Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Microstructure and mechanical properties of TiAl alloys produced by rapid heating and open die forging of blended elemental powder compacts

Ti-43Al-5V-4Nb (at%) intermetallic compounds were fabricated by a rapid heating and open die forging method using blended elemental powders. The process route consisted of powder blending, compacting, rapid heating, open die forging and heat treatment. During heating there is porosity in the blended and warm compacted powder billets which still persists after the first forging. In order to remove this difficulty a two stage forging process was used. A fully lamellar structure was seen in the TiAl alloy after heat treatment. Overall, the TiAl alloy showed moderately good mechanical properties at room temperature and good mechanical properties, with reasonable strength and good ductility at high temperatures

Review of emulsified asphalt modification mechanisms and performance influencing factors

In recent years, with the improvement of the requirements of road performance, modified emulsified asphalts with better performance has gradually replaced the emulsified asphalt and become the primary material for road maintenance. This paper introduces the modified emulsified asphalt materials commonly used in pavement maintenance projects, definitions and modified mechanisms of polymerized styrene butadiene rubber (SBR) modified emulsified asphalt, styrene butadiene styrene block polymer (SBS) modified emulsified asphalt and waterborne epoxy resin (WER) modified emulsified asphalt are summarized. The analysis focused on comparing the effects of modifiers, preparation process, auxiliary additives, and other factors on the performance of modified emulsified asphalt. In this paper, it is considered that the greatest impact on the performance of emulsified asphalt is the modifier, emulsifier mainly affects the speed of breaking the emulsion, stabilizers on the basic performance of emulsified asphalt evaporative residue is small; and when the modifier is distributed in the asphalt in a network, the dosage at this time is the recommended optimum dosage. Finally, this study recommends that in the future, the polymer-asphalt compatibility can be improved through composite modification, chemical grafting and other methods to continue to develop broader applicability and better performance of modified emulsified asphalt

Health-related quality of life in children with haemophilia in China: a 4-year follow-up prospective cohort study

Abstract Background Health-related quality of life (HRQoL) has been brought up for decades in haemophilia patients. However, no data to date are available about HRQoL in children with haemophilia using long-term follow up data. This nearly 4-year follow-up study aimed to assess the long-term HRQoL of haemophilia children. Methods A prospective cohort study among 42 children with haemophilia and their parents was conducted in August 2014 in a children’s hospital; follow-up was completed in January 2018. Primary endpoint was the change in patient HRQoL evaluated by Canadian Haemophilia Outcomes–Kids’ Life Assessment Tool (CHO-KLAT) from baseline to year 4; secondary endpoint was the impact of bleeding rates, physical activity restriction, financial burden and treatment (prophylaxis vs on-demand treatment) on HRQoL, as well as the impact of treatment on event-free survival. Results Totally 42 patients (mean age, 5.48[SD, 4.63] years) and 42 parents were included. 38 families completed 4-year follow up. Patients reported a small increase in HRQoL from baseline to year 4. The mean scores of child self-report and parent proxy report of CHO-KLAT at baseline were 60.69 (SD = 20.28) and 61.01 (SD = 12.14), respectively. Scores at follow-up were 64.69 (SD = 13.71) and 65.33 (SD = 15.78), respectively. Haemophilia patients without physical activity restriction, living in urban areas, and receiving prophylactic treatment and home injection, had higher average values for HRQoL scores than the others. Bleeding rates were proportionally negatively correlated with HRQoL. Patients who had received prophylactic treatment had better event-free survival. Conclusions Haemophilia decreased HRQoL of patients, but this effect weakened after 4 years. HRQoL of children is influenced by severity of haemophilia, bleeding rates, physical activity restriction, financial burden and treatment. Prophylactic treatment is a key factor contributing to event-free survivor prognosis and the optimal form of therapy for childhood haemophilia

Performance of HaiYang-2 Altimetric Data in Marine Gravity Research and a New Global Marine Gravity Model NSOAS22

Haiyang-2 (HY-2) missions have accumulated sea surface height (SSH) observations on a global scale for more than 10 years. Four satellites, HY-2A, HY-2B, HY-2C and HY-2D, provide even but differently distributed data, which play a complementary role in marine gravity studies with other missions. Therefore, this paper evaluates the performances of HY-2 altimetric data in marine gravity modeling from the following four perspectives: SSH accuracy, geoid signal resolution ability, vertical deflections and gravity anomaly. First, the centimeter-magnitude accuracy level of HY-2 data is proved by analyzing SSH discrepancies at crossover points within a certain time limit. Second, the spectral analysis of repetitive along-track data sequences in a time domain shows a geoid resolution range from 18 to 24 km. Taking HY-2 exact repeat missions (ERM), for example, the resolution could be remarkably enhanced by stacking repetitive cycles. Third, validation with an XGM2019 model showed that vertical deflections were reliably computed for all HY-2 missions, but HY-2A performed slightly worse than the other HY-2 missions. Meanwhile, HY-2C and HY-2D with a ~66&deg; orbital inclination obviously had an improved ability to capture east&ndash;west signals compared to HY-2A and HY-2B. Finally, we constructed global marine gravity results based on three input datasets, HY-2 dataset only, multi-satellite dataset without HY-2 and multi-satellite dataset with HY-2. Validations were performed using published models and shipborne gravimetric data. The results showed that the HY-2 dataset is capable of improving marine gravity anomaly recoveries and that the accuracy of NSOAS22 with incorporated HY-2 data is comparable to DTU21 and SS V31.1. Furthermore, HY-2 observations should not be the only input dataset to construct a 1&rsquo; &times; 1&rsquo; resolution marine gravity model

Zero-shot remote sensing image scene classification based on robust cross-domain mapping and gradual refinement of semantic space

Zero-shot classification technology aims to acquire the ability to identify categories that do not appear in the training stage (unseen classes) by learning some categories of the data set (seen classes), which has important practical significance in the era of remote sensing big data. Until now, the zero-shot classification methods in remote sensing field pay little attention to the semantic space optimization after mapping, which results in poor classification performance. Based on this consideration, this paper proposed a zero shot remote sensing image scene classification method based on cross-domain mapping with auto-encoder and collaborative representation learning. In the supervised learning module, based on the class semantic vector of seen class and the scene image sample, the depth feature extractor learning and robust mapping from visual space to semantic space are realized. In the unsupervised learning stage, based on the class semantic vectors of all classes and the unseen remote sensing image samples, collaborative representation learning and k-nearest neighbor algorithm are used to modify the semantic vectors of unseen classes, so as to alleviate the problem of the shift of seen class semantic space and unseen class semantic space one after another and unseen after self coding cross domain mapping model mapping the shift of class semantic space and unseen class semantic space after collaborative representation. In the testing phase, based on the depth feature extractor, self coding cross domain mapping model and modified unseen class semantic vector, the classification of unseen class remote sensing image scene can be realized. We integrate a number of open remote sensing image scene data sets and build a new remote sensing image scene data set, experiments were conducted using this dataset The experimental results show that the algorithm proposed in this paper were significantly better than the existing zero shot classification method in the case of a variety of seen and unseen classes

Microstructure and mechanical properties of large size Ti-43Al-9V-0.2Y alloy pancake produced by pack-forging

A pancake of Ti-43Al-9V-0.2Y (at.%) alloy with dimensions of ϕ480 mm × 46 mm was fabricated by pack-forging with a thick reduction of 80%. The as-forged Ti-43Al-9V-0.2Y alloy pancake has a duplex (DP) microstructure, which is composed of B2/α₂/γ lamellar colonies and massive B2 and γ phase regions distributed along the boundaries between the lamellar colonies. Different microstructures were obtained by heat treatment of samples cut from the as-forged Ti-43Al-9V-0.2Y alloy pancake. A fully lamellar (FL) structure consisting of B2/α₂/γ lamellar colonies was obtained after the heat treatment of 1350 °C/8 h. Tensile test results exhibited that the yield strength (YS) and ultimate tensile strength (UTS) of the alloy with DP microstructure were decreased from 680.7 MPa to 834.3 MPa at room temperature to 589.5 MPa and 693.1 MPa at 700 °C, respectively, and the elongation (δ) of the alloy with DP microstructure was increased from 1.99% at room temperature to 12.12% at 700 °C; the elongation (δ) of the alloy with FL microstructure was increased from 1.52% at room temperature to 85.84% at 800 °C

Association between TGM5, PPAP2B and PSMA4 polymorphisms and NSCLC in never-smoking Chinese population

Aim: To explore the potential association between SNPs in transglutaminase 5 (TGM5), phosphatidic acid phosphatase type 2B (PPAP2B) and proteasome subunit, alpha type 4 (PSMA4) and non-small cell lung cancer (NSCLC) susceptibility in Chinese patients who were non-smokers. Setting and Design: A case-controlled study was conducted among Chinese population. Materials and Methods: Two hundred NSCLC patients and 200 healthy controls who were age and sex matched were genotyped for rs504417 of TGM5, rs1261411 of PPAP2B and rs7164594 of PSMA4. Genotyping was performed using the Sequenom MassARRAY system based on the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry platform. Statistical Analysis Used: The association between genotype and lung cancer risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses. Results: There was no significant difference for the TGM5 rs504417, PPAP2B rs1261411 and PSMA4 rs716459 in allele or genotype frequencies, whether between controls and NSCLC or between controls and subgroups. Conclusions: polymorphisms of TGM5, PPAP2B and PSMA4 are not major contributors to NSCLC susceptibility, this primarily be attributed to the significantly distinct genetic background of Asian populations from western populations

A review on evaluation of crack resistance of asphalt mixture by semi-circular bending test

A B S T R A C T: Although there are many kinds of fracture tests to choose from in evaluating the crack resistance of asphalt mixture, the semi-circular bending (SCB) test has attracted a lot of attention in the academic road engineering community because of its simplicity, stability, and flexibility in testing and evaluation. The SCB test has become a common method to study the cracking resistance of asphalt mixture in recent years. This paper mainly summarizes the overview of the SCB test, summarizes some research results and common characterization parameters of the SCB test method in monotone test and fatigue test in recent years, and predicts and suggests the research direction of the SCB test in the future. It is found that the research on the monotonic SCB test is more comprehensive, and the research on the SCB fatigue test needs to be further improved in the aspects of loading mode, characterization parameter selection, and so on. Researchers can flexibly adjust the geometric dimensions and the test parameters of semi-cylindrical specimens, and conduct comprehensive analysis combined with the results of numerical simulation. The crack resistance of asphalt mixture can be comprehensively evaluated by fracture energy, fracture toughness, stiffness, flexibility index and other fracture indicators, combined with the crack propagation of the specimen. The analysis of numerical simulation can confirm the test results. In order to standardize the setting of fatigue parameters for future application, it is necessary to standardize the setting of bending performance

Molecular Dynamics Simulation of Transport Mechanism of Graphene Quantum Dots through Different Cell Membranes

Exploring the mechanisms underlying the permeation of graphene quantum dots (GQDs) through different cell membranes is key for the practical application of GQDs in medicine. Here, the permeation process of GQDs through different lipid membranes was evaluated using molecular dynamics (MD) simulations. Our results showed that GQDs can easily permeate into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipid membranes with low phospholipid molecule densities but cannot permeate into 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE) lipid membranes with high phospholipid densities. Free energy calculation showed that a high-energy barrier exists on the surface of the POPE lipid membrane, which prevents GQDs from entering the cell membrane interior. Further analysis of the POPE membrane structure showed that sparsely arranged phospholipid molecules of the low-density lipid membrane facilitated the entry of GQDs into the interior of the membrane, compared to compactly arranged molecules in the high-density lipid membrane. Our simulation study provides new insights into the transmembrane transport of GQDs