204 research outputs found

    Metaphor Aptness And Conventionality: A Processing Fluency Account

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    Conventionality and aptness are two dimensions of metaphorical sentences thought to play an important role in determining how quick and easy it is to process a metaphor. Conventionality reflects the familiarity of a metaphor whereas aptness reflects the degree to which a metaphor vehicle captures important features of a metaphor topic. In recent years it has become clear that operationalizing these two constructs is not as simple as asking naïve raters for subjective judgments. It has been found that ratings of aptness and conventionality are highly correlated, which has led some researchers to pursue alternative methods for measuring the constructs. Here, in four experiments, we explore the underlying reasons for the high correlation in ratings of aptness and conventionality, and question the construct validity of various methods for measuring the two dimensions. We find that manipulating the processing fluency of a metaphorical sentence by means of familiarization to similar senses of the metaphor (“in vivo conventionalization”) influences ratings of the sentence\u27s aptness. This misattribution may help explain why subjective ratings of aptness and conventionality are highly correlated. In addition, we find other reasons to question the construct validity of conventionality and aptness measures: for instance, we find that conventionality is context dependent and thus not attributable to a metaphor vehicle alone, and we find that ratings of aptness take more into account than they should

    Alien Registration- Thibodeau, Paul H. (Van Buren, Aroostook County)

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    https://digitalmaine.com/alien_docs/32277/thumbnail.jp

    Lay Theories of Obesity: Causes and Consequences

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    Both the scientific community and the general public have come to recognize the increasing prevalence of obesity as a significant public health crisis. To help address this issue, recent research has begun to explore lay theories of obesity—the mental models that structure how non-experts think about the causes and consequences of the condition. In this chapter, we develop an integrative review of the literature on lay theories of obesity, drawing on research in public health, communications, and psychology to illuminate the factors that shape beliefs and attitudes toward the condition, as well as the consequences of specific lay theories for cognition and behavior. At the individual level, we discuss how certain ways of thinking about obesity facilitate obesity treatment and prevention. At the societal level, we discuss how certain ways of thinking about obesity lead people to support (and oppose) specific types of obesity-related policy interventions. We pay special attention to the role of narrative framing and individual demographics in the etiology of lay beliefs and explore how particular psychological mechanisms (e.g., empathy) can affect attributions and attitudes

    A Connectionist Approach to Embodied Conceptual Metaphor

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    A growing body of data has been gathered in support of the view that the mind is embodied and that cognition is grounded in sensory-motor processes. Some researchers have gone so far as to claim that this paradigm poses a serious challenge to central tenets of cognitive science, including the widely held view that the mind can be analyzed in terms of abstract computational principles. On the other hand, computational approaches to the study of mind have led to the development of specific models that help researchers understand complex cognitive processes at a level of detail that theories of embodied cognition (EC) have sometimes lacked. Here we make the case that connectionist architectures in particular can illuminate many surprising results from the EC literature. These models can learn the statistical structure in their environments, providing an ideal framework for understanding how simple sensory-motor mechanisms could give rise to higher-level cognitive behavior over the course of learning. Crucially, they form overlapping, distributed representations, which have exactly the properties required by many embodied accounts of cognition. We illustrate this idea by extending an existing connectionist model of semantic cognition in order to simulate findings from the embodied conceptual metaphor literature. Specifically, we explore how the abstract domain of time may be structured by concrete experience with space (including experience with culturally specific spatial and linguistic cues). We suggest that both EC researchers and connectionist modelers can benefit from an integrated approach to understanding these models and the empirical findings they seek to explain

    Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for lynch syndrome

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    We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister’s colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified

    Francisella tularensis Elicits IL-10 via a PGE2-Inducible Factor, to Drive Macrophage MARCH1 Expression and Class II Down-Regulation

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    Francisella tularensis is a bacterial pathogen that uses host-derived PGE2 to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE2 acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE2 can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensis macrophage supernatant), which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 “resistant” class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE2 can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE2 drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE2, these results suggest that a yet-to-be-identified PGE2-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens

    Metaphors We Think With: The Role of Metaphor in Reasoning

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    The way we talk about complex and abstract ideas is suffused with metaphor. In five experiments, we explore how these metaphors influence the way that we reason about complex issues and forage for further information about them. We find that even the subtlest instantiation of a metaphor (via a single word) can have a powerful influence over how people attempt to solve social problems like crime and how they gather information to make “well-informed” decisions. Interestingly, we find that the influence of the metaphorical framing effect is covert: people do not recognize metaphors as influential in their decisions; instead they point to more “substantive” (often numerical) information as the motivation for their problem-solving decision. Metaphors in language appear to instantiate frame-consistent knowledge structures and invite structurally consistent inferences. Far from being mere rhetorical flourishes, metaphors have profound influences on how we conceptualize and act with respect to important societal issues. We find that exposure to even a single metaphor can induce substantial differences in opinion about how to solve social problems: differences that are larger, for example, than pre-existing differences in opinion between Democrats and Republicans

    Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures

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    Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 x 10(-23) and p = 6 x 10(-11), respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers. Germline biallelic pathogenic MUTYH variants predispose patients to colorectal cancer (CRC); however, approaches to identify MUTYH variant carriers are lacking. Here, the authors evaluated mutational signatures that could distinguish MUTYH carriers in large CRC cohorts, and found MUTYH-associated somatic mutations
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