Search

Author(s): Eileen Fung [1, 2]; Wilson W. Wong [1]; Jason K. Suen [1]; Thomas Bulter [1]; Sun-gu Lee [1]; James C. Liao (corresponding author) [1, 2] Autonomous oscillations found in [...]

Mililani Trask was born into the world of politics and struggle for Native Hawaiian and human rights. Her grandfather, David Trask, was an early member of the Hawai'i Democratic Party, […]

Cut-and-paste (simple insertion) and replicative transposition pathways are the two classical paradigms by which transposable elements are mobilized. A novel variation of cut and paste, a two-step transposition cycle, has recently been proposed for insertion sequences of the IS3 family. In IS2 this variation involves the formation of a circular, putative transposition intermediate (the minicircle) in the first step. Two aspects of the minicircle may involve its proposed role in the second step (integration into the target). The first is the presence of a highly reactive junction formed by the two abutted ends of the element. The second is the assembly at the minicircle junction of a strong hybrid promoter which generates higher levels of transposase. In this report we show that IS2 possesses a highly reactive minicircle junction at which a strong promoter is assembled and that the promoter is needed for the efficient completion of the pathway. We show that the sequence diversions which characterize the imperfect inverted repeats or ends of this element have evolved specifically to permit the formation and optimal function of this promoter. While these sequence diversions eliminate catalytic activity of the left end (IRL) in the linear element, sufficient sequence information essential for catalysis is retained by the IRL in the context of the minicircle junction. These data confirm that the minicircle is an essential intermediate in the two-step transposition pathway of IS2.

This article identifies existing gaps of theory and practice in public administration between Western and non-Western nations. By placing national bureaucracies within a global context, the article develops a framework that can be applied to bridge the gaps, improve the cumulation of knowledge in public administration, and enhance the relevance of theory for practitioners. Based on the framework, the article hypothesizes ways in which global pressures such as continuously advancing information technology, the impact of global institutions, and demands for public-sector efficiency influence public bureaucracies. It concludes with guidance for future research and implications for practice., Public bureaucracies operate increasingly in a global environment that requires greater communication and cooperation among nations. This globalization of public administration has highlighted the parochial nature of much of the [...]

Cell-based transcriptional reporters are invaluable in high-throughput compound and CRISPR screens for identifying compounds or genes that can impact a pathway of interest. However, many transcriptional reporters have weak activities and transient responses. This can result in overlooking therapeutic targets and compounds that are difficult to detect, necessitating the resource-consuming process of running multiple screens at various timepoints. Here, we present RADAR, a digitizer circuit for amplifying reporter activity and retaining memory of pathway activation. Reporting on the AP-1 pathway, our circuit identifies compounds with known activity against PKC-related pathways and shows an enhanced dynamic range with improved sensitivity compared to a classical reporter in compound screens. In the first genome-wide pooled CRISPR screen for the AP-1 pathway, RADAR identifies canonical genes from the MAPK and PKC pathways, as well as non-canonical regulators. Thus, our scalable system highlights the benefit and versatility of using genetic circuits in large-scale cell-based screening. Cell-based transcriptional reporters are an invaluable part of highthroughput screening, but many such reporters have weak or transient responses. Here, the authors describe a digitizer circuit for amplifying reporter activity, increasing sensitivity, and retaining memory of pathway activation. [ABSTRACT FROM AUTHOR]

Purpose: This paper analyses the escalating Sino-Western race to develop a safe, efficacious and durable vaccine (i.e. "Goldilocks COVID-19 vaccine"). It argues that such efforts would be considerably more effective if there is greater international cooperation instead of the corrosive rivalry driven by misplaced nationalism. Design/methodology/approach: This study deploys a case-study approach, supported by literature on existing coronavirus disease 2019 (COVID-19) vaccine development efforts. Findings: Despite the seeming success of recent COVID-19 vaccines, their actual efficacy is far from certain. Moreover, access to these vaccines would not be equitable internationally. This problem is exacerbated by the fact that their unique properties make storage and distribution prohibitively expensive, and international mechanisms to provide distribution to economically depressed regions are non-existent. Given the significant difficulties, it would be incumbent upon the great powers (i.e. China and America) to work together not only in vaccine development but also in the establishment of a distribution platform to ensure equitable access worldwide. Originality/value: This study is one of the few social science research papers on COVID-19 vaccine development and its implications for society at large. [ABSTRACT FROM AUTHOR]