302 research outputs found

    Diversity with Universality

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    This paper investigates the ‘Diversity’ inferences (D-inferences) arising from disjunction embedded in the scope of a universal quantifier, e.g., Every X is A or B suggests Some Xs are A and Some Xs are B. It has previously been claimed (i) that D-inferences are independent from ‘Negative Universal’ inferences (NU-inferences), which are the negations of Every X is A and Every X is B, but (ii) that for disjunction in the scope of a universal modal the D-inferences cannot be observed independently of the NU-inferences ([3, 7, 9, 13]). Experiment 1 tested the availability of D-inferences in the absence of NU-inferences for the determiner every and the epistemic modal must. Experiment 2 followed up on Experiment 1 by testing the same two quantifiers, only this time the modal must expressed deontic necessity. The results show that, for both types of quantifiers, D-inferences could be derived independently of NU-inferences. While the results for every essentially replicate those reported in [7], the results for must are new and go against the aforementioned claim (ii). In addition, the response time results from both experiments show that D-inferences are associated with response delay effects in the opposite direction to those observed for regular scalar implicatures in similar tasks ([4, 5]). We argue that these findings about the time course of D-inferences raise a new challenge for an implicature-based approach to these inferences

    Molecular Events in the Cell Types of the Olfactory Epithelium during Adult Neurogenesis

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    BACKGROUND: Adult neurogenesis, fundamental for cellular homeostasis in the mammalian olfactory epithelium, requires major shifts in gene expression to produce mature olfactory sensory neurons (OSNs) from multipotent progenitor cells. To understand these dynamic events requires identifying not only the genes involved but also the cell types that express each gene. Only then can the interrelationships of the encoded proteins reveal the sequences of molecular events that control the plasticity of the adult olfactory epithelium. RESULTS: Of 4,057 differentially abundant mRNAs at 5 days after lesion-induced OSN replacement in adult mice, 2,334 were decreased mRNAs expressed by mature OSNs. Of the 1,723 increased mRNAs, many were expressed by cell types other than OSNs and encoded proteins involved in cell proliferation and transcriptional regulation, consistent with increased basal cell proliferation. Others encoded fatty acid metabolism and lysosomal proteins expressed by infiltrating macrophages that help scavenge debris from the apoptosis of mature OSNs. The mRNAs of immature OSNs behaved dichotomously, increasing if they supported early events in OSN differentiation (axon initiation, vesicular trafficking, cytoskeletal organization and focal adhesions) but decreasing if they supported homeostatic processes that carry over into mature OSNs (energy production, axon maintenance and protein catabolism). The complexity of shifts in gene expression responsible for converting basal cells into neurons was evident in the increased abundance of 203 transcriptional regulators expressed by basal cells and immature OSNs. CONCLUSIONS: Many of the molecular changes evoked during adult neurogenesis can now be ascribed to specific cellular events in the OSN cell lineage, thereby defining new stages in the development of these neurons. Most notably, the patterns of gene expression in immature OSNs changed in a characteristic fashion as these neurons differentiated. Initial patterns were consistent with the transition into a neuronal morphology (neuritogenesis) and later patterns with neuronal homeostasis. Overall, gene expression patterns during adult olfactory neurogenesis showed substantial similarity to those of embryonic brain

    Genomics of Mature and Immature Olfactory Sensory Neurons

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    The continuous replacement of neurons in the olfactory epithelium provides an advantageous model for investigating neuronal differentiation and maturation. By calculating the relative enrichment of every mRNA detected in samples of mature mouse olfactory sensory neurons (OSNs), immature OSNs, and the residual population of neighboring cell types, and then comparing these ratios against the known expression patterns of \u3e300 genes, enrichment criteria that accurately predicted the OSN expression patterns of nearly all genes were determined. We identified 847 immature OSN-specific and 691 mature OSN-specific genes. The control of gene expression by chromatin modification and transcription factors, and neurite growth, protein transport, RNA processing, cholesterol biosynthesis, and apoptosis via death domain receptors, were overrepresented biological processes in immature OSNs. Ion transport (ion channels), presynaptic functions, and cilia-specific processes were overrepresented in mature OSNs. Processes overrepresented among the genes expressed by all OSNs were protein and ion transport, ER overload response, protein catabolism, and the electron transport chain. To more accurately represent gradations in mRNA abundance and identify all genes expressed in each cell type, classification methods were used to produce probabilities of expression in each cell type for every gene. These probabilities, which identified 9,300 genes expressed in OSNs, were 96% accurate at identifying genes expressed in OSNs and 86% accurate at discriminating genes specific to mature and immature OSNs. This OSN gene database not only predicts the genes responsible for the major biological processes active in OSNs, but also identifies thousands of never before studied genes that support OSN phenotypes

    Plural priming revisited: inverse preference and spillover effects

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    Maldonado & Chemla & Spector (2017) observe that the distributive interpretation of sentences involving multiple plural expressions gives rise to stronger priming effects than their cumulative interpretation, and propose to interpret this observation in terms of structural priming involving the phonologically silent distributivity operator. We report on a new experiment that included an additional baseline condition, whose results reveal that (i) the observed priming effects are inverse preference effects in that only the less dominant reading in the baseline condition gives rise to sizable priming effects, and (ii) both distributive and cumulative interpretations can have priming effects, depending on speakers’ baseline preferences. We argue that these findings undermine Maldonado et al.’s claim that their results offer empirical evidence in support of the existence of a silent distributivity operator in syntax

    Encoding the Odor of Cigarette Smoke

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    The encoding of odors is believed to begin as a combinatorial code consisting of distinct patterns of responses from odorant receptors (ORs), trace-amine associated receptors (TAARs), or both. To determine how specific response patterns arise requires detecting patterns in vivo and understanding how the components of an odor, which are nearly always mixtures of odorants, give rise to parts of the pattern. Cigarette smoke, a common and clinically relevant odor consisting of \u3e 400 odorants, evokes responses from 144 ORs and 3 TAARs in freely behaving male and female mice, the first example of in vivo responses of both ORs and TAARs to an odor. As expected, a simplified artificial mimic of cigarette smoke odor tested at low concentration to identify highly sensitive receptors evokes responses from four ORs, all also responsive to cigarette smoke. Human subjects of either sex identify 1-pentanethiol as the odorant most critical for perception of the artificial mimic; and in mice the OR response patterns to these two odors are significantly similar. Fifty-eight ORs respond to the headspace above 25% 1-pentanethiol, including 9 ORs responsive to cigarette smoke. The response patterns to both cigarette smoke and 1-pentanethiol have strongly responsive ORs spread widely across OR sequence diversity, consistent with most other combinatorial codes previously measured in vivo. The encoding of cigarette smoke is accomplished by a broad receptor response pattern, and 1-pentanethiol is responsible for a small subset of the responsive ORs in this combinatorial code. SIGNIFICANCE STATEMENT Complex odors are usually perceived as distinct odor objects. Cigarette smoke is the first complex odor whose in vivo receptor response pattern has been measured. It is also the first pattern shown to include responses from both odorant receptors and trace-amine associated receptors, confirming that the encoding of complex odors can be enriched by signals coming through both families of receptors. Measures of human perception and mouse receptor physiology agree that 1-pentanethiol is a critical component of a simplified odorant mixture designed to mimic cigarette smoke odor. Its receptor response pattern helps to link those of the artificial mimic and real cigarette smoke, consistent with expectations about perceptual similarity arising from shared elements in receptor response patterns

    In Vivo Identification of Eugenol-Responsive and Muscone-Responsive Mouse Odorant Receptors

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    Our understanding of mammalian olfactory coding has been impeded by the paucity of information about the odorant receptors (ORs) that respond to a given odorant ligand in awake, freely behaving animals. Identifying the ORs that respond in vivo to a given odorant ligand from among the ∼1100 ORs in mice is intrinsically challenging but critical for our understanding of olfactory coding at the periphery. Here, we report an in vivo assay that is based on a novel gene-targeted mouse strain, S100a5-tauGFP, in which a fluorescent reporter selectively marks olfactory sensory neurons that have been activated recently in vivo. Because each olfactory sensory neuron expresses a single OR gene, multiple ORs responding to a given odorant ligand can be identified simultaneously by capturing the population of activated olfactory sensory neurons and using expression profiling methods to screen the repertoire of mouse OR genes. We used this in vivo assay to re-identify known eugenol- and muscone-responsive mouse ORs. We identified additional ORs responsive to eugenol or muscone. Heterologous expression assays confirmed nine eugenol-responsive ORs (Olfr73, Olfr178, Olfr432, Olfr610, Olfr958, Olfr960, Olfr961, Olfr913, and Olfr1234) and four muscone-responsive ORs (Olfr74, Olfr235, Olfr816, and Olfr1440). We found that the human ortholog of Olfr235 and Olfr1440 responds to macrocyclic ketone and lactone musk odorants but not to polycyclic musk odorants or a macrocyclic diester musk odorant. This novel assay, called the Kentucky in vivo odorant ligand-receptor assay, should facilitate the in vivo identification of mouse ORs for a given odorant ligand of interest

    Thinking about Later Life: Insights from the Capability Approach

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    A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

    Investigating the timecourse of accessing conversational implicatures during incremental sentence interpretation

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    Many contextual inferences in utterance interpretation are explained as following from the nature of conversation and the assumption that participants are rational. Recent psycholinguistic research has focussed on certain of these ‘Gricean’ inferences and have revealed that comprehenders can access them in online interpretation. However there have been mixed results as to the time-course of access. Some results show that Gricean inferences can be accessed very rapidly, as rapidly as any other contextually specified information (Sedivy, 2003; Grodner, Klein, Carbery, & Tanenhaus, 2010); while other studies looking at the same kind of inference suggest that access to Gricean inferences are delayed relative to other aspects of semantic interpretation (Huang & Snedeker, 2009; in press). While previous timecourse research has focussed on Gricean inferences that support the online assignment of reference to definite expressions, the study reported here examines the timecourse of access to scalar implicatures, which enrich the meaning of an utterance beyond the semantic interpretation. Even if access to Gricean inference in support of reference assignment may be rapid, it is still unknown whether genuinely enriching scalar implicatures are delayed. Our results indicate that scalar implicatures are accessed as rapidly as other contextual inferences. The implications of our results are discussed in reference to the architecture of language comprehension

    Early Laser for Burn Scars (ELABS): protocol for a multi-centre randomised, controlled trial of both the effectiveness and cost-effectiveness of the treatment of hypertrophic burn scars with Pulsed Dye Laser and standard care compared to standard care alone [version 1; peer review: 2 approved]

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    This paper outlines the protocol for a study that is being carried out at multiple centres across the UK in the next three years. It is a Research for Patient Benefit (RfPB) study funded by the National Institute for Healthcare Research (NIHR). The aim is to assess the effectiveness of treating hypertrophic burns scars with pulsed dye laser (PDL) at an early stage of scar formation. The objective is to improve Quality of Life for the patient by improving both the appearance and quality of burn scarring, as well as reducing its psychological impact. This is a parallel-arm randomised, controlled trial to compare PDL and standard care against standard care alone. The difference is measured between baseline and six-month follow-up. Recruits are within three months of healing from a burn injury; with wounds showing a defined potential for hypertrophic scarring. A total of 120 patients are recruited in a multi-centre study; with randomisation in a 1:1 allocation to each arm. The treatment arm receives 3 PDL treatments at six-week intervals in addition to standard care, whereas the control arm receives standard care alone. The primary outcome is the patient-rated part of the Patient and Observer Scar Scale (POSAS). Psychological and psycho-social impact is evaluated using the CARe burn scale (UWE, Bristol) and Quality Adjusted Life Years (QALY) is determined using the Short-Form Health Survey (SF-12). The study evaluates both the cost-effectiveness through an economic analysis and the patient-reported experience of the treatment by phone interviews
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