The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer

A hallmark of Spemann organizer function is its expression of Wnt antagonists that regulate axial embryonic patterning. Here we identify the tumor suppressor Protein tyrosine phosphatase receptor-type kappa (PTPRK), as a Wnt inhibitor in human cancer cells and in the Spemann organizer of Xenopus embryos. We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer. Deficiency of Xenopus Ptprk increases Wnt signaling, leading to reduced expression of Spemann organizer effector genes and inducing head and axial defects. We identify a '4Y' endocytic signal in ZNRF3, which PTPRK maintains unphosphorylated to promote Wnt receptor depletion. Our discovery of PTPRK as a negative regulator of Wnt receptor turnover provides a rationale for its tumor suppressive function and reveals that in PTPRK-RSPO3 recurrent cancer fusions both fusion partners, in fact, encode ZNRF3 regulators.

Influence of thermal state of the end area of multiple continuous-cast billet on cracking of the ends of hot-rolled breakdown at rolling

The authors have made an analysis of problems arising in the rolling of continuous-cast billets in the modern mini-metallurgical and rerolling plants. It is shown that the use of trio stands in rolling mills of these plants makes it necessary to obtain billets of multiple lengths from bars (most often of 12-meter length) produced in the rolling shop. The subsequent rolling of such multiple billets has revealed increased cracking of the front edge and, as a result, increased metal consumption. Analysis of the causes of these cracks has been made. It was indicated that this defect can appear as a result of a certain stress-strain state formed at the end of hot-rolled breakdown. It is caused by the presence of an uneven temperature field due to more intensive end cooling, to reduction mode in the trio stand and to the presence of axial defects in the continuous-cast billet. The study was conducted on the industrial medium-grade mill 500/370, as well as using mathematical modeling by finite element method. The influence of a set of technological factors, such as temperature of the billets heating before rolling, the time interval of their transportation on the site “heating furnace – first stand of the rolling mill” and parameters of the macrostructure of axial area of the metal were investigated. Calculations by the developed mathematical model have indicated the need to take into account the presence of a scale layer on the heated continuous-cast billet. It is shown that depending on the heating temperature and transport time, the temperature difference at the billet’s end compared to the heating temperature can be from 45 to 100 °C. It will lead to an uneven distribution of deformation resistance and unfavorable stress-strain state at the billet’s end. In addition, the presence of an axial defect can affect the cracking because of its shape and its transformation during reduction. Obtained experimental data allowed hypothesizing the mechanism of transformation of discontinuity defects into cracks at the billet’s end due to the conditions of continuous casting and cutting of billets during rolling in the reduction stand.

Experimental and FEM Analysis of Void Closure in the Hot Cogging Process of Tool Steel

In the present study, a new complex methodology for the analysis the closure of voids and a new forging system were developed and tested. The efficiency of the forging parameters and the effective geometric shapes of anvils to improve void closure were determined. A new cogging process provided a complete closure of an ingot’s axial defects, as confirmed by experimental tests. The evolution behavior of these defects with different sizes was investigated during the hot cogging process by means of the professional plastic forming software Deform-3D. A comprehensive procedure was developed using the finite-element method (FEM) for the three-dimensional cogging process and laboratory experimentation to predict the degree of void closure. The hot multi-pass cogging process was used to eliminate void defects in the forgings so as to obtain sound products. In the compression process, the effects of the reduction ratio and forging ratio, the void size, and the types of anvil were discussed to obtain the effective elimination of a void. For the purpose of the assessment of the effectiveness of the void closure process, the following indices were introduced: the relative void volume evolution ratio, the relative void diameter ratio, and the internal void closure evaluation index. Moreover, the void closure process was assessed on the basis of stress triaxiality, hydrostatic stress, forging ratio, value of local effective strain around the void, and critical reduction ratio. The results of this research were complemented by experiments predicting the formation of fractures in the regions near the void and in the volume of the forging in the course of the cogging process. The comparison between the predicted and the experimental results showed a good agreement.

Mathematical Model Approach to the Solidification of Different Geometry Ingots and the Development of Shrinkage Defects in them

A mathematical modeling approach as well as experimental data analysis have made it possible to establish significant factors affecting the relative diameter of the axial porosity zone. The minimal values of this parameter determine if the ingot can be used for the fabrication of rolled steel rods over 300 mm in diameter, because chill extensive axial defects prevent from producing high quality bars of a large diameter. Commercial information analysis and experimental results have enabled to develop a model relating the axial porosity zone dimension, ingot geometry and process parameters of teeming 6.61 ton and 7.0 ton ingots. The improvement of the model obtained has enabled to establish that the axial porosity zone is primarily affected by the following factors: hot top size, slenderness ratio, the H/D ratio and insulation heat capacity. When these parameters are controlled to reduce the relative diameter of the axial porosity zone, the number of shrinkage defects decreases and the quality of large diameter rolled steel becomes better. The proposed ingot geometry improves the direction of the advance of the metal solidification front to the ingot thermal center, located in the hot top. Besides, the solidifying metal is better fed with the hot top melt.

Improvement of Plate’s Shape for Ingots Upsetting

A stress-strain state and a resize of an axial defect during upsetting have been investigated in the article. Theoretical research based on a FEM has been conducted. The upsetting of cylindrical steel workpieces which had the axial defect equal to 10 % of the workpiece diameter has been simulated. Upsetting has been carried out by flat, concave-conical and convex plates (solid or with hole). The result of the studies showed that the main influence on the workpiece shape had a ratio of dimensions. The maximal closure of the axial defect provides upsetting by concave-conical solid plates. Upsetting by flat plates does not provide the closure of axial defects. Convex plates provide the uniform stress-strain state along the workpiece cross section. The hole in the plates increases the non-uniformity of strain distribution and also does not provide the axial defects closure.

Local Limit Load Analytical Model for Thick-Walled Pipe With Axial Surface Defect

Based on the previous limit load analytical modeling for cracked thin-walled pipe (Orynyak, I. V., 2006, “Leak and Break Models of Pressurized Pipe With Axial Defects,” Proceedings of the 6th International Pipeline Conference (IPC), Calgary, Alberta, Canada, Paper No. IPC2006-10066, pp. 41–56), the limit load model for thick-walled pipe had developed. There are some additional peculiarities included in the proposed model. First, the distribution of radial stresses is taken into consideration in the limit state formulation using Tresca's criterion. Second, related to the crack location and interaction of hoop stresses (due to the inner pressure) and axial ones (caused by local bending moment) have been assessed in the limit state. Third, hoop stresses redistribution with possibility of plastic hinge formation in zone opposite to the crack is taken into account. Finally, the proposed easy to use analytical formulas have been verified by comparing with full-scale burst tests.