9 research outputs found
How We Express Ourselves Freely: Censorship, Self-censorship, and Anti-censorship on a Chinese Social Media
Censorship, anti-censorship, and self-censorship in an authoritarian regime
have been extensively studies, yet the relationship between these intertwined
factors is not well understood. In this paper, we report results of a
large-scale survey study (N = 526) with Sina Weibo users toward bridging this
research gap. Through descriptive statistics, correlation analysis, and
regression analysis, we uncover how users are being censored, how and why they
conduct self-censorship on different topics and in different scenarios (i.e.,
post, repost, and comment), and their various anti-censorship strategies. We
further identify the metrics of censorship and self-censorship, find the
influence factors, and construct a mediation model to measure their
relationship. Based on these findings, we discuss implications for democratic
social media design and future censorship research.Comment: iConference 2023 has accepte
UV stabilizer intercalated layered double hydroxide to enhance the thermal and UV degradation resistance of polypropylene fiber
Polypropylene (PP) fiber is widely used in construction, transportation, automobile, textile, electronic and electrical appliances, chemical industry, and other fields; however, its nonresistance to UV degradation must be further studied. Herein, 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (UVSA) anion was inserted into zinc-aluminum-layered double hydroxide (ZnAl-LDH) by coprecipitation, and the organic-inorganic synergistic UV-stabilized material UVSA-LDH was successfully synthesized. Furthermore, a new UVSA-LDH/PP fiber with UV aging resistance was prepared by adding UVSA-LDH to the PP matrix through the melt spinning method. The insertion of UVSA improved the ultraviolet absorption of ZnAl-LDH, and the existence of LDH laminates inhibited the thermal degradation of organic UVSA. Moreover, the addition of UVSA-LDH greatly enhanced the thermal stability and UV aging degradation resistance of PP fiber. As expected, compared with pure PP fiber, the thermal decomposition temperature of 3 wt% UVSA-LDH/PP composite fiber increased by 38 °C, and the fiber strength retention was as high as 94.56% after aging for 6 days. Therefore, this organic-inorganic synergistic UVSA-LDH has potential application prospect as a UV-stabilized material for PP fiber
Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies
ABSTRACTPharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool can be used to produce materials for the toxicology (Tox) study, reducing time to the clinic by 4â5âmonths. During the coronavirus disease 2019 (COVID-19) pandemic, the anti-COVID drugs timeline from DNA transfection to the clinical stage was decreased to 6âmonths using a stable pool to generate a clinical drug substrate (DS) with limited stability, virus clearance, and Tox study package. However, a lean chemistry, manufacturing, and controls (CMC) package raises safety and comparability risks and may leave extra work in the late-stage development and commercialization phase. In addition, whether these accelerated COVID-19 drug development strategies can be applied to non-COVID projects and established as a standard practice in biologics development is uncertain. Here, we present a case study of a novel anti-tumor drug in which application of âfast-to-FIHâ approaches in combination with BeiGeneâs de-risk strategy achieved successful delivery of a complete CMC package within 10âmonths. A comprehensive comparability study demonstrated that the DS generated from a stable pool and a single-cell-derived master cell bank were highly comparable with regards to process performance, product quality, and potency. This accomplishment can be a blueprint for non-COVID drug programs that approach the pace of drug development during the pandemic, with no adverse impact on the safety, quality, and late-stage development of biologics
Polymerase IV occupancy at RNA-directed DNA methylation sites requires SHH1
DNA methylation is an epigenetic modification that plays critical roles in gene silencing, development, and genome integrity. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) and targeted by 24 nt small interfering RNAs (siRNAs) through a pathway termed RNA-directed DNA methylation (RdDM)(1). This pathway requires two plant-specific RNA polymerases: Pol-IV, which functions to initiate siRNA biogenesis and Pol-V, which functions to generate scaffold transcripts that recruit downstream RdDM factors(1,2). To understand the mechanisms controlling Pol-IV targeting we investigated the function of SAWADEE HOMEODOMAIN HOMOLOG 1 (SHH1)(3,4), a Pol-IV interacting protein(3). Here we show that SHH1 acts upstream in the RdDM pathway to enable siRNA production from a large subset of the most active RdDM targets and that SHH1 is required for Pol-IV occupancy at these same loci. We also show that the SHH1 SAWADEE domain is a novel chromatin binding module that adopts a unique tandem Tudor-like fold and functions as a dual lysine reader, probing for both unmethylated K4 and methylated K9 modifications on the histone 3 (H3) tail. Finally, we show that key residues within both lysine binding pockets of SHH1 are required in vivo to maintain siRNA and DNA methylation levels as well as Pol-IV occupancy at RdDM targets, demonstrating a central role for methylated H3K9 binding in SHH1 function and providing the first insights into the mechanism of Pol-IV targeting. Given the parallels between methylation systems in plants and mammals(1,5), a further understanding of this early targeting step may aid in our ability to control the expression of endogenous and newly introduced genes, which has broad implications for agriculture and gene therapy