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The present article describes a modified and extended replication of a corpus study by Brewer (2008. Phonetic reflexes of orthographic characteristics in lexical representation . Tucson, AZ: University of Arizona PhD thesis) which reports differences in the acoustic duration of homophonous but heterographic sounds. The original findings point to a quantity effect of spelling on acoustic duration, i.e., the more letters are used to spell a sound, the longer the sound's duration. Such a finding would have extensive theoretical implications and necessitate more research on how exactly spelling would come to influence speech production. However, the effects found by Brewer (2008) did not consistently reach statistical significance and the analysis did not include many of the covariates which are known by now to influence segment duration, rendering the robustness of the results at least questionable. Employing a more nuanced operationalization of graphemic units and a more advanced statistical analysis, the current replication fails to find the reported effect of letter quantity. Instead, we find an effect of graphemic complexity. Speakers realize consonants that do not have a visible graphemic correlate with shorter durations: the /s/ in tux is shorter that the /s/ in fuss . The effect presumably resembles orthographic visibility effects found in perception. In addition, our results highlight the need for a more rigorous approach to replicability in linguistics., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

According to the widely accepted Lexical Category Prominence Rule (LCPR), prominence assignment to triconstituent compounds depends on the branching direction. Left-branching compounds, that is, compounds with a left-hand complex constituent, are held to have highest prominence on the left-most constituent, whereas right-branching compounds have highest prominence on the second of the three constituents. The LCPR is, however, only poorly empirically supported. The present paper tests a new hypothesis concerning the prominence of triconstituent compounds and suggests a new methodology for the empirical investigation of compound prominence. According to this hypothesis, the prominence pattern of the embedded compound has a decisive influence on the prominence of the whole compound. Using a mixed-effects generalized additive model for the analysis of the pitch movements, it is shown that all triconstituent compounds have an accent on the first constituent irrespective of branching, and that the placement of a second, or even a third, accent is dependent on the prominence pattern of the embedded compound. The LCPR is wrong.

Severe congenital neutropenia is associated with a marked propensity to develop myelodysplasia or acute myeloid leukemia (AML). Truncation mutations of CSF3R, encoding the granulocyte colony-stimulating factor receptor (G-CSFR), are associated with development of myelodysplasia/AML in severe congenital neutropenia. However, a causal relationship between CSF3R mutations and leukemic transformation has not been established. Herein, we show that truncated G-CSFR cooperates with the PML-RARα oncogene to induce AML in mice. Expression of truncated G-CSFR significantly shortens the latency of AML in a G-CSF-dependent fashion and it is associated with a distinct AML presentation characterized by higher blast counts and more severe myelosuppression. Basal and G-CSF-induced signal transducer and activator of transcription 3, signal transducer and activator of transcription 5, and extracellular signal-regulated kinase 1/2 phosphorylation were highly variable but similar in leukemic blasts expressing wild-type and truncated G-CSFR. These data provide new evidence suggesting a causative role for CSF3R mutations in human AML., (Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

A fundamental property of leukemic stem cells is clonal dominance of the bone marrow microenvironment. Truncation mutations of CSF3R, which encodes the G-CSF receptor (G-CSFR), are implicated in leukemic progression in patients with severe congenital neutropenia. Here we show that expression of a truncated mutant Csf3r in mice confers a strong clonal advantage at the HSC level that is dependent upon exogenous G-CSF. G-CSF-induced proliferation, phosphorylation of Stat5, and transcription of Stat5 target genes were increased in HSCs isolated from mice expressing the mutant Csf3r. Conversely, the proliferative advantage conferred by the mutant Csf3r was abrogated in myeloid progenitors lacking both Stat5A and Stat5B, and HSC function was reduced in mice expressing a truncated mutant Csf3r engineered to have impaired Stat5 activation. These data indicate that in mice, inappropriate Stat5 activation plays a key role in establishing clonal dominance by stem cells expressing mutant Csf3r.

Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Like most other bone marrow failure syndromes, it is associated with a marked propensity to transform into a myelodysplastic syndrome (MDS) or acute leukemia, with a cumulative rate of transformation to MDS/leukemia that exceeds 20%. The genetic (and/or epigenetic) changes that contribute to malignant transformation in SCN are largely unknown. In this study, we performed mutational profiling of 14 genes previously implicated in leukemogenesis using 14 MDS/leukemia samples from patients with SCN. We used high-throughput exon-based resequencing of whole-genome-amplified genomic DNA with a semiautomated method to detect mutations. The sensitivity and specificity of the sequencing pipeline was validated by determining the frequency of mutations in these 14 genes using 188 de novo AML samples. As expected, mutations of tyrosine kinase genes (FLT3, KIT, and JAK2) were common in de novo AML, with a cumulative frequency of 30%. In contrast, no mutations in these genes were detected in the SCN samples; instead, mutations of CSF3R, encoding the G-CSF receptor, were common. These data support the hypothesis that mutations of CSF3R may provide the "activated tyrosine kinase signal" that is thought to be important for leukemogenesis.

Context: Adrenocortical carcinomas are uncommon, and their evaluation by [(18)F]fluorodeoxyglucose positron emission tomography (FDG PET) has not been well evaluated., Objective: The purpose of this study was to examine the potential utility of FDG PET in the detection of recurrent or metastatic adrenocortical carcinoma., Design: In patients with known adrenocortical carcinoma who underwent FDG-PET imaging for suspected recurrence or metastasis, FDG activity was compared with other imaging findings, clinical features, and the presence or absence of disease as confirmed by resection, biopsy, or clinical follow-up., Setting: The study took place at four tertiary referral centers., Patients or Other Participants: Twelve patients (10 females and two males, 5-71 yr of age) were evaluated., Main Outcome Measures: The main outcome measures were FDG activity, other imaging findings, and clinical features., Results: Abnormal FDG uptake correctly indicated tumor recurrence in 10 patients. One patient with no abnormal FDG activity had a morphological abnormality subsequently proven to be a postoperative scar. Two patients, one with very small pulmonary lesions and one with a hepatic metastasis, had false-negative findings., Conclusions: Most adrenocortical carcinomas accumulate and retain FDG and thus can be visualized by PET. However, false-negative findings are possible, especially with very small lesions.