In recent years, a number of methodological approaches has been developed that allow for identifying patterns in first language acquisition. In most cases, such methods have been used to analyze monolingual acquisition. In a global perspective, however, monolingual acquisition is the exception, and multilingualism is the norm. This raises the question to what extent such pattern-detection methods can be used for multilingual data as well, especially in the case of code-mixing, i.e. the use of more than one language in a single utterance. In this paper, we explore the potential of a data-driven approach to child language data proposed by McCauley & Christiansen (2019a), viz. chunk-based learning, to account for multilingual acquisition data. In particular, we compare the patterns found in the children’s code-mixed utterances with those in their monolingual utterances to test the hypothesis that both types of utterances are ultimately constructed from the same “building blocks”.

Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system. Clin Cancer Res; 22(16); 4005-13. ©2016 AACR.

Words that are learned early were shown to be semantically more stable, and vice versa (Cassani et al. 2021, Cognitive Science). Semantic change, however, has multiple aspects. In this diachronic corpus study, we examine the relationship between the age of acquisition (AoA) of words and a set of different measures of semantic change: change in a word's polysemy; overall semantic displacement; and average extent of semantic fluctuation. All measures are based on diachronically layered sense distributions (Hu et al. 2019, ACL) derived from the Corpus of Historical American English. AoA is taken from Kuperman et al. (2012, Behav. Res. Meth.). Taking interactions with frequency into account, we show that semantic displacement and fluctuation are positively associated with AoA as expected. Early acquisition is associated with an increase in polysemy. This hints at the relevance of semantic (metaphorical) extension in the early acquisition of the lexicon.

Purpose: Human papillomavirus (HPV) 16 plays an etiologic role in a growing subset of head and neck squamous cell carcinomas (HNSCC), where viral expression of the E6 and E7 oncoproteins is necessary for tumor growth and maintenance. Although patients with HPV⁺ tumors have a more favorable prognosis, there are currently no HPV-selective therapies. Recent studies identified differential receptor tyrosine kinase (RTK) profiles in HPV⁺ versus HPV^- tumors. One such RTK, HER3, is overexpressed and interacts with phosphoinositide-3-kinase (PI3K) in HPV⁺ tumors. Therefore, we investigated the role of HPV oncoproteins in regulating HER3-mediated signaling and determined whether HER3 could be a molecular target in HPV⁺ HNSCC.Experimental Design: HER3 was investigated as a molecular target in HPV⁺ HNSCC using established cell lines, patient-derived xenografts (PDX), and human tumor specimens. A mechanistic link between HPV and HER3 was examined by augmenting E6 and E7 expression levels in HNSCC cell lines. The dependency of HPV⁺ and HPV^- HNSCC models on HER3 was evaluated with anti-HER3 siRNAs and the clinical stage anti-HER3 monoclonal antibody KTN3379.Results: HER3 was overexpressed in HPV⁺ HNSCC, where it was associated with worse overall survival in patients with pharyngeal cancer. Further investigation indicated that E6 and E7 regulated HER3 protein expression and downstream PI3K pathway signaling. Targeting HER3 with siRNAs or KTN3379 significantly inhibited the growth of HPV⁺ cell lines and PDXs.Conclusions: This study uncovers a direct relationship between HPV infection and HER3 in HNSCC and provides a rationale for the clinical evaluation of targeted HER3 therapy for the treatment of HPV⁺ patients. Clin Cancer Res; 23(12); 3072-83. ©2016 AACR.

Human papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.Significance: These findings suggest a new therapeutic combination that may improve outcomes in HPV(+) head and neck cancer patients. Cancer Res; 78(9); 2383-95. ©2018 AACR.