Screening and functional analysis of mutations in NEUROD1 gene in pedigrees of maturity-onset diabetes of the young

Objective·To screen the mutations of NEUROD1 gene in families of maturity-onset diabetes of the young (MODY), and investigate the correlation between the mutation and MODY6 and its potential pathogenesis in Chinese.Methods·PCR-direct sequencing was used for screening NEUROD1 mutations from 96 MODY probands who were negative for mutations in the GCK/MODY2, HNF1A/MODY3 and HNF1B/MODY5 genes, and the genotypic frequency of NEUROD1 variations were compared between the 96 MODY probands and 100 non-diabetic control subjects. A de novo modeling method was used to predict the three-dimensional (3D) structures of wild type (WT) and mutated NEUROD1 proteins. Transcriptional activities of both WT and mutant of NEUROD1 on insulin gene were detected by using dual luciferase reporter gene system.Results·Glu59Gln (NM_002500.5, c.175G>C), a heterozygous missense mutation in the NEUROD1 gene, was identified in a MODY pedigree. 3D structural analysis showed that the mutation transformed the negatively charged Glu59 of WT into uncharged mutation Gln59, leading to the loss of Glu59-Arg54 and Glu59-Lys88, two salt bridge bonds, and the formation of Gln59-Arg54, one new hydrogen bond. Transcriptional activity of Glu59Gln mutant for insulin gene was reduced by 36.3% when compared with that of WT (P<0.05). A common variation Ala45Thr (G-A) was identified, and AA+GA genotypic frequency of the variation was significantly elevated in the 96 MODY probands in comparison to non-diabetic control subjects (P=0.002).Conclusion·Glu59Gln mutation alters the N-terminal molecular conformation of NEUROD1 protein, resulting in decreased transcriptional activity of insulin gene, which is the cause of the defective insulin secretion in mutation carriers of the MODY6 pedigree. The Ala45Thr variation is associated with earlier age of onset of diabetes in MODY6 probands

Towards Predicting Equilibrium Distributions for Molecular Systems with Deep Learning

Advances in deep learning have greatly improved structure prediction of molecules. However, many macroscopic observations that are important for real-world applications are not functions of a single molecular structure, but rather determined from the equilibrium distribution of structures. Traditional methods for obtaining these distributions, such as molecular dynamics simulation, are computationally expensive and often intractable. In this paper, we introduce a novel deep learning framework, called Distributional Graphormer (DiG), in an attempt to predict the equilibrium distribution of molecular systems. Inspired by the annealing process in thermodynamics, DiG employs deep neural networks to transform a simple distribution towards the equilibrium distribution, conditioned on a descriptor of a molecular system, such as a chemical graph or a protein sequence. This framework enables efficient generation of diverse conformations and provides estimations of state densities. We demonstrate the performance of DiG on several molecular tasks, including protein conformation sampling, ligand structure sampling, catalyst-adsorbate sampling, and property-guided structure generation. DiG presents a significant advancement in methodology for statistically understanding molecular systems, opening up new research opportunities in molecular science.Comment: 80 pages, 11 figure

Traditional Chinese medicine residues promote the growth and quality of Salvia miltiorrhiza Bunge by improving soil health under continuous monoculture

Continuous monoculture of crops has resulted in reduced yields and quality, as well as soil deterioration. Although traditional Chinese medicine residues (TCMRs) are known to promote plant growth and soil health, few studies have investigated their effectiveness in continuous monoculture soils. Here, we studied the impact of chemical fertilizers (CF) and four TCMRs with antibacterial activities on the growth of S. miltiorrhiza (a widely used medicinal plant in China), accumulation of active ingredients in plants, and soil health under continuous monoculture conditions. Compared with no fertilizer (CK) and CF, fermented Sophora flavescens radix residue (SFRf) and fermented and unfermented Moutan cortex residue (MCRf and MCRu, respectively) resulted in a reduction of the disease index of root rot, while CF did not. The CF and four TCMR treatments increased the accumulation of nitrogen (N) (42.8-124.6% and 17.0-101.7%), phosphorous (P) (19.8-74.7% and 8.3-27.4%), and potassium (K) (104.1-212.0% and 9.3-51.8%) in shoots and roots compared to CK. The differences in nutrient accumulation between the CF and TCMR treatments were statistically insignificant, excepted for the N accumulation in the roots. All fertilization treatments increased plant biomass compared to CK, with increases of 25.57-89.86% and 2.62-35.28% in shoots and roots, respectively. The SFRf treatment exhibited the most significant enhancement in both shoot and root biomass. CF significantly reduced the accumulation of seven active ingredients in roots by 23.90-78.95% compared to CK, whereas each TCMR increased accumulation of certain active ingredients. The TCMR treatments effectively improved the health of deteriorated soil by enhancing soil physicochemical properties, restoring the balance of the microbial community, recruiting beneficial bacteria, and reducing the relative abundance of the pathogen Fusarium. The SFRf treatment exhibited superior performance in improving soil health than other treatments. Overall, the TCMRs outperformed CF in restoring soil health and promoting the yield and quality of S. miltiorrhiza. These findings offer guidance for improving the health of continuous cropping soil and recycling TCMRs

Air pollution perception in ten countries during the COVID-19 pandemic

NTNU Norwegian University of Science and TechnologypublishedVersionPaid Open AccessUNIT agreemen

The Localization Style Design Analysis of Domestic Animation The case study of

Scissors Seven as a GuangZhou native animation works has won a large number of fans on the Internet, network playback volume reached 260 million, and in 2018 became the only domestic animation in the Annecy international animation film festival, in 2019,in 2020 Magnolia Award for Best Animated Screenplay at the 26th Shanghai TV Festival became the only domestic animation work award in the past five years.Further more the film became Netflix online products, The Japanese and English versions can be seen in 29 countries and 190 regions .Most of the audiences love this work and gave a good comments. This paper will analyze the visual and auditory elements of the work around the localized style design of the film, so as to obtain the inspiration and thinking of domestic animation design

Energy Consumption and Environment Performance Analysis of Induction-Healed Asphalt Pavement by Life Cycle Assessment (LCA)

In this paper, the sustainability of induced healing asphalt pavement is demonstrated by comparing the impact of asphalt pavement maintained by induced healing asphalt pavement technology and traditional maintenance methods (such as milling and overlaying). The functional unit selected is a 1-km lane with an analysis period of 20 years. The stages to be considered are material manufacturing, paving, maintenance, milling and demolition. Two case studies were analyzed to assess the impact of different technologies on the energy consumption and environmental performance of each maintenance alternative. By comparing the energy consumption and environmental emissions of the whole life cycle of pavement under the two technical conditions, the results show that the total energy consumption of traditional asphalt pavement is about 2.5 times that of induction-healed asphalt pavement, and the total greenhouse gas (GHG) emissions of the former are twice as much as that of the latter

Railway ballast stabilising agents: Comparison of mechanical properties

Expensive and time-consuming maintenance operations are routinely performed to preserve the ballast mechanical properties in railway lines. Binding agents are used for ballast stabilisation. Four different additives based on bitumen, organosilane, lignosulphonate and polyurethane are investigated in the laboratory by means of repeated load triaxial tests. The parameters that are directly relevant for use in railway structures are assessed. Each binder type significantly influences both the resilient modulus and the resistance to permanent deformation of the treated specimens. The ballast mechanical properties can be conveniently modified, thus being beneficial to track stability and railway maintenance programme

Investigation of Permanent Deformation Behavior of Steel Slag Asphalt Mixture under Indoor Simulation

Previous studies have indicated that steel slag can be used as a substitute for natural aggregates in asphalt mixture, while little attention has been paid to systematic investigation of the influences of various external environmental factors on deformation resistance of steel slag asphalt mixture. In order to understand the service behavior of steel slag asphalt mixture, its permanent deformation under different condition was investigated based on an indoor simulation test. The chemical composition, microscopic structure, surface texture, and volume stability of steel slag were firstly characterized. The uniaxial repeated loading test and standard wheel-tracking test were applied to evaluate the effect of temperature, stress levels, and water damage on the permanent deformation of AC-16 and AC-20 steel slag asphalt mixtures. The results indicate that a higher content of alkaline oxide and high-grade texture index existing in steel slag contribute to its strong absorptivity and adhesion of asphalt. The steel slag demonstrates fine volume stability due to its lower free-CaO (f-CaO) content, autoclave chalked ratio, and immersion expansion ratio. The permanent deformation of steel slag asphalt mixtures increases rapidly under higher stress and temperatures in contrast to lower increment at lower stress and temperatures. Asphalt mixtures at higher stress and higher temperatures and water condition exhibit larger rutting deformation and inferior rutting resistance. AC-16 steel slag asphalt mixture has superior resistance to permanent deformation than AC-20 asphalt mixture. Rutting factors show different degrees of impact in a decreasing order of temperature, water damage, and stress levels. The findings have significant implications for providing a theoretical basis for reusing steel slag in pavement construction and facilitating engineering application of steel slag asphalt mixture

A Methodological Review on Development of Crack Healing Technologies of Asphalt Pavement

Crack healing has been a key area of asphalt pavement research. In this review, different crack-healing theories and crack-healing evaluation methods in bitumen and asphalt mixtures are summarized and presented. Then different crack healing technologies have highlighted the problems and solutions associated with their implementation. Detailly, traditional technologies (hot pouring and fog seal) are introduced. They mainly fill cracks from the outside, which can effectively prevent further damage to the asphalt pavement, when the cracks have generally developed to the middle and late stages of practical engineering. Their extension of the life of the asphalt pavement is relatively limited. Energy supply technologies (induction and microwave heating) have demonstrated significant efficacy in enhancing the crack healing capability of asphalt pavement, particularly in microcracks. Now, Extensive laboratory testing and some field test sections have been conducted and they are waiting for the promotion from the industry. The agents encapsulated technologies (Saturated porous aggregates encapsulate rejuvenators, Core-shell polymeric microcapsules, Ca-alginate capsule, Hollow fibers and Compartment fibers) not only heal cracks but rejuvenate the aged asphalt pavement. In order to promote industrial application, more field test sections and large industrial mixing and compaction equipment applications need to be implemented. Finally, some other potential crack healing techniques (coupling application, electrical conductivity, 3D printing, and modifications) are also mentioned

Research on asphalt surface layer performance over service time and establishment of ageing model for in-service bitumen under Norwegian conditions

Asphalt surface layer as one of the significant pavement layers is directly withstanding traffic loading and external service conditions, and its performance highly determines the life cycle cost of asphalt pavements. Bitumen ageing is an unavoidable process for asphalt surface layer, and it shortens the service life and increases the risk of distress of asphalt pavements. A large number of studies have been conducted on the consequences of asphalt surface layer ageing under ambient environmental conditions. However, the development of asphalt mixture performance under Norwegian conditions and ageing model for the in-service bitumen have not been extensively investigated. Therefore, this work aims to investigate asphalt surface layer performance over service time and establish ageing model for the in-service bitumen. To achieve this goal, core samples acquired from the field and bitumen extracted from in-service field cores were analysed by comparing them with reference bitumen and asphalt mixtures. The physical, chemical, viscoelastic and performance grade variables of the bitumen were characterised, as well as the dynamic modulus and density of asphalt mixtures. The ageing models for bitumen property parameters were established using bitumen type, service time and average annual temperature as independent variables after statistical data processing. As a result, a good agreement between predicted values and measured values of property parameters was achieved because of the high accuracy of prediction of the ageing model. The proposed ageing model for bitumen under Norwegian conditions is beneficial for predicting bitumen properties at specific service time