Gradient categories in lexically-conditioned phonology: An example from sound symbolism

There are many approaches to modeling lexically-conditioned phonology in current formal theories, including lexically-indexed constraints and cophonologies. Nearly all of these existing approaches assume categorical membership in the lexical classes that condition differential phonotactics or phonological behaviours: for example, a lexical item is either a noun or a verb, or of one gender class or another. This paper proposes an implementation of Maximum Entropy Harmonic Grammar with lexically-indexed constraints and gradient symbolic activations over classes that allows us to model differences in phonological patterns over both discrete and gradient class membership. This theoretical implementation is a natural extension of the scales and gradient activations that have been shown to be necessary in recent phonological theory: sound symbolic evidence highlights the necessity for such increased explanatory power in our phonological models. Crucially, we find gradient lexically-conditioned patterns not only in sound symbolism—where they are often most obvious—but also in what is considered “core” language (e.g., morphosyntactic classes), and allowing gradient class structures in our phonological models may ultimately make for cleaner interfaces with other parts of grammar such as morphosyntax

Subsegments and the emergence of segments

Q Theory proposes that the most granular and basic temporal unit of abstract phonological representation is not the segment, as widely assumed in classic generative phonology, but the quantized subsegment. With a more granular quantization of the speech stream, Q Theory provides phonological grammar with the representational capability to model behaviors that affect both the parts and the wholes of segments. In Q Theory, segments are emergent from strings of subsegments and from subsegmental interactions based on the principles of similarity, proximity, and co-occurrence that already underlie phonological operations. Evidence is presented from linguistic typology, and mechanics are drawn from speech segmentation and recognition. Q Theory makes it possible to develop an advanced theory of complex segments

Morphologically-conditioned tonotactics in multilevel Maximum Entropy grammar

This paper presents a novel approach to probabilistic morphologically-conditioned tonotactics, featuring a case study of Mende, in which tonotactics vary by lexical category. This variation in surface tone patterns is modeled via indexed weight adjustments (i.e., varying slopes) for each constraint in a Maximum Entropy Harmonic Grammar, quantifying the degree to which each lexical class follows basic tonotactic principles in a common base grammar. Approaching morphologically-conditioned phonotactics as indexed weight adjustments of a base grammar offers a solution to the existing stalemate between single grammar (e.g., indexed constraints) and multiple grammar (e.g., Stratal OT; cophonologies) models of lexically-sensitive phonological patterns

Looking into Segments

This paper outlines Q theory, in which the traditional segment (consonant, vowel) is decomposed into a string of three ordered subsegments, or q, representing the onset, target, and offset of the segment. The postulation of subsegmental structure permits the representation of complex (contour) segments as well as subtle contrasts in segment-internal changes of state. Q Theory synthesizes insights from Autosegmental Phonology, Aperture Theory, and Articulatory Phonology in a representation that standard phonological constraints can refer to. Q theory is supported by arguments that subsegments act independently and need to be independently referenced by the phonological grammar. Embedded into Agreement by Correspondence Theory, Q theory permits the analysis of contour assimilation as well as contour formation, both in the tonal and segmental domains.

Pokémonikers: A study of sound symbolism and Pokémon names

Sound symbolism flouts the core assumption of the arbitrariness of the sign in human language. The cross-linguistic prevalence of sound symbolism raises key questions about the universality versus language-specificity of sound symbolic correspondences. One challenge to studying cross-linguistic sound symbolic patterns is the difficulty of holding constant real-world referents across cultures. In this study, we address the challenge of cross-linguistic comparison by utilising a rich, cross-linguistic dataset drawn from the Pokémon game franchise. Within this controlled universe, we compare the sound symbolisms of Japanese and English Pokémon names (pokemonikers). Our results show a tendency in both languages to encode the same attributes with sound symbolism, but also reveal key differences rooted in language-specific structural and lexical constraints

Diagnostic biomarkers in ovarian cancer: advances beyond CA125 and HE4

Ovarian cancer (OC) is the most lethal gynaecologic malignancy, attributed to its insidious growth, non-specific symptoms and late presentation. Unfortunately, current screening modalities are inadequate at detecting OC and many lack the appropriate specificity and sensitivity that is desired from a screening test. Nearly 70% of cases are diagnosed at stage III or IV with poor 5-year overall survival. Therefore, the development of a sensitive and specific biomarker for early diagnosis and screening for OC is of utmost importance. Currently, diagnosis is guided by CA125, the patient’s menopausal status and imaging features on ultrasound scan. However, emerging evidence suggests that a combination of CA125 and HE4 (another serum biomarker) and patient characteristics in a multivariate index assay may provide a higher specificity and sensitivity than either CA125 and HE4 alone in the early detection of OC. Other attempts at combining various serum biomarkers into one multivariate index assay such as OVA1, ROMA and Overa have all shown promise. However, significant barriers exist before these biomarkers can be implemented in clinical practice. This article aims to provide an up-to-date review of potential biomarkers for screening and early diagnosis of OC which may have the potential to transform its diagnostic landscape

Critical roles for WDR72 in calcium transport and matrix protein removal during enamel maturation

Defects in WDR72 (WD repeat‐containing protein 72) cause autosomal recessive hypomaturation amelogenesis imperfecta. We generated and characterized Wdr72‐knockout/lacZ‐knockin mice to investigate the role of WDR72 in enamel formation. In all analyses, enamel formed by Wdr72 heterozygous mice was indistinguishable from wild‐type enamel. Without WDR72, enamel mineral density increased early during the maturation stage but soon arrested. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Despite the failure to further mineralize enamel deposited during the secretory stage, ectopic mineral formed on the enamel surface and penetrated into the overlying soft tissue. While the proteins in the enamel matrix were successfully degraded, the digestion products remained inside the enamel. Interactome analysis of WDR72 protein revealed potential interactions with clathrin‐associated proteins and involvement in ameloblastic endocytosis. The maturation stage mandibular incisor enamel did not stain with methyl red, indicating that the enamel did not acidify beneath ruffle‐ended ameloblasts. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Fewer blood vessels were observed in the papillary layer supporting ameloblasts. Specific WDR72 expression by maturation stage ameloblasts explained the observation that enamel thickness and rod decussation (established during the secretory stage) are normal in the Wdr72 null mice. We conclude that WDR72 serves critical functions specifically during the maturation stage of amelogenesis and is required for both protein removal and enamel mineralization.We generated knockout mice lacking the ability to make WDR72. Deletion of WDR72 caused retention of degraded enamel proteins within the mineral layer and significantly reduced mineralization. The null enamel layer was only a tenth as hard as wild‐type enamel and underwent rapid attrition following eruption. Attachment of maturation ameloblasts to the enamel layer was weakened, and SLC24A4, a critical ameloblast calcium transporter, did not localize appropriately along the ameloblast distal membrane. Interactome analysis of WDR72 protein revealed potential involvement in ameloblastic endocytosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112233/1/mgg3143.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112233/2/mgg3143-sup-0001-SuppInfo.pd

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P < 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification