Contributions of temporal encodings of voicing, voicelessness, fundamental frequency, and amplitude variation to audiovisual and auditory speech perception

Auditory and audio-visual speech perception was investigated using auditory signals of invariant spectral envelope that temporally encoded the presence of voiced and voiceless excitation, variations in amplitude envelope and F-0. In experiment 1, the contribution of the timing of voicing was compared in consonant identification to the additional effects of variations in F-0 and the amplitude of voiced speech. In audio-visual conditions only, amplitude variation slightly increased accuracy globally and for manner features. F-0 variation slightly increased overall accuracy and manner perception in auditory and audio-visual conditions. Experiment 2 examined consonant information derived from the presence and amplitude variation of voiceless speech in addition to that from voicing, F-0, and voiced speech amplitude. Binary indication of voiceless excitation improved accuracy overall and for voicing and manner. The amplitude variation of voiceless speech produced only a small increment in place of articulation scores. A final experiment examined audio-visual sentence perception using encodings of voiceless excitation and amplitude variation added to a signal representing voicing and F-0. There was a contribution of amplitude variation to sentence perception, but not of voiceless excitation. The timing of voiced and voiceless excitation appears to be the major temporal cues to consonant identity. (C) 1999 Acoustical Society of America. [S0001-4966(99)01410-1]

Acoustic cues to tonal contrasts in Mandarin: Implications for cochlear implants

The present study systematically manipulated three acoustic cues-fundamental frequency (f0), amplitude envelope, and duration-to investigate their contributions to tonal contrasts in Mandarin. Simplified stimuli with all possible combinations of these three cues were presented for identification to eight normal-hearing listeners, all native speakers of Mandarin from Taiwan. The f0 information was conveyed either by an f0-controlled sawtooth carrier or a modulated noise so as to compare the performance achievable by a clear indication of voice f0 and what is possible with purely temporal coding of f0. Tone recognition performance with explicit f0 was much better than that with any combination of other acoustic cues (consistently greater than 90% correct compared to 33%-65%; chance is 25%). In the absence of explicit f0, the temporal coding of f0 and amplitude envelope both contributed somewhat to tone recognition, while duration had only a marginal effect. Performance based on these secondary cues varied greatly across listeners. These results explain the relatively poor perception of tone in cochlear implant users, given that cochlear implants currently provide only weak cues to f0, so that users must rely upon the purely temporal (and secondary) features for the perception of tone. (c) 2008 Acoustical Society of America

Exploring the Roles of Spectral Detail and Intonation Contour in Speech Intelligibility:An fMRI Study

The melodic contour of speech forms an important perceptual aspect of tonal and nontonal languages and an important limiting factor on the intelligibility of speech heard through a cochlear implant. Previous work exploring the neural correlates of speech comprehension identified a left-dominant pathway in the temporal lobes supporting the extraction of an intelligible linguistic message, whereas the right anterior temporal lobe showed an overall preference for signals clearly conveying dynamic pitch information. The current study combined modulations of overall intelligibility (through vocoding and spectral inversion) with a manipulation of pitch contour (normal vs. falling) to investigate the processing of spoken sentences in functional MRI. Our overall findings replicate and extend those of Scott et al., whereas greater sentence intelligibility was predominately associated with increased activity in the left STS, the greatest response to normal sentence melody was found right superior temporal gyrus. These data suggest a spatial distinction between brain areas associated with intelligibility and those involved in the processing of dynamic pitch information in speech. By including a set of complexity-matched unintelligible conditions created by spectral inversion, this is additionally the first study reporting a fully factorial exploration of spectrotemporal complexity and spectral inversion as they relate to the neural processing of speech intelligibility. Perhaps surprisingly, there was no evidence for an interaction between the two factors—we discuss the implications for the processing of sound and speech in the dorsolateral temporal lobes

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Hemispheric Asymmetries in Speech Perception: Sense, Nonsense and Modulations

Background: The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'.Methodology: A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds.Conclusions: Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07