113 research outputs found
Rhythm and Meter as Text Expression: Jake Runestad\u27s Come to the Woods
Core to Western music education curriculum is the teaching and history of “word painting,” or text expression particularly as it pertains to the sixteenth-century madrigal. This approach to text expression is explored primarily through the lens of melodic and harmonic movement through a vocal line and the manner in which the line allows for better portrayal of the text or poem. The purpose of this thesis is to take a new approach to text expression in contemporary choral literature through the viewpoint of rhythm and meter. In this thesis, various analytical techniques from decades past and present are applied to Jake Runestad’s 2015 choral work Come to the Woods, composed of text samplings from naturalist John Muir. The thesis explores rhythmic and metric analytical methods outlined by Harald Krebs, Christopher Hasty, Wallace Berry and Godfried T. Toussaint and applies them to Runestad’s choral work, subsequently demonstrating the distinct purpose each method possesses for the utmost portrayal of Muir’s text
Survey of Canine Monogenetic Diseases with Established Molecular Bases
The development of a dog breed often involves selection, which intentionally propagates valued genetic traits. Unfortunately, untoward traits can be collaterally propagated during this process. For the purpose of identifying trends in canine genetic diseases, we examined 36 randomly chosen canine pathologies involving single gene mutations. For each disease we provide a brief summary of breed predilection, clinical signs, the underlying genetic mutation, and the availability of a commercial diagnostic test. The following trends were noted in this non-exhaustive list of diseases. First, these genetic diseases primarily involve the ophthalmic (28%) and nervous systems (28%). Second, no single breed was over-represented in these genetic diseases. Third, the majority (89%) of the mutations involve coding regions of the respective genes. Fourth, most (78%) mutations were autosomal recessive. Fifth, nucleotide substitutions were the most common mutation (42%). Finally, genetic testing is available for 89% of these diseases. This review encapsulates canine pathologies associated with single genetic defects, thus providing a resource for practitioners and researchers
Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination
Although RNA polymerase II (Pol II) productively transcribes very long genes in vivo, transcription through extragenic sequences often terminates in the promoter-proximal region and the nascent RNA is degraded. Mechanisms that induce early termination and RNA degradation are not well understood in multicellular organisms. Here, we present evidence that the suppressor of sable [su(s)] regulatory pathway of Drosophila melanogaster plays a role in this process. We previously showed that Su(s) promotes exosome-mediated degradation of transcripts from endogenous repeated elements at an Hsp70 locus (Hsp70-αβ elements). In this report, we identify Wdr82 as a component of this process and show that it works with Su(s) to inhibit Pol II elongation through Hsp70-αβ elements. Furthermore, we show that the unstable transcripts produced during this process are polyadenylated at heterogeneous sites that lack canonical polyadenylation signals. We define two distinct regions that mediate this regulation. These results indicate that the Su(s) pathway promotes RNA degradation and transcription termination through a novel mechanism
Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome
Restless Legs Syndrome (RLS) is often and successfully treated with dopamine receptor
agonists that target the inhibitory D3 receptor subtype, however there is no clinical
evidence of a D3 receptor dysfunction in RLS patients. In contrast, genome-wide
association studies in RLS patients have established that a mutation of the MEIS1 gene is
associated with an increased risk in developing RLS, but the effect of MEIS1 dysfunction
on sensorimotor function remain unknown. Mouse models for a dysfunctional D3
receptor (D3KO) and Meis1 (Meis1KO) were developed independently, and each animal
expresses some features associated with RLS in the clinic, but they have not been
compared in their responsiveness to treatment options used in the clinic. We here confirm
that D3KO and Meis1KO animals show increased locomotor activities, but that only
D3KO show an increased sensory excitability to thermal stimuli. Next we compared
the effects of dopaminergics and opioids in both animal models, and we assessed D1
and D3 dopamine receptor expression in the spinal cord, the gateway for sensorimotor
processing. We found that Meis1KO share most of the tested behavioral properties with
their wild type (WT) controls, including the modulation of the thermal pain withdrawal
reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and antagonists. However,
Meis1KO and D3KO were behaviorally more similar to each other than to WT when tested
with D1 receptor (D1R) agonists and antagonists. Subsequent Western blot analyses of
D1R and D3R protein expression in the spinal cord revealed a significant increase in D1R
but not D3R expression in Meis1KO and D3KO over WT controls. As the D3R is mostly
present in the dorsal spinal cord where it has been shown to modulate sensory pathways,
while activation of the D1Rs can activate motoneurons in the ventral spinal cord, we
speculate that D3KO and Meis1KO represent two complementary animal models for
RLS, in which the mechanisms of sensory (D3R-mediated) and motor (D1R-mediated)
dysfunctions can be differentially explored
Considering the ethical implications of digital collaboration in the Food Sector
The Internet of Food Things Network+ (IoFT) and the Artificial Intelligence and Augmented Intelligence for Automated Investigation for Scientific Discovery Network+ (AI3SD) brought together an interdisciplinary multi-institution working group to create an ethical framework for digital collaboration in the food industry. This will enable the exploration of implications and consequences (both intentional and unintentional) of using cutting-edge technologies to support the implementation of data trusts and other forms of digital collaboration in the food sector. This article describes how we identified areas for ethical consideration with respect to digital collaboration and the use of Industry 4.0 technologies in the food sector and describes the different interdisciplinary methodologies being used to produce this framework. The research questions and objectives that are being addressed by the working group are laid out, with a report on our ongoing work. The article concludes with recommendations about working on projects in this area
Palaeolimnological evidence for an east-west climate see-saw in the Mediterranean since AD 900
During the period of instrumental records, the North Atlantic Oscillation (NAO) has strongly influenced inter-annual precipitation variations in the western Mediterranean, while some eastern parts of the basin have shown an anti-phase relationship in precipitation and atmospheric pressure. Here we explore how the NAO and other atmospheric circulation modes operated over the longer timescales of the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA). High-resolution palaeolimnological evidence from opposite ends of the Mediterranean basin, supplemented by other palaeoclimate data, is used to track shifts in regional hydro-climatic conditions. Multiple geochemical, sedimentological, isotopic and palaeoecological proxies from Estanya and Montcortés lakes in northeast Spain and Nar lake in central Turkey have been cross-correlated at decadal time intervals since AD 900. These dryland lakes capture sensitively changes in precipitation/evaporation (P/E) balance by adjustments in water level and salinity, and are especially valuable for reconstructing variability over decadal-centennial timescales. Iberian lakes show lower water levels and higher salinities during the 11th to 13th centuries synchronous with the MCA and generally more humid conditions during the 'LIA' (15th-19th centuries). This pattern is also clearly evident in tree-ring records from Morocco and from marine cores in the western Mediterranean Sea. In the eastern Mediterranean, palaeoclimatic records from Turkey, Greece and the Levant show generally drier hydro-climatic conditions during the LIA and a wetter phase during the MCA. This implies that a bipolar climate see-saw has operated in the Mediterranean for the last 1100. years. However, while western Mediterranean aridity appears consistent with persistent positive NAO state during the MCA, the pattern is less clear in the eastern Mediterranean. Here the strongest evidence for higher winter season precipitation during the MCA comes from central Turkey in the northeastern sector of the Mediterranean basin. This in turn implies that the LIA/MCA hydro-climatic pattern in the Mediterranean was determined by a combination of different climate modes along with major physical geographical controls, and not by NAO forcing alone, or that the character of the NAO and its teleconnections have been non-stationary. © 2011 Elsevier B.V
Increase of Direct C-C Coupling Reaction Yield by Identifying Structural and Electronic Properties of High-Spin Iron Tetra-azamacrocyclic Complexes
Macrocyclic ligands have been explored extensively as scaffolds for transition metal catalysts for oxygen and hydrogen atom transfer reactions. C–C reactions facilitated using earth abundant metals bound to macrocyclic ligands have not been well-understood but could be a green alternative to replacing the current expensive and toxic precious metal systems most commonly used for these processes. Therefore, the yields from direct Suzuki–Miyaura C–C coupling of phenylboronic acid and pyrrole to produce 2-phenylpyrrole facilitated by eight high-spin iron complexes ([Fe3+L1(Cl)2]+, [Fe3+L4(Cl)2]+, [Fe2+L5(Cl)]+, [Fe2+L6(Cl)2], [Fe3+L7(Cl)2]+, [Fe3+L8(Cl)2]+, [Fe2+L9(Cl)]+, and [Fe2+L10(Cl)]+) were compared to identify the effect of structural and electronic properties on catalytic efficiency. Specifically, catalyst complexes were compared to evaluate the effect of five properties on catalyst reaction yields: (1) the coordination requirements of the catalyst, (2) redox half-potential of each complex, (3) topological constraint/rigidity, (4) N atom modification(s) increasing oxidative stability of the complex, and (5) geometric parameters. The need for two labile cis-coordination sites was confirmed based on a 42% decrease in catalytic reaction yield observed when complexes containing pentadentate ligands were used in place of complexes with tetradentate ligands. A strong correlation between iron(III/II) redox potential and catalytic reaction yields was also observed, with [Fe2+L6(Cl)2] providing the highest yield (81%, −405 mV). A Lorentzian fitting of redox potential versus yields predicts that these catalysts can undergo more fine-tuning to further increase yields. Interestingly, the remaining properties explored did not show a direct, strong relationship to catalytic reaction yields. Altogether, these results show that modifications to the ligand scaffold using fundamental concepts of inorganic coordination chemistry can be used to control the catalytic activity of macrocyclic iron complexes by controlling redox chemistry of the iron center. Furthermore, the data provide direction for the design of improved catalysts for this reaction and strategies to understand the impact of a ligand scaffold on catalytic activity of other reactions
Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure
Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes
What Does the Geometry of the HβBLR Depend On?
We combine our dynamical modeling black-hole mass measurements from the Lick AGN Monitoring Project 2016 sample with measured cross-correlation time lags and line widths to recover individual scale factors, f, used in traditional reverberation-mapping analyses. We extend our sample by including prior results from Code for AGN Reverberation and Modeling of Emission Lines (CARAMEL) studies that have utilized our methods. Aiming to improve the precision of black-hole mass estimates, as well as uncover any regularities in the behavior of the broad-line region (BLR), we search for correlations between f and other AGN/BLR parameters. We find (i) evidence for a correlation between the virial coefficient log10(fmean,σ) and black-hole mass, (ii) marginal evidence for a similar correlation between log10( frms,σ) and black-hole mass, (iii) marginal evidence for an anticorrelation of BLR disk thickness with log10( fmean,FWHM) and log10( frms,FWHM), and (iv) marginal evidence for an anticorrelation of inclination angle with log10( fmean,FWHM), log10( frms,σ), and log10( fmean,σ). Last, we find marginal evidence for a correlation between line-profile shape, when using the root-mean-square spectrum, log10(FWHM/σ)rms, and the virial coefficient, log10( frms,σ), and investigate how BLR properties might be related to line-profile shape using CARAMEL models
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
- …