Research and Development Trend of Shape Control for Cold Rolling Strip

Shape is an important quality index of cold rolling strip. Up to now, many problems in the shape control domain have not been solved satisfactorily, and a review on the research progress in the shape control domain can help to seek new breakthrough directions. In the past 10 years, researches and applications of shape control models, shape control means, shape detection technology, and shape con- trol system have achieved significant progress. In the aspect of shape control models, the researches in the past improve the accuracy, speed and robustness of the models. The intelligentization of shape control models should be strengthened in the future. In the aspect of the shape control means, the researches in the past focus on the roll opti- mization, mill type selection, process optimization, local strip shape control, edge drop control, and so on. In the future, more attention should be paid to the coordination control of both strip shape and other quality indexes, and the refinement of control objective should be strengthened. In the aspects of shape detection technology and shape control system, some new types of shape detection meters and shape control systems are developed and have successfully indus- trial applications. In the future, the standardization of shape detection technology and shape control system should be promoted to solve the problem of compatibility. In general,the four expected development trends of shape control for cold roiling strip in the future are intelligentization, coordi- nation, refinement, and standardization. The proposed research provides new breakthrough directions for improv- ing shape quality.

Intelligent representation method of image flatness for cold rolled strip

Real flatness images are the bases for flatness detection based on machine vision of cold rolled strip.The characteristics of a real flatness image are analyzed,and a lightweight strip location detection(SLD)model with deep semantic segmentation networks is established.The interference areas in the real flatness image can be eliminated by the SLD model,and valid information can be retained.On this basis,the concept of image flatness is proposed for the first time.An image flatness representation(IFAR)model is established on the basis of an autoencoder with a new structure.The optimal structure of the bottleneck layer is 16×16×4,and the IFAR model exhibits a good representation effect.Moreover,interpretability analysis of the representation factors is carried out,and the difference and physical meaning of the representation factors for image flatness with different categories are analyzed.Image flatness with new defect morphologies(bilateral quarter waves and large middle waves)that are not present in the original dataset are generated by modifying the representation factors of the no wave image.Lastly,the SLD and IFAR models are used to detect and represent all the real flatness images on the test set.The average processing time for a single image is 11.42 ms,which is suitable for industrial applications.The research results provide effective methods and ideas for intelligent flatness detection technology based on machine vision.

Discovery of TK-642 as a highly potent,selective,orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor

Src homology-2-containing protein tyrosine phosphatase 2(SHP2)is a promising therapeutic target for cancer therapy.In this work,we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors,leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent,selective,orally bioavailable allosteric SHP2 inhibitor(SHP2WT IC_(50)=2.7 nmol/L)with favorable pharmacokinetic profiles(F=42.5%;t_(1/2)=2.47 h).Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the“tunnel”allosteric site of SHP2.TK-642 could effectively suppress cell proliferation(KYSE-520 cells IC_(50)=5.73μmol/L)and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling pathways.Additionally,oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model,with a T/C value of 83.69%.Collectively,TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

Data-driven flatness intelligent representation method of cold rolled strip

A high-accuracy flatness prediction model is the basis for realizing flatness control.Real flatness is typically reflected as the strain distribution,which is a vector.However,it is difficult to obtain ideal results if the real flatness is directly used as the output value of the flatness intelligent prediction model.Thus,it is necessary to seek an abstract representation method of real flatness.For this reason,two new intelligent flatness representation models were proposed based on the autoencoder of unsupervised learning theory:the flatness autoencoder representation(FAR)model and the flatness stacked sparse autoencoder representation(FSSAR)model.Compared with the traditional Legendre fourth-order polynomial representation model,the representation accuracies of the FAR and FSSAR models are significantly improved,better representing the flatness defects,like the double tight edge.The optimal number of bottleneck layer neurons in the FAR and FSSAR models is 5,which means that five basic patterns can accurately represent real flatness.Compared with the FAR model,the FSSAR model has higher representation accuracy,although the flatness basic pattern is more abstract,and the physical meaning is not clear enough.Furthermore,the accuracy of the FAR model is slightly lower than that of the FSSAR model.However,it can automatically learn the flatness basic pattern with a very clear physical meaning for both the theoretical and real flatness,which is an optimal intelligent representation method for flatness.

Skp2 is a novel regulator of LSD1 expression and function in gastric cancer

S-phase kinase-associated protein 2(Skp2)is a well-characterized oncoprotein localized mainly in the nucleus and cytoplasm.It is an integral component of SCFskp2 E3 ubiquitin ligase complex which confers substrate selectivity to the ligase by specifically targeting a distinct set of proteins destined for proteasomal degradation such as p21,p27,cyclin E,and c-Myc.1 Skp2 is crucial in a multitude of cellular processes including cell cycle,cell proliferation,apoptosis,differentiation,and survival.However,despite its immense and well-established role in ubiquitin-proteasome system-mediated protein turnover,much is unknown about the function of Skp2 independent of the ubiquitination pathway.Previously,Skp2 has been reported to regulate RhoA gene transcription and the p300 signaling pathway in an E3 ligase-independent manner.2Moreover,Skp2 also acts as a cofactor for c-Myc-regulated gene expression.

Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing

Targeting immune checkpoints such as programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for treating melanoma,gastric cancer(GC)and bladder cancer with clinical benefit.Nevertheless,many patients failed to respond to anti-PD-1/PD-L1 treatment,so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy.Here with the data from The Cancer Genome Atlas(TCGA)and our in-house tissue library,PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7(USP7)in GC.Furthermore,USP7 directly interacted with PD-L1 in order to stabilize it,Gastric cancer;Immunosuppression;Cancer biologywhile abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing in vitro and in vivo.Besides,USP7 inhibitor suppressed GC cells proliferation by stabilizing P53 in vitro and in vivo.Collectively,our findings indicate that in addition to inhibiting cancer cells proliferation,USP7 inhibitor can also downregulate PD-L1 expression to enhance anti-tumor immune response simultaneously.Hence,these data posit USP7 inhibitor as an anti-proliferation agent as well as a novel therapeutic agent in PD-L1/PD-1 blockade strategy that can promote the immune response of the tumor.

Detailed resume of RNA m^(6)A demethylases

N6-Methyladenosine(m^(6)A) is the most abundant internal modification in eukaryotic mRNA,playing critical role in various bioprocesses. Like other epigenetic modifications, m^(6)A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m^(6)A demethylases have been reported, fat mass and obesity-associated protein(FTO)and alkylation protein AlkB homolog 5(ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

Spatial Vibration and Its Numerical Analytical Method of Four-high Rolling Mills

The rolls in contemporary four-high mills cannot be maintained parallel during the rolling process. There- fore, four-high rolling mill vibrations take place in six degree of freedom （DOF） leading to spatial behaviors invol- ving vertical, horizontal, axial, torsional, cross and swinging vibration modes resulting in complex relative motions between the rolls. Two numerical methods, modified Riccati-transfer matrix method （Riccati-TMM） and finite ele- ment method （FEM）, are presented to analyze a spatial vibration characteristic of two four-high rolling mills with different stability. The natural frequency and mode shape of four-high rolling mills are obtained, and the clearance has a great effect on natural frequency and mode shape. In addition, field testing experiment is also conducted to measure natural frequency by power spectrum analysis of rolling mill vibration. Experimental results basically agree with those calculated by Riccati-TMM and FEM, which means that the Riccati-TMM and the FEM can be used for analysis of spatial vibration of four-high rolling mill. Meanwhile, the spatial vibration shows more compound vibra- tion behaviors and the negative effect of horizontal, vertical, cross and swinging vibration modes are effectively con- trolled after redesign of rolling mill. These advantages have a great significance for the rolling mill to be operated with a much higher rolling speed and improved yield of products.

A multifunctional cross-validation high-throughput screening protocol enabling the discovery of new SHP2 inhibitors

The protein tyrosine phosphatase Src homology phosphotyrosyl phosphatase 2(SHP2) is implicated in various cancers, and targeting SHP2 has become a promising therapeutic approach. We herein described a robust cross-validation high-throughput screening protocol that combined the fluorescence-based enzyme assay and the conformation-dependent thermal shift assay for the discovery of SHP2 inhibitors. The established method can effectively exclude the false positive SHP2 inhibitors with fluorescence interference and was also successfully employed to identify new protein tyrosine phosphatase domain of SHP2(SHP2-PTP) and allosteric inhibitors. Of note, this protocol showed potential for identifying SHP2 inhibitors against cancer-associated SHP2 mutation SHP2-E76 A. After initial screening of our in-house compound library(w2300 compounds), we identified 4 new SHP2-PTP inhibitors(0.17%hit rate) and 28 novel allosteric SHP2 inhibitors(1.22% hit rate), of which SYK-85 and WS-635 effectively inhibited SHP2-PTP(SYK-85: IC_(50) Z 0.32 mmol/L;WS-635: IC_(50) Z 4.13 mmol/L) and thus represent novel scaffolds for designing new SHP2-PTP inhibitors. TK-147, an allosteric inhibitor, inhibited SHP2 potently(IC_(50) Z 0.25 mmol/L). In structure, TK-147 could be regarded as a bioisostere of the well characterized SHP2 inhibitor SHP-099, highlighting the essential structural elements for allosteric inhibition of SHP2. The principle underlying the cross-validation protocol is potentially feasible to identify allosteric inhibitors or those inactivating mutants of other proteins.

Velocity Preset and Transitional Zone′s Shape Optimization for Tailor Rolled Blank

Tailor rolled blank （TRB） is a type of emerging material to produce lightweight vehicle parts. Transitional zoners shape is an important parameter for tailor rolled blank. It not only affects mold design and the local carrying capacity of the stamping parts, but also determines the maximum value and variation characteristics of rolling force. How to get the best transitional zone＇s shape is a key problem for production of tailor rolled blank. A double power function is put forward using for transitional curve, which is continuous and smooth at all connection points inde- pendent of its parameters, so the sudden change of mechanical parameters during rolling and forming process can be avoided. At the same time, the velocity formula and restriction for arbitrary transitional curve are derived to preset vertical velocity of the roller and judge whether the curve can be rolled successfully or not. Then, the finite element method （FEM） is used to verify the precision of velocity formula and study the mechanical characteristics of different curves. Finally, a method to obtain the optimal curve equation is put forward and verified.

Slab Analysis of Large Cylindrical Shell Rolling

Considering the characteristics of large cylindrical shell rolling, such as double driving rolls, asymmetrical rolling and huge workpiece, a slab method was developed to establish the rolling force model. In this model, the non- uniform normal and shear stresses and the upper and lower surface temperatures of the workpiece were taken into ac- count. Moreover, the flow stress model, considering the dynamic recovery and dynamic recrystallization behaviors of the material, was established. The rolling pressure distribution, the rolling force, the rolling torque and the neutral points could be calculated quickly and easily by the roiling force model. The predicted results were shown to be in good agreement with the measured values, which indicated that the model can satisfy the requirement of industrial application.

Absence Importance and Its Application to Feature Detection and Matching

Feature detection and matching play important roles in many fields of computer vision, such as image understanding, feature recognition, 3D-reconstruction, video analysis, etc. Extracting features is usually the first step for feature detection or matching, and the gradient feature is one of the most used selections. In this paper, a new image feature-absence importance （AI） feature, which can directly characterize the local structure information, is proposed. Greatly different from the most existing features, the proposed absence importance feature is mainly based on the consideration that the absence of the important pixel will have a great effect on the local structure. Two absence importance features, mean absence importance （MAI） and standard deviation absence importance （SDAI）, are defined and used subsequently to construct new algorithms for feature detection and matching. Experiments demonstrate that the proposed absence importance features can be used as an important complement of the gradient feature and applied successfully to the fields of feature detection and matching.

Preclinical studies of the triazolo[1,5-a]pyrimidine derivative WS-716 as a highly potent,specific and orally active P-glycoprotein(P-gp)inhibitor

Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft(PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones from indoles and isatins

The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones(27 examples,up to 98% yield) from readily available indoles and isatin derivatives are described.This protocol shows well tolerance of different functional groups and features mild reaction conditions such as short reaction time(~1 h),no usage of catalyst,easy operation and product isolation.Of particular intere st is the formation of two C-C bonds and one all-carbon quaternary center.This protocol could serve as an alternative strategy to synthesize biologically important 3,3-di(indolyl)indolin-2-ones for biological testing.

MFSR: Maximum Feature Score Region-based Captions Locating in News Video Images

For news video images, caption recognizing is a useful and important step for content understanding. Caption locating is usually the first step of caption recognizing and this paper proposes a simple but effective caption locating algorithm called maximum feature score region （MFSR） based method, which mainly consists of two stages： In the first stage, up/down boundaries are attained by turning to edge map projection. Then, maximum feature score region is defined and left/right boundaries are achieved by utilizing MFSR. Experiments show that the proposed MFSR based method has superior and robust performance on news video images of different types.