Driving Simulator Validity of Driving Behavior in Work Zones

Driving simulation is an efficient, safe, and data-collection-friendly method to examine driving behavior in a controlled environment. However, the validity of a driving simulator is inconsistent when the type of the driving simulator or the driving scenario is different. The purpose of this research is to verify driving simulator validity in driving behavior research in work zones. A field experiment and a corresponding simulation experiment were conducted to collect behavioral data. Indicators such as speed, car-following distance, and reaction delay time were chosen to examine the absolute and relative validity of the driving simulator. In particular, a survival analysis method was proposed in this research to examine the validity of reaction delay time. The result indicates the following: (1) most indicators are valid in driving behavior research in the work zone. For example, spot speed, car-following distance, headway, and reaction delay time show absolute validity. (2) Standard deviation of the car-following distance shows relative validity. Consistent with previous researches, some driving behaviors appear to be more aggressive in the simulation environment. Document type: Articl

Lattice dynamics and heat transport in zeolitic imidazolate framework glasses

The glassy state of zeolitic imidazolate frameworks (ZIFs) has shown great potential for energy-related applications, including solid electrolytes. However, their thermal conductivity (κ), an essential parameter influencing thermal dissipation, remains largely unexplored. In this work, using a combination of experiments, atomistic simulations, and lattice dynamics calculations, we investigate κ and the underlying heat conduction mechanism in ZIF glasses with varying ratios of imidazolate (Im) to benzimidazolate (bIm) linkers. The substitution of bIm for Im tunes the node-linker couplings but exhibits only a minor impact on the average diffusivity of low-frequency lattice modes. On the other hand, the linker substitution induces significant volume expansion, which, in turn, suppresses the contributions from lattice vibrations to κ, leading to decreased total heat conduction. Furthermore, spatial localization of internal high-frequency linker vibrations is promoted upon substitution, reducing their mode diffusivities. This is ascribed to structural deformations of the bIm units in the glasses. Our work unveils the detailed influences of linker substitution on the dual heat conduction characteristics of ZIF glasses and guides the κ regulation of related hybrid materials in practical applications.</p

Development of AlphaLISA high throughput technique to screen for small molecule inhibitors targeting protein arginine methyltransferases

The protein arginine methyltransferase (PRMT) family of enzymes comprises nine family members in mammals. They catalyze arginine methylation, either monomethylation or symmetric/asymmetric dimethylation of histone and non-histone proteins. PRMT methylation of its substrate proteins modulates cellular processes such as signal transduction, transcription, and mRNA splicing. Recent studies have linked overexpression of PRMT5, a member of the PRMT superfamily, to oncogenesis, making it a potential target for cancer therapy. In this study, we developed a highly sensitive (Z' score = 0.7) robotic high throughput screening (HTS) platform to discover small molecule inhibitors of PRMT5 by adapting the AlphaLISA™ technology. Using biotinylated histone H4 as a substrate, and S-adenosyl-l-methionine as a methyl donor, PRMT5 symmetrically dimethylated H4 at arginine (R) 3. Highly specific acceptor beads for symmetrically dimethylated H4R3 and streptavidin-coated donor beads bound the substrate, emitting a signal that is proportional to the methyltransferase activity. Using this powerful approach, we identified specific PRMT5 inhibitors P1608K04 and P1618J22, and further validated their efficacy and specificity for inhibiting PRMT5. Importantly, these two compounds exhibited much more potent efficacy than the commercial PRMT5 inhibitor EPZ015666 in both pancreatic and colorectal cancer cells. Overall, our work highlights a novel, powerful, and sensitive approach to identify specific PRMT5 inhibitors. The general principle of this HTS screening method can not only be applied to PRMT5 and the PRMT superfamily, but may also be extended to other epigenetic targets. This approach allows us to identify compounds that inhibit the activity of their respective targets, and screening hits like P1608K04 and P1618J22 may serve as the basis for novel drug development to treat cancer and/or other diseases

Mapping and functional characterization of structural variation in 1060 pig genomes

BACKGROUND: Structural variations (SVs) have significant impacts on complex phenotypes by rearranging large amounts of DNA sequence.RESULTS: We present a comprehensive SV catalog based on the whole-genome sequence of 1060 pigs (Sus scrofa) representing 101 breeds, covering 9.6% of the pig genome. This catalog includes 42,487 deletions, 37,913 mobile element insertions, 3308 duplications, 1664 inversions, and 45,184 break ends. Estimates of breed ancestry and hybridization using genotyped SVs align well with those from single nucleotide polymorphisms. Geographically stratified deletions are observed, along with known duplications of the KIT gene, responsible for white coat color in European pigs. Additionally, we identify a recent SINE element insertion in MYO5A transcripts of European pigs, potentially influencing alternative splicing patterns and coat color alterations. Furthermore, a Yorkshire-specific copy number gain within ABCG2 is found, impacting chromatin interactions and gene expression across multiple tissues over a stretch of genomic region of ~200 kb. Preliminary investigations into SV's impact on gene expression and traits using the Pig Genotype-Tissue Expression (PigGTEx) data reveal SV associations with regulatory variants and gene-trait pairs. For instance, a 51-bp deletion is linked to the lead eQTL of the lipid metabolism regulating gene FADS3, whose expression in embryo may affect loin muscle area, as revealed by our transcriptome-wide association studies.CONCLUSIONS: This SV catalog serves as a valuable resource for studying diversity, evolutionary history, and functional shaping of the pig genome by processes like domestication, trait-based breeding, and adaptive evolution.</p

P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer.</p> <p>Methods</p> <p>Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA.</p> <p>Results</p> <p>HMBA increased p27Kip1 expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3β inhibition.</p> <p>Conclusions</p> <p>The results presented herein suggest that GSK-3β functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial cell differentiation.</p

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

A Methodology and Tool for Concurrent Fault Injection

As the speed of microprocessors tails off, utilizing multiple processing cores per chip is becoming a common way for developers to achieve higher performance. However, writing concurrent programs can be a big challenge because of common concurrency faults. Because concurrency faults are hard to detect and reproduce, traditional testing techniques are not suitable. New techniques are needed, and these must be assessed. A typical method for assessing testing techniques is to embed faults in programs using mutation tools, and assess the ability of techniques to detect these. Although mutation testing techniques can be used to represent common faults, approaches for representing concurrency faults have not been created. In this paper, we introduce a methodology for injecting mutations related to concurrency faults, focusing on four common concurrency fault patterns as mutant operators. We implement the approach in the Eclipse IDE. We empirically study our approach\u27s effectiveness by using it to seed various types of concurrency faults based on the four fault patterns in a set of programs. This approach generates many times more mutants than can be seeded by hand. We then execute the original programs and these mutants. We characterize the mutants in terms of detectability as part of our study. The results show that using the proposed tool, concurrent fault injection tool (CFIT) is feasible and efficient. Adviser: Gregg Rothermel and Witty Srisa-a

Driving Simulator Validity of Driving Behavior in Work Zones

Driving simulation is an efficient, safe, and data-collection-friendly method to examine driving behavior in a controlled environment. However, the validity of a driving simulator is inconsistent when the type of the driving simulator or the driving scenario is different. The purpose of this research is to verify driving simulator validity in driving behavior research in work zones. A field experiment and a corresponding simulation experiment were conducted to collect behavioral data. Indicators such as speed, car-following distance, and reaction delay time were chosen to examine the absolute and relative validity of the driving simulator. In particular, a survival analysis method was proposed in this research to examine the validity of reaction delay time. The result indicates the following: (1) most indicators are valid in driving behavior research in the work zone. For example, spot speed, car-following distance, headway, and reaction delay time show absolute validity. (2) Standard deviation of the car-following distance shows relative validity. Consistent with previous researches, some driving behaviors appear to be more aggressive in the simulation environment

Effectiveness of Active Luminous Lane Markings on Highway at Night: A Driving Simulation Study

Road lane markings play an essential role in maintaining traffic order and improving traffic safety and efficiency. Active luminous lane markings have emerged with advances in technology recently. However, it is still not completely clear what impact their application will have on drivers. This paper aimed to study the effectiveness of active luminous lane markings on highways at night. A driving simulation experiment was carried out based on advanced driving simulators at Tongji University. The driving simulation experiment involved 31 participants and 9 simulation scenes with 6 different types of lane markings models and the same 2-way highway segment, which was 5300-m long with four 3.75-m wide driving lanes. The study participants drove through the simulated highway while the vehicle operation data and the driver’s eyes changing data were continuously captured. Overall, the pupil area change rate, steering wheel speed, brake pedal force, gas pedal, lane departure, and operating speed indicators were selected to evaluate the effectiveness of the active luminous lane markings. The results are shown as follows: (1) the active luminous lane markings have excellent visual recognition performance at night. Compared with the passive luminous lane markings, the active luminous markings can reduce the mental and physical loads of drivers, increase the early braking distance significantly, improve the lane-keeping ability and smooth the operating speed; (2) for the specific parameter settings of the active luminous lane markings at night, the yellow lane markings are better than the white ones, the point-line-type lane markings are superior to the conventional-type ones, and the blinking frequency is reasonable to set, at a moderate level, as 40 times per min. The results suggest that there are positive effects of active luminous lane markings on the promotion of highway traffic safety and efficiency at night, providing theoretical support for the popularization and application of active luminous road lane markings