter cells reset their clock to zero and enjoy the full lifespan characteristic for the strain. This kind of replicative ageing of a cell population based on asymmetric cell divisions is investigated as a model for the ageing of a stem cell population in higher organisms. The simple fact that the daughter cells can reset their clock to zero precludes the accumulation of chromosomal mutations as the cause of ageing, because semiconservative replication would lead to the same mutations in the daughters. However, nature is more complicated than that because, (i) the very last daughters of old mothers do not reset the clock; and (ii) mutations in mitochondrial DNA could play a role in ageing due to the large copy number in the cell and a possible asymmetric distribution of damaged mitochondrial DNA between mother and daughter cell. Investigation of the loss of heterozygosity in diploid cells at the end of their mother cell-specific lifespan has shown that genomic rearrangements do occur in old mother cells. However, it is not clear if this kind of genomic instability is causative for the ageing process. Damaged material other than DNA, for instance misfolded, oxidized or otherwise damaged proteins, seem to play a major role in ageing, depending on the balance between production and removal through various repair processes, for instance several kinds of proteolysis and autophagy. We are reviewing here the evidence for genetic change and its causality in the mother cell-specific ageing process of yeast

The effect of erythrosine-B on the structuration of poloxamer 407 and cellulose derivative blends: in silico modelling supporting experimental studies

© 2021 Elsevier B.V. All rights reserved. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1016/j.msec.2021.112440Erythrosine is a dye approved for medical use that has shown promising photodynamic activity, allowing for the inactivation of microorganisms and activity against malignant cells. Despite the great photodynamic potential, erythrosine exhibits hydrophilicity, negatively impacting its action in biological membranes. Therefore, the incorporation of erythrosine in micellar polymeric systems, such as poloxamers, may overcome this limitation. Moreover, using bioadhesive and thermoresponsive polymers to combine in situ gelation and bioadhesion may enhance retention of this topically applied drug. In this work, mucoadhesive and thermoresponsive micellar systems were prepared containing erythrosine in two states: the native form (ERI) and the disodium salt (ERIs). The systems were evaluated based on the effect of ERI/ERIs on the micellar structure of the binary polymer mixtures. Optimised combinations of poloxamer 407 (polox407) and mucoadhesive sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as micellar systems for ERI or ERIs delivery. The systems were studied with respect to theoretical interactions, qualitative composition, morphology, and micellar properties. In silico modelling indicated a higher interaction of the drug with poly(ethylene oxide) (PEO) than poly(propylene oxide) (PPO) fragments of polox407. Systems containing NaCMC displayed a repulsive effect in the presence of erythrosine, due to the polymer's charge density. Both systems could convert the photosensitizer in its monomeric form, ensuring photodynamic activity. In these mixtures, crystallinity, critical micellar temperature and enthalpy of polox407 micellisation were reduced, and micellar size, evaluated by transmission electron microscopy (TEM), showed low impact of ERI/ERIs in HPMC preparations. Aiming toward photodynamic applications, the findings showed how ERI or ERIs can affect the micellar formation of gels composed of 17.5% (w/w) polox407 and 3% (w/w) HPMC or 1% (w/w) NaCMC, important for understating their behaviour and future utilisation as erythrosine delivery systems.Peer reviewe

Psychopathological Features of Bipolar Depression: Italian Validation of the Bipolar Depression Rating Scale (I-BDRS)

Background: Aim of the study was the validation of the Bipolar Disorder Rating Scale (BDRS) in an Italian population. Secondary aim was the evaluation of differences between unipolar and bipolar depression and between bipolar I and II depressed patients.Method: 125 Bipolar Disorder and 60 Major Depressive Disorder patients were administered an Italian translation of the BDRS (I-BDRS), Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Temperament and Character Inventory-Revised (TCI-R).Results: I-BDRS showed considerable validity and reliability. Factor analysis found 3 subscales, two linked to depressive symptoms and one to mixed symptoms. Measures concerning depression (MADRS and HAM-D) were positively related to the I-BDRS's subscales, but mostly to the two subscales measuring depression. In mixed symptoms, the mean of the bipolar group was significantly higher than the unipolar group suggesting that the BDRS was able to distinguish between unipolar and bipolar depressed patients.Conclusion: I-BDRS is a valid scale for the measurement of depression in BD patients, with a notable internal consistency (Cronbach's α 0.82), a significant consistency between items/total (Cronbach's α from 0.80 to 0.82) and positive correlation with other scales (MADRS r = 0.67, p < 0.001; HDRS r = 0.81, p < 0.001; YMRS r = 0.46 p < 0.0001). The mixed state sub-scale shows usefulness in differentiating bipolar from unipolar patients. I-BDRS could be a sensitive tool, both in pure depression and in mixed states, and could be used in the everyday screening and treatment of Bipolar Disorder

Absence of Adiponutrin (PNPLA3) and Monoacylglycerol Lipase Synergistically Increases Weight Gain and Aggravates Steatohepatitis in Mice

Altered lipid metabolic pathways including hydrolysis of triglycerides are key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether adiponutrin (patatin-like phospholipase domain containing protein-3-PNPLA3) and monoacylglycerol lipase (MGL) synergistically contribute to disease progression remains unclear. We generated double knockout (DKO) mice lacking both Mgl and Pnpla3; DKO mice were compared to Mgl-/- after a challenge by high-fat diet (HFD) for 12 weeks to induce steatosis. Serum biochemistry, liver transaminases as well as histology were analyzed. Fatty acid (FA) profiling was assessed in liver and adipose tissue by gas chromatography. Markers of inflammation and lipid metabolism were analyzed. Bone marrow derived macrophages (BMDMs) were isolated and treated with oleic acid. Combined deficiency of Mgl and Pnpla3 resulted in weight gain on a chow diet; when challenged by HFD, DKO mice showed increased hepatic FA synthesis and diminished beta-oxidation compared to Mgl-/-.DKO mice exhibited more pronounced hepatic steatosis with inflammation and recruitment of immune cells to the liver associated with accumulation of saturated FAs. Primary BMDMs isolated from the DKO mice showed increased inflammatory activities, which could be reversed by oleic acid supplementation. Pnpla3 deficiency aggravates the effects of Mgl deletion on steatosis and inflammation in the liver under HFD challenge

Thermoresponsive systems composed of poloxamer 407 and HPMC or NaCMC: mechanical, rheological and sol-gel transition analysis

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Poloxamer 407 (polox407) is widely studied as thermogelling polymer, transitioning to a gel state when warmed Polox407 forms weak hydrogels with rapid dissolution in excess solvent. This study reports the development of binary systems composed of polox407 and hydroxypropyl methylcellulose (HPMC) or sodium carboxymethylcellulose (NaCMC) aiming to improve the rheological and mechanical properties of the hydrogel. The interaction between polox407 and cellulose derivatives was studied, and their interaction with biological surfaces predicted. The carbohydrates affected the mechanical and rheological behavior of polox407 in different ways, dependent on polymer type, concentration, and temperature. Tsol/gel and rheological interaction parameters were useful to select the most suitable formulations for topical or local application. Most of the binary systems exhibited plastic behavior, thixotropy and viscoelastic properties. Appropriate formulations were identified for local application, such as 17.5/3; 17.5/4; 20/3 and 20/4 (%, w/w) for polox407/HPMC; and 17.5/1; 17.5/1.5; 20/1 and 20/1.5 (%, w/w) for polox407/NaCMC.Peer reviewe