Interactions between extracellular signal‐regulated kinase 1/2 and P38 Map kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity

RUNX2, a key transcription factor for osteoblast differentiation, is regulated by ERK1/2 and p38 MAP kinase‐mediated phosphorylation. However, the specific contribution of each kinase to RUNX2‐dependent transcription is not known. Here we investigate ERK and p38 regulation of RUNX2 using a unique P‐RUNX2‐specific antibody. Both MAP kinases stimulated RUNX2 Ser319 phosphorylation and transcriptional activity. However, a clear preference for ERK1 versus p38α/β was found when the ability of these MAPKs to phosphorylate and activate RUNX2 was compared. Similarly, ERK1 preferentially bound to a consensus MAPK binding site on RUNX2 that was essential for the activity of either kinase. To assess the relative contribution of ERK1/2 and p38 to osteoblast gene expression, MC3T3‐E1 preosteoblast cells were grown in control or ascorbic acid (AA)‐containing medium ± BMP2/7. AA‐induced gene expression, which requires collagen matrix synthesis, was associated with parallel increases in P‐ERK and RUNX2‐S319‐P in the absence of any changes in P‐p38. This response was blocked by ERK, but not p38, inhibition. Significantly, in the presence of AA, BMP2/7 synergistically stimulated RUNX2 S319 phosphorylation and transcriptional activity without affecting total RUNX2 and this response was totally dependent on ERK/MAPK activity. In contrast, although p38 inhibition partially blocked BMP‐dependent transcription, it did not affect RUNX2 S319 phosphorylation, suggesting the involvement of other phosphorylation sites and/or transcription factors in this response. Based on this work, we conclude that extracellular matrix and BMP regulation of RUNX2 phosphorylation and transcriptional activity in osteoblasts is predominantly mediated by ERK rather than p38 MAPKs. © 2012 American Society for Bone and Mineral Research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90254/1/561_ftp.pd

Transformer-based Acoustic Modeling for Hybrid Speech Recognition

We propose and evaluate transformer-based acoustic models (AMs) for hybrid speech recognition. Several modeling choices are discussed in this work, including various positional embedding methods and an iterated loss to enable training deep transformers. We also present a preliminary study of using limited right context in transformer models, which makes it possible for streaming applications. We demonstrate that on the widely used Librispeech benchmark, our transformer-based AM outperforms the best published hybrid result by 19% to 26% relative when the standard n-gram language model (LM) is used. Combined with neural network LM for rescoring, our proposed approach achieves state-of-the-art results on Librispeech. Our findings are also confirmed on a much larger internal dataset.Comment: to appear in ICASSP 202

Aggregate manganese Schiff base moieties by terephthalate or acetate: Dinuclear manganese and trinuclear mixed metal Mn-2/Na complexes

A reaction system consisting of terephthalic acid, NaOH, inorganic Mn(II) or Mn(III) salt, and salicylidene alkylimine resulted in dinuclear manganese complexes (salpn)(2)Mn-2(mu-phth)(CH3OH)(2) (1, salpn = N,N'-1,3-propylene-bis(salicylideneiminato); phth = terephthalate dianion), (salen)(2)Mn-2(mu-phth)(CH3OH)(2) (2, salen = N,N'-ethylene-bis(salicylideneiminato)), (salen)(2)Mn-2(mu-phth)(CH3OH)(H2O) (3), and (salen)(2)Mn-2(mu-phth) (4), while the absence of NaOH in the reaction led to a mononuclear Mn complex (salph)Mn(CH3OH)(NO3) (5, salph = N,N'-1,2-phenylene-bis(salicylideneiminato)). In addition, a trinuclear mixed metal complex H{Mn2Na(salpn)(2)(mu-OAc)(2)(H2O)(2)}(OAc)(2) (6) was obtained from the reaction system by using maleic acid instead of terephthalic acid. Five-coordinate Mn ions were found in 4 giving rise to an intermolecular interaction and constructing a one-dimensional linear structure. Antiferromagnetic exchange interactions were observed for 1-3, and a total ferromagnetic exchange of 4 was considered to stem from intermolecular magnetic coupling. H-1 NMR signals of phenolate ring and alkylene (or phenylene) backbone of the diamine are similar to those reported in the literature, and the phth protons are at -2.3 to -10.1 ppm. Studies on structure, bond valence sum analysis, and magnetic properties indicate the oxidation states of the Mn ions in 6 to be +3, which are also indicated by ESR spectra in dual mode. Ferromagnetic exchange interaction between the Mn(III) sites was observed with J = 1.74 cm(-1). A quasireversible redox pair at -0.29V/0.12V has been assigned to the redox of Mn-2(III)/Mn(III)Mn(II), implying the intactness of the complex backbone in solution