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1.
  • Bragina, Olga, et al. (författare)
  • Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first in-human study was to evaluate biodistribution, dosimetry, and safety of HER2-specific 99mTc-ADAPT6.METHODS. Twenty-two patients with HER2-positive (n=11) or HER2-negative (n=11) primary breast cancer were intravenously injected with 385125 MBq. The injected amount of protein was either 500 μg (n=11) or 1000 μg (n=11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort received a dose of 250 μg, and the planar scintigraphy followed by SPECT imaging was performed after 2 h only.RESULTS. Injection of 99mTc-ADAPT6 was well tolerated for all doses evaluated in the study, and was not associated with any adverse effects. 99mTc-ADAPT6 cleared rapidly from the blood and the majority of tissues. The normal organs with the highest accumulation were kidney, liver and lung. The effective doses were determined to 0.0090.002 and 0.0100.003 mSv/MBq when injecting protein amounts of 500 and 1000 μg, respectively. Injection of 500 μg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 3719 vs 52, p < 0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p < 0.5) higher for the injected  mass of 500 μg than for both 250 and 1000 μg. In one patient, the imaging using 99mTc-ADAPT6 revealed three bone metastases, which were not found at the time of diagnosis by CT or 99mTcpyrophosphate bone scan. MRI imaging confirmed this finding.CONCLUSION. Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. A protein dose of 500 μg is preferable for discrimination between tumors with high and low expression of HER2. 99mTc-ADAPT6 is a promising imaging probe for the stratification of patients for HER2-targeting therapy.
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2.
  • Bragina, Olga, et al. (författare)
  • Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
  • 2021
  • Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:4, s. 493-499
  • Tidskriftsartikel (refereegranskat)abstract
    • Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6.METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only.RESULTS: Injections of 99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p<0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p<0.05) higher for injected mass of 500 µg than for both 250 and 1000 µg.CONCLUSION: Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. Protein dose of 500 µg is preferable for discrimination between tumors with high and low expression of HER2. Further studies are justified to evaluate if 99mTc-ADAPT6 can be used as an imaging probe for stratification of patients for HER2-targeting therapy in the areas where PET imaging is not readily available.
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3.
  • Bragina, Olga, et al. (författare)
  • Phase I Trial of 99mTc-(HE)3-G3, a DARPin-Based Probe for Imaging of HER2 Expression in Breast Cancer
  • 2022
  • Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 63:4, s. 528-535
  • Tidskriftsartikel (refereegranskat)abstract
    • Radionuclide molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression may enable a noninvasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin (designed ankyrin repeat proteins) G3 is a small (molecular weight, 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this first-in-humans study was to evaluate the safety, biodistribution, and dosimetry of 99mTc-(HE)3-G3.Methods: Three cohorts of patients with primary breast cancer (each including at least 4 patients with HER2-negative and 5 patients with HER2-positive tumors) were injected with 1,000, 2,000, or 3,000 μg of 99mTc-(HE)3-G3 (287 ± 170 MBq). Whole-body planar imaging followed by SPECT was performed at 2, 4, 6, and 24 h after injection. Vital signs and possible side effects were monitored during imaging and up to 7 d after injection.Results: All injections were well tolerated. No side effects were observed. The results of blood and urine analyses did not differ before and after studies. 99mTc-(HE)3-G3 cleared rapidly from the blood. The highest uptake was detected in the kidneys and liver followed by the lungs, breasts, and small intestinal content. The hepatic uptake after injection of 2,000 or 3,000 μg was significantly (P < 0.05) lower than the uptake after injection of 1,000 μg. Effective doses did not differ significantly between cohorts (average, 0.011 ± 0.004 mSv/MBq). Tumor–to–contralateral site ratios for HER-positive tumors were significantly (P < 0.05) higher than for HER2-negative at 2 and 4 h after injection.Conclusion: Imaging of HER2 expression using 99mTc-(HE)3-G3 is safe and well tolerated and provides a low absorbed dose burden on patients. This imaging enables discernment of HER2-positive and HER2-negative breast cancer. Phase I study data justify further clinical development of 99mTc-(HE)3-G3.
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4.
  • Chernov, Vladimir, et al. (författare)
  • Phase I Trial of [Tc-99m]Tc-maSSS-PEG(2)-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors
  • 2023
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [Tc-99m]Tc-maSSS-PEG(2)-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 mu g of [Tc-99m]Tc-maSSS-PEG(2)-RM26 (600-700 MBq). No adverse events or pathological changes were observed. The rapid blood clearance of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was observed with predominantly hepatobiliary excretion. The effective doses were 0.0053 +/- 0.0007 for male patients and 0.008 +/- 0.003 mSv/MBq for female patients. The accumulation of [Tc-99m]Tc-maSSS-PEG(2)-RM26 in tumors was observed in four out of six PCa and in seven out of seven BCa patients. In four BCa patients, a high uptake of the agent into the axillary lymph nodes was detected. Immunohistochemistry revealed positive GRPR expression in 60% of primary PCa, 71.4% of BCa tumors, and 50% of examined BCa lymph nodes. In conclusion, a single administration of [Tc-99m]Tc-maSSS-PEG(2)-RM26 was safe and well tolerated. [Tc-99m]Tc-maSSS-PEG(2)-RM26 SPECT may be useful for tumor detection in PCa and BCa patients, pending further studies.
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5.
  • Xie, Meng, et al. (författare)
  • Secondary ossification center induces and protects growth plate structure
  • 2020
  • Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth plate and articular cartilage constitute a single anatomical entity early in development but later separate into two distinct structures by the secondary ossification center (SOC). The reason for such separation remains unknown. We found that evolutionarily SOC appears in animals conquering the land - amniotes. Analysis of the ossification pattern in mammals with specialized extremities (whales, bats, jerboa) revealed that SOC development correlates with the extent of mechanical loads. Mathematical modeling revealed that SOC reduces mechanical stress within the growth plate. Functional experiments revealed the high vulnerability of hypertrophic chondrocytes to mechanical stress and showed that SOC protects these cells from apoptosis caused by extensive loading. Atomic force microscopy showed that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC has evolved to protect the hypertrophic chondrocytes from the high mechanical stress encountered in the terrestrial environment.
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6.
  • Anantha, Krishnan Hariramabadran, et al. (författare)
  • Correlative Microstructure Analysis and In Situ Corrosion Study of AISI 420 Martensitic Stainless Steel for Plastic Molding Applications
  • 2017
  • Ingår i: Journal of the Electrochemical Society. - : Electrochemical Society. - 0013-4651 .- 1945-7111. ; 164:4, s. C85-C93
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, the corrosion behavior of tempered AISI 420 martensitic stainless steel (MSS) was studied by in-situ atomic force microscopy (AFM) in 0.1M NaCl and correlated with the microstructure. Thermocalc simulation, dilatometry, and X-ray diffraction (XRD) were performed to investigate phase transformation which showed the formation of M3C, M7C3, and M23C6 type of carbides and also retained austenite. Optical microscopy, scanning electron microscopy (SEM), and AFM characterization revealed undissolved carbides and tempering carbides in the martensitic matrix. Volta potential mapping measured by scanning Kelvin probe force microscopy (SKPFM) indicated higher electrochemical (practical) nobility of the carbides with respect to the martensitic matrix whereas regions adjacent to carbides showed lower nobilities due to chromium depletion. Open circuit potential and cyclic potentiodynamic polarization measurements showed metastable corrosion activities associated with a weak passive behavior and a risk for localized corrosion along certain carbide boundaries. In-situ AFM measurements revealed selective dissolution of certain carbide interphases and martensitic inter-lath regions indicating higher propensity to localized corrosion.
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7.
  • Anantha, Krishnan Hariramabadran, et al. (författare)
  • Experimental and modelling study of the effect of tempering on the susceptibility to environment-assisted cracking of AISI 420 martensitic stainless steel
  • 2019
  • Ingår i: Corrosion Science. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0010-938X .- 1879-0496. ; 148, s. 83-93
  • Tidskriftsartikel (refereegranskat)abstract
    • The resistance to environment-assisted cracking (EAC) of AISI 420 martensitic stainless steel (MSS) was investigated in 0.3 M NaCl solution (room temperature) at constant loads for 30 days. The steel tempered at 250 degrees C was superior to the 500 degrees C-temper, which showed corrosion pits favouring cracking. The fracture surface showed faceted grains, cleavage, striations, and inter- and transgranular cracks, suggesting a mixed stress corrosion cracking (SCC) and hydrogen embrittlement (HE) mechanism as the cause for EAC. Finite element modelling (FEM) indicated strain/stress localization at the mouth of deep pits and at the wall of shallow pits, displaying the favoured locations for pit-to-crack transition.
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8.
  • Chernov, Vladimir, et al. (författare)
  • Phase I Clinical Trial Using [Tc-99m]Tc-1-thio-D-glucose for Diagnosis of Lymphoma Patients
  • 2022
  • Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Similar to [F-18]-FDG, [Tc-99m]Tc-1-thio-D-glucose ([Tc-99m]Tc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of [Tc-99m]Tc-TG. Twelve lymphoma patients were injected with 729 +/- 102 MBq [Tc-99m]Tc-TG. Whole-body planar imaging was performed in 10 patients at 2, 4, 6 and 24 h after injection. In all 12 patients, SPECT/CT (at 2 h) and SPECT (at 4 and 6 h) imaging was performed. Vital signs and possible side effects were monitored during imaging and up to 7 days after injection. [Tc-99m]Tc-TG injections were well-tolerated and no side effects or alterations in blood and urine analyses data were observed. The highest absorbed dose was in the kidneys and urinary bladder wall, followed by the adrenals, prostate, bone marrow, lungs, myocardium, ovaries, uterus, liver and gall bladder wall. [Tc-99m]Tc-TG SPECT/CT revealed foci of high activity uptake in the lymph nodes of all nine patients with known nodal lesions. Extranodal lesions were detected in all nine cases. In one patient, a lesion in the humerus head, which was not detected by CT, was visualized using [Tc-99m]Tc-TG. Potentially, [Tc-99m]Tc-TG can be considered as an additional diagnostic method for imaging GLUT receptors in lymphoma patients.
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12.
  • Krakhmalev, Pavel, 1973-, et al. (författare)
  • Influence of heat treatment under hot isostatic pressing (HIP) on microstructure of intermetallic-reinforced tool steel manufactured by laser powder bed fusion
  • 2020
  • Ingår i: Materials Science & Engineering A: Structural Materials: Properties, Microstructure and Processing. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 772
  • Tidskriftsartikel (refereegranskat)abstract
    • Microstructure and properties of as-built laser powder bed fusion (LPBF) steels differ from the conventional ones, and they may contain some porosity and lack of fusion. Therefore, post-treatments, including hot isostatic pressing (HIP), are used to density the material, and tailor the properties of the final product. Usually, HIP is performed as an operation separate from heat treatment. In the present investigation a new approach was used, in which the whole cycle of the heat treatment was carried out in HIP under pressure, and the influence of HIP on microstructure of an advanced stainless maraging tool steel manufactured by LPBF was investigated. For a comparison, a conventional steel grade of the same chemical composition, after a heat treatment at the same temperature-time conditions, was also characterized. The microstructure of the steel was investigated by means of advanced microscopy and atom probe tomography. The influence of the manufacturing route, heat treatment and HIP on microstructure, austenitic phase fraction and size distribution of precipitates was investigated, and the role of high pressure in stabilization of austenite in the microstructure was discussed. It was concluded that since HIP influences phase transformations, a fundamental understanding of the influence of HIP on microstructure is nececcary, and development of new post processing regimes guaranteeing the best performance of the material is required.
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13.
  • Lindwall, Greta, 1981-, et al. (författare)
  • Coarsening investigations of precipitates in PM tool steel grades - an effect of nitrogen
  • 2012
  • Ingår i: Berg- und Huttenmännische Monatshefte (BHM). - : Springer Science and Business Media LLC. - 0005-8912 .- 1613-7531. ; 157:11, s. 406-413
  • Tidskriftsartikel (refereegranskat)abstract
    • We present experimental and theoretical comparisons of the coarsening rate for the MX(X=C, N or C+N) precipitate in five different tool steel grades produced by PowderMetallurgy (PM). The alloys contain different amounts of nitrogen and carbon; ranging fromhigh carbon/low nitrogen to high nitrogen/low carbon. Common for the grades is a highamount of precipitate forming alloying elements resulting in a high fraction of hard phase.Experimentally we have found out that the nitrogen rich precipitates coarsen slower, both forhigher and lower carbon content, than the carbon rich precipitates. Coarsening simulations areperformed utilizing the DICTRA software and an agreement between calculations andmeasurements can be concluded.
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14.
  • Medvedeva, Anna, 1981-, et al. (författare)
  • High-temperature properties and microstructural stability of hot-work tool steels
  • 2009
  • Ingår i: Materials Science & Engineering. - : Elsevier BV. - 0921-5093 .- 1873-4936. ; 523:1-2, s. 39-46
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Indexable insert tools for machining operations are in service exposed to high temperatures and cyclic mechanical loads. Secondary hardening steels such as hot-work steels are commonly used for tools subjected to thermal exposure. However, these steels, highly alloyed with strong carbide forming elements as Cr, V and Mo, are generally difficult to machine and machining represents a large fraction of the production cost of a tool. Thus, the present study concerns the development of a new steel with improved machinability and meeting the requirements for high-temperature properties. Softening resistance of the THG2000 and QRO90 tool steels, commonly used in hot-work applications, and a newly developed tool steel MCG2006 with lower alloying content of carbide forming elements, was investigated by tempering and isothermal fatigue testing. Mechanisms of high-temperature softening of the tested tool steels were discussed with respect to their microstructure and high-temperature mechanical properties. Carbide morphology and precipitation as well as dislocation structure were determined using transmission electron microscopy and X-ray line broadening analysis. No difference in softening behaviour was found among the QRO90 and MCG2006 regarding hot hardness measurements. The THG2000 indicated some stabilization of the hardness between 450 and 550 °C and a considerable hardness decrease at higher temperatures. The short-time cyclic softening in isothermal fatigue was controlled by dislocation rearrangement and annihilation. The alloying composition of the steels presently tested had no influence on the dislocation density decrease. The long-time softening was affected by the material's temper resistance and strongly depended on the carbide morphology and their over-ageing resistance. The QRO90 with greater molybdenum and lower chromium contents than in the THG2000 show the best resistance to softening among the tested grades at all temperatures. The MCG2006, leaner alloyed with the carbide forming elements and alloyed with 4 wt% nickel, has better temper resistance than THG2000 at higher temperatures and longer tempering times.
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16.
  • Medvedeva, Anna, 1981-, et al. (författare)
  • Influence of nickel content on machinability of a hot-work tool steel in prehardened condition
  • 2011
  • Ingår i: Materials & design. - Amsterdam : Elsevier. - 0264-1275 .- 1873-4197 .- 0261-3069. ; 32:2, s. 706-715
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, the influence of nickel content on the machinability of a prehardened hot-work tool steel was investigated. The machinability with varying nickel content from 1 to 5 wt% was characterized in end milling and drilling by evaluating tool life, cutting forces, and tool/chip interface temperature.Nickel content showed to have a positive effect on the machinability of the hot-work tool steel; with increasing nickel content in the steel, the longer tool life was reached in end milling and drilling operations. Machining the higher nickel containing steels generated lower cutting forces and tool/workpiece interface temperature. In addition, less adhesive wear and built-up edge formation were observed on the tools.The difference in the steel machinability was discussed in terms of their microstructure and mechanical properties. Increasing nickel content tends to decrease the carbon in the martensite and to retain a fine distribution of small primary carbides. It resulted in a reduction in yield strength with increasing nickel content related to the cutting force reduction and machinability improvement.
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17.
  • Medvedeva, Anna, 1981- (författare)
  • Performance of advanced tool steels for cutting tool bodies
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Performance of indexable insert cutting tools is not only about the performance of cutting inserts. It is also about the cutting tool body, which has to provide a secure and accurate insert positioning as well as its quick and easy handling under severe working conditions. The common damage mechanisms of cutting tool bodies are fatigue and plastic deformation. Cutting tools undergo high dynamic stresses going in and out cutting engagement; as a result, an adequate level of fatigue strength is the essential steel property. Working temperatures of tool bodies in the insert pocket can reach up to 600°C, why the tool steel requires high softening resistance to avoid plastic deformation. Machinability is also essential, as machining of the steel represents a large fraction of the production cost of a cutting tool. The overall aim of the study is to improve the tool body performance by use of an advanced steel grade with an optimized combination of all the demanding properties. Due to the high-temperature conditions, the thesis concerns mostly hot-work tool steels increasing also the general knowledge of their microstructure, mechanical properties and machinability. Knowing the positive effect of sulphur on machinability of steels, the first step was to indentify a certain limit of the sulphur addition, which would not reduce the fatigue strength of the tool body below an acceptable level. In tool bodies, where the demand on surface roughness was low and a geometrical stress concentrator was present, the addition of sulphur could be up to 0.09 wt%. Fatigue performance of the cutting tools to a large extent depended on the steel resistance to stress relaxation under high dynamic loading and elevated temperatures. The stress relaxation behaviour, material substructure and dislocation characteristics in low-alloyed and hot-work tool steels were studied using X-ray diffraction under thermal and mechanical loading.  Different tool steels exhibited different stress relaxation resistance depending on their microstructure, temper resistance and working temperature. Hot-work tool steels showed to be more preferable to low-alloyed tool steels because of their ability to inhibit the rearrangement and annihilation of induced dislocations. High-temperature softening resistance of the hot-work tool steels was investigated during high-temperature hold-times and isothermal fatigue and discussed with respect to their microstructure. Carbide morphology and precipitation were determined using scanning and transmission electron microscopy. Machinability of a prehardened hot-work tool steel of varying nickel content from 1 to 5 wt% was investigated in end milling and drilling operations. Machining the higher nickel containing steels resulted in longer tool life and generated lower cutting forces and tool/workpiece interface temperature. The difference in machinability of the steels was discussed in terms of their microstructure and mechanical properties. 
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18.
  • Medvedeva, Anna, 1981- (författare)
  • Properties of tool steel for tool holder application : A litterature review
  • 2008
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Large improvements in cutting tool design and technology have been achieved in the last decades. But the problem of improving the tool body material is not adequately studied. In the present study, the different aspects associated with the steel properties as related to the milling cutter body application are reviewed. The working performance of a tool holder depends in particular on the fatigue strength, high temperature properties and machinability of the tool steel used. Rotating tools, tool going in and out of cutting engagement, impose dynamic stresses and require adequate fatigue strength off the tool. Different publications, as well as internal investigation at Uddeholm Tooling AB show that the working temperatures of milling cutter bodies in the insert pocket vary from 300 to 600 degrees Celsius depending on the cutting conditions and material of the workpiece. As a result, steel for this application needs good hot properties such as high temper resistance, high hot hardness values, etc. Machinability is also essential as machining of steel represents a large fraction of the production cost of a milling cutter. Its complex shape with flutes and insert pockets as well as small thread holes and small deep holes for cooling channels require time consuming and advanced machining operations. The essential properties mentioned above were characterized with the emphasis to the steel type, its microstructure and purity, processing and surface treatment and strong interrelations between them.
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19.
  • Medvedeva, Anna, 1981-, et al. (författare)
  • Stress relaxation resistance for improved fatigue performance of shot peened tool components
  • 2008
  • Ingår i: Proceedings of the 10<sup>th</sup> International Conference on Shot Peening, 15-18 September, Tokyo, Japan, 2008. - Tokyo : Academy Common Meiji University. ; , s. 286-295
  • Konferensbidrag (refereegranskat)abstract
    • Shot peening is an extensively used process in the production of mechanical components to improve their fatigue strength at ambient temperature. At higher working temperatures of some mechanical components, e.g. from 300 to 600°C, the influence and behaviour of the compressive residual stresses are more uncertain, since they tend to relieve at higher temperatures. The response to shot peening induced residual stresses of low alloyed and hot work tool steels was evaluated with respect to stress relief heat treatments and isothermal high temperature fatigue testing. Not only the residual stresses, but also the material substructure and its dislocation characteristics are of importance. Dislocation structures were determined using X-ray diffraction to explain the preference of the different steel grades. Also, results obtained from bending fatigue testing at ambient temperature of tool components after shot peening and stress relief heat treatments demonstrated the different ability of retaining the fatigue strength.
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22.
  • Medvedeva, Anna, 1981- (författare)
  • Tool steel for tool holder applications : microstructure and mechanical properties
  • 2008
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Large improvements in cutting tool design and technology, including the application of advanced surface engineering treatments on the cemented carbide insert, have been achieved in the last decades to enhance tool performance. However, the problem of improving the tool body material is not adequately studied. Fatigue is the most common failure mechanism in cutting tool bodies. Rotating tools, tool going in and out of cutting engagement, impose dynamic stresses and require adequate fatigue strength of the tool. Working temperatures of milling cutter bodies in the insert pocket can reach up to 600°C depending on the cutting conditions and material of the workpiece. As a result, steel for this application shall have good hot properties such as high temper resistance and high hot hardness values to avoid plastic deformation in the insert pocket of the cutting tool. Machinability of the steel is also essential, as machining of steel represents a large fraction of the production cost of a milling cutter. This thesis focus on the improvement of the cutting tool performance by the use of steel grades for tool bodies with optimized combination of fatigue strength, machinability and properties at elevated temperatures. The first step was to indentify the certain limit of the sulphur addition for improved machinability which is allowable without reducing the fatigue strength of the milling cutter body below an acceptable level. The combined effect of inclusions, surface condition and geometrical stress concentrator on the fatigue life of the tool steel in smooth specimens and in tool components were studied in bending fatigue. As the fatigue performance of the tools to a large extent depends on the stress relaxation resistance at elevated temperature use, the second step in this research was to investigate the stress relaxation of the commonly used milling cutter body materials and a newly steel developed within the project. Compressive residual stresses were induced by shot peening and their response to mechanical and thermal loading as well as the material substructures and their dislocation characteristics were studied using X-ray diffraction. Softening resistance of two hot work tool steels and a newly developed steel was investigated during high temperature hold times and isothermal fatigue and discussed of with respect to their microstructure. Carbide morphology and precipitation as well as dislocation structure were determined using transmission electron microscopy and X-ray line broadening analysis.
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23.
  • Rehan, Arbab, et al. (författare)
  • Effect of Austenitization and Tempering on the Microstructure and Mechanical Properties of a 5 wt% Cr Cold Work Tool Steel
  • 2016
  • Ingår i: Steel Research International. - : Wiley. - 1611-3683 .- 1869-344X. ; 12:1 December, s. 1609-1618
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of austenitization and tempering temperatures for a 5 wt% Cr cold work tool steel are studied with an aim of understanding the influence on microstructure and mechanical properties. Microstructures are characterized with scanning electron microscopy and light optical microscopy. Retained austenite contents and martensite start temperatures are measured by X-ray diffraction and dilatometry, respectively. Hardness, impact toughness, and compressive yield strength are also determined. When the austenitization temperature is increased from 1020 or 1050 to 1075 °C, followed by tempering at 525 °C, significant hardness is gained while there is no increase in compressive yield strength. Higher austenitization temperatures also produce larger amounts of retained austenite. At the same time, the impact toughness is reduced due to coarsening of the martensitic microstructure. When the steel is tempered at 200 °C, a higher impact toughness and a higher volume fraction of retained austenite are observed. Retained austenite is not found after tempering at temperatures of 525 °C or above. It is concluded that the best combination of mechanical properties is achieved by austenitization at 1020 or 1050 °C followed by tempering at 525 °C.
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24.
  • Rehan, Arbab (författare)
  • Effect of heat treatment on microstructure and mechanical properties of a 5 wt.% Cr cold work tool steel
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This work presents investigations related to phase transformations occurring inthe 5 wt.% Cr cold work tool steel Caldie during hardening and tempering treatments. The influence of austenitisation temperature, cooling rate, sub-zero cooling, isothermal treatment during cooling, tempering temperature and holding time on the microstructure and mechanical properties were investigated.The hardened microstructure of the investigated steel consisted of a mixture ofplate and lath martensite, minor amounts of bainite, blocky and thin retained austenite and M7C3 carbides. Increasing austenitisation temperature from 1020°Cto 1050°C was found useful as it provided higher hardness, good compressive strength and sufficient toughness. However, a further increase to 1075°C resulted in large prior austenite grains which produced coarse martensite containing somewhat increased carbon content. This was found to reduce the impacttoughness of the steel. Significant amounts of retained austenite were present after tempering for 2x2 h between 200°C and 500°C while tempering at 525°C or higher, reduced retained austenite content to below 2%. During holding at tempering temperature carbides precipitated in martensite and possibly in retained austenite. The retained austenite was thereby destabilised and transformed to martensite on cooling. This fresh martensite was tempered by following tempering treatments. It was concluded that tempering at 525°C for 2x2 h was suitable to achieve a good combination of hardness, compressive strength and impact toughness. Retained austenite was also found to transform during holding at 600°C for longer times. Initially, carbides formed in the austenite and after some time transformation of retained austenite to ferrite and carbides took place. Results were used to discuss alternative heat treatment procedures for the 5wt.% Cr cold work tool steel Caldie and some changes of current heat treatment recommendations were suggested.
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25.
  • Rehan, Arbab, et al. (författare)
  • Effects of Austenitisation Temperature and Multiple Tempering on the Microstructure and Impact Toughness of a 5 wt. % Cr Cold Work Tool Steel
  • 2016
  • Ingår i: 10th TOOL Conference, Tool, conference proceedings. - : 10th TOOL Conference. ; , s. 1-10
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • The microstructure and properties of a 5 wt.% Cr cold work tool steel were studied after austenitisation at 1020°C, 1050°C or 1075°C followed by single, double and triple tempering treatments at 525°C. The microstructures were investigated with scanning electron microscopy and X-ray diffraction and phase transformations were studied by dilatometry. Furthermore, hardness and Charpy un-notched and V-notched impact toughness testing was performed and results were correlated to observed microstructures. With higher austenitisation temperature, the martensite and bainite start temperatures were lowered resulting in microstructures containing a higher volume fraction of retained austenite. Retained austenite transformed into martensite on cooling from the tempering temperature. Specimens that were austenitised at 1050°C or 1075°C and tempered twice contained fresh martensite. Applying a third tempering was therefore required to guarantee a fully tempered microstructure. The second tempering resulted in an increase of the un-notched impact energy while the third tempering did not have a pronounced effect. A triple tempering procedure could be preferable when austenitising at high temperatures to avoid undesirable fresh martensite in the tool microstructure.
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26.
  • Rehan, Arbab, et al. (författare)
  • Retained Austenite Transformation during Heat Treatment of a 5 Wt Pct Cr Cold Work Tool Steel
  • 2017
  • Ingår i: Metallurgical and Materials Transactions. A. - : Springer Science and Business Media LLC. - 1073-5623 .- 1543-1940. ; 48A:11, s. 5233-5243
  • Tidskriftsartikel (refereegranskat)abstract
    • Retained austenite transformation was studied for a 5 wt pct Cr cold work tool steel tempered at 798 K and 873 K (525 degrees C and 600 degrees C) followed by cooling to room temperature. Tempering cycles with variations in holding times were conducted to observe the mechanisms involved. Phase transformations were studied with dilatometry, and the resulting microstructures were characterized with X-ray diffraction and scanning electron microscopy. Tempering treatments at 798 K (525 degrees C) resulted in retained austenite transformation to martensite on cooling. The martensite start (M-s) and martensite finish (M-f) temperatures increased with longer holding times at tempering temperature. At the same time, the lattice parameter of retained austenite decreased. Calculations from the Ms temperatures and lattice parameters suggested that there was a decrease in carbon content of retained austenite as a result of precipitation of carbides prior to transformation. This was in agreement with the resulting microstructure and the contraction of the specimen during tempering, as observed by dilatometry. Tempering at 873 K (600 degrees C) resulted in precipitation of carbides in retained austenite followed by transformation to ferrite and carbides. This was further supported by the initial contraction and later expansion of the dilatometry specimen, the resulting microstructure, and the absence of any phase transformation on cooling from the tempering treatment. It was concluded that there are two mechanisms of retained austenite transformation occurring depending on tempering temperature and time. This was found useful in understanding the standard tempering treatment, and suggestions regarding alternative tempering treatments are discussed. (C) The Author(s) 2017.
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27.
  •  
28.
  • Xie, Meng, et al. (författare)
  • Secondary ossification center induces and protects growth plate structure
  • Ingår i: eLIFE. - 2050-084X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth plate and articular cartilage constitute a single anatomical entity, but later separate into two distinct structures by the formation of secondary ossification center (SOC). The reason for such spatial separation remains unknown. Here, we demonstrate that evolutionarily SOC first appears in amniotes. Mathematical modelling reveals that SOC reduces mechanical stress within the growth plate. Analysis of mammals with specialized extremities reveals that SOC size correlates with the extent of mechanical demands. Ex and in vivo experiments demonstrate that SOC allows epiphyseal chondrocytes to withstand a several-fold higher load before activation of the YAP-p73 signalling pathway and caspase-dependent apoptosis, with hypertrophic chondrocytes being the most load-sensitive cells. Atomic force microscopy shows  that hypertrophic chondrocytes are the least mechanically stiff cells within the growth plate. Altogether, these findings suggest that SOC is evolved to protect epiphyseal chondrocytes, especially the hypertrophic chondrocytes, from the high mechanical stress encountered in the terrestrial environment.
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