Despite a long-standing effort to characterize various aspects of the singing voice and their relations to speech, the lack of a suitable and publicly available dataset has precluded any systematic study on the quantitative difference between singing and speech at the phone level. We hereby present the NUS Sung and Spoken Lyrics Corpus (NUS-48E corpus) as the first step toward a large, phonetically annotated corpus for singing voice research. The corpus is a 169-min collection of audio recordings of the sung and spoken lyrics of 48 (20 unique) English songs by 12 subjects and a complete set of transcriptions and duration annotations at the phone level for all recordings of sung lyrics, comprising 25,474 phone instances. Using the NUS-48E corpus, we conducted a preliminary, quantitative study on the comparison between singing voice and speech. The study includes duration analyses of the sung and spoken lyrics, with a primary focus on the behavior of consonants, and experiments aiming to gauge how acoustic representations of spoken and sung phonemes differ, as well as how duration and pitch variations may affect the Mel Frequency Cepstral Coefficients (MFCC) features.
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease whose underlying molecular mechanisms are largely unknown. Herein, we show that focal adhesion kinase-related nonkinase (FRNK) plays a key role in limiting the development of lung fibrosis. Loss of FRNK function in vivo leads to increased lung fibrosis in an experimental mouse model. The increase in lung fibrosis is confirmed at the histological, biochemical, and physiological levels. Concordantly, loss of FRNK function results in increased fibroblast migration and myofibroblast differentiation and activation of signaling proteins that drive these phenotypes. FRNK-deficient murine lung fibroblasts also have an increased capacity to produce and contract matrix proteins. Restoration of FRNK expression in vivo and in vitro reverses these profibrotic phenotypes. These data demonstrate the multiple antifibrotic actions of FRNK. More important, FRNK expression is down-regulated in human IPF, and down-regulation of FRNK in normal human lung fibroblasts recapitulates the profibrotic phenotype seen in FRNK-deficient cells. The effect of loss and gain of FRNK in the experimental model, when taken together with its down-regulation in human IPF, suggests that FRNK acts as an endogenous negative regulator of lung fibrosis by repressing multiple profibrotic responses.
Accurate calculation of root water uptake (RWU) is the key to improving vegetation water use efficiency and identifying water cycle evolution patterns, and root tips play an important role in RWU. However, most of the current RWU models in the alpine meadow are calculated based on the root length density (RLD) function. In this study, a large number of roots, soil hydraulic conductivity, and physicochemical property indices were obtained by continuous field prototype observation experiments for up to 2 years. It was found that the RLD and root tip density (RTD) in alpine meadows decrease by 16.2% and 14.6%, respectively, in the wilting stage compared to the regreening stage. The RTD distribution function of the alpine meadow was constructed, and the RWU model was established accordingly. The results show that the RTD function is more accurate than the RLD function to reflect the RWU pattern. Compared with RLD, the simulated RWU model constructed by using RTD as the root index that can effectively absorb water increased by 24.64% on average, and the simulated values were more consistent with the actual situation. It can be seen that there is an underestimation of RWU calculated based on the RLD function, which leads to an underestimation of the effect of climate warming on evapotranspiration. The simulation results of the RWU model based on RTD showed that the RWU rate in the regreening stage increased by 30.24% on average compared with that in the wilting stage. Meanwhile, the top 67% of the rhizosphere was responsible for 86.76% of the total RWU on average. This study contributes to the understanding of the alpine meadow water cycle system and provides theoretical support for the implementation of alpine meadow vegetation protection and restoration projects.
Permanent and reversible genetic modifications are important approaches to study gene function in different cell types. They are also important for stem cell researchers to explore and test the therapeutic potential of stem cells. The piggyBac transposon from insects is a rising nonviral system that efficiently mutagenizes and mediates gene transfer into the mammalian genome. It is also characterized by its precise excision, leaving no trace sequence behind so that the genomic integrity of the mutated cell can be restored. Here, we use an optimized piggyBac transposon system to mediate gene transfer and expression of a bifunctional fluorescent reporter in human embryonic stem (ES) cells. We provide molecular evidence for transposase-mediated piggyBac integration events and functional evidence for successful expression of a transferred fluorescent protein genes in human ES cells and their in vitro differentiated derivatives. We also demonstrate that the integrated piggyBac transposon can be removed and an undisrupted insertion site can be restored, which implies potential applications for its use in gene therapy and genetics studies.
The Model AI Assignments session seeks to gather and disseminate the best assignment designs of the Artificial Intelligence (AI) Education community. Recognizing that assignments form the core of student learning experience, we here present abstracts of six AI assignments from the 2022 session that are easily adoptable, playfully engaging, and flexible for a variety of instructor needs. Assignment specifications and supporting resources may be found at http://modelai.gettysburg.edu.
Myofibroblasts are implicated in pathological stromal responses associated with lung fibrosis. One prominent phenotypic marker of fully differentiated myofibroblasts is the polymerized, thick cytoplasmic filaments containing newly synthesized α-smooth muscle actin (α-SMA). These α-SMA-containing cytoplasmic filaments are important for myofibroblast contractility during tissue remodeling. However, the molecular mechanisms regulating the formation and maturation of α-SMA-containing filaments have not been defined. This study demonstrates a critical role for neuronal Wiskott-Aldrich syndrome protein (N-WASP) in regulating the formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and in myofibroblast contractility. Focal adhesion kinase (FAK) is activated by transforming growth factor-β1 (TGF-β1) and is required for phosphorylation of tyrosine residue 256 (Y256) of N-WASP. Phosphorylation of Y256 of N-WASP is essential for TGF-β1-induced formation of α-SMA-containing cytoplasmic filaments in primary human lung fibroblasts. In addition, we demonstrate that actin-related protein (Arp) 2/3 complex is downstream of N-WASP and mediates the maturation of α-SMA-containing cytoplasmic filaments. Together, this study supports a critical role of N-WASP in integrating FAK and Arp2/3 signaling to mediate formation of α-SMA-containing cytoplasmic filaments during myofibroblast differentiation and maturation.
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