The Four Horsemen

http://deepblue.lib.umich.edu/bitstream/2027.42/108391/1/anniech_1366881472.pd

Attainment of a global perspective through study abroad programmes in Hong Kong

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Analysis of congestion key parameters, dynamic discharge process, and capacity estimation at urban freeway bottlenecks: a case study in Beijing, China

Recurring bottlenecks significantly contribute to urban freeway congestion, making their analysis essential. This study examines six bottlenecks on Beijing’s Ring Road using multi-day data, identifying them via Dynamic Time Warping and Fuzzy C-Means Clustering (DTW+FCM). Key parameters—free-flow speed, critical speed, critical density, and jam density—are calibrated using fundamental diagram models. The Weibull distribution analyzes flow and speed patterns during congestion phases. The DTW+FCM method effectively identified bottlenecks and congestion levels. Severe congestion lasting over 10 hours on the West Second and Third Ring Roads averaged speeds of 15 km/h. The S3 model best fits data for the West Ring Roads, while the Van Aerde model suits the North Ring Roads. Different methods yield varying traffic capacity estimates, highlighting the need for nuanced approaches in urban expressway planning to maintain traffic quality and comfort. These findings offer valuable guidance for research and practical traffic management solutions

DCB-3503, a Tylophorine Analog, Inhibits Protein Synthesis through a Novel Mechanism

BACKGROUND: DCB-3503, a tylophorine analog, inhibits the growth of PANC-1 (human pancreatic ductal cancer cell line) and HepG2 (human hepatocellular cancer cell line) tumor xenografts in nude mice. The inhibition of growth leads to cancer cell differentiation instead of cell death. However, the mechanisms of action of tylophorine analogs is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that DCB-3503 suppresses the expression of pro-oncogenic or pro-survival proteins with short half-lives, including cyclin D1, survivin, beta-catenin, p53, and p21, without decreasing their mRNA levels. Proteasome inhibitor reversed the inhibitory effect of DCB-3503 on expression of these proteins. DCB-3503 inhibited the incorporation of radiolabeled amino acid and thymidine, and to a much lesser degree of uridine, in a panel of cell lines. The mechanism of inhibition of protein synthesis is different from that of cycloheximide (CHX) as assayed in cell culture and HeLa in vitro translation system. Furthermore, in contrast to rapamycin, DCB-3503 does not affect protein synthesis through the mTOR pathway. DCB-3503 treatment shifts the sedimentation profiles of ribosomes and mRNAs towards the polysomal fractions while diminishing monosome abundance, indicative of the inhibition of the elongation step of protein synthesis. Preferential down regulation of several studied proteins under these conditions is likely due to the relative short half-lives of these proteins. CONCLUSION/SIGNIFICANCE: The inhibitory effect of DCB-3503 on translation is apparently distinct from any of the current anticancer compounds targeting protein synthesis. Translation inhibitors with novel mechanism could complement current chemotherapeutic agents for the treatment of human cancers and suppress the occurrence of drug resistance

HIMA2: High-dimensional mediation analysis and its application in epigenome-wide DNA methylation data

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150-3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849-911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

An Analysis of Extreme Price Shocks and Illiquidity among Systematic Trend Followers

Also presented in the R/Rmetrics Singapore Conference 2010 - Computational Topics in Finance, Singapore, February 2010 and 5th International Symposium on Financial Engineering and Risk Management, Taipei, Taiwan, June 2010</p

The Ubiquitin Binding Domain ZnF UBP Recognizes the C-Terminal Diglycine Motif of Unanchored Ubiquitin

SummaryUbiquitin binding proteins regulate the stability, function, and/or localization of ubiquitinated proteins. Here we report the crystal structures of the zinc-finger ubiquitin binding domain (ZnF UBP) from the deubiquitinating enzyme isopeptidase T (IsoT, or USP5) alone and in complex with ubiquitin. Unlike other ubiquitin binding domains, this domain contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted, thus explaining the specificity of IsoT for an unmodified C terminus on the proximal subunit of polyubiquitin. Mutations in the domain demonstrate that it is required for optimal catalytic activation of IsoT. This domain is present in several other protein families, and the ZnF UBP domain from an E3 ligase also requires the C terminus of ubiquitin for binding. These data suggest that binding the ubiquitin C terminus may be necessary for the function of other proteins

An Analysis of Extreme Price Shocks and Illiquidity among Systematic Trend Followers

Ministry of Education, Singapore under its Academic Research Funding Tier