Real-time Traveler Information Performance Measures for Work Zone Congestion Management

To mitigate the work zone impacts on freeways, an advanced traveler information system (ATIS) was designed to promote the utilization of alternative routes and improve local road network performance. The system evaluation was performed during a bridge reconstruction project on the four-lane divided I-39/90 near the interchange with WIS59 at Edgerton, Wisconsin. Field comparisons between ATIS presence and absence discovered different diversion patterns in northbound and southbound directions associated with traffic delay. Drivers remained on the freeway when the displayed delay was less than 15 minutes while more drivers chose to leave the freeway with displayed delay greater than or equal to 15 minutes. A linear regression analysis was further conducted to investigate the impact of several factors, such as displayed delay time, freeway volume, exiting volume during the normal days (without a work zone), and the number of days after system implementation, on driver’s diversion behavior. The results showed that freeway volume, ramp exiting volume during normal days, and delay time were significant variables in causing a high diversion rate.In addition, it was demonstrated that ATIS performed effectively in increasing the work zone operational capacity. Furthermore, the reduced operating speed associated with the advance speed warning (part of the system) suggested that drivers reacted to the warning messages responding to the real-time speed collected through detectors. This comprehensive evaluation enriched the knowledge of driver behavior and reaffirmed the effectiveness of ITS applications in congestion mitigation

Kinship can hinder cooperation in heterogeneous populations

Kin selection and direct reciprocity are two most basic mechanisms for promoting cooperation in human society. Generalizing the standard models of the multi-player Prisoner's Dilemma and the Public Goods games for heterogeneous populations, we study the effects of genetic relatedness on cooperation in the context of repeated interactions. Two sets of interrelated results are established: a set of analytical results focusing on the subgame perfect equilibrium and a set of agent-based simulation results based on an evolutionary game model. We show that in both cases increasing genetic relatedness does not always facilitate cooperation. Specifically, kinship can hinder the effectiveness of reciprocity in two ways. First, the condition for sustaining cooperation through direct reciprocity is harder to satisfy when relatedness increases in an intermediate range. Second, full cooperation is impossible to sustain for a medium-high range of relatedness values. Moreover, individuals with low cost-benefit ratios can end up with lower payoffs than their groupmates with high cost-benefit ratios. Our results point to the importance of explicitly accounting for within-population heterogeneity when studying the evolution of cooperation

Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers

AbstractBackgroundFew pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China.Purpose1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions.MethodsThis open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests.ResultsTotally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94±6.59 and 9.47±5.47h, Cmax 435.74±348.10 and 346.54±155.66ng·mL−1, AUC0-t 8600.52±5264.77 and 9315.10±6820.03ng·mL−1·h, AUC0–∞ 8845.38±5838.18 and 9669.24±7326.53ng·mL−1·h, t1/2 10.06±8.83 and 9.87±10.35h; single dosing under fasting conditions, Tmax 7.29±4.87 and 6.57±1.85h, Cmax 247.85±110.05 and 244.64±132.43ng·mL−1, AUC0-t 3385.41±1418.92 and 3496.24±1767.29ng·mL−1·h, AUC0–∞ 3781.53±1556.96 and 3829.56±1981.25ng·mL−1·h, t1/2 13.07±17.24 and 10.26±7.78h; single dosing under fed conditions, Tmax 17.72±9.42 and 19.50±9.84h, Cmax 183.90±74.52 and 168.14±60.67ng·mL−1, AUC0-t 3181.71±1368.24 and 3575.11±1416.39ng·mL−1·h, AUC0–∞3442.39±2002.53 and 3624.44±1418.12ng·mL−1·h, t1/2 8.76±12.28 and 6.67±4.84h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC0–t and AUC0–∞ were located within 80%–125%, 90% CI for Cmax was within 70%–143%.ConclusionsSimilar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence.Chictr.org identifier: ChiCTR-TTRCC-14004853

Polydopamine-assisted immobilization of chitosan brushes on a textured CoCrMo alloy to improve its tribology and biocompatibility

Due to their bioinert and reliable tribological performance, cobalt chromium molybdenum (CoCrMo) alloys have been widely used for articular joint implant applications. However, friction and wear issues are still the main reasons for the failure of implants. As a result, the improvement of the tribological properties and biocompatibility of these alloys is still needed. Thus, surface modification is of great interest for implant manufacturers and for clinical applications. In this study, a strategy combining laser surface texturing and chitosan grafting (mussel inspired) was used to improve the tribological and biocompatible behaviors of CoCrMo. The microstructure and chemical composition were investigated by atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy, respectively. The tribological properties were discussed to determine their synergistic effects. To evaluate their biocompatibility, osteoblast cells were cocultured with the modified surface. The results show that there is a distinct synergistic effect between laser surface texturing and polymer brushes for improving tribological behaviors and biocompatibility. The prepared chitosan brushes on a textured surface are a strong mechanism for reducing friction force. The dimples took part in the hydrodynamic lubrication and acted as the container for replenishing the consumed lubricants. These brushes also promote the formation of a local lubricating film. The wear resistance of the chitosan brushes was immensely improved. Further, the worn process was observed, and the mechanism of destruction was demonstrated. Co-culturing with osteoblast cells showed that the texture and grafting have potential applications in enhancing the differentiation and orientation of osteoblast cell

The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network

SummaryPluripotent embryonic stem cells (ESCs) maintain self-renewal and the potential for rapid response to differentiation cues. Both ESC features are subject to epigenetic regulation. Here we show that the histone acetyltransferase Mof plays an essential role in the maintenance of ESC self-renewal and pluripotency. ESCs with Mof deletion lose characteristic morphology, alkaline phosphatase (AP) staining, and differentiation potential. They also have aberrant expression of the core transcription factors Nanog, Oct4, and Sox2. Importantly, the phenotypes of Mof null ESCs can be partially suppressed by Nanog overexpression, supporting the idea that Mof functions as an upstream regulator of Nanog in ESCs. Genome-wide ChIP-sequencing and transcriptome analyses further demonstrate that Mof is an integral component of the ESC core transcriptional network and that Mof primes genes for diverse developmental programs. Mof is also required for Wdr5 recruitment and H3K4 methylation at key regulatory loci, highlighting the complexity and interconnectivity of various chromatin regulators in ESCs

CNV discovery for milk composition traits in dairy cattle using whole genome resequencing

General statistics of 487 differential CNVRs between high and low group based on UMD3.1. (XLSX 28 kb

A colorimetric method for point mutation detection using high-fidelity DNA ligase

The present study reported proof-of-principle for a genotyping assay approach that can detect single nucleotide polymorphisms (SNPs) through the gold nanoparticle assembly and the ligase reaction. By incorporating the high-fidelity DNA ligase (Tth DNA ligase) into the allele-specific ligation-based gold nanoparticle assembly, this assay provided a convenient yet powerful colorimetric detection that enabled a straightforward single-base discrimination without the need of precise temperature control. Additionally, the ligase reaction can be performed at a relatively high temperature, which offers the benefit for mitigating the non-specific assembly of gold nanoparticles induced by interfering DNA strands. The assay could be implemented via three steps: a hybridization reaction that allowed two gold nanoparticle-tagged probes to hybrid with the target DNA strand, a ligase reaction that generates the ligation between perfectly matched probes while no ligation occurred between mismatched ones and a thermal treatment at a relatively high temperature that discriminate the ligation of probes. When the reaction mixture was heated to denature the formed duplex, the purple color of the perfect-match solution would not revert to red, while the mismatch gave a red color as the assembled gold nanoparticles disparted. The present approach has been demonstrated with the identification of a single-base mutation in codon 12 of a K-ras oncogene that is of significant value for colorectal cancers diagnosis, and the wild-type and mutant type were successfully scored. To our knowledge, this was the first report concerning SNP detection based on the ligase reaction and the gold nanoparticle assembly. Owing to its ease of operation and high specificity, it was expected that the proposed procedure might hold great promise in practical clinical diagnosis of gene-mutant diseases

Constructing a dual-function surface by microcasting and nanospraying for efficient drag reduction and potential antifouling capabilities

To improve the drag-reducing and antifouling performance of marine equipment, it is indispensable to learn from structures and materials that are found in nature. This is due to their excellent properties, such as intelligence, microminiaturization, hierarchical assembly, and adaptability. Considerable interest has arisen in fabricating surfaces with various types of biomimetic structures, which exhibit promising and synergistic performances similar to living organisms. In this study, a dual bio-inspired shark-skin and lotus-structure (BSLS) surface was developed for fabrication on commercial polyurethane (PU) polymer. Firstly, the shark-skin pattern was transferred on the PU by microcasting. Secondly, hierarchical micro- and nanostructures were introduced by spraying mesoporous silica nanospheres (MSNs). The dual biomimetic substrates were characterized by scanning electron microscopy, water contact angle characterization, antifouling, self-cleaning, and water flow impacting experiments. The results revealed that the BSLS surface exhibited dual biomimetic features. The micro- and nano-lotus-like structures were localized on a replicated shark dermal denticle. A contact angle of 147° was observed on the dual-treated surface and the contact angle hysteresis was decreased by 20% compared with that of the nontreated surface. Fluid drag was determined with shear stress measurements and a drag reduction of 36.7% was found for the biomimetic surface. With continuous impacting of high-speed water for up to 10 h, the biomimetic surface stayed superhydrophobic. Material properties such as inhibition of protein adsorption, mechanical robustness, and self-cleaning performances were evaluated, and the data indicated these behaviors were significantly improved. The mechanisms of drag reduction and self-cleaning are discussed. Our results indicate that this method is a potential strategy for efficient drag reduction and antifouling capabilities

Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway

Growing evidence indicates that aberrant methylation is pivotal in the development and progression of endometriosis (EMs). This study explores the relationship between abnormal methylation of the ENPP3 promoter and the pathogenesis of ovarian EMs, focusing on its regulatory effect on ENPP3 expression. We analyzed the methylation levels of ENPP3 in ectopic endometrial tissues from ovarian EMs patients and in normal endometrial tissues from women without EMs. The expression and distribution of ENPP3 were evaluated using RT-qPCR and immunohistochemistry. Transwell assays were conducted to examine the impact of ENPP3 overexpression on the migratory and invasive capabilities of endometrial stromal cells. Our results demonstrated significantly reduced methylation levels at the CpG sites of the ENPP3 promoter region in ectopic endometrial tissues compared to normal endometrial tissues. RT-qPCR findings revealed a marked increase in ENPP3 expression in ovarian EMs tissues relative to endometrial tissues from patients without EMs, and this upregulation was negatively correlated with the methylation levels of the ENPP3 promoter region. Immunohistochemical analyses confirmed elevated ENPP3 expression in the glandular epithelial cells and stroma of ovarian EMs tissues. Furthermore, in vitro experiments showed that overexpressed ENPP3 notably intensified the invasion and migration of endometrial stromal cells. Transcriptome sequencing and functional analyses indicated that the increased ENPP3 expression activated the AKT/mTOR/4EBP1 signaling pathway. In summary, the study suggests that hypomethylation in the ENPP3 promoter region may contribute to the initiation and advancement of ovarian EMs by activating the AKT/mTOR/4EBP1 pathway, supporting the theory that EMs might be an epigenetically regulated disorder