432 research outputs found

    Evaluational adjectives

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    This paper demarcates a theoretically interesting class of "evaluational adjectives." This class includes predicates expressing various kinds of normative and epistemic evaluation, such as predicates of personal taste, aesthetic adjectives, moral adjectives, and epistemic adjectives, among others. Evaluational adjectives are distinguished, empirically, in exhibiting phenomena such as discourse-oriented use, felicitous embedding under the attitude verb `find', and sorites-susceptibility in the comparative form. A unified degree-based semantics is developed: What distinguishes evaluational adjectives, semantically, is that they denote context-dependent measure functions ("evaluational perspectives")—context-dependent mappings to degrees of taste, beauty, probability, etc., depending on the adjective. This perspective-sensitivity characterizing the class of evaluational adjectives cannot be assimilated to vagueness, sensitivity to an experiencer argument, or multidimensionality; and it cannot be demarcated in terms of pretheoretic notions of subjectivity, common in the literature. I propose that certain diagnostics for "subjective" expressions be analyzed instead in terms of a precisely specified kind of discourse-oriented use of context-sensitive language. I close by applying the account to `find x PRED' ascriptions

    Polarization transfer in wide-angle Compton scattering and single-pion photoproduction from the proton

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    Wide-angle exclusive Compton scattering and single-pion photoproduction from the proton have been investigated via measurement of the polarization transfer from a circularly polarized photon beam to the recoil proton. The wide-angle Compton scattering polarization transfer was analyzed at an incident photon energy of 3.7 GeV at a proton scattering angle of θpcm=70°. The longitudinal transfer KLL, measured to be 0.645±0.059±0.048, where the first error is statistical and the second is systematic, has the same sign as predicted for the reaction mechanism in which the photon interacts with a single quark carrying the spin of the proton. However, the observed value is ∼3 times larger than predicted by the generalized-parton-distribution-based calculations, which indicates a significant unknown contribution to the scattering amplitude

    Atomic-scale confinement of optical fields

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    In the presence of matter there is no fundamental limit preventing confinement of visible light even down to atomic scales. Achieving such confinement and the corresponding intensity enhancement inevitably requires simultaneous control over atomic-scale details of material structures and over the optical modes that such structures support. By means of self-assembly we have obtained side-by-side aligned gold nanorod dimers with robust atomically-defined gaps reaching below 0.5 nm. The existence of atomically-confined light fields in these gaps is demonstrated by observing extreme Coulomb splitting of corresponding symmetric and anti-symmetric dimer eigenmodes of more than 800 meV in white-light scattering experiments. Our results open new perspectives for atomically-resolved spectroscopic imaging, deeply nonlinear optics, ultra-sensing, cavity optomechanics as well as for the realization of novel quantum-optical devices

    Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism That Increases Risk of Docetaxel-Induced Neuropathy

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    Purpose Discovery of single nucleotide polymorphisms (SNPs) that predict a patient\u27s risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy. Experimental Design A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence of grade 3+ sensory neuropathy using a cause-specific hazard model that accounted for early treatment discontinuation. Genes with SNPs significantly associated with neuropathy were knocked down in cellular and mouse models of drug-induced neuropathy. Results 498,081 SNPs were analyzed in 623 Caucasian patients, 50 (8%) of whom experienced grade 3+ neuropathy. The 1000 SNPs most associated with neuropathy clustered in relevant pathways including neuropathic pain and axonal guidance. A SNP in VAC14 (rs875858) surpassed genome-wide significance (p=2.12×10-8 adjusted p=5.88×10-7). siRNA knockdown of VAC14 in stem cell derived peripheral neuronal cells increased docetaxel sensitivity as measured by decreased neurite processes (p=0.0015) and branches (p\u3c0.0001). Prior to docetaxel treatment VAC14 heterozygous mice had greater nociceptive sensitivity than wild-type litter mate controls (p=0.001). Conclusions VAC14 should be prioritized for further validation of its potential role as a predictor of docetaxel-induced neuropathy and biomarker for treatment individualization
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