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A light-driven redox deracemization to prepare optically pure cyclamines from their racemates is developed. This reaction provides a wide range of chiral indolines and tetrahydroquinolines with high yields and enantioselectivities.

Epigenetic alterations, including histone acetylation, contribute to the malignant transformation of hematopoietic cells and disease progression, as well as the emergence of chemotherapy resistance. Targeting histone acetylation provides new strategies for the treatment of cancers. As a pan-histone deacetylase inhibitor, panobinostat has been approved by the US Food and Drug Administration for the treatment of multiple myeloma and has shown promising antileukemia effects in acute lymphoblastic leukemia (ALL). However, the underlying drug resistance mechanism in ALL remains largely unknown. Using genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated (Cas)9 (CRISPR/Cas9) screening, we identified mitochondrial activity as the driver of panobinostat resistance in ALL. Mechanistically, ectopic SIRT1 expression activated mitochondrial activity and sensitized ALL to panobinostat through activating mitochondria-related apoptosis pathway. Meanwhile, the transcription level of SIRT1 was significantly associated with panobinostat sensitivity across diverse tumor types and thus could be a potential biomarker of panobinostat response in cancers. Our data suggest that patients with higher SIRT1 expression in cancer cells might benefit from panobinostat treatment, supporting the implementation of combinatorial therapy with SIRT1 or mitochondrial activators to overcome panobinostat resistance.

Herein, a protocol for the copper-catalyzed direct monofluoroalkenylation of C(sp3)–H bonds is reported.

488210 Supplemental Document

Precise point positioning (PPP) is used in many fields. However, pseudorange multipath delay is an important error that restricts its accuracy. Pseudorange multipath delay can be considered as the combination of effective information and observation noise; it can be modeled after removing the observation noise. In this work, elastic nets (EN) regularization denoising method is proposed and compared with L2-norm regularization denoising method. Then, quadratic polynomial (QP) model plus autoregressive (AR) model (QP + AR) are used to model the denoised pseudorange multipath delays. Finally, the modeling results are corrected to the observations to verify the improvement of BDS-3 single-frequency PPP accuracy. Three single-frequency PPP schemes are designed to verify the effectiveness of denoising method and QP + AR model. The experimental results show that the accuracy improvement of B3I and B2a is more obvious than that of B1I and B1C when the modeling values are corrected to the pseudorange observations. The improvement of B3I and B2a in the east (E) and up (U) directions can reach 10.6%∼34.4% and 5.9%∼65.7%, and the improvement of the north (N) direction is mostly less than 10.0%. The accuracy of B1I and B1C in E and U directions can be improved by 0%∼30.7% and 0.4%∼28.6%, respectively, while the accuracy of N direction can be improved slightly or even decreased. Using EN regularization denoising and QP + AR model correction, single-frequency PPP performs better at B3I and B2a, while L2-norm regularization denoising and QP + AR model correction perform better at B1I and B1C. The accuracy improvement of B2a and B3I is more obvious than that of B1I and B1C. The convergence time after MP correction of each frequency is slightly shorter. Overall, the proposed pseudorange multipath delays processing strategy is beneficial in improving the single-frequency PPP of BDS-3 satellite.

Monitoring and predicting mining area subsidence caused by coal mining help effectively control geological disasters. Information regarding small surface deformations can be obtained using a differential interferometric synthetic aperture radar (D-InSAR), which exhibits high monitoring accuracy and can cover large areas; thus, D-InSAR are being applied for mining area settlement monitoring. However, mining areas are prone to large gradient deformations in short durations; obtaining information regarding such deformations is outside the scope of D-InSAR monitoring. To adapt to the characteristics of D-InSAR monitoring, this study selected a Boltzmann function model with a slow boundary convergence rate to address the problem of probabilistic integration methods exhibiting a high boundary convergence rate. The three-dimensional surface deformation of the mining area can be accurately obtained. According to the projection relationship between D-InSAR line of sight (LOS) directional deformation, subsidence, and horizontal movement, a D-InSAR monitoring equation for mining subsidence assisted by Boltzmann is derived. This equation is combined with the shuffled frog leaping algorithm (SFLA) to obtain the parameters to be estimated from the equation. The D-InSAR LOS deformation information of the 13121 working face in the Huainan mining area was obtained from July 14 to October 30, 2019. The proposed method was then used to obtain the predicted parameters of the working face under insufficient mining. The predicted parameters of mining subsidence were calculated to obtain the predicted parameters when it was fully mined. Then, the revised parameters were used to predict the subsidence and horizontal movement of the mining area and compared with the actual leveling observations. The results show that the mean square error of predicted subsidence is 97.1 mm, which is about 3.09% of the maximum subsidence value; the mean square error of predicted horizontal movement is 46.1 mm, which is about 4.1% of the maximum horizontal movement value. The predicted results of the aforementioned method were used to analyze the damage to the buildings above the working face and determine the damage level of the buildings to provide a reference for the demolition and maintenance of the Zhaimiao village.

Photocatalytic degrading pollutants driven by visible-light irradiation has attracted tremendous attention. One strategy of preparing carbonized cellulose nanofibrils/Ti

Cycloid gear is an important transmission part of RV reducer of robot. Its surface mechanical properties significantly affect the precision and life of robot. During the forming and grinding process of the cycloid, the temperature gradient of the tooth surface changes greatly, resulting in residual stress, which is very important to the yield limit and service life of the cycloid. The thermal-mechanical coupling model of cycloid wheel grinding is established by using moving heat source method and load step loading method. The magnitude and direction of the first, second, and third principal stresses are obtained by calculating the Mises equivalent stress in the three-dimensional space of the grinding area. The temperature field and thermal stress of multi-tooth form grinding are simulated by finite element method, and the influence of grinding parameters on stress distribution is analyzed. The X-ray method is used to detect the residual stress of cycloid gear in form grinding, and the variation law of residual stress on the tooth surface under different process parameters is analyzed, and the change trend is basically consistent with the simulation results. The results show that the grinding process parameters can be optimized by theoretical calculation and finite element simulation, which can effectively reduce the residual tensile stress and increase the residual compressive stress. A method for predicting the residual stress of the cycloid gear form grinding is proposed, which provides a basis for the selection of the process parameters of the cycloid gear form grinding

The gauge fields dramatically alter the algebraic structure of spatial symmetries and make them projectively represented, giving rise to novel topological phases. Here, we propose a photonic Möbius topological insulator enabled by projective translation symmetry in multiorbital waveguide arrays, where the artificial π gauge flux is aroused by the inter-orbital coupling between the first (s) and third (d) order modes. In the presence of π flux, the two translation symmetries of rectangular lattices anti-commute with each other. By tuning the spatial spacing between two waveguides to break the translation symmetry, a topological insulator is created with two Möbius twisted edge bands appearing in the bandgap and featuring 4π periodicity. Importantly, the Möbius twists are accompanied by discrete diffraction in beam propagation, which exhibit directional transport by tuning the initial phase of the beam envelope according to the eigenvalues of translation operators. This work manifests the significance of gauge fields in topology and provides an efficient approach to steering the direction of beam transmission.

The cutting area and cutting force are important factors that affect the tool life and the machining performance of the machine tool. According to the characteristics and actual working conditions of hypoid gear processed by generating method, a new method for calculating the tangential milling force of multi-cutter teeth is presented. The changing rule of cutting area of the tooth surface is analyzed, the boundaries of the cutting area, such as the meshing line, the intersection line between the tool tip and the face cone of the wheel blank, the intersection line between the tool tip and the end face of wheel blank, are calculated, and the formula for calculating the cutting area is derived. According to the relationship of the motion and position between the cutting tool and workpiece, the dynamic tangential cutting force is calculated. The calculation of constant cutting force is completed based on the optimization of feed velocity, and an example is introduced to calculate the cutting area and cutting force. The experiment of variable tangential cutting force and constant tangential cutting force is completed, and the accuracy of the dynamic cutting force model is verified.

Accurately forecasting the scope of coal mining subsidence area is of great significance to the protection of surface structures. Due to the peculiarities of the unconsolidated layers rock formation, the surface movement of the thick unconsolidated layers mining area converges slowly at the boundary of the basin, and the boundary of the subsidence basin is larger than under conventional conditions. It is found that the existing models have a poor prediction effect at the boundary, and the predicted subsidence basin range is smaller than the actual basin range. To solve this problem, a new surface deformation prediction model based on Boltzmann function (IB) is proposed in this paper. Aiming at the problem that the model function is highly nonlinear and difficult to obtain parameters, the multi-population genetic algorithm (MPGA) is introduced into the parameter solution of the prediction model, and the parameter calculation model based on multi-population genetic algorithm (MPGAIB) is constructed. The simulation experiment and engineering example analysis show that both the overall fitting effect and the fitting effect at the boundary of IB model are closer to the actual situation, The MPGAIB model has good ability to anti-random error and gross error, and the result is stable.

Background: Previous studies about liver metastases (LM) in newly diagnosed ovarian cancer (NDOC) patients based on Surveillance, Epidemiology, and End Results (SEER) program disregarded selection bias of missing data. Methods: We identified Data of NDOC patients from SEER between 2010 and 2016, presented a comprehensive description of this dataset, and limited possible biases due to missing data by applying multiple imputation (MI). We determined predictive factors for underlying LM development in NDOC patients and evaluated prognostic factors in NDOC patients with LM (OCLM). We then established predictive nomograms, assessed by the concordance index, calibration curve, decision curve analysis (DCA), and clinical impact curves (CIC). Results: The amount of missing data for different variables in SEER dataset ranges from 0 to 36.11%. The results between complete dataset and MI datasets are similar. LM prevalence in NDOC patients was 7.18%, and median overall survival for OCLM patients was 11 months. The C-index of risk nomogram for LM development in the training cohort (TC) and validation cohort (VC) were 0.764 and 0.759, respectively. The C-index and integrated area under curve within five years of prognostic nomogram for OCLM patients in the TC and VC were 0.743 and 0.773, 0.714 and 0.733, respectively. For both nomograms, DCA revealed favorable clinical use and calibration curves suggested good consistency. Conclusion: The risk nomogram is expected to aid clinicians in identifying high-risk groups of LM development in NDOC patients for intensive screening. The prognostic nomogram could facilitate individualized prediction and stratification for clinical trials in OCLM patients.

The mining subsidence in mining area could cause large-gradient deformation in a short period of time. When the deformation gradient exceeds the threshold value of the Differential Interferometry Synthetic Aperture Radar (D-InSAR) technology monitoring gradient, D-InSAR technology is likely to cause the failure of InSAR phase unwrapping algorithm. At this time, the InSAR technology is unable to monitor the 3D surface deformation. Aiming at these problems, an dynamic probability integral method (DPIM)-based InSAR phase unwrapping model and a method of extracting 3D surface deformation were proposed. The phase unwrapping model firstly used the empirical parameters of the probability integral of the mining face to predict the line of sight (LOS) direction deformation phase of the mining subsidence surface. Secondly, the phase of differential interferogram was unwrapped with the assist of the predicted LOS deformation phase under the constraint of DPIM, and the true LOS deformation phase was obtained, then the true LOS deformation phase transformed into LOS deformation. Finally, according to the geometric projection relationship between the LOS deformation and 3D deformation of mining subsidence surface, the probability integral prior model was brought into the equation of the geometric projection relationship. On the basis of relevant boundary conditions, the 3D surface deformation was extracted from the LOS direction deformation field of mining subsidence. The feasibility of the method was verified by the simulation experiment results. The differential interferogram of the subsidence basin was obtained by the differential interference processing of image data of Sentinel-1A on Nov. 16, 2017 and Dec. 10, 2017 of 1613 working face of Guqiao South Mine. By using the DPIM-based phase unwrapping model, the phase of differential interferogram was unwrapped and the 3D surface deformation during this period as well as the deformation extraction method were developed. The results showed that the maximum fitting error value of subsidence was 79 mm, about 8.33% of the maximum value of subsidence, and the fitting error of mean square of subsidence was ±33.5 mm. The results showed that the DPIM-based phase unwrapping model and the method of extracting 3D surface deformation proposed in this paper have certain engineering application values.

6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide metabolites (TGN). Recent genome-wide association study has identified germline polymorphisms (e.g., rs72846714) in the NT5C2 gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation in NT5C2 is unclear and its impact on 6-MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing of NT5C2 in 588 children with ALL and identified 121 single nucleotide polymorphisms (SNPs) nominally associated with erythrocyte TGN during 6-MP treatment (P < 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6-MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activated NT5C2 transcription in-cis. Our results indicated that NT5C2 germline variation significantly contributes to inter-patient variability in thiopurine drug disposition.

After underground coal resources are mined out in mining areas, large-gradient deformation is prone to occur on the ground surface during a short period of time. When the deformation gradient excee...

Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 × 10−8) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 × 10−9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.

How to accurately estimate the probability integral parameters based on the measured data has always been a difficult point in the application of the probability integral method. This paper introdu...

A Ni-catalyzed Suzuki-type cross-coupling of boronic acids with epoxides without an exogenous base and with broad substrate scope has been developed. The product selectivity of styrenyl epoxides is different from that of previous work. This methodology uses readily available starting materials to access a range of substituted alcohols, which are valuable feedstock chemicals.

A nickel-catalyzed defluorinative reductive cross-coupling of trifluoromethyl alkenes with epoxides has been developed. Various substituted trifluoromethyl alkenes and epoxides were found to be suitable reaction substrates. This reaction enabled C(sp3)-C(sp3) bond construction through allylic defluorinative cross-coupling of trifluoromethyl alkenes under mild reaction conditions. This methodology was highly compatible with various sensitive functional groups, providing access to a diverse array of functionalized gem-difluoroalkene-containing alcohol compounds.

Mining subsidence disasters are common geological disasters. Accurate and effective identification of their deformation position is significant in preventing and controlling geological disasters and monitoring illegal mining. In this study, we used deep learning combined with support vector machine (SVM) to establish an automatic detection method for mining subsidence basins using Sentinel-1A data. The Huainan mining area was selected as the experimental area to verify the method. The interferogram was obtained using differential radar interferometry (D-InSAR), and the mining subsidence basin and other targets were extracted manually as training samples. Subsequently, AlexNet, VGG19, and ResNet50 convolutional neural networks (CNNs) were used to extract feature vectors of mining subsidence basins for the SVM classifier, and mining subsidence basins were detected in a large-area InSAR interferogram; The artificial fish swarm algorithm with strong optimization ability and good global convergence is introduced into SVM parameter optimization to construct an improved ResNet50_ SVM model. The experimental results show that (1) the three CNN_SVM methods can accurately detect dry mining subsidence basins automatically in large regional interference maps, providing an essential scientific basis for the government to monitor illegal mining activities and prevent and control geological disasters in mining areas; (2) the accuracy of the CNN_SVM automatic detection methods for mining subsidence basins is approximately 80%, and that of ResNet50_SVM for mining subsidence basin detection is 83.7%, superior to that of AlexNet_SVM and VGG19_SVM, The accuracy of the improved ResNet50_SVM based on AFSA algorithm is 88.3%, which is better than the unimproved Resnet50_SVM model.

Because of the limited knowledge on the relationship between molecular structure and analytical performance, developing a small molecule fluorescent probe with desirable response properties is usually a laborious work. On the other hand, the application of small molecule fluorescent probe in biological samples is always limited due to the unwanted interaction between dyes and biomacromolecules. Polymer micelles, thanks to its unique core-shell structure, may have the potential to improve these situations. However, utilization of polymer micelles to improve these situations is rarely explored. Herein, we engineered the first micellar SO

The data of surface movement observation points could be used to obtain the synthetic angles of draw and critical deformation of surface movement basin in the mining area with unconsolidated thick layers. However, they couldn’t be used to get the angles of draw and critical deformation of unconsolidated layers and rock layers, which are called angular parameters of surface movement basin and can be used to describe the outermost boundary and the dangerous boundary. Therefore, the paper presented an estimation method of angular parameters of surface moving basin based on least squares of Huber selecting weight iteration (LSHSWI). The method firstly classified the surface movement observation points with similar geological and mining conditions as the same kinds. Then, the synthetic angles of critical deformation and draw obtained by the observation points were taken as observation values, and angular parameters of surface movement basin were taken as unknown parameters. According to the geometric relationship between the synthetic angles and the angular parameters, the observation equation was established. Finally, the parameters estimation method based on LSHSWI was constructed with consideration of errors in the synthetic angles of draw and critical deformation. The simulation experiments show that the LSHSWI estimation method of angular parameters of surface movement basin has a strong anti-interference ability to errors of observation values. The engineering application shows that the parameter estimation method based on LSHSWI is scientific and practical.

Mining subsidence disasters are common geological disasters. Accurate and effective identification of their deformation position is significant in preventing and controlling geological disasters and monitoring illegal mining. In this study, deep learning, combined with a support vector machine (SVM), has been used to establish an automatic-detection method for mining subsidence basins using Sentinel-1A data. The Huainan mining area was selected as the experimental area to verify the method. The interferogram was obtained using differential radar interferometry (D-InSAR) to process the Sentinel-1A radar data of seven landscapes, and the mining subsidence basin and other targets were extracted manually as training samples. Subsequently, AlexNet, VGG19, and ResNet50 convolutional neural networks (CNNs) were used to extract feature vectors of mining subsidence basins for the SVM classifier, and mining subsidence basins were detected in a large-area InSAR interferogram. Non-maximum suppression was used to remove the repeated search box to improve the detection accuracy of mining subsidence basins; the artificial fish swarm algorithm with strong optimization ability and good global convergence is introduced into SVM parameter optimization to construct an improved ResNet50_SVM model. The experimental results show that: (1) the three CNN_SVM methods can accurately detect dry-mining subsidence basins automatically in large regional interference maps, providing an essential scientific basis for the government to monitor illegal mining activities and prevent and control geological disasters in mining areas; (2) the accuracy of the CNN_SVM automatic-detection methods for mining subsidence basins is approximately 80%, and that of ResNet50_SVM for mining subsidence basin detection is 83.7%, superior to that of AlexNet_SVM and VGG19_SVM; (3) the accuracy of the improved ResNet50_SVM based on AFSA algorithm is 88.3%, which is better than the unimproved Resnet50_SVM model.

BackgroundThe purpose of this study was to construct and external validate a nomogram for predicting overall survival(OS) in intrahepatic cholangiocarcinoma (ICC) patients classified as N0M0 according to the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system.Methods:812 ICC patients without distant and lymph node metastasis between 2011 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, then randomly assigned to the training cohort(n=648) or internal validation cohort(n=164), external validation cohort consisted of 136 ICC patients with N0M0 stage treated in West China Hospital of Sichuan University from 2013 to 2015. The precision of the nomogram was validated internally using SEER validation cohort and externally using the patients’ data of West China Hospital. Results :The nomogram was established to predict 1-year, 3-year and 5-year OS and the calibration curve showed nomogram prediction performance was in good agreement with the actual results. The C‑index of the nomogram was 0.750(95% CI:0.731-0.769) in the training cohort, and the internal and external validated C-indexes were 0.803(95% CI:0.783-0.823) and 0.681(95% CI:0.524-0.838), respectively. In the training, internal and external validation cohort, the 1-year, 3‑year and 5‑year AUCs were (0.772,0.809,0.798),(0.896,0.868,0.896) and (0.673,0.786,0.886), respectively.Conclusions This nomogram has an excellent predictive effect on the 1- ,3-, 5-year OS of ICC patients with stage N0M0 and guide the optimal treatment for these type of patients.

An integration of different pretreatments is important to overcome recalcitrance and realize efficient bioconversion of lignocellulosic biomass. This study aims at the effects of combination of hydrothermal pretreatment and different chemi-mechanical pretreatments on enzymatic hydrolysis, and understanding the enzymes adsorption mechanism. The combination of hydrothermal and chemi-mechanical pretreatments effectively improved the enzymatic hydrolysis of poplar substrates, in which the enzymatic hydrolysis of substrates pretreated by hydrothermal pretreatment + Fenton pretreatment + mechanical refining (HFM) was the highest (92.39% of glucose conversion yield, and 20.88 g/L of glucose concentration). The substrates’ main characteristics were obviously changed after combined pretreatments, such as swelling ability and specific surface area of substrates were increased. The Langmuir adsorption model (R2 > 0.98) and pseudo second-order adsorption kinetic model (R2≈1) were well suitable to describe the adsorption of enzymes on substrates, meanwhile the adsorption mechanism was summarized.

Herein, a dual nickel/ruthenium strategy is developed for photoinduced decarboxylative cross-coupling between α,β-unsaturated carboxylic acids and cycloketone oxime esters. The reaction mechanism is distinct from previous photoinduced decarboxylation of α,β-unsaturated carboxylic acids. This reaction might proceed through a nickelacyclopropane intermediate. The C(sp2)-C(sp3) bond constructed by the aforementioned reaction provides an efficient approach to obtaining various cyanoalkyl alkenes, which are synthetically valuable organic skeletons in organic and medicinal chemistry, under mild reaction conditions. The protocol tolerates many critical functional groups and provides a route for the modification of complex organic molecules.

Background Roses are famous ornamental plants worldwide. Floral coloration is one of the most prominent traits in roses and is mainly regulated through the anthocyanin biosynthetic pathway. In this study, we investigated the key genes and metabolites of the anthocyanin biosynthetic pathway involved in color mutation in miniature roses. A comparative metabolome and transcriptome analysis was carried out on the Neptune King rose and its color mutant, Queen rose, at the blooming stage. Neptune King rose has light pink colored petals while Queen rose has deep pink colored petals. Result A total of 190 flavonoid-related metabolites and 38,551 unique genes were identified. The contents of 45 flavonoid-related metabolites, and the expression of 15 genes participating in the flavonoid pathway, varied significantly between the two cultivars. Seven anthocyanins (cyanidin 3-O-glucosyl-malonylglucoside, cyanidin O-syringic acid, cyanidin 3-O-rutinoside, cyanidin 3-O-galactoside, cyanidin 3-O-glucoside, peonidin 3-O-glucoside chloride, and pelargonidin 3-O-glucoside) were found to be the major metabolites, with higher abundance in the Queen rose. Thirteen anthocyanin biosynthetic related genes showed an upregulation trend in the mutant flower, which may favor the higher levels of anthocyanins in the mutant. Besides, eight TRANSPARENT TESTA 12 genes were found upregulated in Queen rose, probably contributing to a high vacuolar sequestration of anthocyanins. Thirty transcription factors, including two MYB and one bHLH, were differentially expressed between the two cultivars. Conclusions This study provides important insights into major genes and metabolites of the anthocyanin biosynthetic pathway modulating flower coloration in miniature rose. The results will be conducive for manipulating the anthocyanin pathways in order to engineer novel miniature rose cultivars with specific colors.

Special cold rotary forging method for the fabrication of the big wheels of hypoid gears is proposed. The proposed method is established on the basis of the requirements of antifatigue manufacturing processes and the tooth profile characteristics of hypoid gears combined with the movement and forming methods of cold rotary forging. The geometric grid model is constructed on the basis of the basic theory of elastic-plastic thermo-mechanical coupling finite element for metal. Reasonable process parameters and boundary conditions are established. Thus, the cold rotary forging finite element model is built. The springback tooth surface is reconstructed through the results of finite element numerical simulation. The size and distribution of the springback error is the detected. In the springback process, a large displacement and large rotation can occur, so a comprehensive displacement compensation algorithm is adopted to modify the rotary forging die, and a springback error compensation iteration system is constructed based on the modified algorithm. In the case of a camion driving axle gear, the correction of the rotary forging die is analyzed. Results show that the error is already within the allowed range through only three iterations, which proves the efficiency of the system. The modified die is used for machining experiments. The measurement results of the experiment gear are consistent with the simulation results, which proves the reliability of the system. The LTCA of the gear further proves its reliability in compensating for springback error using numerical simulation technique.

The linear combination of multi-frequency carrier-phase and pseudorange observations can form the combined observations with special properties. The type and number of combined frequencies will directly affect the characteristics of the combined observations. BDS-2 and BDS-3 broadcast three and five signals, respectively, and the study of their linear combination is of great significance for precision positioning. In this contribution, the linear combination form of multi-frequency carrier-phase observations in cycles and meters is sorted out. Seven frequency combination modes are formed, and some special combinations for positioning are searched. Then, based on the principle of minimum combined noise, a simpler search method for the optimal real coefficients of ionosphere-free (IF) combination based on the least squares (LS) principle is proposed. The general analytical expressions of optimal real coefficients for multi-frequency geometry-based and ionosphere-free (GBIF), geometry-free and ionosphere-free (GFIF), and pseudorange multipath (PMP) combinations with the first-order ionosphere delay taken into account are derived. And the expression derivation process is given when both the first-order and second-order ionospheric delays are eliminated. Based on this, the characteristics of the optimal real coefficient combination in various modes are compared and discussed. The various combinations reflect that the accuracy of the combined observations from dual-frequency (DF) to five-frequency (FF) is gradually improving. The combination coefficient becomes significantly larger after taking the second-order ionospheric delay into account. In addition, the combined accuracy of BDS-3 is better than that of BDS-2. When only the first-order ionosphere is considered, the combination attribute of (B1C, B1I, B2a) is the best among the triple-frequency (TF) combinations of BDS-3. When both the first-order and second-order ionospheric delays are considered, the (B1C, B3I, B2a) combination is recommended.

Because of the limited knowledge on the relationship between molecular structure and analytical performance, developing a small molecule fluorescent probe with desirable response properties is usua...

Portal vein tumor thrombus (PVTT) is one of the most common complications of hepatocellular carcinoma (HCC), which refers to the advanced stage of HCC and indicates an extremely poor prognosis. Monotherapy cannot effectively prolong the survival benefit of patients with HCC-PVTT characterized by a high recurrence rate. With great progress in the area of immune and molecular targeted therapy, there comes a promising era of multidisciplinary management of HCC. Survival benefits can be achieved based on accurate diagnosis, staging, and multidisciplinary management. Additionally, in terms of the presence of controversy about the standard treatment algorithm and the absence of universal treatment guidelines, a multidisciplinary management program may afford the best hope for HCC-PVTT patients via appropriate implement of various treatment protocols.

Background Desmoid-type fibromatosis (DTF) is a rare kind of soft-tissue tumors of unknown origin, which is a benign mesenchymal neoplasm with monoclonal proliferation with local invasion, easy recurrence and non-distant metastasis. It is usually arising from the aponeurosis, muscle, and deep fascia, but DTF arsing from the fat layer have not been previously reported. Case presentation: A 22-year-old male was presented with a recurrence of lower abdominal wall mass(LAWM) after multiple operations and a new mass in the skin flap donor area of the right abdominal wall. Magnetic resonance imaging (MRI) revealed multiple soft tissue masses and nodules in the subcutaneous fat layer of the lower abdomen and right abdomen wall, which was considered a diagnosis of fibrosarcoma, then pathological consultation was performed on the paraffin specimens from previous operations, and finally confirmed the diagnosis of desmoid-type fibromatosis in combination with pathological characteristics of the resected specimens in this visit. In general, DTF did not have the ability to metastasize, but we extracted paraffin sections and performed full exon sequencing. After personalized analysis, the results showed that there was a possibility of implantative metastasis. Due to the aggressive growth and recurrence of the tumor, the patient was subsequently treated with radiotherapy and no recurrence was observed 6 months later. Continued follow-up is ongoing. Conclusions We report the first case of DTF that occurs in the superficial layer of fat with the possibility of surgically induced implantative metastasis, for such patients, diagnosis of DTF is more difficult and surgical treatment should be treated with greater caution.

Real-time modeling of regional troposphere has attracted considerable research attention in the current GNSS field, and its modeling products play an important role in global navigation satellite system (GNSS) real-time precise positioning and real-time inversion of atmospheric water vapor. Multicore support vector machine (MS) based on genetic optimization algorithm, single-core support vector machine (SVM), four-parameter method (FP), neural network method (BP), and root mean square fusion method (SUM) are used for real-time and final zenith tropospheric delay (ZTD) modeling of Hong Kong CORS network in this study. Real-time ZTD modeling experiment results for five consecutive days showed that the average deviation (bias) and root mean square (RMS) of FP, BP, SVM, and SUM reduced by 48.25%, 54.46%, 41.82%, and 51.82% and 43.16%, 48.46%, 30.09%, and 33.86%, respectively, compared with MS. The final ZTD modeling experiment results showed that the bias and RMS of FP, BP, SVM, and SUM reduced by 3.80%, 49.78%, 25.71%, and 49.35% and 43.16%, 48.46%, 30.09%, and 33.86%, respectively, compared with MS. Accuracy of the five methods generally reaches millimeter level in most of the time periods. MS demonstrates higher precision and stability in the modeling of stations with an elevation at the average level of the survey area and higher elevation than that of other models. MS, SVM, and SUM exhibit higher precision and stability in the modeling of the station with an elevation at the average level of the survey area than FP. Meanwhile, real-time modeling error distribution of the five methods is significantly better than the final modeling. Standard deviation and average real-time modeling improved by 43.19% and 24.04%, respectively.

A method for Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters was developed. The reaction has a broad substrate scope. This hydroalkylation shows excellent regio- and stereo-selectivity. This method enables readily available starting materials to be used to access a range of cyano-substituted single-configuration trisubstituted alkenes. These are valuable feedstock chemicals and are widely used in synthetic and medicinal chemistry.

6-mercaptopurine (6-MP) is widely used in the treatment of acute lymphoblastic leukemia (ALL), and its cytotoxicity is primarily mediated by thioguanine nucleotide metabolites (TGN). Recent genome-wide association study has identified germline polymorphisms (e.g., rs72846714) in theNT5C2gene associated with 6-MP metabolism in patients with ALL. However, the full spectrum of genetic variation inNT5C2is unclear and its impact on 6-MP drug activation has not been comprehensively examined. To this end, we performed targeted sequencing ofNT5C2in 588 children with ALL and identified 121 single nucleotide polymorphisms (SNPs) nominally associated with erythrocyte TGN during 6-MP treatment (P< 0.05). Of these, 61 variants were validated in a replication cohort of 372 children with ALL. After considering linkage disequilibrium and multivariate analysis, we confirmed two clusters of variants, represented by rs72846714 and rs58700372, that independently affected 6-MP metabolism. Functional studies showed that rs58700372 directly altered the activity of an intronic enhancer, with the variant allele linked to higher transcription activity and reduced 6-MP metabolism (lower TGN). By contrast, rs72846714 was not located in a regulatory element and instead its association signal was explained by linkage disequilibrium with a proximal functional variant rs12256506 that activatedNT5C2transcription in-cis. Our results indicated thatNT5C2germline variation significantly contributes to inter-patient variability in thiopurine drug disposition.

A spiral bevel gear is subject to a special load in ultrasonic lapping, which is not only a processing object but also a processing tool, it is necessary to study dynamic characteristics of an ultrasonic vibration system. First, the spiral bevel gear is reasonably simplified to a frustum, which is then combined with a horn to form a new type of composite horn. Based on the theory of plane longitudinal wave propagation, the resonance mathematical model of the gear’s ultrasonic vibration system is established, and the frequency equation of the vibration system with gear characteristic parameters is obtained. Second, the frequency and displacement characteristics of an ultrasonic vibration system are analyzed by means of design examples, and the influence of the law of gear characteristic parameters on dynamic characteristics of the vibration system is studied. Finally, ultrasonic lapping and vibration measurement experiments are carried out using two pairs of different hypoid gears. The results show that the change in dynamic characteristics of an ultrasonic vibration system has a large influence on the finished machining quality of the gear. Therefore, it is necessary to consider the gear characteristic parameters when ultrasonic vibration system is designed. The research results provide an accurate theoretical basis for the detailed design of an ultrasonic lapping vibration system.

A novel pyrene-based fluorescent probe (3-methyl-2-(pyren-1-yl)benzo[d]thiazol-3-ium iodide) (PBT) was found to be a fast-responsive and highly selective towards G-quadruplexes. PBT exhibited an opposite fluorescent variation tendency on binding with G-quadruplexes and ds-DNAs.

The organization of organic chromophores to form H-/J-aggregates can result in new biomaterials with unique properties and applications. DNA-template self-assembly is one of the most attractive strategies to guide the formation of chromophore aggregates. However, the DNA templates are mainly limited to canonical nucleic acids structures [single (ss)- and double (ds)-stranded DNA]. DNA G-quadruplexes (GQs), with distinct and various structural features, were rarely exploited to guide the formation of dye aggregates. In this study, we present the spontaneous assembly of cyanine dye IR786 to form H-aggregates on DNA GQs exclusively, but no IR786 aggregates formed by adjusting the experimental parameters or on ss-/ds-DNA. Furthermore, on the basis of the assembly entity (GQs-IR786), an adaptive GQs-FID (fluorescence intercalator displacement) assay for screening of GQs ligands was developed. In contrast with the existing GQs-FID screening schemes, this assay displayed attractive performance in many aspects (such as turn-on signal output, broad screening range, and time saving). All these results have undoubtedly demonstrated the great values of DNA GQs as a template to guide the formation of dye aggregates. We hope that more GQs structures would be exploited as templates to expand the variety of functional materials in the future. Moreover, the specifically formed H-aggregates of IR786 on GQs are significant for GQs' detection, and we also expect that this GQs-FID assay would be further studied and finally applied to screen GQs ligands in a high-throughput manner in the future.

Accompanied with the widespread application of complex wells such as cluster wells in the exploitation of oil and gas resources, it is becoming more and more important to reduce or accurately describe the size of the wellbore position uncertainty as much as possible. It is well known that axial magnetic interference affects azimuth measurement. In this paper, the correction method of axial magnetic interference in azimuth measurement and uncertainty ellipsoid calculation method considering axial magnetic interference correction are introduced, and the influence of axial magnetic interference correction on the position uncertainty of a horizontal well is analyzed through an example. The research shows that the influence of axial magnetic interference on wellbore position measurement error varies with measurement depth, and axial magnetic interference plays an increasing role in the influence of wellbore position measurement error. Therefore, well trajectory should be measured in an environment free of axial magnetic interference.