New and Lesser Known Works for Saxophone Quartet: A Recording, Performance Guide, and Composer Interviews

abstract: This project includes composer biographies, program notes, performance guides, composer questionnaires, and recordings of five new and lesser known works for saxophone quartet. Three of the compositions are new pieces commissioned by Woody Chenoweth for the Midwest-based saxophone quartet, The Shredtet. The other two pieces include a newer work for saxophone quartet never recorded in its final version, as well as an unpublished arrangement of a progressive rock masterpiece. The members of The Shredtet include saxophonists Woody Chenoweth, Jonathan Brink, Samuel Lana, and Austin Atkinson. The principal component of this project is a recording of each work, featuring the author and The Shredtet. The first piece, Sax Quartet No. 2 (2018), was commissioned for The Shredtet and written by Frank Nawrot (b. 1989). The second piece, also commissioned for The Shredtet, was written by Dan Puccio (b. 1980) and titled, Scherzos for Saxophone Quartet (2018). The third original work for The Shredtet, Rhythm and Tone Study No. 3 (2018), was composed by Josh Bennett (b. 1982). The fourth piece, Fragments of a Narrative, was written by Ben Stevenson (b. 1979) in 2014 and revised in 2016, and was selected as runner-up in the Donald Sinta Quartet’s 2016 National Composition Competition. The final piece included in this project is a transcription and arrangement of Tarkus (1971), written by Keith Emerson (1944-2016) and Greg Lake (1947-2016) for the iconic progressive rock supergroup, Emerson, Lake & Palmer. This unique and unpublished arrangement was crafted by Peter Ford (b. 1964) for Ohio-based saxophone quartet Sax 4th Avenue and first featured on the ensemble’s 1998 album, Delusions de Grandeur. These pieces were recorded in the E-Media Studios of the College Conservatory of Music at the University of Cincinnati, as well as A2 Audio Studios in Cincinnati, Ohio, in January and February of 2019.Dissertation/ThesisSaxophone Quartet No. 2 by Frank NawrotScherzos for Saxophone Quartet by Dan Puccio - Mvt 1. All Together, NowScherzos for Saxophone Quartet by Dan Puccio - Mvt 2. Play PrettyScherzos for Saxophone Quartet by Dan Puccio - Mvt 3. A Minute Past CrazyScherzos for Saxophone Quartet by Dan Puccio - Mvt 4. Is This Funky?Scherzos for Saxophone Quartet by Dan Puccio - Mvt 5. No, But This IsRhythm and Tone Study #3 by Josh BennettFragments of A Narrative by Ben Stevenson - Mvt 1. SkittishFragments of A Narrative by Ben Stevenson - Mvt 2. TenseFragments of A Narrative by Ben Stevenson - Mvt 3. Rock ForeverTarkus by Emerson, Lake & Palmer - Arranged by Pete FordDoctoral Dissertation Music 201

GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology

Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by an unstable GAA repeat expansion mutation within intron 1 of the FXN gene. However, the origins of the GAA repeat expansion, its unstable dynamics within different cells and tissues, and its effects on frataxin expression are not yet completely understood. Therefore, we have chosen to generate representative FRDA mouse models by using the human FXN GAA repeat expansion itself as the genetically modified mutation. We have previously reported the establishment of two lines of human FXN YAC transgenic mice that contain unstable GAA repeat expansions within the appropriate genomic context. We now describe the generation of FRDA mouse models by crossbreeding of both lines of human FXN YAC transgenic mice with heterozygous Fxn knockout mice. The resultant FRDA mice that express only human-derived frataxin show comparatively reduced levels of frataxin mRNA and protein expression, decreased aconitase activity, and oxidative stress, leading to progressive neurodegenerative and cardiac pathological phenotypes. Coordination deficits are present, as measured by accelerating rotarod analysis, together with a progressive decrease in locomotor activity and increase in weight. Large vacuoles are detected within neurons of the dorsal root ganglia (DRG), predominantly within the lumbar regions in 6-month-old mice, but spreading to the cervical regions after 1 year of age. Secondary demyelination of large axons is also detected within the lumbar roots of older mice. Lipofuscin deposition is increased in both DRG neurons and cardiomyocytes, and iron deposition is detected in cardiomyocytes after 1 year of age. These mice represent the first GAA repeat expansion-based FRDA mouse models that exhibit progressive FRDA-like pathology and thus will be of use in testing potential therapeutic strategies, particularly GAA repeat-based strategies. © 2006 Elsevier Inc. All rights reserved

Biology and interspecific interactions of the alien crab Percnon gibbesi in the Maltese Islands

Spatial and bathymetric distribution, population density, habitat preferences, fecundity, breeding season and interspecific interactions of the alien grapsoid crab Percnon gibbesi (H. Milne-Edwards, 1853) from the Maltese Islands (Malta and Gozo) are compared among localities in the Mediterranean where established populations have been reported since 1999. In the Maltese Islands, habitat preferences and bathymetric distribution were similar to those in other Mediterranean localities. Spatial distribution was found to be limited by the availability of the boulder habitat in which this crab nearly always occurs. Fecundity was higher in the Maltese Islands than in Linosa and Lampedusa, the breeding season lasting from the end of May until September. On Maltese shores the habitat of the alien overlapped with that of the native grapsid Pachygrapsus marmoratus (Fabricius, 1787) (Crustacea: Brachyura: Grapsoidea) and, to a lesser extent, that of the native xanthid Eriphia verrucosa (Forska°l, 1775). Laboratory studies to assess the possible interactions of the alien species with P. marmoratus suggest that the latter shows a competitive advantage over P. gibbesi, since 80.8% of encounters between the two species were initiated by P. marmoratus, and in 80% of the encounters it prevailed. This suggests that P. marmoratus is unlikely to be excluded from its natural habitat by the alien species, and that significant spatial resource partitioning on the part of P. marmoratus is unlikely to occur.peer-reviewe

Magnetic Resonance Imaging Pilot Study of Intravenous Glyburide in Traumatic Brain Injury.

Pre-clinical studies of traumatic brain injury (TBI) show that glyburide reduces edema and hemorrhagic progression of contusions. We conducted a small Phase II, three-institution, randomized placebo-controlled trial of subjects with TBI to assess the safety and efficacy of intravenous (IV) glyburide. Twenty-eight subjects were randomized and underwent a 72-h infusion of IV glyburide or placebo, beginning within 10 h of trauma. Of the 28 subjects, 25 had Glasgow Coma Scale (GCS) scores of 6-10, and 14 had contusions. There were no differences in adverse events (AEs) or severe adverse events (ASEs) between groups. The magnetic resonance imaging (MRI) percent change at 72-168 h from screening/baseline was compared between the glyburide and placebo groups. Analysis of contusions (7 per group) showed that lesion volumes (hemorrhage plus edema) increased 1036% with placebo versus 136% with glyburide (p = 0.15), and that hemorrhage volumes increased 11.6% with placebo but decreased 29.6% with glyburide (p = 0.62). Three diffusion MRI measures of edema were quantified: mean diffusivity (MD), free water (FW), and tissue MD (MDt), corresponding to overall, extracellular, and intracellular water, respectively. The percent change with time for each measure was compared in lesions (n = 14) versus uninjured white matter (n = 24) in subjects receiving placebo (n = 20) or glyburide (n = 18). For placebo, the percent change in lesions for all three measures was significantly different compared with uninjured white matter (analysis of variance [ANOVA], p < 0.02), consistent with worsening of edema in untreated contusions. In contrast, for glyburide, the percent change in lesions for all three measures was not significantly different compared with uninjured white matter. Further study of IV glyburide in contusion TBI is warranted

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model

NOTICE: this is the author’s version of a work that was accepted for publication in Neurobiology of Disease. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication.Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model. We show that there is no overt toxicity up to 5 months of treatment and there is amelioration of the FRDA-like disease phenotype. Thus, while the neurological deficits of this model are mild, 109 and 106 both produced an improvement of motor coordination, whereas 109 and 136 produced increased locomotor activity. All three compounds increased global histone H3 and H4 acetylation of brain tissue, but only 109 significantly increased acetylation of specific histone residues at the FXN locus. Effects on FXN mRNA expression in CNS tissues were modest, but 109 significantly increased frataxin protein expression in brain tissue. 109 also produced significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG). Overall, these results support further assessment of HDAC inhibitors for treatment of Friedreich ataxia.This work was supported by Repligen Corporation; Muscular Dystrophy Association (MDA) USA; Ataxia UK; Friedreich's Ataxia Research Alliance (FARA); GoFAR; and the Wellcome Trust [089757]

Foreign Aid – A Fillip for Development or a Fuel for Corruption?

We present an analysis of the effects of foreign aid on economic development when the quality of governance may be compromised by corruption. The analysis is based on a dynamic general equilibrium model in which growth is driven by capital accumulation and public policy is administered by government-appointed bureaucrats. Corruption may arise due to the opportunity for bureaucrats to embezzle public funds which are otherwise used to provide productive public goods and services. Our main results may be summarized as follows: (1) corruption impedes economic development and compromises the effectiveness of aid programmers; (2) the incidence of corruption may, itself, be affected by both the development process and the donation of aid; (3) foreign aid is good for development when governance is good, but may be bad (perhaps very bad) for development when governance is bad; and (4) corruption and poverty may co-exist as permanent, rather than just transitory, fixtures of an economy.Corruption; Development; Foreign aid