Pan-tissue analysis of APA regulation in hybrid mice

Alternative polyadenylation (APA), which is regulated by both cis-elements and trans-factors, is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. It could change the 3'UTR of an mRNA transcript affecting its stability, translation efficiency, nuclear export and mRNA or translated protein localization, or, if an exonic/intronic polyadenylation site (PAS) upstream of the stop codon is used, it could affect a gene's coding region to produce different protein isoforms with distinct properties. Accumulating evidence suggests that global APA-mediated 3'UTR length change might play an important role in oncogenic transformation, pluripotency, lymphocyte activation, neuronal stimulation and in embryonic development and differentiation. However, recent studies found limited effects of 3'UTRs in most genes compared to other regulatory elements located in 5'UTRs or coding sequence. APA as a molecular trait is a low-level phenotype in the hierarchy of biological organization, and might only exert very limited effects on organismal fitness. Therefore, some researchers proposed the “error hypothesis”, stating that most observed APA is noise and that APA diversity within and between tissues is generally neutral or deleterious, and not functional. Similarly, it has been suggested that APA divergence between species is largely non-adaptive. This scenario would be consistent with the (nearly) neutral theory of molecular evolution, which predicts that genes under relaxed selective constraints accumulate neutral (or slightly deleterious) changes at a faster rate than those under stronger purifying selection. In order to clarify the general and tissue-dependent function and regulation of APA and its evolution in mammals, we applied 3'mRNA sequencing for multiple tissues of an F1 hybrid between the C57BL/6J (Mus musculus) and SPRET/EiJ (Mus spretus) mouse strains. We analyzed the factors regulating APA diversity and addressed the question whether APA is generally non-adaptive as proposed by the error hypothesis. In this study, we quantified all annotated PASs in nine tissues of the F1 hybrid mouse and comprehensively characterized different features of single-PAS genes and multi-PAS genes. Next, we checked the positional effects on PAS strength and discussed the functional difference between rank 1 and rank 2 PASs among distinct gene groups. By quantifying PAS usage in each allele, we studied the genes with divergent major PAS expression level and dN/dS ratio difference, and unveiled different evolutionary patterns between APA patterns and gene expression (mRNA levels). We found that in general APA of multi-PAS genes is consistent with the error hypothesis, and that most APA diversity within and between tissues appears to reflect noise, resulting from molecular error due to weak cis-regulation. However, we did not find different selective constraint in dN/dS between genes with high and with low APA diversity, but found strong correlation between mRNA abundance and APA accuracy. The minor and major relative PAS usage is also affected by PAS position. In addition to most major PAS, many minor PASs appear to have functional importance. They are highly conserved and can compete with the major PASs. Last, we found a small fraction of genes exhibits strongly tissue-regulated APA patterns. In these genes, PAS usage is under intensive trans-regulation between the C57BL/6J and SPRET/EiJ alleles in the F1 hybrid mouse. Whereas many divergent PASs exist between the two alleles in genes with low expression level and under relax selective constraints, comparing these with genes showing allelic mRNA transcript level differences, we unveiled different evolutionary patterns between APA and gene expression

Study on Spatial Variation of Shear Mechanical Properties of Soil-rock Mixture

The soil-rock mixture (SRM) is a kind of special engineering geological material, which has been exposed to the field for a long time and is affected by rainwater seepage, geological force, slope sliding force and human activities, resulting in the spatial variability of its mechanical properties. Taking the SRM distributed on a slope of the Three Gorges Reservoir area as the research object, four test locations were selected along and transverse the slope. First, in-situ large-scale direct shear test was carried out, and then the laboratory large-scale direct shear test, particle sieving test, and water content test were carried out in the undisturbed sample to study the variation of shear mechanical properties of SRM distributed in different spatial locations. The results show that: (1) Under the same normal stress, the peak strength of the SRM decreases at a similar rate along the slope direction and the transverse slope direction. (2) The cohesion of the SRM is continuously strengthened, and the friction angle is continuously deteriorated along the slope from high to low, the cohesion and friction angle are almost no variability along the transverse slope. (3) The mechanism of the above-mentioned variation in the shear mechanics parameters of SRM is that the lower the elevation along the slope, the more fragmented the rock, the lower the rock content. (4) Spatial variability models of cohesion and friction angle of SRM were established, which can provide references for related engineering applications

Revealing driver psychophysiological response to emergency braking in distracted driving based on field experiments

Purpose – The purpose of this paper is to characterize distracted driving by quantifying the response time and response intensity to an emergency stop using the driver’s physiological states. Design/methodology/approach – Field tests with 17 participants were conducted in the connected and automated vehicle test field. All participants were required to prioritize their primary driving tasks while a secondary nondriving task was asked to be executed. Demographic data, vehicle trajectory data and various physiological data were recorded through a biosignalsplux signal data acquisition toolkit, such as electrocardiograph for heart rate, electromyography for muscle strength, electrodermal activity for skin conductance and force-sensing resistor for braking pressure. Findings – This study quantified the psychophysiological responses of the driver who returns to the primary driving task from the secondary nondriving task when an emergency occurs. The results provided a prototype analysis of the time required for making a decision in the context of advanced driver assistance systems or for rebuilding the situational awareness in future automated vehicles when a driver’s take-over maneuver is needed. Originality/value – The hypothesis is that the secondary task will result in a higher mental workload and a prolonged reaction time. Therefore, the driver states in distracted driving are significantly different than in regular driving, the physiological signal improves measuring the brake response time and distraction levels and brake intensity can be expressed as functions of driver demographics. To the best of the authors’ knowledge, this is the first study using psychophysiological measures to quantify a driver’s response to an emergency stop during distracted driving

RenewNAT: Renewing Potential Translation for Non-Autoregressive Transformer

Non-autoregressive neural machine translation (NAT) models are proposed to accelerate the inference process while maintaining relatively high performance. However, existing NAT models are difficult to achieve the desired efficiency-quality trade-off. For one thing, fully NAT models with efficient inference perform inferior to their autoregressive counterparts. For another, iterative NAT models can, though, achieve comparable performance while diminishing the advantage of speed. In this paper, we propose RenewNAT, a flexible framework with high efficiency and effectiveness, to incorporate the merits of fully and iterative NAT models. RenewNAT first generates the potential translation results and then renews them in a single pass. It can achieve significant performance improvements at the same expense as traditional NAT models (without introducing additional model parameters and decoding latency). Experimental results on various translation benchmarks (e.g., \textbf{4} WMT) show that our framework consistently improves the performance of strong fully NAT methods (e.g., GLAT and DSLP) without additional speed overhead.Comment: Accepted by AAAI2

catena-Poly[[(1,10-phenanthroline-κ2 N,N′)copper(I)]-μ2-iodido]

The solvothermal reaction of copper(I) iodide and 1,10-phenanthroline (phen) in ethanol yielded the title polymeric compound, [CuI(C12H8N2)]n. The asymmmetric unit comprises one Cu+ cation, one I− anion and one phen ligand. Each Cu+ cation is in a distorted tetrahedral coordination by two iodide anions and two N atoms from a bidentate chelating phen ligand. The Cu+ cations are bridged through the iodide anions, leading to a zigzag chain structure extending parallel to [100]. There are π–π inter­actions among adjacent phen ligands of one chain [centroid–centroid distance = 3.693 (3) Å]