The disparate effects of different flow patterns play important roles in regulating the functions of vascular endothelial cells (ECs). The focal nature of atherosclerotic plaque formation reveals that the pulsatile flow (PS) along the straight part of arterial tree exerts athero-protective effects on the ECs, while the disturbed flow characterized as the oscillatory flow (OS) found at the arterial bifurcation induces pro- atherogenic responses. MicroRNAs (miRNAs) can regulate many vascular functions, but their roles in regulating endothelial responses to different types of fluid shear stresses remain unexplored. Using a genome-wide microarray approach, I profiled miRNA and mRNA expression levels in human ECs under 24-h PS and OS flows, as well as static control. Bioinformatics analyses of mRNA profiles indicate that PS flow predominantly regulates EC growth arrest genes, while OS flow primarily modulates EC inflammatory genes. Functional and miRNA studies show that PS flow suppresses EC proliferation through the effects of miR-23b on cell cycle machinery, and that OS causes sustained expression of miR-21 to contribute to pro-inflammatory responses. Further mechanistic studies indicate that the PS flow-induced miR-23b modulates the integrity and activity of CDK-activating kinase (CAK) by directly targeting the cyclin H (CCNH) expression post- transcriptionally, which in turn suppresses the transcriptions and activities of CDK2, CDK4, as well as RNA polymerase II (Pol II). The reductions in basal transcriptions and cell cycle regulatory proteins result in the hypo-phosphorylation state of retinoblastoma (Rb) gene and protein, and hence EC growth arrest. These results reveal that the miR-23b/CAK/Pol II pathway is differentially regulated by PS and OS flows to result in their opposite effects on EC proliferation. Such a flow pattern-dependent correlation is validated in studies in vivo on rat carotid artery stenosis and ligation: the flow disturbance/reduction induced in the carotid artery in vivo led to a lower expression of miR-23b and a higher EC proliferation, in agreement with the studies on cultured ECs in vitro. These findings provide the functional understanding of the role of miRNAs in vascular biology, and also provide directions for the development of novel approaches for the diagnosis, treatment, and prevention of atherosclerotic diseases

This volume adds to the body of emerging studies of telecollaboration among learners of Asian and Pacific languages.

In the last fifteen years, there have been major paradigm shifts in both general and applied linguistics toward acknowledging intonation as an indispensable component of language and communication. In addition, the hardware and software for conducting acoustic phonetic signal analysis have recently become more accessible. The main goal of this paper is thus to integrate the two seemingly disparate subfields of linguistics, acoustic phonetics, and discourse intonation, and to suggest a new framework for facilitating and studying the acquisition of suprasegmental phonology. The purpose of this article is threefold: (1) to review previous research on the acquisition of suprasegmentale by L2 learners and the potential of computer-based instructional materials for improving intonation; (2) to briefly describe and critique some of the software previously available for this purpose; and (3) to suggest criteria for the conceptualization of multimedia software and concomitant research on the teaching of discourse-based phonology and intonation. In looking toward the future, this article will focus on providing learners with discourse-level language input and with specific feedback regarding acoustic features of the intonation patterns they produce. Finally, the article urges that software be designed to include both research tools and tools to facilitate, record, and analyze the intonation produced in real interactions between speakers.

The purpose of this study is to analyze the effectiveness of the global Programme for International Student Assessment (PISA) in tackling educational inequity, with an emphasis on the academic experiences of UCSB students. This research was done amidst the various controversies among local academic institutions, which included the 2019 California college admissions scandals and 2020 cost of living adjustment (COLA) protests. PISA is primarily a topdown initiative as it mainly champions educational equity through collaborations with government officials. This neglects the key role of community actors, such as governors and principals, and does not account for localized complexities, such as federalism in the United States. To identify bottom-up approaches that would complement PISA, a pilot study on the academic experiences of UCSB students was done. Key findings included 88% of the respondents coming from counties with higher standards of living, and only 3% having considered an overseas university education. The paper thus suggests that the global PISA initiative is inadequate in resolving localized educational inequities and raises two bottom-up programs – college open-day sessions in disadvantaged counties and local forums on state education policies – to improve socio-spatial disparities in educational equity.

A short commentary on Jonathan B. Jarvis's essay "Designing climate resilience for people and nature at the landscape scale," published in this issue of Parks Stewardship Forum.