Universal and language-specific processing : the case of prosody

A key question in the science of language is how speech processing can be influenced by both language-universal and language-specific mechanisms (Cutler, Klein, & Levinson, 2005). My graduate research aimed to address this question by adopting a crosslanguage approach to compare languages with different phonological systems. Of all components of linguistic structure, prosody is often considered to be one of the most language-specific dimensions of speech. This can have significant implications for our understanding of language use, because much of speech processing is specifically tailored to the structure and requirements of the native language. However, it is still unclear whether prosody may also play a universal role across languages, and very little comparative attempts have been made to explore this possibility. In this thesis, I examined both the production and perception of prosodic cues to prominence and phrasing in native speakers of English and Mandarin Chinese. In focus production, our research revealed that English and Mandarin speakers were alike in how they used prosody to encode prominence, but there were also systematic language-specific differences in the exact degree to which they enhanced the different prosodic cues (Chapter 2). This, however, was not the case in focus perception, where English and Mandarin listeners were alike in the degree to which they used prosody to predict upcoming prominence, even though the precise cues in the preceding prosody could differ (Chapter 3). Further experiments examining prosodic focus prediction in the speech of different talkers have demonstrated functional cue equivalence in prosodic focus detection (Chapter 4). Likewise, our experiments have also revealed both crosslanguage similarities and differences in the production and perception of juncture cues (Chapter 5). Overall, prosodic processing is the result of a complex but subtle interplay of universal and language-specific structure

The effect of nutrient limitation on bacterial wax ester production

Nutrient limitation is widely employed to alter the behaviour of micro-organisms. Here, the impact of nitrogen and, for the first time, phosphate limitation is investigated on the production of bacterial storage lipids; specifically wax esters, a class of storage lipids of industrial interest, by the bacterium Acinetobacter baylyi ADP1 grown on the low-cost substrate acetate. Studies determined the absolute and temporal effects of nutrient limitation and identified a maximum wax titre of 132 mg/L and content of 17 % of biomass. A 4-fold increase in wax production was achievable by manipulating carbon: phosphate ratio. Multivariable analysis identified a novel interaction effect between carbon: nitrogen and carbon: phosphate ratios on wax production. Extreme phosphate starvation shifted the dominant lipid class from wax esters to triacylglycerols, the first report of the potential of phosphate limitation to alter the type of lipid generated. These findings offer valuable insights for future microbial bioproduction studies

Juncture prosody across languages : similar production but dissimilar perception

How do speakers of languages with different intonation systems produce and perceive prosodic junctures in sentences with identical structural ambiguity? Native speakers of English and of Mandarin produced potentially ambiguous sentences with a prosodic juncture either earlier in the utterance (e.g., “He gave her # dog biscuits,” “他给她 # 狗饼干”), or later (e.g., “He gave her dog # biscuits,” “他给她狗 # 饼干”). These production data showed that prosodic disambiguation is realized very similarly in the two languages, despite some differences in the degree to which individual juncture cues (e.g., pausing) were favoured. In perception experiments with a new disambiguation task, requiring speeded responses to select the correct meaning for structurally ambiguous sentences, language differences in disambiguation response time appeared: Mandarin speakers correctly disambiguated sentences with earlier juncture faster than those with later juncture, while English speakers showed the reverse. Mandarin speakers also showed higher levels of accuracy in disambiguation compared to English speakers, indicating language-specific differences in the extent to which prosodic cues are used. However, Mandarin, but not English, speakers showed a decrease in accuracy when pausing cues were removed. Thus even with high similarity in both structural ambiguity and production cues, prosodic juncture perception across languages can differ

Lipopolysaccharide-primed heterotolerant dendritic cells suppress experimental autoimmune uveoretinitis by multiple mechanisms

Exposure of bone-marrow-derived dendritic cells (BMDC) to high-dose ultrapure lipopolysaccharide for 24 hr (LPS-primed BMDC) enhances their potency in preventing inter-photoreceptor retinoid binding protein: complete Freund's adjuvant-induced experimental autoimmune uveoretinitis (EAU). LPS-primed BMDC are refractory to further exposure to LPS (= endotoxin tolerance), evidenced here by decreased phosphorylation of TANK-binding kinase 1, interferon regulatory factor 3 (IRF3), c-Jun N-terminal kinase and p38 mitogen-activated protein kinase as well as impaired nuclear translocation of nuclear factor κB (NF-κB) and IRF3, resulting in reduced tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12 and interferon-β secretion. LPS-primed BMDC also show reduced surface expression of Toll-like receptor-4 and up-regulation of CD14, followed by increased apoptosis, mediated via nuclear factor of activated T cells (NFATc)-2 signalling. LPS-primed BMDC are not only homotolerant to LPS but are heterotolerant to alternative pathogen-associated molecular pattern ligands, such as mycobacterial protein extract (Mycobacterium tuberculosis). Specifically, while M. tuberculosis protein extract induces secretion of IL-1β, TNF-α and IL-6 in unprimed BMDC, LPS-primed BMDC fail to secrete these cytokines in response to M. tuberculosis. We propose that LPS priming of BMDC, by exposure to high doses of LPS for 24 hr, stabilizes their tolerogenicity rather than promoting immunogenicity, and does so by multiple mechanisms, namely (i) generation of tolerogenic apoptotic BMDC through CD14:NFATc signalling; (ii) reduction of NF-κB and IRF3 signalling and downstream pro-inflammatory cytokine production; and (iii) blockade of inflammasome activation

The key role of nitric oxide in hypoxia: hypoxic vasodilation and energy supply-demand matching

Significance: a mismatch between energy supply and demand induces tissue hypoxia with the potential to cause cell death and organ failure. Whenever arterial oxygen concentration is reduced, increases in blood flow - 'hypoxic vasodilation' - occur in an attempt to restore oxygen supply. Nitric oxide is a major signalling and effector molecule mediating the body's response to hypoxia, given its unique characteristics of vasodilation (improving blood flow and oxygen supply) and modulation of energetic metabolism (reducing oxygen consumption and promoting utilization of alternative pathways). Recent advances: this review covers the role of oxygen in metabolism and responses to hypoxia, the hemodynamic and metabolic effects of nitric oxide, and mechanisms underlying the involvement of nitric oxide in hypoxic vasodilation. Recent insights into nitric oxide metabolism will be discussed, including the role for dietary intake of nitrate, endogenous nitrite reductases, and release of nitric oxide from storage pools. The processes through which nitric oxide levels are elevated during hypoxia are presented, namely (i) increased synthesis from nitric oxide synthases, increased reduction of nitrite to nitric oxide by heme- or pterin-based enzymes and increased release from nitric oxide stores, and (ii) reduced deactivation by mitochondrial cytochrome c oxidase. Critical issues: several reviews covered modulation of energetic metabolism by nitric oxide, while here we highlight the crucial role NO plays in achieving cardiocirculatory homeostasis during acute hypoxia through both vasodilation and metabolic suppression Future directions: we identify a key position for nitric oxide in the body's adaptation to an acute energy supply-demand mismatc

The effect of minor allele frequency on the likelihood of obtaining false positives

Determining the most promising single-nucleotide polymorphisms (SNPs) presents a challenge in genome-wide association studies, when hundreds of thousands of association tests are conducted. The power to detect genetic effects is dependent on minor allele frequency (MAF), and genome-wide association studies SNP arrays include SNPs with a wide distribution of MAFs. Therefore, it is critical to understand MAF's effect on the false positive rate

Developments in CLARA accelerator design and simulations

We present recent developments in the accelerator design of CLARA (Compact Linear Accelerator for Research and Applications), the proposed UK FEL test facility at Daresbury Laboratory. Updates on the electron beam simulations and code comparisons including wakefields are described. Simulations of the effects of geometric wakefields in the small-aperture FEL undulator are shown, as well as further simulations on potential FEL experiments using chirped beams. We also present the results of simulations on post-FEL diagnostics

PD-1 Regulates Neural Damage in Oligodendroglia-Induced Inflammation

We investigated the impact of immune regulatory mechanisms involved in the modulation of the recently presented, CD8+ lymphocyte mediated immune response in a mouse model of oligodendropathy-induced inflammation (PLPtg-mutants). The focus was on the role of the co-inhibitory molecule PD-1, a CD28-related receptor expressed on activated T- and B-lymphocytes associated with immune homeostasis and autoimmunity. PLPtg/PD-1-deficient double mutants and the corresponding bone marrow chimeras were generated and analysed using immunohistochemistry, light- and electron microscopy, with particular emphasis on immune-cell number and neural damage. In addition, the immune cells in both the CNS and the peripheral immune system were investigated by IFN-gamma elispot assays and spectratype analysis. We found that mice with combined pathology exhibited significantly increased numbers of CD4+ and CD8+ T-lymphocytes in the CNS. Lack of PD-1 substantially aggravated the pathological phenotype of the PLPtg mutants compared to genuine PLPtg mutants, whereas the PD-1 deletion alone did not cause alterations in the CNS. CNS T-lymphocytes in PLPtg/PD-1-/- double mutants exhibited massive clonal expansions. Furthermore, PD-1 deficiency was associated with a significantly higher propensity of CNS but not peripheral CD8+ T-cells to secrete proinflammatory cytokines. PD-1 could be identified as a crucial player of tissue homeostasis and immune-mediated damage in a model of oligodendropathy-induced inflammation. Alterations of this regulatory pathway lead to overt neuroinflammation of high pathogenetic impact. Our finding may have implications for understanding the mechanisms leading to the high clinical variability of polygenic or even monogenic disorders of the nervous system

Lattice QCD without topology barriers

As the continuum limit is approached, lattice QCD simulations tend to get trapped in the topological charge sectors of field space and may consequently give biased results in practice. We propose to bypass this problem by imposing open (Neumann) boundary conditions on the gauge field in the time direction. The topological charge can then flow in and out of the lattice, while many properties of the theory (the hadron spectrum, for example) are not affected. Extensive simulations of the SU(3) gauge theory, using the HMC and the closely related SMD algorithm, confirm the absence of topology barriers if these boundary conditions are chosen. Moreover, the calculated autocorrelation times are found to scale approximately like the square of the inverse lattice spacing, thus supporting the conjecture that the HMC algorithm is in the universality class of the Langevin equation.Comment: Plain TeX source, 26 pages, 4 figures include