Sound-discrimination learning and auditory displays

Proceedings of the 9th International Conference on Auditory Display (ICAD), Boston, MA, July 7-9, 2003.Human listeners can learn to discriminate between sounds that are initially indistinguishable. To better understand the nature of this learning, we have been using behavioral techniques to examine training-induced improvements on basic auditory discrimination tasks. Here we report how multiple-hour training differentially affects the discrimination of sound frequency, intensity, location, and duration, and how learning on a given discrimination condition generalizes, or fails to generalize, to stimuli not encountered during training. We discuss how these data contribute to our understanding of discrimination learning and of the mechanisms underlying performance on particular trained tasks, and explore the implications of this learning for the design and evaluation of auditory displays

Dopaminergic basis for signalling belief updates, but not surprise, and the link to paranoia

Distinguishing between meaningful and meaningless sensory information is fundamental to forming accurate representations of the world. Dopamine is thought to play a central role in processing the meaningful information content of observations, which motivates an agent to update their beliefs about the environment. However, direct evidence for dopamine’s role in human belief updating is lacking. We addressed this question in healthy volunteers who performed a model-based functional magnetic resonance imaging (fMRI) task designed to separate the neural processing of meaningful and meaningless sensory information. We modelled participant behaviour using a normative Bayesian observer model, and used the magnitude of the model-derived belief update following an observation to quantify its meaningful information content. We also acquired positron emission tomography (PET) imaging measures of dopamine function in the same subjects. We show that the magnitude of belief updates about task structure (meaningful information), but not pure sensory surprise (meaningless information), are encoded in midbrain and ventral striatum activity. Using PET we show that the neural encoding of meaningful information is negatively related to dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced dopamine release capacity in the striatum. Trial-by-trial analysis of task performance indicated that subclinical paranoid ideation is negatively related to behavioural sensitivity to observations carrying meaningful information about the task structure. The findings provide direct evidence implicating dopamine in model-based belief updating in humans, and have implications for understating the pathophysiology of psychotic disorders where dopamine function is disrupted

A FUSE Survey of Interstellar Molecular Hydrogen in the Small and Large Magellanic Clouds

We describe a moderate-resolution FUSE survey of H2 along 70 sight lines to the Small and Large Magellanic Clouds, using hot stars as background sources. FUSE spectra of 67% of observed Magellanic Cloud sources (52% of LMC and 92% of SMC) exhibit absorption lines from the H2 Lyman and Werner bands between 912 and 1120 A. Our survey is sensitive to N(H2) >= 10^14 cm^-2; the highest column densities are log N(H2) = 19.9 in the LMC and 20.6 in the SMC. We find reduced H2 abundances in the Magellanic Clouds relative to the Milky Way, with average molecular fractions = 0.010 (+0.005, -0.002) for the SMC and = 0.012 (+0.006, -0.003) for the LMC, compared with = 0.095 for the Galactic disk over a similar range of reddening. The dominant uncertainty in this measurement results from the systematic differences between 21 cm radio emission and Lya in pencil-beam sight lines as measures of N(HI). These results imply that the diffuse H2 masses of the LMC and SMC are 8 x 10^6 Msun and 2 x 10^6 Msun, respectively, 2% and 0.5% of the H I masses derived from 21 cm emission measurements. The LMC and SMC abundance patterns can be reproduced in ensembles of model clouds with a reduced H2 formation rate coefficient, R ~ 3 x 10^-18 cm^3 s^-1, and incident radiation fields ranging from 10 - 100 times the Galactic mean value. We find that these high-radiation, low-formation-rate models can also explain the enhanced N(4)/N(2) and N(5)/N(3) rotational excitation ratios in the Clouds. We use H2 column densities in low rotational states (J = 0 and 1) to derive a mean kinetic and/or rotational temperature = 82 +/- 21 K for clouds with N(H2) >= 10^16 cm^-2, similar to Galactic gas. We discuss the implications of this work for theories of star formation in low-metallicity environments. [Abstract abridged]Comment: 30 pages emulateapj, 14 figures (7 color), 7 tables, accepted for publication in the Astrophysical Journal, figures 11 and 12 compressed at slight loss of quality, see http://casa.colorado.edu/~tumlinso/h2/ for full version

Extracellular superoxide dismutase (SOD3) regulates oxidative stress at the vitreoretinal interface

Oxidative stress is a pathogenic feature in vitreoretinal disease. However, the ability of the inner retina to manage metabolic waste and oxidative stress is unknown. Proteomic analysis of antioxidants in the human vitreous, the extracellular matrix opposing the inner retina, identified superoxide dismutase-3 (SOD3) that localized to a unique matrix structure in the vitreous base and cortex. To determine the role of SOD3, Sod3-/- mice underwent histological and clinical phenotyping. Although the eyes were structurally normal, at the vitreoretinal interface Sod3-/- mice demonstrated higher levels of 3-nitrotyrosine, a key marker of oxidative stress. Pattern electroretinography also showed physiological signaling abnormalities within the inner retina. Vitreous biopsies and epiretinal membranes collected from patients with diabetic vitreoretinopathy (DVR) and a mouse model of DVR showed significantly higher levels of nitrates and/or 3-nitrotyrosine oxidative stress biomarkers suggestive of SOD3 dysfunction. This study analyzes the molecular pathways that regulate oxidative stress in human vitreous substructures. The absence or dysregulation of the SOD3 antioxidant at the vitreous base and cortex results in increased oxidative stress and tissue damage to the inner retina, which may underlie DVR pathogenesis and other vitreoretinal diseases

Critical animal and media studies: Expanding the understanding of oppression in communication research

Critical and communication studies have traditionally neglected the oppression conducted by humans towards other animals. However, our (mis)treatment of other animals is the result of public consent supported by a morally speciesist-anthropocentric system of values. Speciesism or anthroparchy, as much as any other mainstream ideologies, feeds the media and at the same time is perpetuated by them. The goal of this article is to remedy this neglect by introducing the subdiscipline of Critical Animal and Media Studies. Critical Animal and Media Studies takes inspiration both from critical animal studies – which is so far the most consolidated critical field of research in the social sciences addressing our exploitation of other animals – and from the normative-moral stance rooted in the cornerstones of traditional critical media studies. The authors argue that the Critical Animal and Media Studies approach is an unavoidable step forward for critical media and communication studies to engage with the expanded circle of concerns of contemporary ethical thinking

Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.

The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole-genome sequencing and phylogenetic analysis of 388 samples across 18 individuals with EAC showed, in 90% of patients, that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues-a mode of dissemination that we term 'clonal diaspora'. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time points. These findings have implications for our understanding and clinical evaluation of EAC.MRC core grant (RG84369), an NIHR Research Professorship (RG67258) and Cancer Research UK (RG66287)