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Creating an artificial head for acoustic testing requires an in-depth understanding of how humans speak and hear. HEAD acoustics explains the technology underpinning their HMS II.3 test devices.

Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation. In lieu of viral ssRNA activation, we explored EV-encapsulated miR-21 as an endogenous ligand and observed induction of both TLR8 and cytokine expression in vitro. Moreover, extracellular miR detection was found predominantly within EVs. Thus, just as a cytokine or chemokine, EV-encapsulated miR-21 can act as an inflammatory signaling molecule, or miRokine, by virtue of being an endogenous ligand of TLR8. Collectively, our data elucidates a novel innate inflammatory pathway in SLE.

Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology.

German manifests a phonological pattern of word-final consonant devoicing, with an underlying voicing contrast that is largely ‘‘neutralized’’ in speech, whereas English has a surface voicing contrast in final position. This raises questions concerning how well native German speakers learning English can produce a voicing contrast in English while continuing to neutralize the underlying German contrast, and especially how German speakers produce similar word pairs in the two languages (e.g., English: rod/rot; German: Rad/ Rat). The present study examined the speech of 13 native Germans producing words in both languages and 13 native English speakers’ productions of English words. Acoustic analyses indicated that the native Germans showed more evidence of a final voicing distinction when producing English words than for phonologically similar German words. However, they typically produced fewer or less robust acoustic cues to word-final voicing when speaking English than the native English speakers did. An auditory word identification task also assessed intelligibility of German-accented and native English for German and English listeners. In contrast to studies showing an interlanguage speech intelligibility benefit, German listeners found native English speech to be more intelligible than German-accented English for the English word-final voicing contrast; they also did not find German-accented English more intelligible than native English listeners did. r 2009 Elsevier Ltd. All rights reserved.

Despite the widespread use of curcumin for centuries in Eastern medicine as an anti-inflammatory agent, its molecular actions and therapeutic viability have only recently been explored. While curcumin does have potential therapeutic efficacy, both solubility and bioavailability must be improved before it can be more successfully translated to clinical care. We have previously reported a novel formulation of nano-emulsion curcumin (NEC) that achieves significantly greater plasma concentrations in mice after oral administration. Here, we confirm the immunosuppressive effects of NEC in vivo and further examine its molecular mechanisms to better understand therapeutic potential. Using transgenic mice harboring an NFκB-luciferase reporter gene, we demonstrate a novel application of this in vivo inflammatory model to test the efficacy of NEC administration by bioluminescent imaging and show that LPS-induced NFκB activity was suppressed with NEC compared to an equivalent amount of curcumin in aqueous suspension. Administration of NEC by oral gavage resulted in a reduction of blood monocytes, decreased levels of both TLR4 and RAGE expression, and inhibited secretion of MCP-1. Mechanistically, curcumin blocked LPS-induced phosphorylation of the p65 subunit of NFκB and IκBα in murine macrophages. In a mouse model of peritonitis, NEC significantly reduced macrophage recruitment, but not T-cell or B-cell levels. In addition, curcumin treatment of monocyte derived cell lines and primary human macrophages in vitro significantly inhibited cell migration. These data demonstrate that curcumin can suppress inflammation by inhibiting macrophage migration via NFκB and MCP-1 inhibition and establish that NEC is an effective therapeutic formulation to increase the bioavailability of curcumin in order to facilitate this response.

A number of languages manifest a pattern of word‐final obstruent devoicing, i.e., words ending with underlying voiced obstruents are pronounced so as to be (largely) indistinguishable from words ending with final voiceless obstruents. One question regarding this tendency to devoice voiced obstruent targets is what occurs when native speakers of such a language learn a second language that has a word‐final obstruent voicing contrast. For example, do German speakers neutralize voicing contrasts in English as they tend to do in German, or can they learn to produce voiced obstruents in Englis, despite devoicing them in German? To examine this issue, ten native speakers of German produced various phonologically‐similar minimal pairs in German and English (e.g., English: Lied/light; German: Leid/leit). Acoustic measurements were made of their productions in both languages, viz., vowel duration preceding final consonants, final consonant duration, duration of voicing during final consonants, and final release burst duration; their English productions were also compared to those of native English speakers. The native German speakers tended to neutralize the voicing distinction to a greater extent when producing German words versus phonologically‐similar English words, but they typically did not produce as much of a contrast in English as native English speakers.