Probing the neutron star interior and the Equation of State of cold dense matter with the SKA

With an average density higher than the nuclear density, neutron stars (NS) provide a unique test-ground for nuclear physics, quantum chromodynamics (QCD), and nuclear superfluidity. Determination of the fundamental interactions that govern matter under such extreme conditions is one of the major unsolved problems of modern physics, and -- since it is impossible to replicate these conditions on Earth -- a major scientific motivation for SKA. The most stringent observational constraints come from measurements of NS bulk properties: each model for the microscopic behaviour of matter predicts a specific density-pressure relation (its `Equation of state', EOS). This generates a unique mass-radius relation which predicts a characteristic radius for a large range of masses and a maximum mass above which NS collapse to black holes. It also uniquely predicts other bulk quantities, like maximum spin frequency and moment of inertia. The SKA, in Phase 1 and particularly in Phase 2 will, thanks to the exquisite timing precision enabled by its raw sensitivity, and surveys that dramatically increase the number of sources: 1) Provide many more precise NS mass measurements (high mass NS measurements are particularly important for ruling out EOS models); 2) Allow the measurement of the NS moment of inertia in highly relativistic binaries such as the Double Pulsar; 3) Greatly increase the number of fast-spinning NS, with the potential discovery of spin frequencies above those allowed by some EOS models; 4) Improve our knowledge of new classes of binary pulsars such as black widows and redbacks (which may be massive as a class) through sensitive broad-band radio observations; and 5) Improve our understanding of dense matter superfluidity and the state of matter in the interior through the study of rotational glitches, provided that an ad-hoc campaign is developed.Comment: 22 pages, 8 figures, to be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14)04

Impact of gastric per‐oral endoscopic myotomy on static and dynamic pyloric function in gastroparesis patients

BackgroundFunctional Lumen Imaging Probe (EndoFLIP) tests typically measure static pyloric parameters, but the pylorus exhibits phasic variations on manometry. Dynamic changes in pyloric function have not been quantified using EndoFLIP, and the impact of Gastric Per‐Oral Endoscopic Myotomy (G‐POEM) on static and dynamic pyloric activity in gastroparesis is unknown.MethodsEndoFLIP balloon inflation to 30, 40, and 50 mL was performed to measure mean, maximum, and minimum values and variability in pyloric diameter and distensibility before and after G‐POEM in 20 patients with refractory gastroparesis. The impact of phasic contractions on these pyloric measures was compared.Key ResultsG‐POEM increased mean (P < .0001) and maximum (P = .0002) pyloric diameters and mean (P = .02) and maximum (P = .02) pyloric distensibility on 50 mL EndoFLIP inflation but not intraballoon pressures or minimum diameters or distensibility. Temporal variability of pyloric diameter (P = .02) and distensibility (P = .02) also increased after G‐POEM. Phasic coupled contractions propagating from the antrum through the pylorus were observed in 37.5% of recordings; other phasic activity including isolated pyloric contractions were seen in 23.3%. Variability of pyloric diameter and distensibility tended to be higher during recordings with phasic activity. Some pyloric responses to G‐POEM were influenced by age, gastroparesis etiology, gastric emptying, and prior botulinum toxin injection.Conclusions & InferencesPyloric activity exhibits dynamic changes on EndoFLIP testing in gastroparesis. G‐POEM increases maximal but not minimal diameter and distensibility with increased variations, suggesting this therapy enhances pyloric opening but may not impair pyloric closure. Phasic pyloric contractions contribute to variations in pyloric activity.We employed Functional Lumen Imaging Probe (EndoFLIP)tests toshowincreases in pyloric diameter and variability of diameter after gastricperoralendoscopicmyotomy(G‐POEM ingastroparesis patients (left graphs). Variability of pyloric activity was noted before and after G‐POEM which was partly due to propagated antropyloriccontractions (3‐D plot on right) detected by EndoFLIP.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163489/2/nmo13892_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163489/1/nmo13892.pd

Where do the improvements come from in sequence-to-sequence neural TTS?

Sequence-to-sequence neural networks with attention mechanisms have recently been widely adopted for text-to-speech. Compared with older, more modular statistical parametric synthesis systems, sequence-to-sequence systems feature three prominent innovations: 1) They replace substantial parts of traditional fixed front-end processing pipelines (like Festival's) with learned text analysis; 2) They jointly learn to align text and speech and to synthesise speech audio from text; 3) They operate autoregressively on previously-generated acoustics. Naturalness improvements have been reported relative to earlier systems which do not contain these innovations. It would be useful to know how much each of the various innovations contribute to the improved performance. We here propose one way of associating the separately-learned components of a representative older modular system, specifically Merlin, with the different sub-networks within recent neural sequence-to-sequence architectures, specifically Tacotron 2 and DCTTS. This allows us to swap in and out various components and subnets to produce intermediate systems that step between the two paradigms; subjective evaluation of these systems then allows us to isolate the perceptual effects of the various innovations. We report on the design, evaluation, and findings of such an experiment.QC 20200219Swedish Foundation for Strategic Research no. RIT15-0107 (EACare)EPSRC Standard Research Grant EP/P011586/1 SCRIPT (Speech Synthesis for Spoken Content Production

Could e-learning Change How we Think About Scholarship and Teaching?

We are three Final Year Chemistry students investigating the impact of new Virtual Learning Environments on the Student Learning Experience. Together with the School of Chemistry at the University of Glasgow, and Learning Science Ltd, Pre- lab online interactive simulations and post-lab auto-grading environments were developed. We are currently leading evaluations of the impact these online resources have on the student learning experience. We have carefully developed a consistent methodology for data collection and for analysis. We have focussed on gathering feedback from students who have been supported with these online resources, and those who have not (for comparison). To present our findings we would use video demonstrations and graphical results from the investigation. We hope that our final report can be used as a case study, to help demystify design and implementation of effective e-resources, to highlight considerations and challenges in the process, and ultimately to encourage uptake across disciplines

Could e-learning Change How we Think About Scholarship and Teaching?

We are three Final Year Chemistry students investigating the impact of new Virtual Learning Environments on the Student Learning Experience. Together with the School of Chemistry at the University of Glasgow, and Learning Science Ltd, Pre- lab online interactive simulations and post-lab auto-grading environments were developed. We are currently leading evaluations of the impact these online resources have on the student learning experience. We have carefully developed a consistent methodology for data collection and for analysis. We have focussed on gathering feedback from students who have been supported with these online resources, and those who have not (for comparison). To present our findings we would use video demonstrations and graphical results from the investigation. We hope that our final report can be used as a case study, to help demystify design and implementation of effective e-resources, to highlight considerations and challenges in the process, and ultimately to encourage uptake across disciplines

Clinical and Molecular Aspects of Senataxin Mutations in Amyotrophic Lateral Sclerosis 4

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154673/1/ana25681_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154673/2/ana25681.pd

Evaluation of AaDOP2 Receptor Antagonists Reveals Antidepressants and Antipsychotics as Novel Lead Molecules for Control of the Yellow Fever Mosquito, Aedes aegypti s

ABSTRACT The yellow fever mosquito, Aedes aegypti, vectors disease-causing agents that adversely affect human health, most notably the viruses causing dengue and yellow fever. The efficacy of current mosquito control programs is challenged by the emergence of insecticideresistant mosquito populations, suggesting an urgent need for the development of chemical insecticides with new mechanisms of action. One recently identified potential insecticide target is the A. aegypti D 1 -like dopamine receptor, AaDOP2. The focus of the present study was to evaluate AaDOP2 antagonism both in vitro and in vivo using assay technologies with increased throughput. The in vitro assays revealed AaDOP2 antagonism by four distinct chemical scaffolds from tricyclic antidepressant or antipsychotic chemical classes, and elucidated several structure-activity relationship trends that contributed to enhanced antagonist potency, including lipophilicity, halide substitution on the tricyclic core, and conformational rigidity. Six compounds displayed previously unparalleled potency for in vitro AaDOP2 antagonism, and among these, asenapine, methiothepin, and cis-(Z)-flupenthixol displayed subnanomolar IC 50 values and caused rapid toxicity to A. aegypti larvae and/or adults in vivo. Our study revealed a significant correlation between in vitro potency for AaDOP2 antagonism and in vivo toxicity, suggesting viability of AaDOP2 as an insecticidal target. Taken together, this study expanded the repertoire of known AaDOP2 antagonists, enhanced our understanding of AaDOP2 pharmacology, provided further support for rational targeting of AaDOP2, and demonstrated the utility of efficiency-enhancing in vitro and in vivo assay technologies within our genome-to-lead pipeline for the discovery of next-generation insecticides